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Zhang X, Li Q, Wang Z, Zhou W, Zhang L, Liu Y, Xu Z, Li Z, Zhu C, Zhang X. Bone regeneration materials and their application over 20 years: A bibliometric study and systematic review. Front Bioeng Biotechnol 2022; 10:921092. [PMID: 36277397 PMCID: PMC9581237 DOI: 10.3389/fbioe.2022.921092] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2022] [Accepted: 08/25/2022] [Indexed: 12/02/2022] Open
Abstract
Bone regeneration materials (BRMs) bring us new sights into the clinical management bone defects. With advances in BRMs technologies, new strategies are emerging to promote bone regeneration. The aim of this study was to comprehensively assess the existing research and recent progress on BRMs, thus providing useful insights into contemporary research, as well as to explore potential future directions within the scope of bone regeneration therapy. A comprehensive literature review using formal data mining procedures was performed to explore the global trends of selected areas of research for the past 20 years. The study applied bibliometric methods and knowledge visualization techniques to identify and investigate publications based on the publication year (between 2002 and 2021), document type, language, country, institution, author, journal, keywords, and citation number. The most productive countries were China, United States, and Italy. The most prolific journal in the BRM field was Acta Biomaterialia, closely followed by Biomaterials. Moreover, recent investigations have been focused on extracellular matrices (ECMs) (370 publications), hydrogel materials (286 publications), and drug delivery systems (220 publications). Research hotspots related to BRMs and extracellular matrices from 2002 to 2011 were growth factor, bone morphogenetic protein (BMP)-2, and mesenchymal stem cell (MSC), whereas after 2012 were composite scaffolds. Between 2002 and 2011, studies related to BRMs and hydrogels were focused on BMP-2, in vivo, and in vitro investigations, whereas it turned to the exploration of MSCs, mechanical properties, and osteogenic differentiation after 2012. Research hotspots related to BRM and drug delivery were fibroblast growth factor, mesoporous materials, and controlled release during 2002–2011, and electrospinning, antibacterial activity, and in vitro bioactivity after 2012. Overall, composite scaffolds, 3D printing technology, and antibacterial activity were found to have an important intersection within BRM investigations, representing relevant research fields for the future. Taken together, this extensive analysis highlights the existing literature and findings that advance scientific insights into bone tissue engineering and its subsequent applications.
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Affiliation(s)
- Xudong Zhang
- Department of Orthopedics, The Affiliated Provincial Hospital of Anhui Medical University, Anhui Medical University, Hefei, China
| | - Qianming Li
- The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China
| | - Zhengxi Wang
- Department of Orthopedics, Anhui Provincial Hospital, Wannan Medical College, Hefei, China
| | - Wei Zhou
- The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China
- Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Linlin Zhang
- The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China
| | - Yingsheng Liu
- The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China
| | - Ze Xu
- The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China
| | - Zheng Li
- The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China
| | - Chen Zhu
- Department of Orthopedics, The Affiliated Provincial Hospital of Anhui Medical University, Anhui Medical University, Hefei, China
- The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China
| | - Xianzuo Zhang
- The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China
- *Correspondence: Xianzuo Zhang,
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Murugan NJ, Vigran HJ, Miller KA, Golding A, Pham QL, Sperry MM, Rasmussen-Ivey C, Kane AW, Kaplan DL, Levin M. Acute multidrug delivery via a wearable bioreactor facilitates long-term limb regeneration and functional recovery in adult Xenopus laevis. SCIENCE ADVANCES 2022; 8:eabj2164. [PMID: 35080969 PMCID: PMC8791464 DOI: 10.1126/sciadv.abj2164] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/13/2023]
Abstract
Limb regeneration is a frontier in biomedical science. Identifying triggers of innate morphogenetic responses in vivo to induce the growth of healthy patterned tissue would address the needs of millions of patients, from diabetics to victims of trauma. Organisms such as Xenopus laevis-whose limited regenerative capacities in adulthood mirror those of humans-are important models with which to test interventions that can restore form and function. Here, we demonstrate long-term (18 months) regrowth, marked tissue repatterning, and functional restoration of an amputated X. laevis hindlimb following a 24-hour exposure to a multidrug, pro-regenerative treatment delivered by a wearable bioreactor. Regenerated tissues composed of skin, bone, vasculature, and nerves significantly exceeded the complexity and sensorimotor capacities of untreated and control animals' hypomorphic spikes. RNA sequencing of early tissue buds revealed activation of developmental pathways such as Wnt/β-catenin, TGF-β, hedgehog, and Notch. These data demonstrate the successful "kickstarting" of endogenous regenerative pathways in a vertebrate model.
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Affiliation(s)
- Nirosha J. Murugan
- Department of Biology, Tufts University, Medford, MA, USA
- Allen Discovery Center at Tufts University, Medford, MA, USA
| | - Hannah J. Vigran
- Department of Biology, Tufts University, Medford, MA, USA
- Allen Discovery Center at Tufts University, Medford, MA, USA
| | - Kelsie A. Miller
- Department of Biology, Tufts University, Medford, MA, USA
- Allen Discovery Center at Tufts University, Medford, MA, USA
| | - Annie Golding
- Allen Discovery Center at Tufts University, Medford, MA, USA
- Department of Biomedical Engineering, Tufts University, Medford, MA, USA
| | - Quang L. Pham
- Allen Discovery Center at Tufts University, Medford, MA, USA
- Department of Biomedical Engineering, Tufts University, Medford, MA, USA
| | - Megan M. Sperry
- Department of Biology, Tufts University, Medford, MA, USA
- Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA
| | - Cody Rasmussen-Ivey
- Department of Biology, Tufts University, Medford, MA, USA
- Allen Discovery Center at Tufts University, Medford, MA, USA
| | - Anna W. Kane
- Department of Biology, Tufts University, Medford, MA, USA
- Allen Discovery Center at Tufts University, Medford, MA, USA
- Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA
| | - David L. Kaplan
- Allen Discovery Center at Tufts University, Medford, MA, USA
- Department of Biomedical Engineering, Tufts University, Medford, MA, USA
| | - Michael Levin
- Department of Biology, Tufts University, Medford, MA, USA
- Allen Discovery Center at Tufts University, Medford, MA, USA
- Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA
- Corresponding author.
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Jelodari S, Sadroddiny E. Decellularization of Small Intestinal Submucosa. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2021; 1345:71-84. [PMID: 34582015 DOI: 10.1007/978-3-030-82735-9_7] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Small intestinal submucosa (SIS) is the most studied extracellular matrix (ECM) for repair and regeneration of different organs and tissues. Promising results of SIS-ECM as a vascular graft, led scientists to examine its applicability for repairing other tissues. Overall results indicated that SIS grafts induce tissue regeneration and remodeling to almost native condition. Investigating immunomodulatory effects of SIS is another interesting field of research. SIS can be utilized in different forms for multiple clinical and experimental studies. The aim of this chapter is to investigate the decellularization process of SIS and its common clinical application.
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Affiliation(s)
- Sahar Jelodari
- Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Esmaeil Sadroddiny
- Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran.
