|
1
|
Golebiowska AA, Intravaia JT, Sathe V, Kumbar SG, Nukavarapu SP. Engineered Osteochondral Scaffolds with Bioactive Cartilage Zone for Enhanced Articular Cartilage Regeneration. Ann Biomed Eng 2025; 53:597-611. [PMID: 39602036 PMCID: PMC11835937 DOI: 10.1007/s10439-024-03655-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2024] [Accepted: 11/18/2024] [Indexed: 11/29/2024]
Abstract
Despite progress, osteochondral (OC) tissue engineering strategies face limitations in terms of articular cartilage layer development and its integration with the underlying bone tissue. The main objective of this study is to develop a zonal OC scaffold with native biochemical signaling in the cartilage zone to promote articular cartilage development devoid of cells and growth factors. Herein, we report the development and in vivo assessment of a novel gradient and zonal-structured scaffold for OC defect regeneration. The scaffold system is composed of a mechanically supportive 3D-printed template containing decellularized cartilage extracellular matrix (ECM) biomaterial in the cartilage zone that possesses bioactive characteristics, such as chemotactic activity and native tissue biochemical composition. OC scaffolds with a bioactive cartilage zone were implanted in vivo in a rabbit osteochondral defect model and assessed for gross morphology, matrix deposition, cellular distribution, and overall tissue regeneration. The scaffold system supported recruitment and infiltration of host cells into the cartilage zone of the graft, which led to increased ECM deposition and physiologically relevant articular cartilage tissue formation. Semi-quantitative ICRS scoring (overall score double for OC scaffold with bioactive cartilage zone compared to PLA scaffold) further confirm the bioactive scaffold enhanced articular cartilage engineering. This strategy of designing bioactive scaffolds to promote endogenous cellular infiltration can be a much simpler and effective approach for OC tissue repair and regeneration.
Collapse
Affiliation(s)
- Aleksandra A Golebiowska
- Department of Biomedical Engineering, University of Connecticut, 260 Glenbrook Road, Unit 3247, Storrs, CT, 06269, USA
| | - Jonathon T Intravaia
- Department of Biomedical Engineering, University of Connecticut, 260 Glenbrook Road, Unit 3247, Storrs, CT, 06269, USA
| | - Vinayak Sathe
- Department of Orthopaedic Surgery, University of Connecticut Health, Farmington, CT, 06032, USA
| | - Sangamesh G Kumbar
- Department of Biomedical Engineering, University of Connecticut, 260 Glenbrook Road, Unit 3247, Storrs, CT, 06269, USA
- Department of Materials Science & Engineering, University of Connecticut, Storrs, CT, 06269, USA
- Department of Orthopaedic Surgery, University of Connecticut Health, Farmington, CT, 06032, USA
| | - Syam P Nukavarapu
- Department of Biomedical Engineering, University of Connecticut, 260 Glenbrook Road, Unit 3247, Storrs, CT, 06269, USA.
- Department of Materials Science & Engineering, University of Connecticut, Storrs, CT, 06269, USA.
- Department of Orthopaedic Surgery, University of Connecticut Health, Farmington, CT, 06032, USA.
| |
Collapse
|
|
2
|
Prakash R, Waseem A, Siddiqui AJ, Naime M, Khan MA, Robertson AA, Boltze J, Raza SS. MCC950 mitigates SIRT3-NLRP3-driven inflammation and rescues post-stroke neurogenesis. Biomed Pharmacother 2025; 183:117861. [PMID: 39874781 DOI: 10.1016/j.biopha.2025.117861] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2024] [Revised: 12/23/2024] [Accepted: 01/18/2025] [Indexed: 01/30/2025] Open
Abstract
Sustained activation of the SIRT3-NLRP3 inflammasome has been associated with worse outcomes after ischemic stroke. The objective of this study was to examine the potential mechanism by which the SIRT3-NLRP3 inflammasome affects neural stem and progenitor cells (NSPCs) after transient middle cerebral artery occlusion (tMCAO) in rats. Following tMCAO, significantly elevated levels of NLRP3, ASC, cleaved caspase 1, IL-1β, and IL-18 were observed in the ischemic subventricular zone. Moreover, tMCAO increased NLRP3 expression while decreasing SIRT3 levels, suggesting a connection between these two processes. Furthermore, we discovered that inflammation induced by the NLRP3 inflammasome impaired post-stroke hippocampal and subventricular neurogenesis, while nestin (a marker for NSPCs) and Sox2 (a marker for stem cell pluripotency) were downregulated after tMCAO. However, systemic administration of MCC950 reduced inflammatory signaling and effectively restored neurogenesis. Overall, our results suggest that protecting NSPCs and neurogenesis in the ischemically damaged brain by mitigating the impact of the SIRT3-NLRP3 inflammasome may be a feasible treatment strategy for ischemic stroke.
Collapse
Affiliation(s)
- Ravi Prakash
- Laboratory for Stem Cell & Restorative Neurology, Department of Biotechnology, Era's Lucknow Medical College and Hospital, Era University, Sarfarazganj, Lucknow 226003, India
| | - Arshi Waseem
- Laboratory for Stem Cell & Restorative Neurology, Department of Biotechnology, Era's Lucknow Medical College and Hospital, Era University, Sarfarazganj, Lucknow 226003, India
| | - Abu Junaid Siddiqui
- Laboratory for Stem Cell & Restorative Neurology, Department of Biotechnology, Era's Lucknow Medical College and Hospital, Era University, Sarfarazganj, Lucknow 226003, India
| | - Mohammad Naime
- Central Research Institute of Unani Medicine (Under Central Council for Research in Unani Medicine, Ministry of Ayush, Govt of India), Lucknow-226026, Uttar Pradesh, India
| | | | - Avril Ab Robertson
- School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, QLD, Australia
| | - Johannes Boltze
- School of Life Sciences, University of Warwick, Coventry, UK
| | - Syed Shadab Raza
- Laboratory for Stem Cell & Restorative Neurology, Department of Biotechnology, Era's Lucknow Medical College and Hospital, Era University, Sarfarazganj, Lucknow 226003, India; Department of Stem Cell Biology and Regenerative Medicine, Era's Lucknow Medical College Hospital, Era University, Sarfarazganj, Lucknow 226003, India.
| |
Collapse
|
|
3
|
Hang R, Zhao Y, Chen H, Li X, Yao R, Sun Y, Yao X, Bai L, Wang H, Han Y, Hang R. Construction and high-throughput screening of gradient nanowire coatings on titanium surface towards ameliorated osseointegration. Mater Today Bio 2025; 30:101392. [PMID: 39759850 PMCID: PMC11697249 DOI: 10.1016/j.mtbio.2024.101392] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2024] [Revised: 12/02/2024] [Accepted: 12/06/2024] [Indexed: 01/07/2025] Open
Abstract
Surface nano-modification has emerged as an effective strategy to enhance osseointegration of titanium (Ti) implants. Despite its promise, rational optimization of surface nanomorphology for ameliorated osseointegration remains a significant challenge. Our research pioneering developed a one-step alkali etching technique to produce a gradient nanowire coating with continuously varied dimensions on Ti surfaces, which was subsequently served as a versatile platform for high-throughput screening of optimal dimensions to enhance osseointegration. The results showed that macrophages (MФs) that mainly governed the initial inflammatory reaction exhibited a polarization tendency towards pro-healing M2 phenotype with decreased nanowire dimension due to nanomorphology-mediated focal adhesion formation and activation of its downstream signaling pathways (typically PI3K-Akt). Simultaneously, small-sized nanowires with diameter of 5.63-14.25 nm and inter-spacing of 29.42-57.97 nm were conductive to angiogenesis of endothelial cells (ECs) and osteogenesis of bone marrow mesenchymal stem cells (BMSCs), which may share similar mechanisms of MФs. The in vivo results well corroborated these in vitro observations. The knowledge gained from the present work not only advance our understanding of the interaction between surface morphology and cells, but also potentially pave the way for efficient and cost-effective design of advanced biomaterial surfaces for better osseointegration.
Collapse
Affiliation(s)
- Ruiyue Hang
- Shanxi Key Laboratory of Biomedical Metal Materials, College of Materials Science and Engineering, Taiyuan University of Technology, Taiyuan, 030024, China
| | - Yuyu Zhao
- Shanxi Key Laboratory of Biomedical Metal Materials, College of Materials Science and Engineering, Taiyuan University of Technology, Taiyuan, 030024, China
| | - Huanming Chen
- Shanxi Key Laboratory of Biomedical Metal Materials, College of Materials Science and Engineering, Taiyuan University of Technology, Taiyuan, 030024, China
| | - Xiaomei Li
- Shanxi Provincial Key Laboratory of Protein Structure Determination, Shanxi Academy of Advanced Research and Innovation, Taiyuan, 030012, China
| | - Runhua Yao
- Shanxi Key Laboratory of Biomedical Metal Materials, College of Materials Science and Engineering, Taiyuan University of Technology, Taiyuan, 030024, China
| | - Yonghua Sun
- Shanxi Key Laboratory of Biomedical Metal Materials, College of Materials Science and Engineering, Taiyuan University of Technology, Taiyuan, 030024, China
| | - Xiaohong Yao
- Shanxi Key Laboratory of Biomedical Metal Materials, College of Materials Science and Engineering, Taiyuan University of Technology, Taiyuan, 030024, China
| | - Long Bai
- Institute of Translational Medicine, Shanghai University, Shanghai, 200444, China
| | - Huaiyu Wang
- Center for Human Tissues and Organs Degeneration, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, China
| | - Yong Han
- State-Key Laboratory for Mechanical Behavior of Materials, Xi'an Jiaotong University, Xi'an, 710049, China
| | - Ruiqiang Hang
- Shanxi Key Laboratory of Biomedical Metal Materials, College of Materials Science and Engineering, Taiyuan University of Technology, Taiyuan, 030024, China
- State-Key Laboratory for Mechanical Behavior of Materials, Xi'an Jiaotong University, Xi'an, 710049, China
| |
Collapse
|
|
4
|
Miron RJ, Moraschini V, Estrin N, Shibli JA, Cosgarea R, Jepsen K, Jervøe‐Storm P, Wang H, Sculean A, Jepsen S. Autogenous platelet concentrates for treatment of intrabony defects-A systematic review with meta-analysis. Periodontol 2000 2025; 97:153-190. [PMID: 39425513 PMCID: PMC11808470 DOI: 10.1111/prd.12598] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2024] [Revised: 06/21/2024] [Accepted: 07/16/2024] [Indexed: 10/21/2024]
Abstract
To provide an overview of the use of autogenous platelet concentrates (APCs) in periodontal regeneration and to conduct a systematic review (SR) of the treatment outcomes of periodontal intrabony defects by using platelet-rich fibrin (PRF) compared with other commonly utilized modalities. The eligibility criteria comprised randomized controlled trials (RCTs) comparing the clinical outcomes of PRF with that of other modalities. Studies were classified into 21 categories and into five different groups as follows: Group I (1) open flap debridement (OFD) alone versus OFD/PRF, (2) OFD versus Titanium-PRF (T-PRF) Group II, (3) Comparative PRF protocols (PRF vs. T-PRF), Group III (Comparative Studies to PRF): (4) OFD/PRP versus OFD/PRF, (5) OFD/bone graft(BG)/PRGF versus OFD/BG/PRF, (6) OFD/EMD versus OFD/PRF, (7) OFD/BG/EMD versus OFD/BG/PRF, (8) OFD/collagen membrane (CM) versus OFD/PRF, (9) OFD/BG/BM versus OFD/BG/PRF, (10) OFD/BG versus OFD/PRF, Group IV (Addition of PRF to treatment groups) (11) OFD/BG versus OFD/BG/PRF, (12) OFD/GTR versus OFD/GTR + PRF (13) OFD/EMD versus OFD/EMD/PRF (14) OFD/BG/BM versus OFD/BG/BM/PRF, Group V (Addition of Biomaterial/Biomolecule to PRF): OFD/PRF versus … (15) OFD/PRF/BG, (16) OFD/PRF/antibiotic, (17) OFD/PRF/Metformin, (18) OFD/PRF/Bisphosphonates, (19) OFD/PRF/Statins, (20) OFD/BG/PRF versus OFD/BG/PRF/Statins, and (21) OFD/PRF/low-level laser therapy (LLLT). Weighted means and forest plots were calculated for probing pocket depth (PPD), clinical attachment level (CAL), and radiographic bone fill (RBF). From 596 records identified, 55 RCTs were included. Group I: The use of OFD/PRF statistically significantly reduced PPD and improved CAL and RBF when compared to OFD. Group II: A significant difference between various PRF protocols was only observed for PPD. Group III: No significant advantage was found when comparing OFD/PRF to the following groups: OFD/PRP, OFD/EMD, OFD/BM, or OFD/BG. Group IV: The addition of PRF to OFD/BG led to significant improvements in PPD, CAL and RBF compared with OFD/BG alone. Group V: The addition of either a BG as well as three of the following biomolecules (metformin, bisphosphonates, and statins) to OFD/PRF led to statistically significant improvements in PPD, CAL, and/or RBF when compared to OFD/PRF alone. The use of PRF significantly improved clinical outcomes in intrabony defects when compared to OFD alone. Similar results were observed when OFD/PRF was compared with OFD/BG, OFD/EMD, OFD/PRP, and OFD/BM. The addition of PRF to a bone grafting material as well as the addition of various small biomolecules to PRF may offer additional clinical advantages, thus warranting further investigations. Future research investigating various protocols of PRF, longer-term outcomes, as well as PRF at the human histological level remains needed.
Collapse
Affiliation(s)
| | - Vittorio Moraschini
- Department of Oral Surgery, School of Dentistry, Fluminense Federal UniversityNiteróiRio de JaneiroBrazil
| | - Nathan Estrin
- School of Dental MedicineLake Erie College of Osteopathic MedicineBradentonFloridaUSA
| | - Jamil Awad Shibli
- Department of Implant Dentistry, School of DentistryGuarulhos UniversityGuarulhosBrazil
| | - Raluca Cosgarea
- Department of Periodontology, Operative and Preventive DentistryUniversity of BonnBonnGermany
- Department of PeriodontologyUniversity of MarburgGermany
- Faculty of DentistryUniversity Iuliu Hatieganu Cluj‐NapocaRomania
| | - Karin Jepsen
- Department of Periodontology, Operative and Preventive DentistryUniversity of BonnBonnGermany
| | - Pia‐Merete Jervøe‐Storm
- Department of Periodontology, Operative and Preventive DentistryUniversity of BonnBonnGermany
| | - Hom‐Lay Wang
- Department of Periodontics and Oral MedicineUniversity of MichiganAnn ArborMichiganUSA
| | - Anton Sculean
- Department of PeriodontologyUniversity of BernBernSwitzerland
| | - Søren Jepsen
- Department of Periodontology, Operative and Preventive DentistryUniversity of BonnBonnGermany
| |
Collapse
|
|
5
|
Moyo MTG, Adali T. Gellan gum as a promising transplantation carrier for differentiated progenitor cells in ophthalmic therapies. J BIOACT COMPAT POL 2025; 40:136-157. [DOI: 10.1177/08839115241278739] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
Abstract
Stem cell-based therapies for various ocular conditions are increasingly gaining traction in ophthalmic treatments, with hydrogel-based polymers playing a pivotal role. Current stem cell delivery methods face challenges such as limited cell retention, immunological rejection, and uneven dispersion. Hence, there is a critical demand for innovative delivery systems to enhance the viability, localization, and integration of transplanted stem cells while minimizing adverse effects. Central to this advancement is the meticulous selection of appropriate materials. Among the promising options, gellan gum, a versatile polysaccharide, is emerging as a potential carrier for differentiated progenitor cells in regenerative medicine, particularly in ophthalmology. This study explores the utilization of gellan gum hydrogels as carriers, focusing on their biocompatibility, customizable gelation properties, and ability to encapsulate, transplant, and biofunctionalize cells. Through a review of literature, the impact of gellan gum hydrogels on cell viability parameters is investigated, revealing their potential for promoting tissue regeneration and functional recovery in ocular diseases. Furthermore, this study compares gellan gum systems utilizing natural and synthetic polymers, discerning differences in efficacy, biocompatibility, and suitability for diverse applications in regenerative ophthalmology. This review highlights the promising role of gellan gum in ophthalmic therapies, providing valuable insights into future directions and hurdles in this evolving field.
Collapse
Affiliation(s)
- Mthabisi Talent George Moyo
- Department of Biomedical Engineering, Faculty of Engineering, Near East University, Nicosia, North Cyprus, Mersin, Turkey
- Department of Medical Biochemistry, Faculty of Medicine, Girne American University, North Cyprus, Mersin, Turkey
- Research and Application Center of Biomedical Sciences, Girne American University, North Cyprus, Mersin, Turkey
| | - Terin Adali
- Department of Medical Biochemistry, Faculty of Medicine, Girne American University, North Cyprus, Mersin, Turkey
- Research and Application Center of Biomedical Sciences, Girne American University, North Cyprus, Mersin, Turkey
| |
Collapse
|
|
6
|
Chen TY, Dai NT, Wen TK, Hsu SH. An Acellular, Self-Healed Trilayer Cryogel for Osteochondral Regeneration in Rabbits. Adv Healthc Mater 2024; 13:e2400462. [PMID: 38948966 DOI: 10.1002/adhm.202400462] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2024] [Revised: 06/13/2024] [Indexed: 07/02/2024]
Abstract
Osteochondral regeneration remains formidable challenges despite significant advances in microsurgery. Herein, an acellular trilayer cryogel (TC) with injectability, tunable pore sizes (80-200 µm), and appropriate compressive modulus (10.8 kPa) is manufactured from self-healable hydrogel under different gelling times through Schiff reaction between chitosan and difunctionalized polyurethane (DFPU). Bioactive molecules (Y27632 and dexamethasone) are respectively loaded in the top and bottom layers to form the Y27632/dexamethasone-loaded trilayer cryogel (Y/DEX-TC). Mesenchymal stem cells (MSCs) seeded in Y/DEX-TC proliferated ≈350% in vitro and underwent chondrogenesis or osteogenesis in response to the respective release of Y or DEX in 14 days. Acupuncture is administered to animals in an attempt to modulate the innate regulatory system and mobilize endogenous MSCs for osteochondral defect regeneration. In vivo rabbit experiments using Y/DEX-TC combined with acupuncture successfully regulate SDF-1 and TGF-β1 levels, which possibly cause MSC migration toward Y/DEX-TC. The synergistic effect of cryogel and acupuncture on immunomodulation is verified with a ≈7.3-fold enhancement of the M2-/M1-macrophage population ratio by treatment of Y/DEX-TC combining acupuncture, significantly greater than ≈1.5-fold increase by acupuncture or ≈2.2-fold increase by Y/DEX-TC alone. This novel strategy using acellular drug-loaded cryogel and accessible acupuncture shows promise in treating osteochondral defects of joint damage.
Collapse
Affiliation(s)
- Tsai-Yu Chen
- Institute of Polymer Science and Engineering, National Taiwan University, Taipei, Taiwan, 106319, R.O.C
| | - Niann-Tzyy Dai
- Division of Plastic and Reconstructive Surgery, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, 114202, R.O.C
| | - Tsung-Kai Wen
- School of Post-Baccalaureate Chinese Medicine, Tzu Chi University, Hualien, Taiwan, 970374, R.O.C
| | - Shan-Hui Hsu
- Institute of Polymer Science and Engineering, National Taiwan University, Taipei, Taiwan, 106319, R.O.C
- Institute of Cellular and System Medicine, National Health Research Institutes, Miaoli, Taiwan, 350401, R.O.C
| |
Collapse
|
|
7
|
Chen X, Xu Z, Gao Y, Chen Y, Yin W, Liu Z, Cui W, Li Y, Sun J, Yang Y, Ma W, Zhang T, Tian T, Lin Y. Framework Nucleic Acid-Based Selective Cell Catcher for Endogenous Stem Cell Recruitment. ADVANCED MATERIALS (DEERFIELD BEACH, FLA.) 2024; 36:e2406118. [PMID: 39543443 DOI: 10.1002/adma.202406118] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/29/2024] [Revised: 09/23/2024] [Indexed: 11/17/2024]
Abstract
Cell-surface engineering holds great promise in boosting endogenous stem cell attraction for tissue regeneration. However, challenges such as cellular internalization of ligand and the dynamic nature of cell membranes often complicate ligand-receptor interactions. The aim of this study is to harness the innovative potential of programmable tetrahedral framework nucleic acid (tFNA) to enable precise, tunable ligand-receptor interactions, thereby improving stem cell recruitment efficiency. This approach involves experimental screening and theoretical analysis using dissipative particle dynamics. The results demonstrate that altering the flexibility and topology of ligands on tFNA changes their cellular internalization and membrane binding efficiency. Furthermore, optimizing the distribution of the mesenchymal stem cell (MSC)-binding aptamer 19S (Apt19S) on the tFNA enhances the stem cell capture efficiency. Following successful in vitro MSC capture, Apt19S-modified tFNA is chemically linked to a hyaluronic acid hydrogel, forming an efficient "stem cell catcher" system. Subsequent in vivo experiments demonstrate that this system effectively promotes early stem cell recruitment and accelerates bone regeneration in different bone healing scenarios, including cranial and maxillary defects.
Collapse
Affiliation(s)
- Xingyu Chen
- State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, 610041, China
- Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, P. R. China
| | - Ziang Xu
- State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, 610041, China
- Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, P. R. China
| | - Yang Gao
- State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, 610041, China
- Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, P. R. China
| | - Ye Chen
- State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, 610041, China
- Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, P. R. China
| | - Wumeng Yin
- State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, 610041, China
- Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, P. R. China
| | - Zhiqiang Liu
- State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, 610041, China
- Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, P. R. China
| | - Weitong Cui
- State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, 610041, China
- Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, P. R. China
| | - Yong Li
- State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, 610041, China
- Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, P. R. China
| | - Jiafei Sun
- State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, 610041, China
- Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, P. R. China
| | - Yuting Yang
- State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, 610041, China
- Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, P. R. China
| | - Wenjuan Ma
- State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, 610041, China
- Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, P. R. China
| | - Tao Zhang
- State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, 610041, China
- Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, P. R. China
| | - Taoran Tian
- State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, 610041, China
- Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, P. R. China
| | - Yunfeng Lin
- State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, 610041, China
- Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, P. R. China
- Sichuan Provincial Engineering Research Center of Oral Biomaterials, Chengdu, Sichuan, 610041, China
| |
Collapse
|
|
8
|
Zuo X, Xiao Y, Yang J, He Y, He Y, Liu K, Chen X, Guo J. Engineering collagen-based biomaterials for cardiovascular medicine. COLLAGEN AND LEATHER 2024; 6:33. [DOI: 10.1186/s42825-024-00174-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/27/2024] [Revised: 07/25/2024] [Accepted: 08/21/2024] [Indexed: 01/06/2025]
Abstract
AbstractCardiovascular diseases have been the leading cause of global mortality and disability. In addition to traditional drug and surgical treatment, more and more studies investigate tissue engineering therapeutic strategies in cardiovascular medicine. Collagen interweaves in the form of trimeric chains to form the physiological network framework of the extracellular matrix of cardiac and vascular cells, possessing excellent biological properties (such as low immunogenicity and good biocompatibility) and adjustable mechanical properties, which renders it a vital tissue engineering biomaterial for the treatment of cardiovascular diseases. In recent years, promising advances have been made in the application of collagen materials in blood vessel prostheses, injectable cardiac hydrogels, cardiac patches, and hemostatic materials, although their clinical translation still faces some obstacles. Thus, we reviewed these findings and systematically summarizes the application progress as well as problems of clinical translation of collagen biomaterials in the cardiovascular field. The present review contributes to a comprehensive understanding of the application of collagen biomaterials in cardiovascular medicine.
Graphical abstract
Collapse
|
|
9
|
Wu Y, Wu Z, Li Z, Hong Y. Simulation of the bone remodelling microenvironment by calcium compound-loaded hydrogel fibrous membranes for in situ bone regeneration. J Mater Chem B 2024; 12:10012-10027. [PMID: 39248119 DOI: 10.1039/d4tb01088d] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/10/2024]
Abstract
The endowment of guided bone regeneration (GBR) membranes with the ability to activate the endogenous regenerative capability of bone to regenerate bone defects is of clinical significance. Herein we explored the preparation of the calcium compound (CC) (calcium sulfate (CaSL), calcium hydrophosphate (CaHP), or tricalcium phosphate (TCaP)) loaded ultrathin silk fibroin (SF)/gelatin (G) fibre membranes via electrospinning as the GBR membranes to regenerate the calvarial bone defects. The in vitro experiments demonstrated that the CaSL-loaded ultrathin fibrous membranes could simulate optimally the bone remodelling microenvironment in comparison with the CaHP- and TCaP-loaded fibrous membranes, displaying the highest activity to regulate the migration, proliferation, and differentiation of mesenchymal stem cells (MSCs). Also, the in vivo experiments demonstrated that the CaSL-loaded fibrous membranes presented the highest intrinsic osteoinduction to guide in situ regeneration of bone. Furthermore, the in vivo experiments demonstrated that the as-prepared composite fibrous membranes possessed good degradability. In summary, our results suggested that the CaSL-loaded fibrous membranes with high intrinsic osteoinduction and good degradability have potential to translate into clinical practice.
Collapse
Affiliation(s)
- Yanmei Wu
- National Engineering Research Centre for Biomaterials, College of Biomedical Engineering, Sichuan University, Chengdu 610064, P. R. China.
| | - Zhen Wu
- National Engineering Research Centre for Biomaterials, College of Biomedical Engineering, Sichuan University, Chengdu 610064, P. R. China.
- School of Medicine and Health, Zhengzhou Research Institute, Harbin Institute of Technology, Zhengzhou, Henan 450000, China
| | - Zhe Li
- National Engineering Research Centre for Biomaterials, College of Biomedical Engineering, Sichuan University, Chengdu 610064, P. R. China.
| | - Youliang Hong
- National Engineering Research Centre for Biomaterials, College of Biomedical Engineering, Sichuan University, Chengdu 610064, P. R. China.
| |
Collapse
|
|
10
|
Sun L, Qu H, He X, Tian B, Wu R, Yin Y, Zou J, Sun H, Li X, Chen F. Pyroptotic macrophages induce disruption of glutamate metabolism in periodontal ligament stem cells contributing to their compromised osteogenic potential. Cell Prolif 2024; 57:e13663. [PMID: 38803043 PMCID: PMC11471398 DOI: 10.1111/cpr.13663] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2024] [Revised: 05/07/2024] [Accepted: 05/09/2024] [Indexed: 05/29/2024] Open
Abstract
Macrophage pyroptosis is of key importance to host defence against pathogen infections and may participate in the progression and recovery of periodontitis. However, the role of pyroptotic macrophages in regulating periodontal ligament stem cells (PDLSCs), the main cell source for periodontium renewal, remains unclear. First, we found that macrophage pyroptosis were enriched in gingiva tissues from periodontitis patients compared with those of healthy people through immunofluorescence. Then the effects of pyroptotic macrophages on the PDLSC osteogenic differentiation were investigated in a conditioned medium (CM)-based coculture system in vitro. CM derived from pyroptotic macrophages inhibited the osteogenic differentiation-related gene and protein levels, ALP activity and mineralized nodule formation of PDLSCs. The osteogenic inhibition of CM was alleviated when pyroptosis was inhibited by VX765. Further, untargeted metabolomics showed that glutamate limitation may be the underlying mechanism. However, exogenous glutamate supplementation aggravated the CM-inhibited osteogenic differentiation of PDLSCs. Moreover, CM increased extracellular glutamate and decreased intracellular glutamate levels of PDLSCs, and enhanced the gene and protein expression levels of system xc - (a cystine/glutamate antiporter). After adding cystine to CM-based incubation, the compromised osteogenic potency of PDLSCs was rescued. Our data suggest that macrophage pyroptosis is related to the inflammatory lesions of periodontitis. Either pharmacological inhibition of macrophage pyroptosis or nutritional supplements to PDLSCs, can rescue the compromised osteogenic potency caused by pyroptotic macrophages.
Collapse
Affiliation(s)
- Li‐Juan Sun
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi International Joint Research Center for Oral Diseases, Department of Periodontology, School of StomatologyThe Fourth Military Medical UniversityXi'anChina
| | - Hong‐Lei Qu
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi International Joint Research Center for Oral Diseases, Department of Periodontology, School of StomatologyThe Fourth Military Medical UniversityXi'anChina
| | - Xiao‐Tao He
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi International Joint Research Center for Oral Diseases, Department of Periodontology, School of StomatologyThe Fourth Military Medical UniversityXi'anChina
| | - Bei‐Min Tian
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi International Joint Research Center for Oral Diseases, Department of Periodontology, School of StomatologyThe Fourth Military Medical UniversityXi'anChina
| | - Rui‐Xin Wu
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi International Joint Research Center for Oral Diseases, Department of Periodontology, School of StomatologyThe Fourth Military Medical UniversityXi'anChina
| | - Yuan Yin
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi International Joint Research Center for Oral Diseases, Department of Periodontology, School of StomatologyThe Fourth Military Medical UniversityXi'anChina
| | - Jie‐Kang Zou
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi International Joint Research Center for Oral Diseases, Department of Periodontology, School of StomatologyThe Fourth Military Medical UniversityXi'anChina
| | - Hai‐Hua Sun
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi International Joint Research Center for Oral Diseases, Department of General Dentistry and Emergency, School of StomatologyThe Fourth Military Medical UniversityXi'anChina
| | - Xuan Li
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi International Joint Research Center for Oral Diseases, Department of Periodontology, School of StomatologyThe Fourth Military Medical UniversityXi'anChina
| | - Fa‐Ming Chen
- State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi International Joint Research Center for Oral Diseases, Department of Periodontology, School of StomatologyThe Fourth Military Medical UniversityXi'anChina
| |
Collapse
|
|
11
|
Kumar J, Karim A, Sweety UH, Sarma H, Nurunnabi M, Narayan M. Bioinspired Approaches for Central Nervous System Targeted Gene Delivery. ACS APPLIED BIO MATERIALS 2024; 7:4975-4997. [PMID: 38100377 DOI: 10.1021/acsabm.3c00842] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2023]
Abstract
Disorders of the central nervous system (CNS) which include a wide range of neurodegenerative and neurological conditions have become a serious global issue. The presence of CNS barriers poses a significant challenge to the progress of designing effective therapeutic delivery systems, limiting the effectiveness of drugs, genes, and other therapeutic agents. Natural nanocarriers present in biological systems have inspired researchers to design unique delivery systems through biomimicry. As natural resource derived delivery systems are more biocompatible, current research has been focused on the development of delivery systems inspired by bacteria, viruses, fungi, and mammalian cells. Despite their structural potential and extensive physiological function, making them an excellent choice for biomaterial engineering, the delivery of nucleic acids remains challenging due to their instability in biological systems. Similarly, the efficient delivery of genetic material within the tissues of interest remains a hurdle due to a lack of selectivity and targeting ability. Considering that gene therapies are the holy grail for intervention in diseases, including neurodegenerative disorders such as Alzheimer's disease, Parkinson's Disease, and Huntington's disease, this review centers around recent advances in bioinspired approaches to gene delivery for the prevention of CNS disorders.
Collapse
Affiliation(s)
- Jyotish Kumar
- Department of Chemistry and Biochemistry, The University of Texas at El Paso (UTEP), El Paso, Texas 79968, United States
| | - Afroz Karim
- Department of Chemistry and Biochemistry, The University of Texas at El Paso (UTEP), El Paso, Texas 79968, United States
| | - Ummy Habiba Sweety
- Environmental Science and Engineering, The University of Texas at El Paso (UTEP), El Paso, Texas 79968, United States
| | - Hemen Sarma
- Bioremediation Technology Research Group, Department of Botany, Bodoland University, Rangalikhata, Deborgaon, 783370, Kokrajhar (BTR), Assam, India
| | - Md Nurunnabi
- The Department of Pharmaceutical Sciences, School of Pharmacy, The University of Texas at El Paso, El Paso, Texas 79968, United States
| | - Mahesh Narayan
- Department of Chemistry and Biochemistry, The University of Texas at El Paso (UTEP), El Paso, Texas 79968, United States
| |
Collapse
|
|
12
|
Zhang K, Zhang C, Zhou H, Yang Y, Wen Y, Jiao X, Yao M, Wen Y. Elastic Nanofibrous Dressings with Mesenchymal Stem Cell-Recruiting and Protecting Characteristics for Promoting Diabetic Wound Healing. ACS APPLIED MATERIALS & INTERFACES 2024; 16:41869-41880. [PMID: 39101935 DOI: 10.1021/acsami.4c07369] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 08/06/2024]
Abstract
Diabetic wounds that do not heal for a long time challenge global healthcare. Mesenchymal stem cell (MSC) therapy has positive significance in promoting diabetic wound healing. However, traditional MSC therapy involves exogenous MSCs, which brings many limitations and unsatisfactory treatment. Moreover, the maintenance of MSC viability and function is difficult because of the high level of reactive oxygen species (ROS) in diabetic wounds. Therefore, we developed a nanofibrous dressing to recruit and protect endogenous MSCs while avoiding the inherent disadvantages of exogenous MSCs. Ceria nanoparticles capable of ROS scavenging are integrated into the nanofibrous dressings, together with Apt19S, a DNA aptamer with affinity and selectivity for MSCs. In addition, the homogenization and freeze-drying technology give the nanofibrous dressings good elasticity, which protects the wound from external pressure. Further experiments in diabetic mice show that the dressing has excellent endogenous MSC recruitment and anti-inflammatory properties, thereby synergistically promoting diabetic wound healing. This study is expected to explore an efficient method of stem cell therapy, providing a new way to construct high-performance wound dressings.
Collapse
Affiliation(s)
- Kexin Zhang
- College of Chemical Engineering and Technology, Taiyuan University of Science and Technology, Taiyuan 030024, China
| | - Chenyu Zhang
- College of Chemical Engineering and Technology, Taiyuan University of Science and Technology, Taiyuan 030024, China
| | - Huanxin Zhou
- College of Chemical Engineering and Technology, Taiyuan University of Science and Technology, Taiyuan 030024, China
| | - Yan Yang
- College of Chemical Engineering and Technology, Taiyuan University of Science and Technology, Taiyuan 030024, China
| | - Yanzhen Wen
- College of Chemical Engineering and Technology, Taiyuan University of Science and Technology, Taiyuan 030024, China
| | - Xiangyu Jiao
- Beijing Key Laboratory for Bioengineering and Sensing Technology, Daxing Research Institute, School of Chemistry & Biological Engineering, University of Science & Technology Beijing, Beijing 100083, China
| | - Mingze Yao
- Institutes of Biomedical Sciences, Shanxi Provincial Key Laboratory for Medical Molecular Cell Biology, Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Shanxi University, Taiyuan 030006, China
| | - Yongqiang Wen
- Beijing Key Laboratory for Bioengineering and Sensing Technology, Daxing Research Institute, School of Chemistry & Biological Engineering, University of Science & Technology Beijing, Beijing 100083, China
| |
Collapse
|
|
13
|
Hamandi F, Tsatalis JT, Goswami T. Morphological human bone features and demography controlling damage accumulation and fracture: a finite element study. Comput Methods Biomech Biomed Engin 2024:1-17. [PMID: 39066601 DOI: 10.1080/10255842.2024.2384475] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2024] [Revised: 07/12/2024] [Accepted: 07/19/2024] [Indexed: 07/28/2024]
Abstract
Prediction of bone fracture risk is clinically challenging. Computational modeling plays a vital role in understanding bone structure and diagnosing bone diseases, leading to novel therapies. The research objectives were to demonstrate the anisotropic structure of the bone at the micro-level taking into consideration the density and subject demography, such as age, gender, body mass index (BMI), height, weight, and their roles in damage accumulation. Out of 438 developed 3D bone models at the micro-level, 46.12% were female. The age distribution ranged from 23 to 95 years. The research unfolds in two phases: micro-morphological features examination and stress distribution investigation. Models were developed using Mimics 22.0 and SolidWorks. The anisotropic material properties were defined before importing into Ansys for simulation. Computational simulations further uncovered variations in maximum von-Misses stress, highlighting that young Black males experienced the highest stress at 127.852 ± 10.035 MPa, while elderly Caucasian females exhibited the least stress at 97.224 ± 14.504 MPa. Furthermore, age-related variations in stress levels for both normal and osteoporotic bone micro models were elucidated, emphasizing the intricate interplay of demographic factors in bone biomechanics. Additionally, a prediction equation for bone density incorporating demographic variables was proposed, offering a personalized modeling approach. In general, this study, which carefully examines the complexities of how bones behave at the micro-level, emphasizes the need for an enhanced approach in orthopedics. We suggest taking individual characteristics into account to make therapeutic interventions more precise and effective.