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Shasha L, Zhongjie L, Lingling F, Ustichenko VD, Pakhomov OV, Deng B. Comparison between slow and rapid freezing for adrenal gland cryopreservation and xenotransplantation. Cryobiology 2021; 102:68-75. [PMID: 34324838 DOI: 10.1016/j.cryobiol.2021.07.011] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2021] [Revised: 07/21/2021] [Accepted: 07/23/2021] [Indexed: 12/16/2022]
Abstract
The aim of our study was to examine whether slow or rapid cryopreservation of adrenal xenografts affected xenotransplant outcome. Adrenal xenografts were got from newborn piglets (<24 h after birth). Receptor rats were randomly divided into four groups: a bilateral adrenalectomy group, fresh xenotransplantation group, rapid cryopreservation xenotransplantation group, and a slow cryopreservation xenotransplantation group. 30 days after xenotransplantation, the survival rates of rats in the fresh xenotransplantation group, rapid cryopreservation xenotransplantation group and slow cryopreservation xenotransplantation group were 80 %, 60 % and 60 %, respectively, which were significantly higher than 40 % of the bilateral adrenalectomy group. In addition, the survival rate of rats in the slow cryopreservation group was consistently significantly higher than that in the rapid cryopreservation group at 29 days after xenotransplantation. Morphological observation showed that there were a few medulla cells existed in the adrenal glands in the slow cryopreservation group after 30 days of xenotransplantation, but no medulla cells were found in the rapid cryopreservation group. The plasma cortisol level of rats in the fresh xenotransplantation group and the slow xenotransplantation group 30 days after xenotransplantation was significantly higher than that of the rapid cryopreservation group and bilateral adrenalectomy group (P < 0.05). The levels of liver glycogen and cholesterol in the xenotransplantation rats were increased relative to those of the bilateral adrenalectomy rats, and close to normal level. In conclusion, compared with rapidly frozen preserved grafts, slowly frozen preserved grafts not only ensure the structural integrity of adrenal tissues, but also have corresponding physiological functions, which provid a basic research opportunities for the preservation of xenografts and the treatment of adrenal corticosteroid deficiency. Moreover, these findings can provide evidence for xenotransplantation in the treatment of Addison's disease (adrenal cortex hormone deficiency).
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Affiliation(s)
- Li Shasha
- Basic Medical College of Henan University of Science and Technology, 263 Kaiyuan Avenue, Luoyang City, China
| | - Li Zhongjie
- Basic Medical College of Henan University of Science and Technology, 263 Kaiyuan Avenue, Luoyang City, China
| | - Fan Lingling
- Basic Medical College of Henan University of Science and Technology, 263 Kaiyuan Avenue, Luoyang City, China
| | - V D Ustichenko
- Institute for Problems of Cryobiology and Cryomedicine of the National Academy of Sciences of Ukraine, Kharkiv, Ukraine
| | - O V Pakhomov
- Institute for Problems of Cryobiology and Cryomedicine of the National Academy of Sciences of Ukraine, Kharkiv, Ukraine
| | - Bo Deng
- Basic Medical College of Henan University of Science and Technology, 263 Kaiyuan Avenue, Luoyang City, China.
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Zhao P, Li X, Fang Q, Wang F, Ao Q, Wang X, Tian X, Tong H, Bai S, Fan J. Surface modification of small intestine submucosa in tissue engineering. Regen Biomater 2020; 7:339-348. [PMID: 32793379 PMCID: PMC7414999 DOI: 10.1093/rb/rbaa014] [Citation(s) in RCA: 41] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2020] [Revised: 02/25/2020] [Accepted: 03/10/2020] [Indexed: 12/11/2022] Open
Abstract
With the development of tissue engineering, the required biomaterials need to have the ability to promote cell adhesion and proliferation in vitro and in vivo. Especially, surface modification of the scaffold material has a great influence on biocompatibility and functionality of materials. The small intestine submucosa (SIS) is an extracellular matrix isolated from the submucosal layer of porcine jejunum, which has good tissue mechanical properties and regenerative activity, and is suitable for cell adhesion, proliferation and differentiation. In recent years, SIS is widely used in different areas of tissue reconstruction, such as blood vessels, bone, cartilage, bladder and ureter, etc. This paper discusses the main methods for surface modification of SIS to improve and optimize the performance of SIS bioscaffolds, including functional group bonding, protein adsorption, mineral coating, topography and formatting modification and drug combination. In addition, the reasonable combination of these methods also offers great improvement on SIS surface modification. This article makes a shallow review of the surface modification of SIS and its application in tissue engineering.
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Affiliation(s)
- Pan Zhao
- Department of Tissue Engineering, School of Fundamental Sciences, China Medical University, 77 Puhe Avenue, Shenbei New District, Shenyang 110122, China
| | - Xiang Li
- Department of Cell Biology, School of Life Sciences, China Medical University, 77 Puhe Avenue, Shenbei New District, Shenyang 110122, China
| | - Qin Fang
- Cardiac Surgery, Liaoning First Hospital of China Medical University, No. 155 Nanjing Street, Heping District, Shenyang, Liaoning 110122, China
| | - Fanglin Wang
- Department of Tissue Engineering, School of Fundamental Sciences, China Medical University, 77 Puhe Avenue, Shenbei New District, Shenyang 110122, China
| | - Qiang Ao
- Department of Tissue Engineering, School of Fundamental Sciences, China Medical University, 77 Puhe Avenue, Shenbei New District, Shenyang 110122, China
| | - Xiaohong Wang
- Department of Tissue Engineering, School of Fundamental Sciences, China Medical University, 77 Puhe Avenue, Shenbei New District, Shenyang 110122, China
| | - Xiaohong Tian
- Department of Tissue Engineering, School of Fundamental Sciences, China Medical University, 77 Puhe Avenue, Shenbei New District, Shenyang 110122, China
| | - Hao Tong
- Department of Tissue Engineering, School of Fundamental Sciences, China Medical University, 77 Puhe Avenue, Shenbei New District, Shenyang 110122, China
| | - Shuling Bai
- Department of Tissue Engineering, School of Fundamental Sciences, China Medical University, 77 Puhe Avenue, Shenbei New District, Shenyang 110122, China
| | - Jun Fan
- Department of Tissue Engineering, School of Fundamental Sciences, China Medical University, 77 Puhe Avenue, Shenbei New District, Shenyang 110122, China
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Al-Fotawi R, Muthurangan M, Siyal A, Premnath S, Al-Fayez M, Ahmad El-Ghannam, Mahmood A. The use of muscle extracellular matrix (MEM) and SCPC bioceramic for bone augmentation. ACTA ACUST UNITED AC 2020; 15:025005. [PMID: 31846944 DOI: 10.1088/1748-605x/ab6300] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
BACKGROUND Bone augmentation is a challenging problem in the field of maxillofacial surgery. OBJECTIVE In this study, we prepared and evaluated muscle extracellular matrix (MEM) after adding silica calcium phosphate composite (SCPC) seeded with human bone marrow mesenchymal cells (hBMSCs). We then investigated bone augmentation in vivo using the prepared MEM-SCPC. MATERIALS AND METHODS hBMSCs were seeded on MEM-SCPC, and MEM was characterized. Calvarial bone grafts were prepared using nude mice (n = 12) and grafted separately in two experimental groups: grafts with MEM (control, n = 4) and grafts with MEM-SCPC-hBMSCs (experimental group, n = 8) for 8 weeks. Micro-computed tomography (micro-CT) and histological analysis were then performed. RESULTS Micro-CT analysis demonstrated a thinner trabeculae in grafted defects than normal native bone, with a high degree of anisotropy. Quantitative histomorphometric assessment showed a higher median bone percentage surface area of 80.2% ± 6.0% in the experimental group. CONCLUSION The enhanced bone formation and maturation of bone grafted with MEM-SCPC-hBMSCs suggested the potential use of this material for bone augmentation.