Collapse
Affiliation(s)
- Farah Hamandi
- Department of Biomedical, Industrial, and Human Factors Engineering, Wright State University, Dayton, OH, USA
| | - James T Tsatalis
- Department of Radiology, Orthopaedic Surgery, Miami Valley Hospital, Dayton, OH, USA
| | - Tarun Goswami
- Department of Biomedical, Industrial, and Human Factors Engineering, Wright State University, Dayton, OH, USA
- Department of Orthopedic Surgery, Sports Medicine and Rehabilitation, Wright State University, Dayton, OH, USA
| |
Collapse
|
|
14
|
Wang S, Li C, Chen S, Jia W, Liu L, Liu Y, Yang Y, Jiao K, Yan Y, Cheng Z, Liu G, Liu Z, Luo Y. Multifunctional bilayer nanofibrous membrane enhances periodontal regeneration via mesenchymal stem cell recruitment and macrophage polarization. Int J Biol Macromol 2024; 273:132924. [PMID: 38866282 DOI: 10.1016/j.ijbiomac.2024.132924] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2023] [Revised: 05/16/2024] [Accepted: 06/03/2024] [Indexed: 06/14/2024]
Abstract
The continuous stimulation of periodontitis leads to a decrease in the number of stem cells within the lesion area and significantly impairing their regenerative capacity. Therefore, it is crucial to promote stem cell homing and regulate the local immune microenvironment to suppress inflammation for the regeneration of periodontitis-related tissue defects. Here, we fabricated a novel multifunctional bilayer nanofibrous membrane using electrospinning technology. The dense poly(caprolactone) (PCL) nanofibers served as the barrier layer to resist epithelial invasion, while the polyvinyl alcohol/chitooligosaccharides (PVA/COS) composite nanofiber membrane loaded with calcium beta-hydroxy-beta-methylbutyrate (HMB-Ca) acted as the functional layer. Material characterization tests revealed that the bilayer nanofibrous membrane presented desirable mechanical strength, stability, and excellent cytocompatibility. In vitro, PCL@PVA/COS/HMB-Ca (P@PCH) can not only directly promote rBMSCs migration and differentiation, but also induce macrophage toward pro-healing (M2) phenotype-polarization with increasing the secretion of anti-inflammatory and pro-healing cytokines, thus providing a favorable osteoimmune environment for stem cells recruitment and osteogenic differentiation. In vivo, the P@PCH membrane effectively recruited host MSCs to the defect area, alleviated inflammatory infiltration, and accelerated bone defects repair. Collectively, our data indicated that the P@PCH nanocomposite membrane might be a promising biomaterial candidate for guided tissue regeneration in periodontal applications.
Collapse
Affiliation(s)
- Shaoru Wang
- Hospital of Stomatology, Jilin University, Changchun 130000, China; Scientific and Technological Innovation Center of Health Products and Medical Materials with Characteristic Resources of Jilin Province, Changchun 130000, China
| | - Chiyu Li
- The Second Hospital of Jilin University, Changchun 130000, China
| | - Shu Chen
- The Second Hospital of Jilin University, Changchun 130000, China
| | - Wenyuan Jia
- Scientific and Technological Innovation Center of Health Products and Medical Materials with Characteristic Resources of Jilin Province, Changchun 130000, China; The Second Hospital of Jilin University, Changchun 130000, China
| | - Liping Liu
- Hospital of Stomatology, Jilin University, Changchun 130000, China; Scientific and Technological Innovation Center of Health Products and Medical Materials with Characteristic Resources of Jilin Province, Changchun 130000, China
| | - Yun Liu
- Scientific and Technological Innovation Center of Health Products and Medical Materials with Characteristic Resources of Jilin Province, Changchun 130000, China; The First Hospital of Jilin University, Changchun 130000, China
| | - Yuheng Yang
- Scientific and Technological Innovation Center of Health Products and Medical Materials with Characteristic Resources of Jilin Province, Changchun 130000, China; The Second Hospital of Jilin University, Changchun 130000, China
| | - Kun Jiao
- Scientific and Technological Innovation Center of Health Products and Medical Materials with Characteristic Resources of Jilin Province, Changchun 130000, China; The First Hospital of Jilin University, Changchun 130000, China
| | - Yongzheng Yan
- Scientific and Technological Innovation Center of Health Products and Medical Materials with Characteristic Resources of Jilin Province, Changchun 130000, China; The Second Hospital of Jilin University, Changchun 130000, China
| | - Zhiqiang Cheng
- Scientific and Technological Innovation Center of Health Products and Medical Materials with Characteristic Resources of Jilin Province, Changchun 130000, China; College of Resources and Environment, Jilin Agriculture University, Changchun 130000, China
| | - Guomin Liu
- Scientific and Technological Innovation Center of Health Products and Medical Materials with Characteristic Resources of Jilin Province, Changchun 130000, China; The Second Hospital of Jilin University, Changchun 130000, China
| | - Zhihui Liu
- Hospital of Stomatology, Jilin University, Changchun 130000, China.
| | - Yungang Luo
- The First Hospital of Jilin University, Changchun 130000, China.
| |
Collapse
|
|
15
|
Park HW, Lee CE, Kim S, Jeong WJ, Kim K. Ex Vivo Peptide Decoration Strategies on Stem Cell Surfaces for Augmenting Endothelium Interaction. TISSUE ENGINEERING. PART B, REVIEWS 2024; 30:327-339. [PMID: 37830185 DOI: 10.1089/ten.teb.2023.0210] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/14/2023]
Abstract
Ischemic vascular diseases remain leading causes of disability and death. Although various clinical therapies have been tried, reperfusion injury is a major issue, occurring when blood recirculates at the damaged lesion. As an alternative approach, cell-based therapy has emerged. Mesenchymal stem cells (MSCs) are attractive cellular candidates due to their therapeutic capacities, including differentiation, safety, angiogenesis, and tissue repair. However, low levels of receptors/ligands limit targeted migration of stem cells. Thus, it is important to improve homing efficacy of transplanted MSCs toward damaged endothelium. Among various MSC modulations, ex vivo cell surface engineering could effectively augment homing efficiency by decorating MSC surfaces with alternative receptors/ligands, thereby facilitating intercellular interactions with the endothelium. Especially, exogenous decoration of peptides onto stem cell surfaces could provide appropriate functional signaling moieties to achieve sufficient MSC homing. Based on their protein-like functionalities, high modularity in molecular design, and high specific affinities and multivalency to target receptors, peptides could be representative surface-presentable moieties. Moreover, peptides feature a mild synthetic process, enabling precise control of amino acid composition and sequence. Such ex vivo stem cell surface engineering could be achieved primarily by hydrophobic interactions of the cellular bilayer with peptide-conjugated anchor modules and by covalent conjugation between peptides and available compartments in membranes. To this end, this review provides an overview of currently available peptide-mediated, ex vivo stem cell surface engineering strategies for enhancing MSC homing efficiency by facilitating interactions with endothelial cells. Stem cell surface engineering techniques using peptide-based bioconjugates have the potential to revolutionize current vascular disease treatments while addressing their technical limitations.
Collapse
Affiliation(s)
- Hee Won Park
- Department of Chemical and Biochemical Engineering, Dongguk University, Seoul, Republic of Korea
| | - Chae Eun Lee
- Department of Chemical and Biochemical Engineering, Dongguk University, Seoul, Republic of Korea
| | - Sungjun Kim
- Department of Chemical and Biochemical Engineering, Dongguk University, Seoul, Republic of Korea
| | - Woo-Jin Jeong
- Department of Biological Engineering, Inha University, Incheon, Republic of Korea
| | - Kyobum Kim
- Department of Chemical and Biochemical Engineering, Dongguk University, Seoul, Republic of Korea
| |
Collapse
|
|
16
|
Moyo MTG, Adali T, Tulay P. Exploring gellan gum-based hydrogels for regenerating human embryonic stem cells in age-related macular degeneration therapy: A literature review. Regen Ther 2024; 26:235-250. [PMID: 38966602 PMCID: PMC11222715 DOI: 10.1016/j.reth.2024.05.018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2024] [Revised: 05/15/2024] [Accepted: 05/26/2024] [Indexed: 07/06/2024] Open
Abstract
Age-related macular degeneration (AMD) is a progressive ocular disease marked by the deterioration of retinal photoreceptor cells, leading to central vision decline, predominantly affecting the elderly population worldwide. Current treatment modalities, such as anti-VEGF agents, laser therapy, and photodynamic therapy, aim to manage the condition, with emerging strategies like stem cell replacement therapy showing promise. However, challenges like immune rejection and cell survival hinder the efficacy of stem cell interventions. Regenerative medicine faces obstacles in maximizing stem cell potential due to limitations in mimicking the dynamic cues of the extracellular matrix (ECM) crucial for guiding stem cell behaviour. Innovative biomaterials like gellan gum hydrogels offer tailored microenvironments conducive to enhancing stem cell culture efficacy and tissue regeneration. Gellan gum-based hydrogels, renowned for biocompatibility and customizable mechanical properties, provide crucial support for cell viability, differentiation, and controlled release of therapeutic factors, making them an ideal platform for culturing human embryonic stem cells (hESCs). These hydrogels mimic native tissue mechanics, promoting optimal hESC differentiation while minimizing immune responses and facilitating localized delivery. This review explores the potential of Gellan Gum-Based Hydrogels in regenerative AMD therapy, emphasizing their role in enhancing hESC regeneration and addressing current status, treatment limitations, and future directions.
Collapse
Affiliation(s)
- Mthabisi Talent George Moyo
- Near East University, Faculty of Engineering, Department of Biomedical Engineering, P.O. Box: 99138, Nicosia, Cyprus, Mersin 10, Turkey
- Girne American University, Faculty of Medicine, Department of Medical Biochemistry, PO Box 99428, Karmi Campus, Karaoglanoglu, Kyrenia, Cyprus, Mersin 10, Turkey
- Girne American University, Research and Application Center of Biomedical Sciences, PO Box 99428, Karmi Campus, Karaoglanoglu, Kyrenia, North Cyprus, Mersin 10, Turkey
| | - Terin Adali
- Girne American University, Faculty of Medicine, Department of Medical Biochemistry, PO Box 99428, Karmi Campus, Karaoglanoglu, Kyrenia, Cyprus, Mersin 10, Turkey
- Girne American University, Research and Application Center of Biomedical Sciences, PO Box 99428, Karmi Campus, Karaoglanoglu, Kyrenia, North Cyprus, Mersin 10, Turkey
| | - Pinar Tulay
- Near East University, Faculty of Medicine, Department of Medical Genetics, Nicosia, Cyprus, Mersin 10, Turkey
- Near East University, DESAM Research Institute, Nicosia, Cyprus, Mersin 10, Turkey
| |
Collapse
|
|
17
|
Qin L, Yang S, Zhao C, Yang J, Li F, Xu Z, Yang Y, Zhou H, Li K, Xiong C, Huang W, Hu N, Hu X. Prospects and challenges for the application of tissue engineering technologies in the treatment of bone infections. Bone Res 2024; 12:28. [PMID: 38744863 PMCID: PMC11094017 DOI: 10.1038/s41413-024-00332-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2023] [Revised: 03/08/2024] [Accepted: 04/01/2024] [Indexed: 05/16/2024] Open
Abstract
Osteomyelitis is a devastating disease caused by microbial infection in deep bone tissue. Its high recurrence rate and impaired restoration of bone deficiencies are major challenges in treatment. Microbes have evolved numerous mechanisms to effectively evade host intrinsic and adaptive immune attacks to persistently localize in the host, such as drug-resistant bacteria, biofilms, persister cells, intracellular bacteria, and small colony variants (SCVs). Moreover, microbial-mediated dysregulation of the bone immune microenvironment impedes the bone regeneration process, leading to impaired bone defect repair. Despite advances in surgical strategies and drug applications for the treatment of bone infections within the last decade, challenges remain in clinical management. The development and application of tissue engineering materials have provided new strategies for the treatment of bone infections, but a comprehensive review of their research progress is lacking. This review discusses the critical pathogenic mechanisms of microbes in the skeletal system and their immunomodulatory effects on bone regeneration, and highlights the prospects and challenges for the application of tissue engineering technologies in the treatment of bone infections. It will inform the development and translation of antimicrobial and bone repair tissue engineering materials for the management of bone infections.
Collapse
Affiliation(s)
- Leilei Qin
- Department of Orthopaedics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China
- Orthopedic Laboratory of Chongqing Medical University, Chongqing, 400016, China
| | - Shuhao Yang
- Department of Orthopaedics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China
- Orthopedic Laboratory of Chongqing Medical University, Chongqing, 400016, China
| | - Chen Zhao
- Department of Orthopaedics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China
- Orthopedic Laboratory of Chongqing Medical University, Chongqing, 400016, China
| | - Jianye Yang
- Department of Orthopaedics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China
- Orthopedic Laboratory of Chongqing Medical University, Chongqing, 400016, China
| | - Feilong Li
- Department of Orthopaedics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China
- Orthopedic Laboratory of Chongqing Medical University, Chongqing, 400016, China
| | - Zhenghao Xu
- Department of Orthopaedics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China
- Orthopedic Laboratory of Chongqing Medical University, Chongqing, 400016, China
| | - Yaji Yang
- Department of Orthopaedics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China
- Orthopedic Laboratory of Chongqing Medical University, Chongqing, 400016, China
| | - Haotian Zhou
- Department of Orthopaedics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China
- Orthopedic Laboratory of Chongqing Medical University, Chongqing, 400016, China
| | - Kainan Li
- Clinical Medical College and Affiliated Hospital of Chengdu University, Chengdu University, Chengdu, Sichuan, 610081, China
| | - Chengdong Xiong
- University of Chinese Academy of Sciences, Bei Jing, 101408, China
| | - Wei Huang
- Department of Orthopaedics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China
- Orthopedic Laboratory of Chongqing Medical University, Chongqing, 400016, China
| | - Ning Hu
- Department of Orthopaedics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.
- Orthopedic Laboratory of Chongqing Medical University, Chongqing, 400016, China.
| | - Xulin Hu
- Clinical Medical College and Affiliated Hospital of Chengdu University, Chengdu University, Chengdu, Sichuan, 610081, China.
- Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China.
| |
Collapse
|
|
18
|
Wang X, Wang D, Yin G, Pu X. Integrated GelMA and interleukin 8-loaded liposome composite scaffold for endogenous BMSCs recruitment in bone repair. Biochem Biophys Res Commun 2024; 703:149614. [PMID: 38359611 DOI: 10.1016/j.bbrc.2024.149614] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2024] [Revised: 01/20/2024] [Accepted: 01/30/2024] [Indexed: 02/17/2024]
Abstract
Bone repair strategies, based on endogenous stem cell recruitment, can effectively avoid immune rejection and the low utilization of exogenous stem cells. Endogenous stem cells can be recruited to the implantation site by loading chemokines onto bone tissue-engineered scaffolds. However, challenges such as unstable chemokine activity and easy inactivation after implantation remain significant. In the present study, composite fiber scaffolds ((IL8@LIP)-GelMA) consisting of Interleukin 8 (IL8) -loaded liposomes and GelMA were constructed by electrospinning and photocrosslinking, and its ability to recruit bone marrow-derived mesenchymal stem cells (BMSCs) and immunomodulatory effect was investigated. Compared to GelMA loaded directly with IL8, scaffolds of (IL8@LIP)-GelMA demonstrated superior protection of IL8 activity, ensuring a slow and continuous release. Both in vivo and in vitro experiments demonstrated that the (IL8@LIP)-GelMA scaffolds effectively recruited BMSCs to the desired sites. Additionally, the (IL8@LIP)-GelMA scaffolds exhibited the capacity to recruit more macrophages to the implantation site. Importantly, they promoted the polarization of macrophages toward the M2 anti-inflammatory phenotype, facilitating the transition from the inflammatory stage to the tissue repair stage. Therefore, (IL8@LIP)-GelMA scaffolds show great potential for cell-free tissue engineering applications and provide insights into the loading mode of growth factors in scaffolds.
Collapse
Affiliation(s)
- Xingming Wang
- College of Biomedical Engineering, Sichuan University, Chengdu, China
| | - Danni Wang
- College of Biomedical Engineering, Sichuan University, Chengdu, China
| | - Guangfu Yin
- College of Biomedical Engineering, Sichuan University, Chengdu, China
| | - Ximing Pu
- College of Biomedical Engineering, Sichuan University, Chengdu, China.
| |
Collapse
|
|
19
|
Wu C, Shi Z, Ge Q, Xu H, Wu Z, Tong P, Jin H. Catalpol promotes articular cartilage repair by enhancing the recruitment of endogenous mesenchymal stem cells. J Cell Mol Med 2024; 28:e18242. [PMID: 38509736 PMCID: PMC10955160 DOI: 10.1111/jcmm.18242] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2023] [Revised: 02/27/2024] [Accepted: 03/04/2024] [Indexed: 03/22/2024] Open
Abstract
Articular cartilage defect is challenged by insufficient regenerative ability of cartilage. Catalpol (CA), the primary active component of Rehmanniae Radix, could exert protective effects against various diseases. However, the impact of CA on the treatment of articular cartilage injuries is still unclear. In this study, full-thickness articular cartilage defect was induced in a mouse model via surgery. The animals were intraperitoneally injected with CA for 4 or 8 weeks. According to the results of macroscopic observation, micro-computed tomography CT (μCT), histological and immunohistochemistry staining, CA treatment could promote mouse cartilage repair, resulting in cartilage regeneration, bone structure improvement and matrix anabolism. Specifically, an increase in the expression of CD90, the marker of mesenchymal stem cells (MSCs), in the cartilage was observed. In addition, we evaluated the migratory and chondrogenic effects of CA on MSCs. Different concentration of CA was added to C3H10 T1/2 cells. The results showed that CA enhanced cell migration and chondrogenesis without affecting proliferation. Collectively, our findings indicate that CA may be effective for the treatment of cartilage defects via stimulation of endogenous MSCs.
Collapse
Affiliation(s)
- Congzi Wu
- Institute of Orthopaedics and Traumatology of Zhejiang ProvinceThe First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine)HangzhouZhejiangChina
- The First College of Clinical MedicineZhejiang Chinese Medical UniversityHangzhouChina
| | - Zhenyu Shi
- Department of Orthopaedic SurgeryThe First Affiliated Hospital of Zhejiang Chinese Medical UniversityHangzhouChina
| | - Qinwen Ge
- Institute of Orthopaedics and Traumatology of Zhejiang ProvinceThe First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine)HangzhouZhejiangChina
- The First College of Clinical MedicineZhejiang Chinese Medical UniversityHangzhouChina
| | - HuiHui Xu
- Institute of Orthopaedics and Traumatology of Zhejiang ProvinceThe First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine)HangzhouZhejiangChina
- The First College of Clinical MedicineZhejiang Chinese Medical UniversityHangzhouChina
| | - Zhen Wu
- Department of Orthopaedic SurgeryTongde Hospital of Zhejiang ProvinceHangzhouChina
| | - Peijian Tong
- Institute of Orthopaedics and Traumatology of Zhejiang ProvinceThe First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine)HangzhouZhejiangChina
- Department of Orthopaedic SurgeryThe First Affiliated Hospital of Zhejiang Chinese Medical UniversityHangzhouChina
| | - Hongting Jin
- Institute of Orthopaedics and Traumatology of Zhejiang ProvinceThe First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine)HangzhouZhejiangChina
- Department of Orthopaedic SurgeryThe First Affiliated Hospital of Zhejiang Chinese Medical UniversityHangzhouChina
| |
Collapse
|
|
20
|
Xu C, Xie X, Shi P, Xue K, Li Y, Wu Y, Wang J. LepR-expressing cells are a critical population in periodontal healing post periodontitis. J Bone Miner Res 2024; 39:59-72. [PMID: 38630879 DOI: 10.1093/jbmr/zjad008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/28/2023] [Revised: 11/12/2023] [Accepted: 11/17/2023] [Indexed: 04/19/2024]
Abstract
Identification of promising seed cells plays a pivotal role in achieving tissue regeneration. This study demonstrated that LepR-expressing cells (LepR+ cells) are required for maintaining periodontal homeostasis at the adult stage. We further investigated how LepR+ cells behave in periodontal healing using a ligature-induced periodontitis (PD) and a self-healing murine model with LepRCre/+; R26RtdTomato/+ mice. Lineage tracing experiments revealed that the largely suppressed osteogenic ability of LepR+ cells results from periodontal inflammation. Periodontal defects were partially recovered when the ligature was removed, in which the osteogenic differentiation of LepR+ cell lineage was promoted and contributed to the newly formed alveolar bone. A cell ablation model established with LepRCre/+; R26RtdTomato/+; R26RDTA/+ mice further proved that LepR+ cells are an important cell source of newly formed alveolar bone. Expressions of β-catenin and LEF1 in LepR+ cells were upregulated when the inflammatory stimuli were removed, which are consistent with the functional changes observed during periodontal healing. Furthermore, the conditional upregulation of WNT signaling or the application of sclerostin neutralized antibody promoted the osteogenic function of LepR+ cells. In contrast, the specific knockdown of β-catenin in LepR+ human periodontal ligament cells with small interfering RNA caused arrested osteogenic function. Our findings identified the LepR+ cell lineage as a critical cell population for endogenous periodontal healing post PD, which is regulated by the WNT signaling pathway, making it a promising seed cell population in periodontal tissue regeneration.