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Affiliation(s)
- Randa Al-Fotawi
- Department of Oral and Maxillofacial Surgery, Dental Faculty, King Saud University, Riyadh, Saudi Arabia
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Gonzalez BA, Pour Issa E, Mankame OV, Bustillos J, Cuellar A, Rodriguez AJ, Scholl F, Bibevski S, Hernandez L, Brehier V, Casares M, Rivas-Wagner K, Morales P, Lopez J, Wagner J, Bibevski J, Agarwal A, George F, Ramaswamy S. Porcine Small Intestinal Submucosa Mitral Valve Material Responses Support Acute Somatic Growth. Tissue Eng Part A 2020; 26:475-489. [PMID: 31802695 DOI: 10.1089/ten.tea.2019.0220] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/18/2023] Open
Abstract
Background: Conceptually, a tissue engineered heart valve would be especially appealing in the pediatric setting since small size and somatic growth constraints would be alleviated. In this study, we utilized porcine small intestinal submucosa (PSIS) for valve replacement. Of note, we evaluated the material responses of PSIS and subsequently its acute function and somatic growth potential in the mitral position. Methods and Results: Material and mechanical assessment demonstrated that both fatigued 2ply (∼65 μm) and 4ply (∼110 μm) PSIS specimens exhibited similar failure mechanisms, but at an accelerated rate in the former. Specifically, the fatigued 2ply PSIS samples underwent noticeable fiber pullout and recruitment on the bioscaffold surface, leading to higher yield strength (p < 0.05) and yield strain (p < 0.05) compared to its fatigued 4ply counterparts. Consequently, 2ply PSIS mitral valve constructs were subsequently implanted in juvenile baboons (n = 3). Valve function was longitudinally monitored for 90 days postvalve implantation and was found to be robust in all animals. Histology at 90 days in one of the animals revealed the presence of residual porcine cells, fibrin matrix, and host baboon immune cells but an absence of tissue regeneration. Conclusions: Our findings suggest that the altered structural responses of PSIS, postfatigue, rather than de novo tissue formation, are primarily responsible for the valve's ability to accommodate somatic growth during the acute phase (90 days) following mitral valve replacement. Impact Statement Tissue engineered heart valves (TEHVs) offer the potential of supporting somatic growth. In this study, we investigated a porcine small intestinal submucosa bioscaffold for pediatric mitral heart valve replacement. The novelty of the study lies in identifying material responses under mechanical loading conditions and its effectiveness in being able to function as a TEHV. In addition, the ability of the scaffold valve to support acute somatic growth was evaluated in the Baboon model. The current study contributes toward finding a solution for critical valve diseases in children, whose current prognosis for survival is poor.
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Affiliation(s)
- Brittany A Gonzalez
- Department of Biomedical Engineering and Florida International University, Miami, Florida, USA
| | - Elnaz Pour Issa
- Department of Biomedical Engineering and Florida International University, Miami, Florida, USA
| | - Omkar V Mankame
- Department of Biomedical Engineering and Florida International University, Miami, Florida, USA
| | - Jenniffer Bustillos
- Department of Mechanical and Material Engineering, Florida International University, Miami, Florida, USA
| | - Antonio Cuellar
- Department of Biomedical Engineering and Florida International University, Miami, Florida, USA
| | - Andres J Rodriguez
- Department of Biomedical Engineering and Florida International University, Miami, Florida, USA
| | - Frank Scholl
- Joe DiMaggio Children's Hospital, Memorial Regional Hospital, Hollywood, Florida, USA
| | - Steven Bibevski
- Department of Biomedical Engineering and Florida International University, Miami, Florida, USA.,Joe DiMaggio Children's Hospital, Memorial Regional Hospital, Hollywood, Florida, USA
| | - Lazaro Hernandez
- Joe DiMaggio Children's Hospital, Memorial Regional Hospital, Hollywood, Florida, USA
| | - Vincent Brehier
- Joe DiMaggio Children's Hospital, Memorial Regional Hospital, Hollywood, Florida, USA
| | - Mike Casares
- Joe DiMaggio Children's Hospital, Memorial Regional Hospital, Hollywood, Florida, USA
| | | | - Pablo Morales
- Mannheimer Foundation, Inc., Homestead, Florida, USA
| | - Jesus Lopez
- Mannheimer Foundation, Inc., Homestead, Florida, USA
| | - Joseph Wagner
- Mannheimer Foundation, Inc., Homestead, Florida, USA
| | | | - Arvind Agarwal
- Department of Mechanical and Material Engineering, Florida International University, Miami, Florida, USA
| | - Florence George
- Department of Mathematics and Statistics, Florida International University, Miami, Florida, USA
| | - Sharan Ramaswamy
- Department of Biomedical Engineering and Florida International University, Miami, Florida, USA
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Effect of Multilaminate Small Intestinal Submucosa as a Barrier Membrane on Bone Formation in a Rabbit Mandible Defect Model. BIOMED RESEARCH INTERNATIONAL 2018; 2018:3270293. [PMID: 30018978 PMCID: PMC6029487 DOI: 10.1155/2018/3270293] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/09/2017] [Revised: 04/19/2018] [Accepted: 05/20/2018] [Indexed: 12/14/2022]
Abstract
A barrier membrane (BM) is essential for guided bone regeneration (GBR) procedures. Absorbable BMs based on collagen have been widely applied clinically due to their excellent biocompatibility. The extracellular matrix (ECM) provides certain advantages that can compensate for the rapid degradation and insufficient mechanical strength of pure collagen membrane due to the porous scaffold structure. Recently, small intestinal submucosa (SIS), one of the most widely used ECM materials, has drawn much attention in bone tissue engineering. In this study, we adopted multilaminate SIS (mSIS) as a BM and evaluated its in vivo and in vitro properties. mSIS exhibited a multilaminate structure with a smooth upper surface and a significantly coarser bottom layer according to microscopic observation. Tensile strength was 13.10 ± 2.56 MPa. In in vivo experiments, we selected a rabbit mandibular defect model and subcutaneous implantation to compare osteogenesis and biodegradation properties with one of the most commonly used commercial collagen membranes. mSIS was retained for up to 3 months and demonstrated longer biodegradation time than commercial collagen membrane. Quantification of bone regeneration revealed significant differences in each group. Micro-computed tomography (micro-CT) revealed that the quantity and maturity of bones in the mSIS group were significantly higher than those in the blank control group (P < 0.05) and were similar to those in a commercial collagen membrane group (P > 0.05) at 4 and 12 weeks after surgery. Hematoxylin and eosin staining revealed large amounts of mature lamellar bone at 12 weeks in mSIS and commercial collagen membrane groups. Therefore, we conclude that mSIS has potential as a future biocompatible BM in GBR procedures.