Collapse
Affiliation(s)
- Chunmei Xu
- State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Department of Periodontics, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan, China
| | - Xudong Xie
- State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Department of Periodontics, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan, China
| | - Peilei Shi
- State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Department of Periodontics, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan, China
| | - Kun Xue
- State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Department of Periodontics, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan, China
| | - Yue Li
- State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Department of Periodontics, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan, China
| | - Yafei Wu
- State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Department of Periodontics, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan, China
| | - Jun Wang
- State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Department of Periodontics, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, Sichuan, China
| |
Collapse
|
|
21
|
Chen Y, Huang Y, Li J, Jiao T, Yang L. Enhancing osteoporosis treatment with engineered mesenchymal stem cell-derived extracellular vesicles: mechanisms and advances. Cell Death Dis 2024; 15:119. [PMID: 38331884 PMCID: PMC10853558 DOI: 10.1038/s41419-024-06508-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2023] [Revised: 01/24/2024] [Accepted: 01/26/2024] [Indexed: 02/10/2024]
Abstract
As societal aging intensifies, the incidence of osteoporosis (OP) continually rises. OP is a skeletal disorder characterized by reduced bone mass, deteriorated bone tissue microstructure, and consequently increased bone fragility and fracture susceptibility, typically evaluated using bone mineral density (BMD) and T-score. Not only does OP diminish patients' quality of life, but it also imposes a substantial economic burden on society. Conventional pharmacological treatments yield limited efficacy and severe adverse reactions. In contemporary academic discourse, mesenchymal stem cells (MSCs) derived extracellular vesicles (EVs) have surfaced as auspicious novel therapeutic modalities for OP. EVs can convey information through the cargo they carry and have been demonstrated to be a crucial medium for intercellular communication, playing a significant role in maintaining the homeostasis of the bone microenvironment. Furthermore, various research findings provide evidence that engineered strategies can enhance the therapeutic effects of EVs in OP treatment. While numerous reviews have explored the progress and potential of EVs in treating degenerative bone diseases, research on using EVs to address OP remains in the early stages of basic experimentation. This paper reviews advancements in utilizing MSCs and their derived EVs for OP treatment. It systematically examines the most extensively researched MSC-derived EVs for treating OP, delving not only into the molecular mechanisms of EV-based OP therapy but also conducting a comparative analysis of the strengths and limitations of EVs sourced from various cell origins. Additionally, the paper emphasizes the technical and engineering strategies necessary for leveraging EVs in OP treatment, offering insights and recommendations for future research endeavors.
Collapse
Affiliation(s)
- Yiman Chen
- Departments of Geriatrics, The First Hospital of China Medical University, Shenyang, 110001, Liaoning, PR China
| | - Yuling Huang
- Departments of Geriatrics, The First Hospital of China Medical University, Shenyang, 110001, Liaoning, PR China
| | - Jia Li
- Departments of Geriatrics, The First Hospital of China Medical University, Shenyang, 110001, Liaoning, PR China
| | - Taiwei Jiao
- Department of Gastroenterology and Endoscopy, The First Hospital of China Medical University, Shenyang, 110001, Liaoning, PR China.
| | - Lina Yang
- Departments of Geriatrics, The First Hospital of China Medical University, Shenyang, 110001, Liaoning, PR China.
- Department of International Physical Examination Center, The First Hospital of China Medical University, Shenyang, 110001, Liaoning, PR China.
| |
Collapse
|
|
22
|
Zou X, Xie B, Peng X, Lu M, Xu D, Yuan H, Zhang Y, Wang D, Zhao M, Liu R, Wen X. p75NTR antibody-conjugated microspheres: an approach to guided tissue regeneration by selective recruitment of endogenous periodontal ligament cells. Front Bioeng Biotechnol 2024; 12:1338029. [PMID: 38357709 PMCID: PMC10864659 DOI: 10.3389/fbioe.2024.1338029] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2023] [Accepted: 01/17/2024] [Indexed: 02/16/2024] Open
Abstract
Repairing defects in alveolar bone is essential for regenerating periodontal tissue, but it is a formidable challenge. One promising therapeutic approach involves using a strategy that specifically recruits periodontal ligament cells (PDLCs) with high regenerative potential to achieve in situ regeneration of alveolar bone. In this study, we have created a new type of microsphere conjugated with an antibody to target p75 neurotrophin receptor (p75NTR), which is made of nano-hydroxyapatite (nHA) and chitosan (CS). The goal of this design is to attract p75NTR+hPDLCs selectively and promote osteogenesis. In vitro experiments demonstrated that the antibody-conjugated microspheres attracted significantly more PDLCs compared to non-conjugated microspheres. Incorporating nHA not only enhances cell adhesion and proliferation on the surface of the microsphere but also augments its osteoinductive properties. Microspheres effectively recruited p75NTR+ cells at bone defect sites in SD rats, as observed through immunofluorescent staining of p75NTR antibodies. This p75NTR antibody-conjugated nHA/CS microsphere presents a promising approach for selectively recruiting cells and repairing bone defects.
Collapse
Affiliation(s)
- Xuqiang Zou
- Department of Orthodontics, School of Stomatology, Southwest Medical University, Luzhou, China
| | - Bo Xie
- Department of Orthodontics, School of Stomatology, Southwest Medical University, Luzhou, China
| | - Xuelian Peng
- Department of Orthodontics, School of Stomatology, Southwest Medical University, Luzhou, China
| | - Mingjie Lu
- Department of Orthodontics, School of Stomatology, Southwest Medical University, Luzhou, China
| | - Dan Xu
- Department of Orthodontics, School of Stomatology, Southwest Medical University, Luzhou, China
| | - Hongyan Yuan
- Chongqing Key Laboratory for Oral Diseases and Biomedical Sciences, Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, College of Stomatology, Chongqing Medical University, Chongqing, China
| | - Yixin Zhang
- Department of Orthodontics, School of Stomatology, Southwest Medical University, Luzhou, China
| | - Di Wang
- Chongqing Key Laboratory for Oral Diseases and Biomedical Sciences, Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, College of Stomatology, Chongqing Medical University, Chongqing, China
| | - Manzhu Zhao
- Chongqing Key Laboratory for Oral Diseases and Biomedical Sciences, Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, College of Stomatology, Chongqing Medical University, Chongqing, China
| | - Rui Liu
- Department of Stomatology, Daping Hospital, Third Military Medical University (Army Medical University), Chongqing, China
| | - Xiujie Wen
- Department of Orthodontics, School of Stomatology, Southwest Medical University, Luzhou, China
| |
Collapse
|
|
23
|
Wang T, Huang Q, Rao Z, Liu F, Su X, Zhai X, Ma J, Liang Y, Quan D, Liao G, Bai Y, Zhang S. Injectable decellularized extracellular matrix hydrogel promotes salivary gland regeneration via endogenous stem cell recruitment and suppression of fibrogenesis. Acta Biomater 2023; 169:256-272. [PMID: 37557943 DOI: 10.1016/j.actbio.2023.08.003] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2023] [Revised: 07/26/2023] [Accepted: 08/02/2023] [Indexed: 08/11/2023]
Abstract
Saliva is key to the maintenance of oral homeostasis. However, several forms of salivary gland (SG) disorders, followed by hyposalivation, often result in dental caries, oral infection, and decreased taste, which dramatically affect the quality of patient's life. Functional biomaterials hold great potential for tissue regeneration in damaged or dysfunctional SGs and maintaining the good health of oral cavity. Herein, we prepared an injectable hydrogel derived from decellularized porcine submandibular glands (pDSG-gel), the material and biological properties of the hydrogel were systematically investigated. First, good biocompatibility and bioactivities of the pDSG-gel were validated in 2D and 3D cultures of primary submandibular gland mesenchymal stem cells (SGMSCs). Especially, the pDSG-gel effectively facilitated SGMSCs migration and recruitment through the activation of PI3K/AKT signaling pathway, suggested by transcriptomic analysis and immunoblotting. Furthermore, proteomic analysis of the pDSG revealed that many extracellular matrix components and secreted factors were preserved, which may contribute to stem cell homing. The recruitment of endogenous SG cells was confirmed in vivo, upon in situ injection of the pDSG-gel into the defective SGs in rats. Acinar and ductal-like structures were evident in the injury sites after pDSG-gel treatment, suggesting the reconstruction of functional SG units. Meanwhile, histological characterizations showed that the administration of the pDSG-gel also significantly suppressed fibrogenesis within the injured SG tissues. Taken together, this tissue-specific hydrogel provides a pro-regenerative microenvironment for endogenous SG regeneration and holds great promise as a powerful and bioactive material for future treatments of SG diseases. STATEMENT OF SIGNIFICANCE: Decellularized extracellular matrix (dECM) has been acknowledged as one of the most promising biomaterials that recapitalizes the microenvironment in native tissues. Hydrogel derived from the dECM allows in situ administration for tissue repair. Herein, a tissue-specific dECM hydrogel derived from porcine salivary glands (pDSG-gel) was successfully prepared and developed for functional reconstruction of defective salivary gland (SG) tissues. The pDSG-gel effectively accelerated endogenous SG stem cells migration and their recruitment for acinar- and ductal-like regeneration, which was attributed to the activation of PI3K/AKT signaling pathway. Additionally, the introduction of the pDSG-gel resulted in highly suppressed fibrogenesis in the defective tissues. These outcomes indicated that the pDSG-gel holds great potential in clinical translation toward SG regeneration through cell-free treatments.
Collapse
Affiliation(s)
- Tao Wang
- Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, 510055, China
| | - Qiting Huang
- Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, 510055, China
| | - Zilong Rao
- Guangdong Engineering Technology Research Centre for Functional Biomaterials, PCFM Lab, School of Materials Science and Engineering, Sun Yat-sen University, Guangzhou, 510006, China
| | - Fan Liu
- Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, 510055, China
| | - Xinyun Su
- Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, 510055, China
| | - Xuefan Zhai
- Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, 510055, China
| | - Jingxin Ma
- Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, 510055, China
| | - Yujie Liang
- Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, 510055, China
| | - Daping Quan
- Guangdong Engineering Technology Research Centre for Functional Biomaterials, PCFM Lab, School of Materials Science and Engineering, Sun Yat-sen University, Guangzhou, 510006, China
| | - Guiqing Liao
- Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, 510055, China.
| | - Ying Bai
- Guangdong Engineering Technology Research Centre for Functional Biomaterials, PCFM Lab, School of Materials Science and Engineering, Sun Yat-sen University, Guangzhou, 510006, China.
| | - Sien Zhang
- Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, 510055, China.
| |
Collapse
|
|
24
|
Zhang W, Zha K, Hu W, Xiong Y, Knoedler S, Obed D, Panayi AC, Lin Z, Cao F, Mi B, Liu G. Multifunctional hydrogels: advanced therapeutic tools for osteochondral regeneration. Biomater Res 2023; 27:76. [PMID: 37542353 PMCID: PMC10403923 DOI: 10.1186/s40824-023-00411-9] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2023] [Accepted: 07/05/2023] [Indexed: 08/06/2023] Open
Abstract
Various joint pathologies such as osteochondritis dissecans, osteonecrosis, rheumatic disease, and trauma, may result in severe damage of articular cartilage and other joint structures, ranging from focal defects to osteoarthritis (OA). The osteochondral unit is one of the critical actors in this pathophysiological process. New approaches and applications in tissue engineering and regenerative medicine continue to drive the development of OA treatment. Hydrogel scaffolds, a component of tissue engineering, play an indispensable role in osteochondral regeneration. In this review, tissue engineering strategies regarding osteochondral regeneration were highlighted and summarized. The application of hydrogels for osteochondral regeneration within the last five years was evaluated with an emphasis on functionalized physical and chemical properties of hydrogel scaffolds, functionalized delivery hydrogel scaffolds as well as functionalized intelligent response hydrogel scaffolds. Lastly, to serve as guidance for future efforts in the creation of bioinspired hydrogel scaffolds, a succinct summary and new views for specific mechanisms, applications, and existing limitations of the newly designed functionalized hydrogel scaffolds were offered.
Collapse
Affiliation(s)
- Wenqian Zhang
- Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
- Hubei Province Key Laboratory of Oral and Maxillofacial Development and Regeneration, Wuhan, 430022, China
| | - Kangkang Zha
- Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
- Hubei Province Key Laboratory of Oral and Maxillofacial Development and Regeneration, Wuhan, 430022, China
| | - Weixian Hu
- Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
- Hubei Province Key Laboratory of Oral and Maxillofacial Development and Regeneration, Wuhan, 430022, China
| | - Yuan Xiong
- Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
- Hubei Province Key Laboratory of Oral and Maxillofacial Development and Regeneration, Wuhan, 430022, China
| | - Samuel Knoedler
- Division of Plastic Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02152, USA
| | - Doha Obed
- Division of Plastic Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02152, USA
- Department of Plastic, Aesthetic, Hand and Reconstructive Surgery, Hannover Medical School, Hannover, Germany
| | - Adriana C Panayi
- Department of Hand, Plastic and Reconstructive Surgery, Microsurgery, Burn Center, BG Trauma Center Ludwigshafen, University of Heidelberg, 67071, Ludwigshafen/Rhine, Germany
| | - Ze Lin
- Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
- Hubei Province Key Laboratory of Oral and Maxillofacial Development and Regeneration, Wuhan, 430022, China
| | - Faqi Cao
- Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
- Hubei Province Key Laboratory of Oral and Maxillofacial Development and Regeneration, Wuhan, 430022, China.
| | - Bobin Mi
- Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
- Hubei Province Key Laboratory of Oral and Maxillofacial Development and Regeneration, Wuhan, 430022, China.
- School of Chemistry, Chemical Engineering and Biotechnology, Nanyang Technological University, 21 Nanyang Link, Singapore, 637371, Singapore.
| | - Guohui Liu
- Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
- Hubei Province Key Laboratory of Oral and Maxillofacial Development and Regeneration, Wuhan, 430022, China.
| |
Collapse
|
|
25
|
Kong P, Dong J, Li W, Li Z, Gao R, Liu X, Wang J, Su Q, Wen B, Ouyang W, Wang S, Zhang F, Feng S, Zhuang D, Xie Y, Zhao G, Yi H, Feng Z, Wang W, Pan X. Extracellular Matrix/Glycopeptide Hybrid Hydrogel as an Immunomodulatory Niche for Endogenous Cardiac Repair after Myocardial Infarction. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2023; 10:e2301244. [PMID: 37318159 PMCID: PMC10427380 DOI: 10.1002/advs.202301244] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/23/2023] [Revised: 05/06/2023] [Indexed: 06/16/2023]
Abstract
The treatment of myocardial infarction (MI) remains a substantial challenge due to excessive inflammation, massive cell death, and restricted regenerative potential, leading to maladaptive healing process and eventually heart failure. Current strategies of regulating inflammation or improving cardiac tissue regeneration have limited success. Herein, a hybrid hydrogel coassembled by acellular cardiac extracellular matrix (ECM) and immunomodulatory glycopeptide is developed for endogenous tissue regeneration after MI. The hydrogel constructs a niche recapitulating the architecture of native ECM for attracting host cell homing, controlling macrophage differentiation via glycopeptide unit, and promoting endotheliocyte proliferation by enhancing the macrophage-endotheliocyte crosstalk, which coordinate the innate healing mechanism for cardiac tissue regeneration. In a rodent MI model, the hybrid hydrogel successfully orchestrates a proreparative response indicated by enhanced M2 macrophage polarization, increased angiogenesis, and improved cardiomyocyte survival, which alleviates infarct size, improves wall thicknesses, and enhances cardiac contractility. Furthermore, the safety and effectiveness of the hydrogel are demonstrated in a porcine MI model, wherein proteomics verifies the regulation of immune response, proangiogenesis, and accelerated healing process. Collectively, the injectable composite hydrogel serving as an immunomodulatory niche for promoting cell homing and proliferation, inflammation modulation, tissue remodeling, and function restoration provides an effective strategy for endogenous cardiac repair.