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Ravanetti F, Gazza F, D'Arrigo D, Graiani G, Zamuner A, Zedda M, Manfredi E, Dettin M, Cacchioli A. Enhancement of peri-implant bone osteogenic activity induced by a peptidomimetic functionalization of titanium. Ann Anat 2018; 218:165-174. [PMID: 29679720 DOI: 10.1016/j.aanat.2018.01.011] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2017] [Revised: 01/11/2018] [Accepted: 01/22/2018] [Indexed: 12/18/2022]
Abstract
Osteoblast cell adhesion to the extracellular matrix is established through two main pathways: one is mediated by the binding between integrin and a minimal adhesion sequence (RGD) on the extracellular protein, the other is based on the interactions between transmembrane proteoglycans and heparin-binding sequences found in many matrix proteins. The aim of this study is the evaluation in an in vivo endosseous implant model of the early osteogenic response of the peri-implant bone to a biomimetic titanium surface functionalized with the retro-inverso 2DHVP peptide, an analogue of Vitronectin heparin binding site. The experimental plan is based on a bilateral study design of Control and 2DHVP implants inserted respectively in the right and left femur distal metaphysis of adult male Wistar rats (n=16) weighing about 300grams and evaluated after 15days. Fluorochromic bone vital markers were given in a specific time frame, in order to monitor the dynamic of new bone deposition. The effect inducted by the peptidomimetic coating on the surrounding bone were qualitatively and quantitatively evaluated by means of static and dynamic histomorphometric analyses performed within three concentric and subsequent circular Regions of Interest (ROI) of equivalent thickness (220μm), ROI1 adjacent to the interface, ROI2, the middle, and ROI3 the farthest. The data indicated that these functionalized implants stimulated a higher bone apposition rate (p<0,01) and larger and rapid osteoblast activation in terms of mineralizing surface within ROI1 compared to the control (p<0,01). These higher osteoblast recruitment and activation leads to a greater bone-to-implant contact reached for DHVP samples (p<0,5). This represents an initial stimulus of the osteogenic activity that might results in a faster and better osteointegration process.
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Affiliation(s)
| | - F Gazza
- Dept. of Veterinary Sciences
| | | | - G Graiani
- Dept. of Medicine and Surgery, University of Parma
| | - A Zamuner
- Dept. of Industrial Engineering, University of Padova
| | - M Zedda
- Dept. of Veterinary Medicine, University of Sassari
| | - E Manfredi
- Dept. of Medicine and Surgery, University of Parma
| | - M Dettin
- Dept. of Industrial Engineering, University of Padova
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Osteoinductive potential of small intestinal submucosa/ demineralized bone matrix as composite scaffolds for bone tissue engineering. ASIAN BIOMED 2018. [DOI: 10.2478/abm-2010-0119] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
Abstract
Background: Demineralized bone matrix (DBM) is extensively used in orthopedic, periodontal, and maxillofacial application and investigated as a material to induce new bone formation. Small intestinal submucosa (SIS) derived from the submucosa layer of porcine intestine has widely utilized as biomaterial with minimum immune response. Objectives: Determine the osteoinductive potential of SIS, DBM, SIS/DBM composites in the in vitro cell culture and in vivo animal bioassays for bone tissue engineering. Materials and methods: Human periosteal (HPO) cells were treated in the absence or presence SIS, DBM, and SIS/DBM. Cell proliferation was examined by direct cell counting. Osteoblast differentiation of the HPO cells was analyzed with alkaline phosphatase activity assay. The Wistar rat muscle implant model was used to evaluate the osteoinductive potential of SIS, DBM, and SIS/DBM composites. Results: HPO cells could differentiate along osteogenic lineage when treated with either DBM or SIS/DBM. SIS/ DBM had a tendency to promote more cellular proliferation and osteoblast differentiation than the other treatments. In Wistar rat bioassay, SIS showed no new bone formation and the implants were surrounded by fibrous tissues. DBM demonstrated new bone formation along the edge of old DBM particles. SIS/DBM composite exhibited high osteoinductivity, and the residual SIS/DBM was surrounded by osteoid-like matrix and newly formed bone. Conclusion: DBM and SIS/DBM composites could retain their osteoinductive capability. SIS/DBM scaffolds may provide an alternative approach for bone tissue engineering.
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Li M, Zhang C, Mao Y, Zhong Y, Zhao J. A Cell-Engineered Small Intestinal Submucosa-Based Bone Mimetic Construct for Bone Regeneration. Tissue Eng Part A 2018; 24:1099-1111. [PMID: 29318958 DOI: 10.1089/ten.tea.2017.0407] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/30/2023] Open
Abstract
Extracellular matrix (ECM)-ornamented biomaterials have attracted attention due to their high potential to improve the biofunctionality of original materials. It is thought that ECM with a bone mimetic microenvironment generated by the specific induction of osteoblasts would be more beneficial for bone regeneration than a regular ECM. In this study, we developed an osteogenic and mineralized ECM construct (Os/M-ECM-SIS) under the guidance of osteoblasts on a small intestinal submucosa (SIS) scaffold cotreated with icariin and calcium. The generated Os/M-ECM-SIS scaffolds exhibited similar morphology and inorganic components as natural bone and higher mechanical strength than ECM-SIS. Cell adhesion, proliferation, and differentiation of osteoblasts and fibroblasts were also enhanced in the cells cultured on the Os/M-ECM-SIS scaffolds. The Os/M-ECM-SIS scaffolds even promoted transdifferentiation of fibroblasts with an upregulation of osteogenic differentiation markers. In a calvarial defect model, new bone formation was greatly enhanced in defects implanted with the Os/M-ECM-SIS scaffolds compared with ECM-SIS scaffolds. Further study showed that the Os/M-ECM-SIS scaffolds promoted bone regeneration in vitro and in vivo via the Bmp/Smad-signaling pathway. Thus, this work proposes a valuable method for generating a mineralized bone mimetic scaffold with SIS as off-the-shelf bone graft substitute that provides an excellent osteogenic microenvironment, making it suitable for application in bone tissue engineering.
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Affiliation(s)
- Mei Li
- 1 Zhejiang Key Laboratory of Pathophysiology, Medical School, Ningbo University , Ningbo, People's Republic of China .,2 Ningbo Institute of Medical Sciences , Ningbo, People's Republic of China
| | - Chi Zhang
- 1 Zhejiang Key Laboratory of Pathophysiology, Medical School, Ningbo University , Ningbo, People's Republic of China
| | - Yuxing Mao
- 1 Zhejiang Key Laboratory of Pathophysiology, Medical School, Ningbo University , Ningbo, People's Republic of China
| | - Yi Zhong
- 1 Zhejiang Key Laboratory of Pathophysiology, Medical School, Ningbo University , Ningbo, People's Republic of China
| | - Jiyuan Zhao
- 1 Zhejiang Key Laboratory of Pathophysiology, Medical School, Ningbo University , Ningbo, People's Republic of China
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12
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Sun T, Yao S, Liu M, Yang Y, Ji Y, Cui W, Qu Y, Guo X. Composite Scaffolds of Mineralized Natural Extracellular Matrix on True Bone Ceramic Induce Bone Regeneration Through Smad1/5/8 and ERK1/2 Pathways. Tissue Eng Part A 2018; 24:502-515. [PMID: 28602124 DOI: 10.1089/ten.tea.2017.0179] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Affiliation(s)
- Tingfang Sun
- Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Sheng Yao
- Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Man Liu
- Department of Gastroenterology and Hepatology, Taikang Tongji Hospital, Wuhan, China
| | - Yushi Yang
- State Key Laboratory of Advanced Technology for Materials Synthesis and Processing, Wuhan University of Technology, Wuhan, China
| | - Yanhui Ji
- Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Wei Cui
- Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Yanzhen Qu
- Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Xiaodong Guo
- Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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13
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A Novel Approach to Utilize Icariin as Icariin-Derived ECM on Small Intestinal Submucosa Scaffold for Bone Repair. Ann Biomed Eng 2017; 45:2673-2682. [DOI: 10.1007/s10439-017-1900-y] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2017] [Accepted: 08/09/2017] [Indexed: 12/28/2022]
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14
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Li M, Zhang C, Cheng M, Gu Q, Zhao J. Small intestinal submucosa: A potential osteoconductive and osteoinductive biomaterial for bone tissue engineering. MATERIALS SCIENCE & ENGINEERING. C, MATERIALS FOR BIOLOGICAL APPLICATIONS 2017; 75:149-156. [DOI: 10.1016/j.msec.2017.02.042] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/22/2016] [Revised: 12/26/2016] [Accepted: 02/10/2017] [Indexed: 01/13/2023]
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15
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Zhao L, Zhao J, Yu J, Sun R, Zhang X, Hu S. In vivo investigation of tissue-engineered periosteum for the repair of allogeneic critical size bone defects in rabbits. Regen Med 2017. [PMID: 28621175 DOI: 10.2217/rme-2016-0157] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023] Open
Abstract
Aim: The aim of the study was to evaluate the efficacy of tissue-engineered periosteum (TEP) in repairing allogenic bone defects in the long term. Materials & methods: TEP was biofabricated with osteoinduced rabbit bone marrow mesenchymal stem cells and porcine small intestinal submucosa (SIS). A total of 24 critical sized defects were created bilaterally in radii of 12 New Zealand White rabbits. TEP/SIS was implanted into the defect site. Bone defect repair was evaluated with radiographic and histological examination at 4, 8 and 12 weeks. Results: Bone defects were structurally reconstructed in the TEP group with mature cortical bone and medullary canals, however this was not observed in the SIS group at 12 weeks. Conclusion: The TEP approach can effectively restore allogenic critical sized defects, and achieve maturity of long-bone structure in 12 weeks in rabbit models.