Collapse
Affiliation(s)
- Pengxu Kong
- Department of Structural Heart DiseaseNational Center for Cardiovascular DiseaseChina and State Key Laboratory of Cardiovascular DiseaseFuwai HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeNational Health Commission Key Laboratory of Cardiovascular Regeneration MedicineNational Clinical Research Center for Cardiovascular DiseasesBeijing100037China
| | - Jing Dong
- Department of Structural Heart DiseaseNational Center for Cardiovascular DiseaseChina and State Key Laboratory of Cardiovascular DiseaseFuwai HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeNational Health Commission Key Laboratory of Cardiovascular Regeneration MedicineNational Clinical Research Center for Cardiovascular DiseasesBeijing100037China
| | - Wenchao Li
- Department of Structural Heart DiseaseNational Center for Cardiovascular DiseaseChina and State Key Laboratory of Cardiovascular DiseaseFuwai HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeNational Health Commission Key Laboratory of Cardiovascular Regeneration MedicineNational Clinical Research Center for Cardiovascular DiseasesBeijing100037China
- Department of Pediatric Cardiac SurgeryHuazhong Fuwai HospitalZhengzhou University People's HospitalHenan Provincial People's HospitalZhengzhou450000China
| | - Zefu Li
- Department of Structural Heart DiseaseNational Center for Cardiovascular DiseaseChina and State Key Laboratory of Cardiovascular DiseaseFuwai HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeNational Health Commission Key Laboratory of Cardiovascular Regeneration MedicineNational Clinical Research Center for Cardiovascular DiseasesBeijing100037China
| | - Rui Gao
- Tianjin Key Laboratory of Biomaterial ResearchInstitute of Biomedical EngineeringChinese Academy of Medical Sciences and Peking Union Medical CollegeTianjin300192China
| | - Xiang Liu
- Department of Polymer Science and EngineeringKey Laboratory of Systems Bioengineering (Ministry of Education)School of Chemical Engineering and TechnologyTianjin UniversityTianjin300072China
| | - Jingrong Wang
- Tianjin Key Laboratory of Biomaterial ResearchInstitute of Biomedical EngineeringChinese Academy of Medical Sciences and Peking Union Medical CollegeTianjin300192China
| | - Qi Su
- Tianjin Key Laboratory of Biomaterial ResearchInstitute of Biomedical EngineeringChinese Academy of Medical Sciences and Peking Union Medical CollegeTianjin300192China
| | - Bin Wen
- Department of Cardiac SurgeryBeijing Chao‐Yang HospitalCapital Medical UniversityBeijing100020China
| | - Wenbin Ouyang
- Department of Structural Heart DiseaseNational Center for Cardiovascular DiseaseChina and State Key Laboratory of Cardiovascular DiseaseFuwai HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeNational Health Commission Key Laboratory of Cardiovascular Regeneration MedicineNational Clinical Research Center for Cardiovascular DiseasesBeijing100037China
- Key Laboratory of Innovative Cardiovascular DevicesChinese Academy of Medical SciencesBeijing100037China
| | - Shouzheng Wang
- Department of Structural Heart DiseaseNational Center for Cardiovascular DiseaseChina and State Key Laboratory of Cardiovascular DiseaseFuwai HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeNational Health Commission Key Laboratory of Cardiovascular Regeneration MedicineNational Clinical Research Center for Cardiovascular DiseasesBeijing100037China
- Key Laboratory of Innovative Cardiovascular DevicesChinese Academy of Medical SciencesBeijing100037China
| | - Fengwen Zhang
- Department of Structural Heart DiseaseNational Center for Cardiovascular DiseaseChina and State Key Laboratory of Cardiovascular DiseaseFuwai HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeNational Health Commission Key Laboratory of Cardiovascular Regeneration MedicineNational Clinical Research Center for Cardiovascular DiseasesBeijing100037China
- Key Laboratory of Innovative Cardiovascular DevicesChinese Academy of Medical SciencesBeijing100037China
| | - Shuyi Feng
- Department of Structural Heart DiseaseNational Center for Cardiovascular DiseaseChina and State Key Laboratory of Cardiovascular DiseaseFuwai HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeNational Health Commission Key Laboratory of Cardiovascular Regeneration MedicineNational Clinical Research Center for Cardiovascular DiseasesBeijing100037China
| | - Donglin Zhuang
- Department of Structural Heart DiseaseNational Center for Cardiovascular DiseaseChina and State Key Laboratory of Cardiovascular DiseaseFuwai HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeNational Health Commission Key Laboratory of Cardiovascular Regeneration MedicineNational Clinical Research Center for Cardiovascular DiseasesBeijing100037China
| | - Yongquan Xie
- Department of Structural Heart DiseaseNational Center for Cardiovascular DiseaseChina and State Key Laboratory of Cardiovascular DiseaseFuwai HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeNational Health Commission Key Laboratory of Cardiovascular Regeneration MedicineNational Clinical Research Center for Cardiovascular DiseasesBeijing100037China
| | - Guangzhi Zhao
- Department of Structural Heart DiseaseNational Center for Cardiovascular DiseaseChina and State Key Laboratory of Cardiovascular DiseaseFuwai HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeNational Health Commission Key Laboratory of Cardiovascular Regeneration MedicineNational Clinical Research Center for Cardiovascular DiseasesBeijing100037China
| | - Hang Yi
- Department of Thoracic SurgeryNational Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing100021China
| | - Zujian Feng
- Tianjin Key Laboratory of Biomaterial ResearchInstitute of Biomedical EngineeringChinese Academy of Medical Sciences and Peking Union Medical CollegeTianjin300192China
| | - Weiwei Wang
- Tianjin Key Laboratory of Biomaterial ResearchInstitute of Biomedical EngineeringChinese Academy of Medical Sciences and Peking Union Medical CollegeTianjin300192China
- Key Laboratory of Innovative Cardiovascular DevicesChinese Academy of Medical SciencesBeijing100037China
| | - Xiangbin Pan
- Department of Structural Heart DiseaseNational Center for Cardiovascular DiseaseChina and State Key Laboratory of Cardiovascular DiseaseFuwai HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeNational Health Commission Key Laboratory of Cardiovascular Regeneration MedicineNational Clinical Research Center for Cardiovascular DiseasesBeijing100037China
- Key Laboratory of Innovative Cardiovascular DevicesChinese Academy of Medical SciencesBeijing100037China
| |
Collapse
|
|
26
|
Hasani-Sadrabadi MM, Yuan W, Sevari S, Yu B, Ansari S, Moshaverinia A. An engineered biomaterial to harness the differentiation potential of endogenous human gingival mesenchymal stem cells (hGMSCs). FRONTIERS IN DENTAL MEDICINE 2023; 4:1235096. [PMID: 39916923 PMCID: PMC11797836 DOI: 10.3389/fdmed.2023.1235096] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2023] [Accepted: 07/14/2023] [Indexed: 02/09/2025] Open
Abstract
Here, we developed a stromal cell-derived factor-1a (SDF-1α) delivery biomaterial as an artificial polymeric-based niche with the ability to recruit local endogenous human gingival mesenchymal stem cells (hGMSCs) for craniofacial bone regeneration applications. Polydopamine-coated poly(ε-caprolactone) (PCL)-gelatin electrospun membranes were loaded with stromal cell-derived factor-1α (SDF-1α) via physical adsorption. Subsequently, the release profile of SDF-1α and the chemotactic capacity on human bone marrow mesenchymal stem cells (hBMMSCs) and hGMSCs were evaluated. The osteogenic differentiation capacity of the recruited MSCs was also assessed in vitro. Our results confirmed the sustainable release of SDF-1α from the developed biomaterial promoting the migration and homing of human bone marrow mesenchymal stem cells (hBMMSCs) and hGMSCs. Moreover, the results of the osteogenic differentiation assay showed that SDF-1α delivery significantly enhanced osteogenic differentiation of hBMMSCs and hGMSCs and up-regulated the gene expression of osteogenic markers compared to the control group. In conclusion, the current study successfully developed a novel and effective treatment modality for craniofacial bone regeneration by recruiting the autogenous progenitor cells including hGMSCs. The developed niches can potentially lead to the development of a novel platform for targeted manipulation of in vivo microenvironment to achieve efficient and safe craniofacial cell reprogramming, which also will pave the road to determine the capacity of local hGMSCs' contribution to in situ bone regeneration.
Collapse
Affiliation(s)
| | - Weihao Yuan
- Weintraub Center for Reconstructive Biotechnology, Section of Prosthodontics, School of Dentistry, University of California, Los Angeles, Los Angeles, CA, United States
| | - Sevda Sevari
- Weintraub Center for Reconstructive Biotechnology, Section of Prosthodontics, School of Dentistry, University of California, Los Angeles, Los Angeles, CA, United States
| | - Bo Yu
- Section of Restorative Dentistry, School of Dentistry, University of California, Los Angeles, Los Angeles, CA, United States
| | - Sahar Ansari
- Weintraub Center for Reconstructive Biotechnology, Section of Prosthodontics, School of Dentistry, University of California, Los Angeles, Los Angeles, CA, United States
| | - Alireza Moshaverinia
- Department of Bioengineering, University of California, Los Angeles, Los Angeles, CA, United States
- Weintraub Center for Reconstructive Biotechnology, Section of Prosthodontics, School of Dentistry, University of California, Los Angeles, Los Angeles, CA, United States
- California NanoSystems Institute (CNSI), University of California, Los Angeles, Los Angeles, CA, United States
| |
Collapse
|
|
27
|
Widbiller M, Galler KM. Engineering the Future of Dental Health: Exploring Molecular Advancements in Dental Pulp Regeneration. Int J Mol Sci 2023; 24:11453. [PMID: 37511210 PMCID: PMC10380375 DOI: 10.3390/ijms241411453] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2023] [Accepted: 07/02/2023] [Indexed: 07/30/2023] Open
Abstract
Protected by the surrounding mineralized barriers of enamel, dentin, and cementum, dental pulp is a functionally versatile tissue that fulfills multiple roles [...].
Collapse
Affiliation(s)
- Matthias Widbiller
- Department of Conservative Dentistry and Periodontology, University Hospital Regensburg, Franz-Josef-Strauß-Allee 11, D-93093 Regensburg, Germany
| | - Kerstin M Galler
- Department of Operative Dentistry and Periodontology, Friedrich-Alexander-University Erlangen-Nuernberg, D-91054 Erlangen, Germany
| |
Collapse
|
|
28
|
Amini N, Hivechi A, Asadpour S, Ebrahimzadeh K, Kargozar S, Gholipourmalekabadi M, Nasrolahi A, Ghasemian M, Shafaat A, Mozafari M, Brouki Milan P, Rezapour A. Fabrication and characterization of bilayer scaffolds made of decellularized dermis/nanofibrous collagen for healing of full-thickness wounds. Drug Deliv Transl Res 2023; 13:1766-1779. [PMID: 36701113 DOI: 10.1007/s13346-023-01292-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/04/2023] [Indexed: 01/27/2023]
Abstract
Skin tissue engineering has progressed from simple wound dressings to biocompatible materials with desired physico-chemical properties that can deliver regenerative biomolecules. This study describes using a novel biomimetic hybrid scaffold of decellularized dermis/collagen fibers that can continuously deliver stromal cell-derived factor-1 alpha (SDF-1α) for skin regeneration. In diabetic rat models, the idea that sustained SDF-1α infusion could increase the recruitment of CXCR4-positive cells at the injury site and improve wound regeneration was investigated. The morphology of the scaffold, its biocompatibility, and the kinetics of SDF-1 release were all assessed. SDF-1α was successfully incorporated into collagen nanofibers, resulting in a 200-h continuous release profile. The microscopic observations exhibited that cells are attached and proliferated on proposed scaffolds. As evaluated by in vivo study and histological examination, fabricated scaffold with SDF-1α release capacity exhibited a remarkably more robust ability to accelerate wound regeneration than the control group. Besides, the SDF-1α-loaded scaffold demonstrated functional effects on the proliferation and recruitment of CD31 and CXCR4-positive cells in the wound bed. Additionally, no adverse effects such as hyperplasia or scarring were found during the treatment period. It may be concluded that the fabricated hybrid scaffold based on natural polymer opens up a new option for topical administration of bioactive molecules. We believe the SDF-1α-loaded hybrid scaffold has promise for skin tissue engineering.
Collapse
Affiliation(s)
- Naser Amini
- Cellular and Molecular Research Centre, Iran University of Medical Sciences, Tehran, Iran
| | - Ahmad Hivechi
- Cellular and Molecular Research Centre, Iran University of Medical Sciences, Tehran, Iran
- Department of Textile Engineering, Amirkabir University of Technology, Tehran, Iran
| | - Shiva Asadpour
- Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies, Shahrekord University of Medical Sciences, Shahrekord, Iran
| | - Kaveh Ebrahimzadeh
- Department of Neurosurgery, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Saeid Kargozar
- Tissue Engineering Research Group (TERG), Department of Anatomy and Cell Biology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Mazaher Gholipourmalekabadi
- Cellular and Molecular Research Centre, Iran University of Medical Sciences, Tehran, Iran
- Department of Medical Biotechnology, Faculty of Allied Medicine, Iran University of Medical Sciences, Tehran, Iran
- Department of Tissue Engineering and Regenerative Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Ahvan Nasrolahi
- Cellular and Molecular Research Centre, Iran University of Medical Sciences, Tehran, Iran
| | - Melina Ghasemian
- Department of Tissue Engineering and Regenerative Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Amir Shafaat
- Department of Mechanical Engineering, Arak University of Technology, Arak, Iran
| | - Masoud Mozafari
- Department of Tissue Engineering and Regenerative Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran
- Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada
| | - Peiman Brouki Milan
- Cellular and Molecular Research Centre, Iran University of Medical Sciences, Tehran, Iran.
- Department of Tissue Engineering and Regenerative Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran.
| | - Alireza Rezapour
- Cellular and Molecular Research Centre, Qom University of Medical Sciences, Qom, Iran.
- Department of Tissue Engineering and Regenerative Medicine, School of Medicine, Qom University of Medical Sciences, Qom, Iran.
| |
Collapse
|
|
29
|
Lu X, Li J, Zhou B, Lu X, Li W, Ouyang J. Taohong Siwu Decoction enhances human bone marrow mesenchymal stem cells proliferation, migration and osteogenic differentiation via VEGF-FAK signaling in vitro. JOURNAL OF ETHNOPHARMACOLOGY 2023; 307:116203. [PMID: 36682599 DOI: 10.1016/j.jep.2023.116203] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/29/2022] [Revised: 01/10/2023] [Accepted: 01/19/2023] [Indexed: 06/17/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Taohong Siwu Decoction (THSWD) is a conventional traditional Chinese prescription aiming at promoting blood circulation and alleviating blood stasis. It is widely prescribed in instances of ischemic strokes, cardiovascular diseases, osteoporosis and bone fracture. However, its molecular functions in bone formation remain uncharacterized. AIM OF STUDY This study aims to explore the potential effects of THSWD treatment on human bone marrow mesenchymal stem cells (BMSCs) proliferation, osteogenic differentiation, and migration. MATERIALS AND METHODS BMSCs undergo osteogenic, adipogenic, and chondrogenic differentiation to determine cell stemness. BMSCs were treated with low dose (200 μg/ml), medium dose (400 μg/ml) and high dose (600 μg/ml) THSWD. The cell viability was determined by CCK-8 assays, the osteogenic differentiation ability was determined by alizarin red staining and ALP staining, and cell migration was determined by wound healing and transwell assays. The effect of THSWD on the vascular endothelial growth factor (VEGF)/focal adhesion kinase (FAK) pathway was determined by immunoblotting. RESULTS THSWD time-dependently and dose-dependently promoted BMSC viability. Moreover, THSWD also promoted BMSC osteogenic differentiation and migration. As opposed to THSWD, VEGF receptor inhibitor Bevacizumab suppressed BMSC osteogenic differentiation and migration. In BMSCs that have been co-treated with THSWD and Bevacizumab, THSWD effects on BMSC functions were partially eliminated by Bevacizumab. Moreover, THSWD treatment boosted VEGF content in the supernatant and was conducive to the phosphorylation of FAK and Src, whereas Bevacizumab exerted opposite effects; similarly, Bevacizumab partially abolished THSWD effects on VEGF and FAK (Tyr397) and Src (Tyr418) phosphorylation. CONCLUSION THSWD enhances the capacities of BMSCs to proliferate, differentiate, and migrate, possibly through VEGF and the FAK-Src, thereby improving fracture healing.
Collapse
Affiliation(s)
- Xiaolong Lu
- Department of Orthopedics, First Affiliated Hospital of Hunan University of Chinese Medicine, Changsha, 410005, Hunan Province, PR China.
| | - Juan Li
- Department of Orthopedics, Second Affiliated Hospital of Hunan University of Chinese Medicine, Changsha, 410005, Hunan Province, PR China
| | - Biao Zhou
- Department of Orthopedics, Wangjing Hospital of Chinese Academy of Chinese Medical Science, Beijing, 100102, PR China; Department of Orthopedics, Xiangtan Hospital Affiliated to University of South China, Xiangtan, 411101, Hunan Province, PR China
| | - Xuedi Lu
- Department of Orthopedics, Second Affiliated Hospital of Hunan University of Chinese Medicine, Changsha, 410005, Hunan Province, PR China
| | - Wei Li
- Department of Orthopedics, Second Affiliated Hospital of Hunan University of Chinese Medicine, Changsha, 410005, Hunan Province, PR China
| | - Jian Ouyang
- Department of Orthopedics, Second Affiliated Hospital of Hunan University of Chinese Medicine, Changsha, 410005, Hunan Province, PR China
| |
Collapse
|
|
30
|
Yang Y, Liu YL, Jia LN, Wang JJ, Zhang M. Rescuing “hopeless” avulsed teeth using autologous platelet-rich fibrin following delayed reimplantation: Two case reports. World J Clin Cases 2023; 11:635-644. [PMID: 36793624 PMCID: PMC9923869 DOI: 10.12998/wjcc.v11.i3.635] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/04/2022] [Revised: 12/10/2022] [Accepted: 01/09/2023] [Indexed: 01/22/2023] Open
Abstract
BACKGROUND Tooth avulsion is one of the most severe types of dental trauma. Most avulsed teeth undergo long-term ankylosis and replacement resorption after delayed reimplantation and exhibit a poor prognosis. The aim of this work was to improve the success rate of avulsed teeth after delayed reimplantation using autologous platelet-rich fibrin (PRF).
CASE SUMMARY Case 1 was a 14-year-old boy who fell and knocked out his left upper central incisor 18 h prior to his arrival at the department. The diagnoses were avulsion of tooth 21, lateral luxation of tooth 11 and alveolar fracture of teeth 11 and 21. In case 2, a 17-year-old boy fell 2 h prior to his presentation to the hospital, and his left upper lateral incisor was completely knocked out of the alveolar socket. The diagnoses included avulsion of tooth 22, complicated crown fracture of tooth 11 and complicated crown-root fracture of tooth 21. The avulsed teeth were reimplanted along with autologous PRF granules and splinted using a semiflexible titanium preshaped labial arch. The root canals of the avulsed teeth were filled with calcium hydroxide paste, and root canal filling was performed 4 wk after reimplantation. The reimplanted teeth showed no symptoms of inflammatory root resorption or ankylosis at the 3-, 6-, and 12-mo follow-up examinations after reimplantation with autologous PRF. In addition to the avulsed teeth, the other injured teeth were treated using corresponding conventional treatment methods.
CONCLUSION These cases provide examples of the successful use of PRF to reduce pathological root resorption of the avulsed teeth, and the application of PRF may provide new healing opportunities for traditionally “hopeless” avulsed teeth.
Collapse
Affiliation(s)
- Yang Yang
- State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi International Joint Research Center for Oral Diseases, Department of General Dentistry and Emergency, School of Stomatology, Fourth Military Medical University, Xi'an 710032, Shaanxi Province, China
| | - Yan-Li Liu
- State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi International Joint Research Center for Oral Diseases, Department of General Dentistry and Emergency, School of Stomatology, Fourth Military Medical University, Xi'an 710032, Shaanxi Province, China
| | - Lie-Ni Jia
- State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi International Joint Research Center for Oral Diseases, Department of General Dentistry and Emergency, School of Stomatology, Fourth Military Medical University, Xi'an 710032, Shaanxi Province, China
| | - Jun-Jun Wang
- State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi International Joint Research Center for Oral Diseases, Department of General Dentistry and Emergency, School of Stomatology, Fourth Military Medical University, Xi'an 710032, Shaanxi Province, China
| | - Min Zhang
- State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi International Joint Research Center for Oral Diseases, Department of General Dentistry and Emergency, School of Stomatology, Fourth Military Medical University, Xi'an 710032, Shaanxi Province, China
| |
Collapse
|
|
31
|
Huang Z, Su X, Julaiti M, Chen X, Luan Q. The role of PRX1-expressing cells in periodontal regeneration and wound healing. Front Physiol 2023; 14:978640. [PMID: 36960156 PMCID: PMC10027693 DOI: 10.3389/fphys.2023.978640] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2022] [Accepted: 02/23/2023] [Indexed: 03/09/2023] Open
Abstract
The ideal outcome of wound healing is the complete restoration of the structure and function of the original tissue. Stem cells are one of the key factors in this process. Currently, the strategy of periodontal regeneration based on mesenchymal stem cells (MSCs) is generally used to expand stem cells in vitro and then transplant them in vivo. However, their clinical application is limited. In fact, the human body has the capacity to regenerate through stem cells residing in different tissues, even without external therapeutic intervention. Stem cell niches are present in many adult tissues, such as the periodontal ligament and gingiva, and stem cells might remain in a quiescent state in their niches until they are activated in response to a regenerative need. Activated stem cells can exit the niche and proliferate, self-renew, and differentiate to regenerate original structures. Thus, harnessing the regenerative potential of endogenous stem cells in situ has gained increasing attention as a simpler, safer, and more applicable alternative to stem cell transplantation. Nevertheless, there are several key problems to be solved in the application of periodontal mesenchymal stem cells. Thus, animal studies will be especially important to deepen our knowledge of the in vivo mechanisms of mesenchymal stem cells. Studies with conditional knockout mice, in which the expression of different proteins can be eliminated in a tissue-specific manner, are especially important. Post-natal cells expressing the paired-related homeobox protein 1 (PRX1 or PRRX1), a transcription factor expressed in the mesenchyme during craniofacial and limb development, have been shown to have characteristics of skeletal stem cells. Additionally, following wounding, dermal Prx1+ cells are found out of their dermal niches and contribute to subcutaneous tissue repair. Postnatal Prx1+ cells are uniquely injury-responsive. Meanwhile, current evidence shows that Prx1+ cells contribute to promote dentin formation, wound healing of alveolar bone and formation of mouse molar and periodontal ligament. Initial result of our research group also indicates Prx1-expressing cells in bone tissue around the punch wound area of gingiva increased gradually. Collectively, this review supports the future use of PRX1 cells to stimulate their potential to play an important role in endogenous regeneration during periodontal therapy.
Collapse
Affiliation(s)
- Zhen Huang
- Beijing Key Laboratory of Digital Stomatology, NMPA Key Laboratory for Dental Materials, Department of Periodontology, National Center for Stomatology, National Clinical Research Center for Oral Diseases, National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Research Center of Engineering and Technology for Computerized Dentistry Ministry of Health, Peking University School and Hospital of Stomatology, Beijing, China
| | - Xu Su
- Department of Stomatology, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, China
| | - Miliya Julaiti
- Department of Stomatology, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, China
| | - Xiaotao Chen
- Department of Stomatology, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, China
- *Correspondence: Xiaotao Chen, ; Qingxian Luan,
| | - Qingxian Luan
- Beijing Key Laboratory of Digital Stomatology, NMPA Key Laboratory for Dental Materials, Department of Periodontology, National Center for Stomatology, National Clinical Research Center for Oral Diseases, National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Research Center of Engineering and Technology for Computerized Dentistry Ministry of Health, Peking University School and Hospital of Stomatology, Beijing, China
- *Correspondence: Xiaotao Chen, ; Qingxian Luan,
| |
Collapse
|
|
32
|
Deng DK, Zhang JJ, Gan D, Zou JK, Wu RX, Tian Y, Yin Y, Li X, Chen FM, He XT. Roles of extracellular vesicles in periodontal homeostasis and their therapeutic potential. J Nanobiotechnology 2022; 20:545. [PMID: 36585740 PMCID: PMC9801622 DOI: 10.1186/s12951-022-01757-3] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2022] [Accepted: 12/23/2022] [Indexed: 01/01/2023] Open
Abstract
Periodontal tissue is a highly dynamic and frequently stimulated area where homeostasis is easily destroyed, leading to proinflammatory periodontal diseases. Bacteria-bacteria and cell-bacteria interactions play pivotal roles in periodontal homeostasis and disease progression. Several reviews have comprehensively summarized the roles of bacteria and stem cells in periodontal homeostasis. However, they did not describe the roles of extracellular vesicles (EVs) from bacteria and cells. As communication mediators evolutionarily conserved from bacteria to eukaryotic cells, EVs secreted by bacteria or cells can mediate interactions between bacteria and their hosts, thereby offering great promise for the maintenance of periodontal homeostasis. This review offers an overview of EV biogenesis, the effects of EVs on periodontal homeostasis, and recent advances in EV-based periodontal regenerative strategies. Specifically, we document the pathogenic roles of bacteria-derived EVs (BEVs) in periodontal dyshomeostasis, focusing on plaque biofilm formation, immune evasion, inflammatory pathway activation and tissue destruction. Moreover, we summarize recent advancements in cell-derived EVs (CEVs) in periodontal homeostasis, emphasizing the multifunctional biological effects of CEVs on periodontal tissue regeneration. Finally, we discuss future challenges and practical perspectives for the clinical translation of EV-based therapies for periodontitis.
Collapse
Affiliation(s)
- Dao-Kun Deng
- State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Engineering Research Center for Dental Materials and Advanced Manufacture, Department of Periodontology, School of Stomatology, The Fourth Military Medical University, Xi'an, People's Republic of China
| | - Jiu-Jiu Zhang
- State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Engineering Research Center for Dental Materials and Advanced Manufacture, Department of Periodontology, School of Stomatology, The Fourth Military Medical University, Xi'an, People's Republic of China
| | - Dian Gan
- State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Engineering Research Center for Dental Materials and Advanced Manufacture, Department of Periodontology, School of Stomatology, The Fourth Military Medical University, Xi'an, People's Republic of China
| | - Jie-Kang Zou
- State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Engineering Research Center for Dental Materials and Advanced Manufacture, Department of Periodontology, School of Stomatology, The Fourth Military Medical University, Xi'an, People's Republic of China
| | - Rui-Xin Wu
- State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Engineering Research Center for Dental Materials and Advanced Manufacture, Department of Periodontology, School of Stomatology, The Fourth Military Medical University, Xi'an, People's Republic of China
| | - Yi Tian
- State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Engineering Research Center for Dental Materials and Advanced Manufacture, Department of Periodontology, School of Stomatology, The Fourth Military Medical University, Xi'an, People's Republic of China
| | - Yuan Yin
- State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Engineering Research Center for Dental Materials and Advanced Manufacture, Department of Periodontology, School of Stomatology, The Fourth Military Medical University, Xi'an, People's Republic of China
| | - Xuan Li
- State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Engineering Research Center for Dental Materials and Advanced Manufacture, Department of Periodontology, School of Stomatology, The Fourth Military Medical University, Xi'an, People's Republic of China.
| | - Fa-Ming Chen
- State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Engineering Research Center for Dental Materials and Advanced Manufacture, Department of Periodontology, School of Stomatology, The Fourth Military Medical University, Xi'an, People's Republic of China.
| | - Xiao-Tao He
- State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Engineering Research Center for Dental Materials and Advanced Manufacture, Department of Periodontology, School of Stomatology, The Fourth Military Medical University, Xi'an, People's Republic of China.
| |
Collapse
|
|
33
|
Zhuang Y, Yang W, Zhang L, Fan C, Qiu L, Zhao Y, Chen B, Chen Y, Shen H, Dai J. A novel leptin receptor binding peptide tethered-collagen scaffold promotes lung injury repair. Biomaterials 2022; 291:121884. [DOI: 10.1016/j.biomaterials.2022.121884] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2022] [Revised: 10/10/2022] [Accepted: 10/23/2022] [Indexed: 11/06/2022]
|
|
34
|
Meng L, Wei Y, Liang Y, Hu Q, Xie H. Stem cell homing in periodontal tissue regeneration. Front Bioeng Biotechnol 2022; 10:1017613. [PMID: 36312531 PMCID: PMC9607953 DOI: 10.3389/fbioe.2022.1017613] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2022] [Accepted: 10/03/2022] [Indexed: 11/29/2022] Open
Abstract
The destruction of periodontal tissue is a crucial problem faced by oral diseases, such as periodontitis and tooth avulsion. However, regenerating periodontal tissue is a huge clinical challenge because of the structural complexity and the poor self-healing capability of periodontal tissue. Tissue engineering has led to advances in periodontal regeneration, however, the source of exogenous seed cells is still a major obstacle. With the improvement of in situ tissue engineering and the exploration of stem cell niches, the homing of endogenous stem cells may bring promising treatment strategies in the future. In recent years, the applications of endogenous cell homing have been widely reported in clinical tissue repair, periodontal regeneration, and cell therapy prospects. Stimulating strategies have also been widely studied, such as the combination of cytokines and chemokines, and the implantation of tissue-engineered scaffolds. In the future, more research needs to be done to improve the efficiency of endogenous cell homing and expand the range of clinical applications.
Collapse
Affiliation(s)
- Lingxi Meng
- State Key Laboratory of Oral Diseases, Department of Head and Neck Oncology Surgery, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Yige Wei
- State Key Laboratory of Oral Diseases, Department of Head and Neck Oncology Surgery, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Yaxian Liang
- State Key Laboratory of Oral Diseases, Department of Head and Neck Oncology Surgery, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Qin Hu
- Faculty of Dentistry, The University of Hong Kong, Hong Kong, China
| | - Huixu Xie
- State Key Laboratory of Oral Diseases, Department of Head and Neck Oncology Surgery, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China
- *Correspondence: Huixu Xie,
| |
Collapse
|
|
35
|
Wei Y, Chen M, Li M, Wang D, Cai K, Luo Z, Hu Y. Aptamer/Hydroxyapatite-Functionalized Titanium Substrate Promotes Implant Osseointegration via Recruiting Mesenchymal Stem Cells. ACS APPLIED MATERIALS & INTERFACES 2022; 14:42915-42930. [PMID: 36107718 DOI: 10.1021/acsami.2c10809] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/15/2023]
Abstract
Endowing bone regeneration materials with both stem cell recruitment and osteoinduction properties is a key factor in promoting osseointegration of titanium (Ti) implants. In this study, Apt19s-grafted oxidized hyaluronic acid (OHA) was deposited onto a protein-mediated biomineralization hydroxyapatite (HAp) coating of Ti. HAp was achieved by the treatment of lysozyme and tris(2-carboxyethyl) phosphonate mixture and then soaked in calcium ion (Ca2+) solution to obtain functional Ti substrate (Ti/HAp/OHA-Apt). In vitro studies confirmed that Ti/HAp/OHA-Apt could effectively maintain the sustained release of Apt19s from Ti for 7 days. The released Apt19s significantly enhanced the migration of bone marrow mesenchymal stem cells (MSCs), which was reflected by the experiment of transwell assay, wound healing, and zymogram detection. Compared with pure Ti, Ti/HAp/OHA-Apt was able to adjust the adsorption of functional proteins at the Ti-based interface to expose their active sites, which significantly increased the expression of adhesion-associated proteins (vinculin and tensin) in MSCs to promote their adhesion on Ti-based interface. In vitro cell experiments of alkaline phosphatase activity staining, mineralization detection, and expression of osteogenesis-related genes showed that Ti/HAp/OHA-Apt significantly enhanced the osteogenic differentiation ability of MSCs, which may be highly related to the porous structure of hydroxyapatite on Ti interface. In vivo test of Micro-CT, H&E staining, and histochemical staining further confirmed that Ti/HAp/OHA-Apt was able to promote MSC recruitment at the peri-implant interface to form new bone. This work provides a new approach to develop functional Ti-based materials for bone defect repair.
Collapse
Affiliation(s)
- Yujia Wei
- Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044, China
| | - Maohua Chen
- Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044, China
| | - Menghuan Li
- School of Life Sciences, Chongqing University, Chongqing 400044, China
| | - Dong Wang
- Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044, China
| | - Kaiyong Cai
- Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044, China
| | - Zhong Luo
- School of Life Sciences, Chongqing University, Chongqing 400044, China
| | - Yan Hu
- Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044, China
| |
Collapse
|
|
36
|
Bai J, Ge G, Wang Q, Li W, Zheng K, Xu Y, Yang H, Pan G, Geng D. Engineering Stem Cell Recruitment and Osteoinduction via Bioadhesive Molecular Mimics to Improve Osteoporotic Bone-Implant Integration. Research (Wash D C) 2022; 2022:9823784. [PMID: 36157511 PMCID: PMC9484833 DOI: 10.34133/2022/9823784] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2022] [Accepted: 08/22/2022] [Indexed: 11/14/2022] Open
Abstract
For patients with osteoporosis, the therapeutic outcomes of osteoimplants are substantially affected by the impaired proliferation, migration, and osteogenic differentiation abilities of bone marrow mesenchymal stem cells (BMSCs). To improve bone-implant integration in osteoporotic condition, here we reported a one-step biomimetic surface strategy to introduce BMSC recruiting and osteoinductive abilities onto metallic osteoimplants. In our design, the bioadhesive molecular peptide mimic inspired by mussel foot proteins (Mfps) was used as molecular bridging for surface functionalization. Specifically, a BMSC-targeting peptide sequence (E7) and an osteogenic growth peptide (Y5) were grafted onto the titanium implant surfaces through a mussel adhesion mechanism. We found that a rational E7/Y5 feeding ratio could lead to an optimal dual functionalization capable of not only significantly improving the biocompatibility of the implant but also enabling it to recruit endogenous BMSCs for colonization, proliferation, and osteogenic differentiation. Mechanistically, the E7-assisted in situ recruitment of endogenous BMSCs as well as the enhanced interfacial osteogenesis and osteointegration was associated with activation of the C-X-C chemokine receptor type 4 (CXCR4) receptor on the cell surface and promotion of stromal cell-derived factor (SDF-1α) autocrine secretion. We anticipated that rational dual-functional surfaces through bioadhesive molecular mimics will provide a simple, effective, nonimmunogenic, and safe means to improve the clinical outcomes of intraosseous implants, especially under osteoporotic conditions.
Collapse
Affiliation(s)
- Jiaxiang Bai
- Department of Orthopaedics, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou, Jiangsu 215006, China
- Institute for Advanced Materials, School of Materials Science and Engineering, Jiangsu University, 301 Xuefu Road, Zhenjiang, Jiangsu 212013, China
| | - Gaoran Ge
- Department of Orthopaedics, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou, Jiangsu 215006, China
| | - Qing Wang
- Department of Orthopaedics, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou, Jiangsu 215006, China
| | - Wenming Li
- Department of Orthopaedics, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou, Jiangsu 215006, China
| | - Kai Zheng
- Department of Orthopaedics, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou, Jiangsu 215006, China
| | - Yaozeng Xu
- Department of Orthopaedics, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou, Jiangsu 215006, China
| | - Huilin Yang
- Department of Orthopaedics, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou, Jiangsu 215006, China
| | - Guoqing Pan
- Institute for Advanced Materials, School of Materials Science and Engineering, Jiangsu University, 301 Xuefu Road, Zhenjiang, Jiangsu 212013, China
| | - Dechun Geng
- Department of Orthopaedics, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou, Jiangsu 215006, China
| |
Collapse
|
|
37
|
Li H, Zhao T, Cao F, Deng H, He S, Li J, Liu S, Yang Z, Yuan Z, Guo Q. Integrated bioactive scaffold with aptamer-targeted stem cell recruitment and growth factor-induced pro-differentiation effects for anisotropic meniscal regeneration. Bioeng Transl Med 2022; 7:e10302. [PMID: 36176622 PMCID: PMC9472018 DOI: 10.1002/btm2.10302] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2021] [Revised: 01/26/2022] [Accepted: 01/29/2022] [Indexed: 12/24/2022] Open
Abstract
Reconstruction of the knee meniscus remains a significant clinical challenge owing to its complex anisotropic tissue organization, complex functions, and limited healing capacity in the inner region. The development of in situ tissue-engineered meniscal scaffolds, which provide biochemical signaling to direct endogenous stem/progenitor cell (ESPC) behavior, has the potential to revolutionize meniscal tissue engineering. In this study, a fiber-reinforced porous scaffold was developed based on aptamer Apt19S-mediated mesenchymal stem cell (MSC)-specific recruitment and dual growth factor (GF)-enhanced meniscal differentiation. The aptamer, which can specifically recognize and recruit MSCs, was first chemically conjugated to the decellularized meniscus extracellular matrix (MECM) and then mixed with gelatin methacrylate (GelMA) to form a photocrosslinkable hydrogel. Second, connective tissue growth factor (CTGF)-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) and transforming growth factor-β3 (TGF-β3)-loaded PLGA microparticles (MPs) were mixed with aptamer-conjugated MECM to simulate anisotropic meniscal regeneration. These three bioactive molecules were delivered sequentially. Apt19S, which exhibited high binding affinity to synovium-derived MSCs (SMSCs), was quickly released to facilitate the mobilization of ESPCs. CTGF incorporated within PLGA NPs was released rapidly, inducing profibrogenic differentiation, while sustained release of TGF-β3 in PLGA MPs remodeled the fibrous matrix into fibrocartilaginous matrix. The in vitro results showed that the sequential release of Apt19S/GFs promoted cell migration, proliferation, and fibrocartilaginous differentiation. The in vivo results demonstrated that the sequential release system of Apt/GF-scaffolds increased neomeniscal formation in rabbit critical-sized meniscectomies. Thus, the novel delivery system shows potential for guiding meniscal regeneration in situ.