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Affiliation(s)
- Lin Zhao
- Orthopaedic Department, Jinshan Branch of the Sixth People’s Hospital of Shanghai, Shanghai Jiao Tong University, Shanghai 201500, China
| | - Junli Zhao
- Department of Nephrology, Shanghai ZhouPu Hospital, Shanghai 201318, China
| | - Jiajia Yu
- Orthopaedic Institute, the Second Hospital of Lanzhou University, Lanzhou 730030, China
| | - Rui Sun
- Orthopaedic Institute, the Second Hospital of Lanzhou University, Lanzhou 730030, China
| | - Xiaofeng Zhang
- Orthopaedic Department, Jinshan Branch of the Sixth People’s Hospital of Shanghai, Shanghai Jiao Tong University, Shanghai 201500, China
| | - Shuhua Hu
- Orthopaedic Department, Jinshan Branch of the Sixth People’s Hospital of Shanghai, Shanghai Jiao Tong University, Shanghai 201500, China
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16
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Link PA, Pouliot RA, Mikhaiel NS, Young BM, Heise RL. Tunable Hydrogels from Pulmonary Extracellular Matrix for 3D Cell Culture. J Vis Exp 2017:55094. [PMID: 28117788 PMCID: PMC5352266 DOI: 10.3791/55094] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022] Open
Abstract
Here we present a method for establishing multiple component cell culture hydrogels for in vitro lung cell culture. Beginning with healthy en bloc lung tissue from porcine, rat, or mouse, the tissue is perfused and submerged in subsequent chemical detergents to remove the cellular debris. Histological comparison of the tissue before and after processing confirms removal of over 95% of double stranded DNA and alpha galactosidase staining suggests the majority of cellular debris is removed. After decellularization, the tissue is lyophilized and then cryomilled into a powder. The matrix powder is digested for 48 hr in an acidic pepsin digestion solution and then neutralized to form the pregel solution. Gelation of the pregel solution can be induced by incubation at 37 °C and can be used immediately following neutralization or stored at 4 °C for up to two weeks. Coatings can be formed using the pregel solution on a non-treated plate for cell attachment. Cells can be suspended in the pregel prior to self-assembly to achieve a 3D culture, plated on the surface of a formed gel from which the cells can migrate through the scaffold, or plated on the coatings. Alterations to the strategy presented can impact gelation temperature, strength, or protein fragment sizes. Beyond hydrogel formation, the hydrogel stiffness may be increased using genipin.
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Affiliation(s)
- Patrick A Link
- Department of Biomedical Engineering, Virginia Commonwealth University
| | - Robert A Pouliot
- Department of Biomedical Engineering, Virginia Commonwealth University
| | - Nabil S Mikhaiel
- Department of Biomedical Engineering, Virginia Commonwealth University
| | - Bethany M Young
- Department of Biomedical Engineering, Virginia Commonwealth University
| | - Rebecca L Heise
- Department of Biomedical Engineering, Virginia Commonwealth University; Department of Physiology and Biophysics, Virginia Commonwealth University;
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17
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Dziki JL, Wang DS, Pineda C, Sicari BM, Rausch T, Badylak SF. Solubilized extracellular matrix bioscaffolds derived from diverse source tissues differentially influence macrophage phenotype. J Biomed Mater Res A 2016; 105:138-147. [DOI: 10.1002/jbm.a.35894] [Citation(s) in RCA: 117] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2015] [Revised: 07/01/2016] [Accepted: 07/06/2016] [Indexed: 01/15/2023]
Affiliation(s)
- Jenna L. Dziki
- McGowan Institute for Regenerative Medicine, University of Pittsburgh; Pittsburgh Pennsylvania
- Department of Bioengineering; University of Pittsburgh; Pittsburgh Pennsylvania
| | - Derek S. Wang
- McGowan Institute for Regenerative Medicine, University of Pittsburgh; Pittsburgh Pennsylvania
| | - Catalina Pineda
- McGowan Institute for Regenerative Medicine, University of Pittsburgh; Pittsburgh Pennsylvania
- Department of Bioengineering; University of Pittsburgh; Pittsburgh Pennsylvania
| | - Brian M. Sicari
- McGowan Institute for Regenerative Medicine, University of Pittsburgh; Pittsburgh Pennsylvania
- Department of Surgery; University of Pittsburgh; Pittsburgh Pennsylvania
| | - Theresa Rausch
- McGowan Institute for Regenerative Medicine, University of Pittsburgh; Pittsburgh Pennsylvania
| | - Stephen F. Badylak
- McGowan Institute for Regenerative Medicine, University of Pittsburgh; Pittsburgh Pennsylvania
- Department of Bioengineering; University of Pittsburgh; Pittsburgh Pennsylvania
- Department of Surgery; University of Pittsburgh; Pittsburgh Pennsylvania
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18
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Guided bone regeneration is promoted by the molecular events in the membrane compartment. Biomaterials 2016; 84:167-183. [DOI: 10.1016/j.biomaterials.2016.01.034] [Citation(s) in RCA: 91] [Impact Index Per Article: 10.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2016] [Accepted: 01/18/2016] [Indexed: 11/18/2022]
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19
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In vitro study of bioactivity of homemade tissue-engineered periosteum. MATERIALS SCIENCE & ENGINEERING. C, MATERIALS FOR BIOLOGICAL APPLICATIONS 2016; 58:1170-6. [DOI: 10.1016/j.msec.2015.09.086] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/20/2015] [Revised: 09/15/2015] [Accepted: 09/23/2015] [Indexed: 11/20/2022]
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de la Portilla F, García-Cabrera AM, Pereira S, de Marco F, Molero M, Muntane J, Padillo FJ. An Experimental Study on the Use of Calcium Alginate to Heal Colonic Anastomoses. J INVEST SURG 2015; 29:32-9. [PMID: 26375677 DOI: 10.3109/08941939.2015.1057305] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
BACKGROUND Anastomotic leak is considered the major complication following abdominal surgery. In recent years, the use of a variety of sealing materials for the prevention of leaks has been analyzed. Different biomaterials have been employed as scaffolds to favour tissue repair and regeneration. Among these materials we must mention alginate, a natural polymer with different applications as temporary supporting matrix. The aim of the present study is to evaluate the behavior of both alginate-impregnated sutures and lyophilized alginate sponges in the healing process of colonic anastomes using an experimental animal model. MATERIAL AND METHODS A preliminary study was undertaken to select the adequate scaffold. Animals (n = 45) were distributed into three groups: control (colonic anastomosis using non-continuous 5-0 Polyglactin 910 suture), suture (colonic anastomosis using suture impregnated with alginate gel at 4%) and sponge (colonic anastomosis using suture reinforced with lyophilized alginate sponge). The macroscopic and histological variables were assessed at 4, 8 and 12 days after surgical intervention. RESULTS No statistically significant differences have been observed between the groups during the analysis of macroscopic variables. Animals with sponge implantation showed a greater degree of epithelial reepithalization, less acute and chronic inflammation and greater collagen deposit. CONCLUSIONS The use of lyophilized alginate sponges to reinforce colonic anastomoses in an animal model reduces inflammation and promotes the earlier formation of greater collagen deposits without increasing the number of adhesions or the incidence of stenosis.