Collapse
Affiliation(s)
- Hao Li
- Institute of Orthopedics, the First Medical Center, Chinese PLA General Hospital; Beijing Key Lab of Regenerative Medicine in OrthopedicsKey Laboratory of Musculoskeletal Trauma & War Injuries PLAHaidian DistrictBeijingChina
- School of MedicineNankai UniversityTianjinChina
| | - Tianyuan Zhao
- Institute of Orthopedics, the First Medical Center, Chinese PLA General Hospital; Beijing Key Lab of Regenerative Medicine in OrthopedicsKey Laboratory of Musculoskeletal Trauma & War Injuries PLAHaidian DistrictBeijingChina
- School of MedicineNankai UniversityTianjinChina
| | - Fuyang Cao
- Institute of Orthopedics, the First Medical Center, Chinese PLA General Hospital; Beijing Key Lab of Regenerative Medicine in OrthopedicsKey Laboratory of Musculoskeletal Trauma & War Injuries PLAHaidian DistrictBeijingChina
- Department of Orthopedicsthe First Affiliated Hospital of Zhengzhou UniversityEqi DistrictZhengzhouChina
| | - Haoyuan Deng
- Institute of Orthopedics, the First Medical Center, Chinese PLA General Hospital; Beijing Key Lab of Regenerative Medicine in OrthopedicsKey Laboratory of Musculoskeletal Trauma & War Injuries PLAHaidian DistrictBeijingChina
- School of MedicineNankai UniversityTianjinChina
| | - Songlin He
- Institute of Orthopedics, the First Medical Center, Chinese PLA General Hospital; Beijing Key Lab of Regenerative Medicine in OrthopedicsKey Laboratory of Musculoskeletal Trauma & War Injuries PLAHaidian DistrictBeijingChina
- School of MedicineNankai UniversityTianjinChina
| | - Jianwei Li
- Institute of Orthopedics, the First Medical Center, Chinese PLA General Hospital; Beijing Key Lab of Regenerative Medicine in OrthopedicsKey Laboratory of Musculoskeletal Trauma & War Injuries PLAHaidian DistrictBeijingChina
- School of MedicineNankai UniversityTianjinChina
| | - Shuyun Liu
- Institute of Orthopedics, the First Medical Center, Chinese PLA General Hospital; Beijing Key Lab of Regenerative Medicine in OrthopedicsKey Laboratory of Musculoskeletal Trauma & War Injuries PLAHaidian DistrictBeijingChina
- School of MedicineNankai UniversityTianjinChina
| | - Zhen Yang
- Institute of Orthopedics, the First Medical Center, Chinese PLA General Hospital; Beijing Key Lab of Regenerative Medicine in OrthopedicsKey Laboratory of Musculoskeletal Trauma & War Injuries PLAHaidian DistrictBeijingChina
- School of MedicineNankai UniversityTianjinChina
- Arthritis Clinic & Research Center, Peking University People's HospitalPeking UniversityBeijingChina
| | - Zhiguo Yuan
- Institute of Orthopedics, the First Medical Center, Chinese PLA General Hospital; Beijing Key Lab of Regenerative Medicine in OrthopedicsKey Laboratory of Musculoskeletal Trauma & War Injuries PLAHaidian DistrictBeijingChina
- Department of Bone and Joint Surgery, Renji Hospital, School of MedicineShanghai Jiaotong UniversityShanghaiChina
| | - Quanyi Guo
- Institute of Orthopedics, the First Medical Center, Chinese PLA General Hospital; Beijing Key Lab of Regenerative Medicine in OrthopedicsKey Laboratory of Musculoskeletal Trauma & War Injuries PLAHaidian DistrictBeijingChina
- School of MedicineNankai UniversityTianjinChina
| |
Collapse
|
|
38
|
Yao D, Lv Y. A cell-free difunctional demineralized bone matrix scaffold enhances the recruitment and osteogenesis of mesenchymal stem cells by promoting inflammation resolution. BIOMATERIALS ADVANCES 2022; 139:213036. [PMID: 35905556 DOI: 10.1016/j.bioadv.2022.213036] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/18/2022] [Revised: 07/14/2022] [Accepted: 07/15/2022] [Indexed: 06/15/2023]
Abstract
The dialogue between host macrophages (Mφs) and endogenous mesenchymal stem cells (MSCs) promotes M2 Mφs polarization to resolve early-stage inflammation, thereby effectively guiding in situ bone regeneration. Once inflammation is unresolved/incontrollable, it will induce the impediment of MSCs homing at bone defect site, implying the seasonable resolution of inflammation in balancing bone homeostasis. Repeatedly, evidence elucidated that specialized pro-resolving mediators (SPMs) could conduce to proper resolve inflammation and promote the repairing of bone defect. A difunctional demineralized bone matrix (DBM) scaffold co-modified by maresin 1 (MaR1) and aptamer 19S (Apt19S) was fabricated to facilitate the osteogenesis of MSCs. To confirm the osteogenesis and immunomodulatory role of the difunctional DBM scaffold, the proliferation, recruitment, and osteogenic differentiation of MSCs and the Mφs M2 subtype polarization were evaluated in vitro. Then, the DBM scaffolds were implanted into mice model with critical size calvarial defect to evaluate bone repair efficiency. Finally, the specific resolution mechanism in Mφs cultured on the difunctional DBM scaffold was further in-depth investigated. This difunctional DBM scaffold exhibited an enhanced function on the recruitment, proliferation, migration, osteogenesis of MSCs and the resolution of inflammation, finally improved bone-scaffold integration. At the same time, MaR1 modified on the difunctional DBM scaffold increased the biosynthesis of 12-lipoxygenase (12-LOX) and 12S-hydroxy-eicosatetraenoic acid (12S-HETE), and also directly stimulated lipid droplets (LDs) biogenesis in Mφs, which suggested that MaR1 regulated Mφ lipid metabolism at bone repair site. Findings based on this synergy strategy demonstrated that Mφ lipid metabolism was essential in bone homeostasis, which might provide a theoretical direction for the treatment-associated application of MaR1 in inflammatory bone disease.
Collapse
Affiliation(s)
- Dongdong Yao
- Mechanobiology and Regenerative Medicine Laboratory, Bioengineering College, Chongqing University, Chongqing 400044, PR China
| | - Yonggang Lv
- State Key Laboratory of New Textile Materials and Advanced Processing Technologies, Wuhan Textile University, Wuhan 430200, PR China.
| |
Collapse
|
|
39
|
Assis JLD, Fernandes AM, Aniceto BS, Fernandes da Costa PP, Banchio C, Girardini J, Vieyra A, Valverde RRHF, Einicker‐Lamas M. Sphingosine 1‐Phosphate Prevents Human Embryonic Stem Cell Death Following Ischemic Injury. EUR J LIPID SCI TECH 2022. [DOI: 10.1002/ejlt.202200019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022]
Affiliation(s)
- Juliane L. de Assis
- Laboratório de Biomembranas Instituto de Biofísica Carlos Chagas Filho–Universidade Federal do Rio de Janeiro Rio de Janeiro Brazil
| | - Aline M. Fernandes
- Laboratório de Biomembranas Instituto de Biofísica Carlos Chagas Filho–Universidade Federal do Rio de Janeiro Rio de Janeiro Brazil
| | - Bárbara S. Aniceto
- Laboratório de Biomembranas Instituto de Biofísica Carlos Chagas Filho–Universidade Federal do Rio de Janeiro Rio de Janeiro Brazil
| | - Pedro P. Fernandes da Costa
- Laboratório de Biomembranas Instituto de Biofísica Carlos Chagas Filho–Universidade Federal do Rio de Janeiro Rio de Janeiro Brazil
| | - Claudia Banchio
- Instituto de Biologia Molecular y Celular de Rosário Rosário Argentina
| | - Javier Girardini
- Instituto de Biologia Molecular y Celular de Rosário Rosário Argentina
| | - Adalberto Vieyra
- Laboratório de Físico‐Química Biológica Instituto de Biofísica Carlos Chagas Filho–Universidade Federal do Rio de Janeiro Rio de Janeiro Brazil
| | - Rafael R. H. F. Valverde
- Laboratório de Biomembranas Instituto de Biofísica Carlos Chagas Filho–Universidade Federal do Rio de Janeiro Rio de Janeiro Brazil
| | - Marcelo Einicker‐Lamas
- Laboratório de Biomembranas Instituto de Biofísica Carlos Chagas Filho–Universidade Federal do Rio de Janeiro Rio de Janeiro Brazil
| |
Collapse
|
|
40
|
Ning LJ, Cui J, He SK, Hu RN, Yao X, Zhang Y, Ding W, Zhang YJ, Luo JC, Qin TW. Constructing a highly bioactive tendon-regenerative scaffold by surface modification of tissue-specific stem cell derived extracellular matrix. Regen Biomater 2022; 9:rbac020. [PMID: 35480863 PMCID: PMC9036902 DOI: 10.1093/rb/rbac020] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2021] [Revised: 01/28/2022] [Accepted: 03/06/2022] [Indexed: 02/05/2023] Open
Abstract
Developing highly bioactive scaffold materials to promote stem cell migration, proliferation and tissue-specific differentiation is a crucial requirement in current tissue engineering and regenerative medicine. Our previous work has demonstrated that the decellularized tendon slices (DTSs) are able to promote stem cell proliferation and tenogenic differentiation in vitro and show certain pro-regenerative capacity for rotator cuff tendon regeneration in vivo. In this study, we present a strategy to further improve the bioactivity of the DTSs for constructing a novel highly bioactive tendon-regenerative scaffold by surface modification of tendon-specific stem cell-derived extracellular matrix (tECM), which is expected to greatly enhance the capacity of scaffold material in regulating stem cell behavior, including migration, proliferation and tenogenic differentiation. We prove that the modification of tECM could change the highly aligned surface topographical cues of the DTSs, retain the surface stiffness of the DTSs and significantly increase the content of multiple ECM components in the tECM-DTSs. As a result, the tECM-DTSs dramatically enhance the migration, proliferation as well as tenogenic differentiation of rat bone marrow-derived stem cells compared with the DTSs. Collectively, this strategy would provide a new way for constructing ECM-based biomaterials with enhanced bioactivity for in situ tendon regeneration applications. ![]()
Collapse
Affiliation(s)
- Liang-Ju Ning
- Laboratory of Stem Cell and Tissue Engineering, Orthopedic Research Institute, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, Sichuan, 610041, P.R. China
| | - Jing Cui
- Laboratory of Stem Cell and Tissue Engineering, Orthopedic Research Institute, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, Sichuan, 610041, P.R. China
| | - Shu-Kun He
- Laboratory of Stem Cell and Tissue Engineering, Orthopedic Research Institute, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, Sichuan, 610041, P.R. China
- Department of Orthopedic Surgery, Orthopedic Research Institute, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, P.R. China
| | - Ruo-Nan Hu
- Laboratory of Stem Cell and Tissue Engineering, Orthopedic Research Institute, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, Sichuan, 610041, P.R. China
| | - Xuan Yao
- Laboratory of Stem Cell and Tissue Engineering, Orthopedic Research Institute, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, Sichuan, 610041, P.R. China
| | - Yi Zhang
- Core Facility, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, P.R. China
| | - Wei Ding
- Laboratory of Stem Cell and Tissue Engineering, Orthopedic Research Institute, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, Sichuan, 610041, P.R. China
| | - Yan-Jing Zhang
- Laboratory of Stem Cell and Tissue Engineering, Orthopedic Research Institute, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, Sichuan, 610041, P.R. China
- Core Facility, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, P.R. China
| | - Jing-Cong Luo
- Laboratory of Stem Cell and Tissue Engineering, Orthopedic Research Institute, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, Sichuan, 610041, P.R. China
| | - Ting-Wu Qin
- Laboratory of Stem Cell and Tissue Engineering, Orthopedic Research Institute, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, Sichuan, 610041, P.R. China
| |
Collapse
|
|
41
|
Bordini EAF, Cassiano FB, Bronze-Uhle ES, Alamo L, Hebling J, de Souza Costa CA, Soares DG. Chitosan in association with osteogenic factors as a cell-homing platform for dentin regeneration: Analysis in a pulp-in-a-chip model. Dent Mater 2022; 38:655-669. [PMID: 35210124 DOI: 10.1016/j.dental.2022.02.004] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2021] [Revised: 01/04/2022] [Accepted: 02/12/2022] [Indexed: 12/18/2022]
Abstract
OBJECTIVE In this paper we propose the association of β-glycerophosphate (βGP) and calcium-hydroxide with chitosan (CH) to formulate a porous bioactive scaffold suitable as a cell-homing platform for dentin regeneration. METHODS Calcium hydroxide and βGP solutions were incorporated into chitosan to modulate scaffold architecture and composition by a phase separation technique. Architecture, chemical composition, and degradability were evaluated, and biological characterizations were performed by the seeding of dental pulp cells (DPCs) onto scaffolds, or by cultivating them in contact with leachable components (extracts), to determine cytocompatibility and odontoblastic differentiation. Cell-free scaffolds were then positioned in intimate contact with a 3D culture of DPCs in a pulp-in-a-chip platform under simulated pulp pressure. Cell mobilization and odontoblastic marker expression were evaluated. Deposition of mineralized matrix was assessed in direct contact with dentin, in the absence of osteogenic factors. RESULTS Incorporation of calcium hydroxide and βGP generated a stable porous chitosan scaffold containing Ca-P nanoglobule topography (CH-Ca-βGP), which favored cell viability, alkaline phosphatase activity, and mineralized matrix deposition by cells seeded onto the scaffold structure and at a distance. The pulp-in-a-chip assay denoted its chemotactic and bioactive potential, since dentin sialoprotein-positive DPCs from 3D culture adhered to CH-Ca-βGP more than to plain chitosan. The higher deposition of mineralized matrix onto the scaffold and surrounding dentin was also observed. SIGNIFICANCE A CH-Ca-βGP scaffold creates a microenvironment capable of mobilizing DPC migration toward its structure, harnessing the odontogenic potential and culminating in the expression of a highly mineralizing phenotype, key factors for a cell-homing strategy.
Collapse
Affiliation(s)
- E A F Bordini
- Department of Physiology and Pathology, Univ. Estadual Paulista - UNESP, Araraquara School of Dentistry, Humaitá Street, 1680, Araraquara, SP 14801-903, Brazil; Department of Operative Dentistry, Endodontics and Dental Materials, Sao Paulo University - USP, Bauru School of Dentistry, Al. Dr. Octávio Pinheiro Brizola, 9-75, Bauru, SP 17012-901, Brazil
| | - F B Cassiano
- Department of Operative Dentistry, Endodontics and Dental Materials, Sao Paulo University - USP, Bauru School of Dentistry, Al. Dr. Octávio Pinheiro Brizola, 9-75, Bauru, SP 17012-901, Brazil
| | - E S Bronze-Uhle
- Department of Operative Dentistry, Endodontics and Dental Materials, Sao Paulo University - USP, Bauru School of Dentistry, Al. Dr. Octávio Pinheiro Brizola, 9-75, Bauru, SP 17012-901, Brazil
| | - L Alamo
- Department of Operative Dentistry, Endodontics and Dental Materials, Sao Paulo University - USP, Bauru School of Dentistry, Al. Dr. Octávio Pinheiro Brizola, 9-75, Bauru, SP 17012-901, Brazil
| | - J Hebling
- Department of Orthodontics and Pediatric Dentistry, Univ. Estadual Paulista - UNESP, Araraquara School of Dentistry, Humaitá Street, 1680, Araraquara, SP 14801-903, Brazil
| | - C A de Souza Costa
- Department of Physiology and Pathology, Univ. Estadual Paulista - UNESP, Araraquara School of Dentistry, Humaitá Street, 1680, Araraquara, SP 14801-903, Brazil
| | - D G Soares
- Department of Operative Dentistry, Endodontics and Dental Materials, Sao Paulo University - USP, Bauru School of Dentistry, Al. Dr. Octávio Pinheiro Brizola, 9-75, Bauru, SP 17012-901, Brazil.
| |
Collapse
|
|
42
|
Tan MH, Xu XH, Yuan TJ, Hou X, Wang J, Jiang ZH, Peng LH. Self-powered smart patch promotes skin nerve regeneration and sensation restoration by delivering biological-electrical signals in program. Biomaterials 2022; 283:121413. [DOI: 10.1016/j.biomaterials.2022.121413] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2021] [Revised: 02/09/2022] [Accepted: 02/13/2022] [Indexed: 11/02/2022]
|
|
43
|
Widbiller M, Rosendahl A, Wölflick M, Linnebank M, Welzenbach B, Hiller KA, Buchalla W, Galler KM. Isolation of Endogenous TGF-β1 from Root Canals for Pulp Tissue Engineering: A Translational Study. BIOLOGY 2022; 11:biology11020227. [PMID: 35205093 PMCID: PMC8869556 DOI: 10.3390/biology11020227] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/21/2021] [Revised: 01/24/2022] [Accepted: 01/28/2022] [Indexed: 11/28/2022]
Abstract
Simple Summary Tissue engineering of the dental pulp has been a goal of dental research for years. In this translational study, a chairside protocol is designed using endogenous dentin matrix proteins as signaling molecules for pulp regeneration. These bioactive molecules can be isolated from root canals by ultrasonic-activated irrigation, further processed chairside, and mixed with a hydrogel. The scaffold material is to be injected into the root canal and effect cell homing, i.e., allowing stem cells from the periapical space to migrate into the root canal. The aim of this innovative approach is the formation of an innervated and vascularized connective tissue that resembles the pulp in form and function. Abstract Cell homing for dental pulp tissue engineering has been advocated as a feasible approach to regenerate dental pulp in a clinical setting. In order to develop a translational protocol for clinical application, we wanted to determine the effects of disinfectants on the availability of growth factors from the root canal, the amount that can be obtained in this context, and whether they can be processed for use in tissue engineering procedures. The extraction of growth factors should also be confirmed in a clinical setting. Root canals were prepared in 36 extracted mature teeth, and the amount of TGF-β1 in solution was quantified after different irrigation protocols (sodium hypochlorite, chlorhexidine) and after intracanal medication (calcium hydroxide). Centrifugal filters with a cut-off of 10,000 Da and 3000 Da were used for efficient concentration, and volumes and amounts of retained TGF-β1 were measured at different time points. During conventional endodontic treatment, ethylenediaminotetraacetic acid (EDTA) solution was collected after ultrasonic activation from the root canals of mature teeth of 38 patients, and growth factor content was quantified via enzyme-linked immunosorbent assay (ELISA). Irrigation with sodium hypochlorite reduced TGF-β1 release into EDTA. This effect was partially reversed by canal enlargement after the use of sodium hypochlorite and by subsequent use of calcium hydroxide. A few minutes of centrifugation with a cut-off of 10,000 Da reduced the initial volume of the irrigant by 90% and led to a continuous increase in concentration to the same extent. Furthermore, TGF-β1 was obtained from root canals of mature teeth during endodontic treatment in quantities that have been shown to elicit desirable cellular responses in a subsequent clinical application. A mixture with a suitable scaffold material and injection into the root canal has the potential to promote dental pulp regeneration.
Collapse
Affiliation(s)
- Matthias Widbiller
- Department of Conservative Dentistry and Periodontology, University Hospital Regensburg, 93053 Regensburg, Germany; (A.R.); (M.W.); (M.L.); (K.-A.H.); (W.B.)