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Affiliation(s)
- F de la Portilla
- a Department of General and Digestive Surgery, Unit Colorrectal Surgery , "Virgen del Rocío" University Hospital/IBiS/CSIC/University of Seville, Seville , Spain
| | - A M García-Cabrera
- a Department of General and Digestive Surgery, Unit Colorrectal Surgery , "Virgen del Rocío" University Hospital/IBiS/CSIC/University of Seville, Seville , Spain
| | - S Pereira
- b Institute of Biomedicine of Seville (IBiS), "Virgen del Rocío" University Hospital/IBiS/CSIC/University of Seville , Seville , Spain
| | - F de Marco
- b Institute of Biomedicine of Seville (IBiS), "Virgen del Rocío" University Hospital/IBiS/CSIC/University of Seville , Seville , Spain
| | - M Molero
- c Faculty of Chemistry, Department of Physical Chemistry, University of Seville , Seville , Spain
| | - J Muntane
- b Institute of Biomedicine of Seville (IBiS), "Virgen del Rocío" University Hospital/IBiS/CSIC/University of Seville , Seville , Spain
| | - F J Padillo
- a Department of General and Digestive Surgery, Unit Colorrectal Surgery , "Virgen del Rocío" University Hospital/IBiS/CSIC/University of Seville, Seville , Spain
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21
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Turner NJ, Badylak SF. The Use of Biologic Scaffolds in the Treatment of Chronic Nonhealing Wounds. Adv Wound Care (New Rochelle) 2015; 4:490-500. [PMID: 26244105 DOI: 10.1089/wound.2014.0604] [Citation(s) in RCA: 108] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2014] [Accepted: 10/28/2014] [Indexed: 01/15/2023] Open
Abstract
Significance: Injuries to the skin as a result of illness or injury, particularly chronic nonhealing wounds, present a major healthcare problem. Traditional wound care approaches attempt to control the underlying causes, such as infection and ischemia, while the application of wound dressings aims to modify a poorly healing wound environment into a microenvironment more closely resembling an acute wound allowing the body to heal the wound naturally. Recent Advances: Regenerative medicine approaches, such as the use of biologic scaffold materials comprising an intact extracellular matrix (ECM) or individual components of the ECM, are providing new therapeutic options that focus upon the provision of biochemical cues that alter the wound microenvironment to facilitate rapid restoration of normal skin architecture. Critical Issues: The incidence of chronic nonhealing wounds continues to increase. For example, between 15% and 20% of diabetics are likely to develop chronic, nonhealing foot wounds creating an increasing burden on healthcare systems worldwide. Future Directions: Developing a thorough understanding of wound microenvironment and the mechanisms by which biologic scaffolds work in vivo has the potential to markedly improve outcomes in the clinical translation for the treatment of chronic wounds.
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Affiliation(s)
- Neill J. Turner
- McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania
- Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania
| | - Stephen F. Badylak
- McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania
- Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania
- Department of Bioengineering, University of Pittsburgh, Pittsburgh, Pennsylvania
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22
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Chen X, Song F, Jhamb D, Li J, Bottino MC, Palakal MJ, Stocum DL. The Axolotl Fibula as a Model for the Induction of Regeneration across Large Segment Defects in Long Bones of the Extremities. PLoS One 2015; 10:e0130819. [PMID: 26098852 PMCID: PMC4476796 DOI: 10.1371/journal.pone.0130819] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2015] [Accepted: 05/26/2015] [Indexed: 12/25/2022] Open
Abstract
We tested the ability of the axolotl (Ambystoma mexicanum) fibula to regenerate across segment defects of different size in the absence of intervention or after implant of a unique 8-braid pig small intestine submucosa (SIS) scaffold, with or without incorporated growth factor combinations or tissue protein extract. Fractures and defects of 10% and 20% of the total limb length regenerated well without any intervention, but 40% and 50% defects failed to regenerate after either simple removal of bone or implanting SIS scaffold alone. By contrast, scaffold soaked in the growth factor combination BMP-4/HGF or in protein extract of intact limb tissue promoted partial or extensive induction of cartilage and bone across 50% segment defects in 30%-33% of cases. These results show that BMP-4/HGF and intact tissue protein extract can promote the events required to induce cartilage and bone formation across a segment defect larger than critical size and that the long bones of axolotl limbs are an inexpensive model to screen soluble factors and natural and synthetic scaffolds for their efficacy in stimulating this process.
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Affiliation(s)
- Xiaoping Chen
- Department of Biology, School of Science, Indiana University-Purdue University Indianapolis, Indianapolis, Indiana, United States of America
| | - Fengyu Song
- Department of Oral Biology, School of Dentistry, Indiana-University-Purdue University, Indianapolis, Indiana, United States of America
| | - Deepali Jhamb
- School of Informatics and Computing, Indiana University-Purdue University Indianapolis, Indianapolis, Indiana, United States of America
| | - Jiliang Li
- Department of Biology, School of Science, Indiana University-Purdue University Indianapolis, Indianapolis, Indiana, United States of America
| | - Marco C. Bottino
- Department of Restorative Dentistry, Division of Dental Biomaterials, School of Dentistry, Indiana-University-Purdue University Indianapolis, Indianapolis, Indiana, United States of America
| | - Mathew J. Palakal
- School of Informatics and Computing, Indiana University-Purdue University Indianapolis, Indianapolis, Indiana, United States of America
| | - David L. Stocum
- Department of Biology, School of Science, Indiana University-Purdue University Indianapolis, Indianapolis, Indiana, United States of America
- * E-mail:
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23
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Aulino P, Costa A, Chiaravalloti E, Perniconi B, Adamo S, Coletti D, Marrelli M, Tatullo M, Teodori L. Muscle extracellular matrix scaffold is a multipotent environment. Int J Med Sci 2015; 12:336-40. [PMID: 25897295 PMCID: PMC4402437 DOI: 10.7150/ijms.10761] [Citation(s) in RCA: 42] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/08/2014] [Accepted: 11/21/2014] [Indexed: 11/05/2022] Open
Abstract
The multipotency of scaffolds is a new concept. Skeletal muscle acellular scaffolds (MAS) implanted at the interface of Tibialis Anterior/tibial bone and masseter muscle/mandible bone in a murine model were colonized by muscle cells near the host muscle and by bone-cartilaginous tissues near the host bone, thus highlighting the importance of the environment in directing cell homing and differentiation. These results unveil the multipotency of MAS and point to the potential of this new technique as a valuable tool in musculo-skeletal tissue regeneration.
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Affiliation(s)
- Paola Aulino
- 1. Section of Histology and Medical Embryology, Department of Anatomical, Histological, Forensic and Orthopaedic Sciences, Sapienza University of Rome, Rome, Italy ; 2. Calabrodental clinic, Biomedical Section, Maxillofacial Surgery Unit, Crotone, Italy
| | - Alessandra Costa
- 1. Section of Histology and Medical Embryology, Department of Anatomical, Histological, Forensic and Orthopaedic Sciences, Sapienza University of Rome, Rome, Italy ; 3. Fondazione San Raffaele, Ceglie Messapica, Italy ; 4. Department of Surgery, McGowan Institute, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Ernesto Chiaravalloti
- 2. Calabrodental clinic, Biomedical Section, Maxillofacial Surgery Unit, Crotone, Italy
| | - Barbara Perniconi
- 2. Calabrodental clinic, Biomedical Section, Maxillofacial Surgery Unit, Crotone, Italy ; 5. UMR 8256 CNRS Biology of Adaptation and Aging, University Pierre et Marie Curie Paris 06, Paris, France
| | - Sergio Adamo
- 1. Section of Histology and Medical Embryology, Department of Anatomical, Histological, Forensic and Orthopaedic Sciences, Sapienza University of Rome, Rome, Italy
| | - Dario Coletti
- 2. Calabrodental clinic, Biomedical Section, Maxillofacial Surgery Unit, Crotone, Italy ; 5. UMR 8256 CNRS Biology of Adaptation and Aging, University Pierre et Marie Curie Paris 06, Paris, France
| | - Massimo Marrelli
- 2. Calabrodental clinic, Biomedical Section, Maxillofacial Surgery Unit, Crotone, Italy
| | - Marco Tatullo
- 2. Calabrodental clinic, Biomedical Section, Maxillofacial Surgery Unit, Crotone, Italy ; 6. Tecnologica Research Institute, Biomedical Section, Crotone, Italy
| | - Laura Teodori
- 3. Fondazione San Raffaele, Ceglie Messapica, Italy ; 7. UTAPRAD-DIM, ENEA Frascati, Rome, Italy
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24
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Bone repair of critical size defects treated with mussel powder associated or not with bovine bone graft: Histologic and histomorphometric study in rat calvaria. J Craniomaxillofac Surg 2014; 42:738-43. [DOI: 10.1016/j.jcms.2013.11.004] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2013] [Revised: 08/22/2013] [Accepted: 11/04/2013] [Indexed: 11/22/2022] Open
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Elkarargy A. Biological functionalization of dental implants with fibronectin: a scanning electron microscopic study. Int J Health Sci (Qassim) 2014; 8:57-66. [PMID: 24899880 DOI: 10.12816/0006072] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022] Open
Abstract
OBJECTIVES Early stages of peri-implant bone formation play an essential role in the osseointegration and long-term success of dental implants. Biological implant surface coatings are an emerging technology to enhance the attachment of the implant to the surrounding bone and stimulate bone regeneration. The purpose of this study was to determine the effect of coating the implant surface with fibronectin on osseointegration. MATERIAL AND METHODS The experiment was conducted on a total of twelve New Zealand white mature male rabbits, weight between 2.5-4 kg. Twenty four pure titanium implants were used in this study. Each rabbits received two implants, one implant in each tibia; the implant in the right limb was coated with fibronectin (experimental group), whilst on the contralateral side the implants were placed without coating (control group). Six rabbits were sacrificed for Scanning Electron Microscopic evaluation after 4 and 8 week healing periods. RESULTS The results of the present study demonstrating the mean gap distance between the bone and implant was greater in the control group compared to fibronection group at both observation periods however, the difference between these two groups was not statistically significant. CONCLUSION Thus, it could be suggested that the biological functionalization of dental implants with fibronectin, may influence the integration or biocompatibility and bonding of the implant to the surrounding bone.
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Affiliation(s)
- Amr Elkarargy
- Associate Professor of Periodontology, College of Dentistry, Qassim University, Qassim, Saudi Arabia
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26
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Turner NJ, Keane TJ, Badylak SF. Lessons from developmental biology for regenerative medicine. ACTA ACUST UNITED AC 2013; 99:149-59. [DOI: 10.1002/bdrc.21040] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2013] [Revised: 07/27/2013] [Accepted: 07/27/2013] [Indexed: 12/17/2022]
Affiliation(s)
- Neill J. Turner
- McGowan Institute for Regenerative Medicine; University of Pittsburgh, Pittsburgh, Pennsylvania and Department of Surgery, University of Pittsburgh; Pittsburgh Pennsylvania
| | - Timothy J. Keane
- McGowan Institute for Regenerative Medicine; University of Pittsburgh, Pittsburgh, Pennsylvania and Department of Bioengineering, University of Pittsburgh; Pittsburgh Pennsylvania
| | - Stephen F. Badylak
- McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, and Department of Bioengineering, University of Pittsburgh; Pittsburgh Pennsylvania
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27
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Lee AJ, Lee SH, Chung WH, Kim DH, Chung DJ, Do SH, Kim HY. Evaluation of a canine small intestinal submucosal xenograft and polypropylene mesh as bioscaffolds in an abdominal full-thickness resection model of growing rats. J Vet Sci 2013; 14:175-84. [PMID: 23628657 PMCID: PMC3694189 DOI: 10.4142/jvs.2013.14.2.175] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2011] [Accepted: 04/04/2012] [Indexed: 01/09/2023] Open
Abstract
We evaluated the biological scaffold properties of canine small intestinal submucosa (SIS) compared to a those of polypropylene mesh in growing rats with full-thickness abdominal defects. SIS is used to repair musculoskeletal tissue while promoting cell migration and supporting tissue regeneration. Polypropylene mesh is a non-resorbable synthetic material that can endure mechanical tension. Canine SIS was obtained from donor German shepherds, and its porous collagen fiber structure was identified using scanning electron microscopy (SEM). A 2.50-cm2 section of canine SIS (SIS group) or mesh (mesh group) was implanted in Sprague-Dawley rats. At 1, 2, 4, 12, and 24 weeks after surgery, the implants were histopathologically examined and tensile load was tested. One month after surgery, CD68+ macrophage numbers in the SIS group were increased, but the number of CD8+ T cells in this group declined more rapidly than that in rats treated with the mesh. In the SIS group, few adhesions and well-developed autologous abdominal muscle infiltration into the SIS collagen fibers were observed. No significant differences in the tensile load test results were found between the SIS and mesh groups at 24 weeks. Canine SIS may therefore be a suitable replacement for artificial biological scaffolds in small animals.