- Correspondence:
| | - Andreas Rosendahl
- Department of Conservative Dentistry and Periodontology, University Hospital Regensburg, 93053 Regensburg, Germany; (A.R.); (M.W.); (M.L.); (K.-A.H.); (W.B.)
| | - Melanie Wölflick
- Department of Conservative Dentistry and Periodontology, University Hospital Regensburg, 93053 Regensburg, Germany; (A.R.); (M.W.); (M.L.); (K.-A.H.); (W.B.)
| | - Moritz Linnebank
- Department of Conservative Dentistry and Periodontology, University Hospital Regensburg, 93053 Regensburg, Germany; (A.R.); (M.W.); (M.L.); (K.-A.H.); (W.B.)
| | | | - Karl-Anton Hiller
- Department of Conservative Dentistry and Periodontology, University Hospital Regensburg, 93053 Regensburg, Germany; (A.R.); (M.W.); (M.L.); (K.-A.H.); (W.B.)
| | - Wolfgang Buchalla
- Department of Conservative Dentistry and Periodontology, University Hospital Regensburg, 93053 Regensburg, Germany; (A.R.); (M.W.); (M.L.); (K.-A.H.); (W.B.)
| | - Kerstin M. Galler
- Department of Operative Dentistry and Periodontology, Friedrich-Alexander-University Erlangen-Nürnberg, 91054 Erlangen, Germany;
| |
Collapse
|
|
44
|
Wang L, Wei X, Duan C, Yang J, Xiao S, Liu H, Sun J. Bone marrow mesenchymal stem cell sheets with high expression of hBD3 and CTGF promote periodontal regeneration. MATERIALS SCIENCE & ENGINEERING. C, MATERIALS FOR BIOLOGICAL APPLICATIONS 2022; 133:112657. [PMID: 35034825 DOI: 10.1016/j.msec.2022.112657] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/19/2021] [Revised: 12/12/2021] [Accepted: 01/06/2022] [Indexed: 12/31/2022]
Abstract
The multi-bacterial environment of the oral cavity makes it hard for periodontal regeneration. As a class of antimicrobial peptide, beta defensin has been found to show broad-spectrum antibacterial ability. In addition, connective tissue growth factor (CTGF) is demonstrated to play a great role in multi-physiological events such as angiogenesis, wound healing and, more importantly, fibrogenesis. In this study, human β defensin 3 (hBD3) and CTGF were co-transfected into bone marrow derived mesenchymal stem cells (BMSCs) for preparing cell sheets. The transfection efficiency was detected through fluorescence of eGFP and western blot assay. Our results showed that the hBD3 and CTGF proteins were highly and stably expressed in the BMSCs after transfection. The results of RT-PCR and induced differentiation indicated that hBD3 promoted osteogenic differentiation of BMSCs, while CTGF significantly increased fibrogenic differentiation even in the presence of hBD3. The BMSCs acquired stronger capacity in terms of promoting M2 polarization of RAW 264.7 macrophages fulfilled by the transfection and secretion of hBD3 and CTGF. To further evaluate the periodontal remodeling performance of cell sheets, a coralline hydroxyapatite (CHA)-chitosan based hydrogel-human tooth system was designed to simulate the natural periodontal environment. The results showed that dense extracellular matrix, oriented fiber arrangement, and abundant collagen deposition appeared in the area of BMSCs sheets after subcutaneous transplantation. Altogether, our data showed that the lentivirus transfected BMSCs sheets had a promising application prospect for periodontal repair.
Collapse
Affiliation(s)
- Li Wang
- Key Laboratory for Biomechanics and Mechanobiology (Beihang University) of Ministry of Education, Beijing Advanced Innovation Center for Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, Beijing 100083, PR China
| | - Xinbo Wei
- Key Laboratory for Biomechanics and Mechanobiology (Beihang University) of Ministry of Education, Beijing Advanced Innovation Center for Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, Beijing 100083, PR China
| | - Cuimi Duan
- Tissue Engineering Research Center, Beijing Institute of Basic Medical Sciences, PR China
| | - Jinjin Yang
- Department of Stomatology, The Fifth Medical Center, Chinese PLA General Hospital, Xisihuan Middle Road 100, Fengtai District, Beijing 100036, PR China
| | - Shengzhao Xiao
- Key Laboratory for Biomechanics and Mechanobiology (Beihang University) of Ministry of Education, Beijing Advanced Innovation Center for Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, Beijing 100083, PR China
| | - Haifeng Liu
- Key Laboratory for Biomechanics and Mechanobiology (Beihang University) of Ministry of Education, Beijing Advanced Innovation Center for Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, Beijing 100083, PR China.
| | - Jie Sun
- Department of Stomatology, The Fifth Medical Center, Chinese PLA General Hospital, Xisihuan Middle Road 100, Fengtai District, Beijing 100036, PR China.
| |
Collapse
|
|
45
|
Goonoo N. Tunable Biomaterials for Myocardial Tissue Regeneration: Promising New Strategies for Advanced Biointerface Control and Improved Therapeutic Outcomes. Biomater Sci 2022; 10:1626-1646. [DOI: 10.1039/d1bm01641e] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
Following myocardial infarction (MI) and the natural healing process, the cardiac mechanostructure changes significantly leading to reduced contractile ability and putting additional pressure on the heart muscle thereby increasing the...
Collapse
|
|
46
|
Periodontal Cell Therapy: A Systematic Review and Meta-analysis. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2022; 1373:377-397. [DOI: 10.1007/978-3-030-96881-6_20] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
|
|
47
|
Advanced approaches to regenerate spinal cord injury: The development of cell and tissue engineering therapy and combinational treatments. Biomed Pharmacother 2021; 146:112529. [PMID: 34906773 DOI: 10.1016/j.biopha.2021.112529] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2021] [Revised: 12/07/2021] [Accepted: 12/08/2021] [Indexed: 12/13/2022] Open
Abstract
Spinal cord injury (SCI) is a central nervous system (CNS) devastate event that is commonly caused by traumatic or non-traumatic events. The reinnervation of spinal cord axons is hampered through a myriad of devices counting on the damaged myelin, inflammation, glial scar, and defective inhibitory molecules. Unfortunately, an effective treatment to completely repair SCI and improve functional recovery has not been found. In this regard, strategies such as using cells, biomaterials, biomolecules, and drugs have been reported to be effective for SCI recovery. Furthermore, recent advances in combinatorial treatments, which address various aspects of SCI pathophysiology, provide optimistic outcomes for spinal cord regeneration. According to the global importance of SCI, the goal of this article review is to provide an overview of the pathophysiology of SCI, with an emphasis on the latest modes of intervention and current advanced approaches for the treatment of SCI, in conjunction with an assessment of combinatorial approaches in preclinical and clinical trials. So, this article can give scientists and clinicians' clues to help them better understand how to construct preclinical and clinical studies that could lead to a breakthrough in spinal cord regeneration.
Collapse
|
|
48
|
Sun T, Meng C, Ding Q, Yu K, Zhang X, Zhang W, Tian W, Zhang Q, Guo X, Wu B, Xiong Z. In situ bone regeneration with sequential delivery of aptamer and BMP2 from an ECM-based scaffold fabricated by cryogenic free-form extrusion. Bioact Mater 2021; 6:4163-4175. [PMID: 33997500 PMCID: PMC8099605 DOI: 10.1016/j.bioactmat.2021.04.013] [Citation(s) in RCA: 32] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2020] [Revised: 04/09/2021] [Accepted: 04/12/2021] [Indexed: 12/11/2022] Open
Abstract
In situ tissue engineering is a powerful strategy for the treatment of bone defects. It could overcome the limitations of traditional bone tissue engineering, which typically involves extensive cell expansion steps, low cell survival rates upon transplantation, and a risk of immuno-rejection. Here, a porous scaffold polycaprolactone (PCL)/decellularized small intestine submucosa (SIS) was fabricated via cryogenic free-form extrusion, followed by surface modification with aptamer and PlGF-2123-144*-fused BMP2 (pBMP2). The two bioactive molecules were delivered sequentially. The aptamer Apt19s, which exhibited binding affinity to bone marrow-derived mesenchymal stem cells (BMSCs), was quickly released, facilitating the mobilization and recruitment of host BMSCs. BMP2 fused with a PlGF-2123-144 peptide, which showed "super-affinity" to the ECM matrix, was released in a slow and sustained manner, inducing BMSC osteogenic differentiation. In vitro results showed that the sequential release of PCL/SIS-pBMP2-Apt19s promoted cell migration, proliferation, alkaline phosphatase activity, and mRNA expression of osteogenesis-related genes. The in vivo results demonstrated that the sequential release system of PCL/SIS-pBMP2-Apt19s evidently increased bone formation in rat calvarial critical-sized defects compared to the sequential release system of PCL/SIS-BMP2-Apt19s. Thus, the novel delivery system shows potential as an ideal alternative for achieving cell-free scaffold-based bone regeneration in situ.
Collapse
Key Words
- 3D, three-dimensional
- Apt19s, aptamer 19s
- Aptamer
- BMD, bone mineral density
- BMP2
- BMP2, bone morphogenic protein 2
- BMSC, bone marrow-derived mesenchymal stem cell
- Bone regeneration in situ
- CLSM, confocal laser scanning microscopy
- CSD, critical-sized calvarial defect
- Cell recruitment
- Controlled delivery
- ECM, decellularized matrix
- FBS, fetal bovine serum
- FDA, US Food and Drug Administration
- FITC, fluorescein isothiocyanate
- FTIR, Fourier transform infrared
- H&E, hematoxylin and eosin
- HA, hydroxyapatite
- PCL, polycaprolactone
- PVDF, polyvinylidene difluoride
- Rh6G, rhodamine 6G
- SIS, small intestine submucosa
- pBMP2, PlGF-2123-144*-fused BMP2
- ssDNA, single-stranded DNA
Collapse
Affiliation(s)
- Tingfang Sun
- Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Chunqing Meng
- Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Qiuyue Ding
- Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Keda Yu
- Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Xianglin Zhang
- State Key Laboratory of Materials Processing and Die & Mould Technology, School of Materials Science and Engineering, Huazhong University of Science and Technology, Wuhan, 430074, China
| | - Wancheng Zhang
- State Key Laboratory of Materials Processing and Die & Mould Technology, School of Materials Science and Engineering, Huazhong University of Science and Technology, Wuhan, 430074, China
| | - Wenqing Tian
- State Key Laboratory of Materials Processing and Die & Mould Technology, School of Materials Science and Engineering, Huazhong University of Science and Technology, Wuhan, 430074, China
| | - Qi Zhang
- Wuhan Hi-tech Medical Tissue Research Center, Wuhan, 430206, China
| | - Xiaodong Guo
- Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Bin Wu
- State Key Laboratory of Materials Processing and Die & Mould Technology, School of Materials Science and Engineering, Huazhong University of Science and Technology, Wuhan, 430074, China
| | - Zekang Xiong
- Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| |
Collapse
|
|
49
|
Mansour AM, Yahia S, Elsayed HRH, El-Attar SAE, Grawish ME, El-Hawary YM, El-Sherbiny IM. Efficacy of biocompatible trilayers nanofibrous scaffold with/without allogeneic adipose-derived stem cells on class II furcation defects of dogs' model. Clin Oral Investig 2021; 26:2537-2553. [PMID: 34661742 DOI: 10.1007/s00784-021-04222-x] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2021] [Accepted: 10/06/2021] [Indexed: 12/16/2022]
Abstract
OBJECTIVE This study aimed to evaluate the regenerative capacity of a newly-developed polycaprolactone (PCL)-based nanofibrous composite scaffold either alone or in combination with adipose-derived mesenchymal stem cells (ADSCs) as a treatment modality for class II furcation defects. MATERIALS AND METHODS After ADSCs isolation and scaffold characterization, the mandibular premolars of adult male mongrel dogs were selected and randomly assigned into three equal groups. In group I, class II furcation defects were surgically induced to the inter-radicular bone. While class II furcation defects of group II were induced as in group I. In addition, the defects were filled with the prefabricated scaffold. Moreover, class II furcation defects of group III were induced as in group II and instead the defects were filled with the prefabricated scaffold seeded with ADSCs. The dogs were sacrificed at 30 days or at 60 days. Periodontal wound healing/regeneration was evaluated by radiological examination using cone beam computed tomography and histologically using ordinary, histochemical, and immunohistochemical staining. RESULTS In the two examination periods, group II defects compared to group I, and group III compared to the other groups showed a decrease in defect dimensions radiographically. Histologically, histochemically, and immunohistochemically, they significantly demonstrated better periodontal wound healing/regeneration, predominant collagen type I of newly formed bone and periodontal ligament with a significant increase in the immunoreactivity of vascular endothelial growth factor and osteopontin. CONCLUSIONS The newly fabricated nanofibrous scaffold has enhanced periodontal wound healing/regeneration of class II furcation defects with further enhancement achieved when ADSCs seeded onto the scaffold before implantation. CLINICAL RELEVANCE The implementation of our newly-developed PCL-based nanofibrous composite scaffolds in class II furcation defect either alone or in conjunction with ADSCs can be considered as a suitable treatment modality to allow periodontal tissues regeneration.
Collapse
Affiliation(s)
- Alaa M Mansour
- Department of Oral Biology, Faculty of Dentistry, Mansoura University, Mansoura, 35511, Egypt
| | - Sarah Yahia
- Nanomedicine Labs, Center of Materials Sciences (CMS), Zewail City of Science and Technology, 6th of October, Giza, 12578, Egypt
| | | | - Saied A E El-Attar
- Department of Oral Biology, Faculty of Dentistry, Mansoura University, Mansoura, 35511, Egypt
| | - Mohammed E Grawish
- Department of Oral Biology, Faculty of Dentistry, Mansoura University, Mansoura, 35511, Egypt
| | - Youssry M El-Hawary
- Department of Oral Biology, Faculty of Dentistry, Mansoura University, Mansoura, 35511, Egypt
| | - Ibrahim M El-Sherbiny
- Nanomedicine Labs, Center of Materials Sciences (CMS), Zewail City of Science and Technology, 6th of October, Giza, 12578, Egypt.
| |
Collapse
|
|
50
|
Hao L, Tianyuan Z, Zhen Y, Fuyang C, Jiang W, Zineng Y, Zhengang D, Shuyun L, Chunxiang H, Zhiguo Y, Quanyi G. Biofabrication of cell-free dual drug-releasing biomimetic scaffolds for meniscal regeneration. Biofabrication 2021; 14. [PMID: 34610586 DOI: 10.1088/1758-5090/ac2cd7] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2021] [Accepted: 10/05/2021] [Indexed: 01/26/2023]
Abstract
Regenerating the meniscus remains challenging because of its avascular, aneural, and alymphatic nature. Three-dimensional (3D) printing technology provides a promising strategy to fabricate biomimetic meniscal scaffolds with an anisotropic architecture, a proper biomechanical microenvironment, and bioactive components. Herein, 3D printing technology is adopted by coencapsulating chemokines (platelet-derived growth factor-BB, PDGF-BB) and small chondroinductive molecules (kartogenin, KGN) within biomimetic polycaprolactone/hydrogel composite scaffolds. The incorporated PDGF-BB is expected to promote endogenous stem cell homing, and KGN in poly(lactic-co-glycolic) acid microspheres is employed to target the chondrogenesis of resident mesenchymal stem cells (MSCs). First, we chose basic bioinks composed of gelatin methacrylamide and hyaluronic acid methacrylate and then incorporated four concentrations (0%, 0.5%, 1.0%, and 2.0%) of meniscal extracellular matrix into the bioink to systematically study the superiority of these combinations and identify the optimally printable bioink. Next, we investigated the scaffold morphology and drug release profile. The effects of releasing the drugs in a sequentially controlled manner from the composite scaffolds on the fate of MSCs were also evaluated. The biofabricated scaffolds, with and without dual drug loading, were further studied in a rabbit model established with a critical-size medial meniscectomy. We found that meniscal scaffolds containing both drugs had combinational advantages in enhancing cell migration and synergistically promoted MSC chondrogenic differentiation. The dual drug-loaded scaffolds also significantly promotedin vivoneomeniscal regeneration three and six months after implantation in terms of histological and immunological phenotypes. The results presented herein reveal that this 3D-printed dual drug-releasing meniscal scaffold possesses the potential to act as an off-the-shelf product for the clinical treatment of meniscal injury and related joint degenerative diseases.
Collapse
Affiliation(s)
- Li Hao
- School of Medicine, Nankai University, Tianjin 300071, People's Republic of China.,Institute of Orthopedics, First Medical Center, Chinese PLA General Hospital; Beijing Key Lab of Regenerative Medicine in Orthopedics; Key Laboratory of Musculoskeletal Trauma and War Injuries PLA, No. 28 Fuxing Road, Haidian District, Beijing 100853, People's Republic of China
| | - Zhao Tianyuan
- School of Medicine, Nankai University, Tianjin 300071, People's Republic of China.,Institute of Orthopedics, First Medical Center, Chinese PLA General Hospital; Beijing Key Lab of Regenerative Medicine in Orthopedics; Key Laboratory of Musculoskeletal Trauma and War Injuries PLA, No. 28 Fuxing Road, Haidian District, Beijing 100853, People's Republic of China
| | - Yang Zhen
- School of Medicine, Nankai University, Tianjin 300071, People's Republic of China.,Institute of Orthopedics, First Medical Center, Chinese PLA General Hospital; Beijing Key Lab of Regenerative Medicine in Orthopedics; Key Laboratory of Musculoskeletal Trauma and War Injuries PLA, No. 28 Fuxing Road, Haidian District, Beijing 100853, People's Republic of China.,Arthritis Clinic and Research Center, Peking University People's Hospital, Peking University, Beijing 100044, People's Republic of China
| | - Cao Fuyang
- Institute of Orthopedics, First Medical Center, Chinese PLA General Hospital; Beijing Key Lab of Regenerative Medicine in Orthopedics; Key Laboratory of Musculoskeletal Trauma and War Injuries PLA, No. 28 Fuxing Road, Haidian District, Beijing 100853, People's Republic of China.,Department of Orthopedics, First Affiliated Hospital of Zhengzhou University, 1 Jian East Road, Eqi District, Zhengzhou 450052, People's Republic of China
| | - Wu Jiang
- Institute of Orthopedics, First Medical Center, Chinese PLA General Hospital; Beijing Key Lab of Regenerative Medicine in Orthopedics; Key Laboratory of Musculoskeletal Trauma and War Injuries PLA, No. 28 Fuxing Road, Haidian District, Beijing 100853, People's Republic of China
| | - Yan Zineng
- Institute of Orthopedics, First Medical Center, Chinese PLA General Hospital; Beijing Key Lab of Regenerative Medicine in Orthopedics; Key Laboratory of Musculoskeletal Trauma and War Injuries PLA, No. 28 Fuxing Road, Haidian District, Beijing 100853, People's Republic of China
| | - Ding Zhengang
- Institute of Orthopedics, First Medical Center, Chinese PLA General Hospital; Beijing Key Lab of Regenerative Medicine in Orthopedics; Key Laboratory of Musculoskeletal Trauma and War Injuries PLA, No. 28 Fuxing Road, Haidian District, Beijing 100853, People's Republic of China
| | - Liu Shuyun
- School of Medicine, Nankai University, Tianjin 300071, People's Republic of China.,Institute of Orthopedics, First Medical Center, Chinese PLA General Hospital; Beijing Key Lab of Regenerative Medicine in Orthopedics; Key Laboratory of Musculoskeletal Trauma and War Injuries PLA, No. 28 Fuxing Road, Haidian District, Beijing 100853, People's Republic of China
| | - Hao Chunxiang
- Institute of Anesthesia, Chinese PLA General Hospital, 28 Fuxing Road, Haidian District, Beijing 100853, People's Republic of China
| | - Yuan Zhiguo
- Department of Bone and Joint Surgery, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200030, People's Republic of China
| | - Guo Quanyi
- School of Medicine, Nankai University, Tianjin 300071, People's Republic of China.,Institute of Orthopedics, First Medical Center, Chinese PLA General Hospital; Beijing Key Lab of Regenerative Medicine in Orthopedics; Key Laboratory of Musculoskeletal Trauma and War Injuries PLA, No. 28 Fuxing Road, Haidian District, Beijing 100853, People's Republic of China
| |
Collapse
|