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Affiliation(s)
- A-Jin Lee
- Department of Veterinary Surgery, College of Veterinary Medicine, Konkuk University, Seoul 143-701, Korea
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28
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Tissue Engineering with Decellularized Tissues. Biomater Sci 2013. [DOI: 10.1016/b978-0-08-087780-8.00140-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/24/2023]
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29
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Dimitriou R, Mataliotakis GI, Calori GM, Giannoudis PV. The role of barrier membranes for guided bone regeneration and restoration of large bone defects: current experimental and clinical evidence. BMC Med 2012; 10:81. [PMID: 22834465 PMCID: PMC3423057 DOI: 10.1186/1741-7015-10-81] [Citation(s) in RCA: 235] [Impact Index Per Article: 18.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/10/2011] [Accepted: 07/26/2012] [Indexed: 12/27/2022] Open
Abstract
Treatment of large bone defects represents a great challenge in orthopedic and craniomaxillofacial surgery. Although there are several methods for bone reconstruction, they all have specific indications and limitations. The concept of using barrier membranes for restoration of bone defects has been developed in an effort to simplify their treatment by offering a single-staged procedure. Research on this field of bone regeneration is ongoing, with evidence being mainly attained from preclinical studies. The purpose of this review is to summarize the current experimental and clinical evidence on the use of barrier membranes for restoration of bone defects in maxillofacial and orthopedic surgery. Although there are a few promising preliminary human studies, before clinical applications can be recommended, future research should aim to establish the 'ideal' barrier membrane and delineate the need for additional bone grafting materials aiming to 'mimic' or even accelerate the normal process of bone formation. Reproducible results and long-term observations with barrier membranes in animal studies, and particularly in large animal models, are required as well as well-designed clinical studies to evaluate their safety, efficacy and cost-effectiveness.
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Affiliation(s)
- Rozalia Dimitriou
- Department of Trauma and Orthopaedics, Leeds Teaching Hospitals NHS Trust, Leeds LS1 3EX, UK
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30
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Nelson MT, Keith JP, Li BB, Stocum DL, Li J. Electrospun composite polycaprolactone scaffolds for optimized tissue regeneration. ACTA ACUST UNITED AC 2012. [DOI: 10.1177/1740349912450828] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
There is evidence to suggest that the development of a stable microvasculature at the site of a critical-sized bone defect or fracture aids in repairing or regenerating bone. Identifying a tissue engineering scaffold that optimizes bone tissue and blood vessel development could improve regenerative capabilities. In this paper we study the proliferation and directed differentiation potentials of endothelial colony forming cells and mesenchymal stem cells cultured on electrospun polycaprolactone matrices and compare them with data obtained for composite polycaprolactone–hydroxyapatite, polycaprolactone–hydroxyapatite/β-tricalcium phosphate and polycaprolactone–small intestine submucosa electrospun matrices. Polycaprolactone–hydroxyapatite and polycaprolactone–hydroxyapatite/β-tricalcium phosphate fibers on average displayed a two-fold increase in fiber diameter and average pore-size area as compared with polycaprolactone or polycaprolactone–small intestine submucosa scaffolds. X-ray diffraction showed that significant additions of hydroxyapatite, hydroxyapatite/β-tricalcium phosphate and small intestine submucosa were present in the composite scaffolds. Incorporating hydroxyapatite or hydroxyapatite/β-tricalcium phosphate into the polycaprolactone fiber increased the modulus and ultimate tensile strength significantly. Both endothelial colony forming cell and mesenchymal stem cell proliferation was two-fold greater on polycaprolactone–small intestine submucosa scaffolds; whereas on polycaprolactone–hydroxyapatite and polycaprolactone–hydroxyapatite/β-tricalcium phosphate scaffolds only endothelial colony forming cell proliferation was observed to be significant. Alkaline phosphatase analysis for mesenchymal stem cell-seeded scaffolds indicated that only polycaprolactone–small intestine submucosa scaffolds displayed significant increases after 10 days of culture, suggesting an osteoblast phenotype. Electrospun polycaprolactone–small intestine submucosa scaffolds stimulated proliferation of both cell types and directed mesenchymal stem cell differentiation, providing a stable platform to investigate the potential of endothelial colony forming cell in directing bone tissue repair or regeneration.
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Affiliation(s)
- M Tyler Nelson
- Department of Biology, Indiana University–Purdue University Indianapolis, USA
| | - Joshua P Keith
- Department of Biology, Indiana University–Purdue University Indianapolis, USA
| | - Bing-Bing Li
- Department of Chemistry, Central Michigan University, USA
- Center for Regenerative Biology and Medicine, Indiana University–Purdue University Indianapolis, USA
| | - David L Stocum
- Department of Biology, Indiana University–Purdue University Indianapolis, USA
- Center for Regenerative Biology and Medicine, Indiana University–Purdue University Indianapolis, USA
| | - Jiliang Li
- Department of Biology, Indiana University–Purdue University Indianapolis, USA
- Center for Regenerative Biology and Medicine, Indiana University–Purdue University Indianapolis, USA
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FDA approved guidance conduits and wraps for peripheral nerve injury: a review of materials and efficacy. Injury 2012; 43:553-72. [PMID: 21269624 DOI: 10.1016/j.injury.2010.12.030] [Citation(s) in RCA: 506] [Impact Index Per Article: 38.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/15/2010] [Accepted: 12/27/2010] [Indexed: 02/02/2023]
Abstract
Several nerve guidance conduits (NGCs) and nerve protectant wraps are approved by the US Food and Drug Administration (FDA) for clinical use in peripheral nerve repair. These devices cover a wide range of natural and synthetic materials, which may or may not be resorbable. This review consolidates the data pertaining to all FDA approved materials into a single reference, which emphasizes material composition alongside pre-clinical and clinical safety and efficacy (where possible). This article also summarizes the key advantages and limitations for each material as noted in the literature (with respect to the indication considered). In this context, this review provides a comprehensive reference for clinicians which may facilitate optimal material/device selection for peripheral nerve repair. For materials scientists, this review highlights predicate devices and evaluation methodologies, offering an insight into current deficiencies associated with state-of-the-art materials and may help direct new technology developments and evaluation methodologies thereof.
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Lee SJ, Lee IW, Lee YM, Lee HB, Khang G. Macroporous biodegradable natural/synthetic hybrid scaffolds as small intestine submucosa impregnated poly(D, L-lactide-co-glycolide) for tissue-engineered bone. JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION 2012; 15:1003-17. [PMID: 15461186 DOI: 10.1163/1568562041526487] [Citation(s) in RCA: 54] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Abstract
Poly(D,L-lactide-co-glycolide) (PLGA), a biodegradable synthetic polymer, is widely used in a variety of tissue-engineered applications, including drug-delivery systems. However, the PLGA scaffolds, macroporous and three-dimensional structure, are difficult to cell attachment and in-growth due to surface hydrophobicity. In order to introduce in new bioactive functionality from porcine small intestine submucosa (SIS) as natural source for PLGA, we fabricated SIS-powder-impregnated PLGA (SIS/PLGA) hybrid scaffolds. Fabrication parameters, including ratios of SIS, PLGA and salt, were optimized to produce the desired macroporous foam. The scaffolds had a relatively homogeneous pore structure, good interconnected pores from the surface to core region and showed an average pore size in the range 69.23-105.82 microm and over 90% porosity. The SIS/PLGA scaffolds degraded with a rate depending on the contents of the SIS. After the fabrication of the SIS/PLGA hybrid scaffolds the wettability of the scaffold was greatly enhanced, resulting in uniform cell seeding and distribution. So, it was observed that BMSC attachment to the SIS/PLGA scaffolds increased gradually with increasing SIS contents. Scaffolds of PLGA alone and SIS/PLGA were implanted subcutaneously under dorsal skin of athymic nude mouse to observe the osteoconductivity. It was found from the result that the effects of the SIS/PLGA scaffolds on bone formation are stronger than control PLGA scaffolds. In summary, the SIS/PLGA scaffolds have osteoconductive effects to allow remodeling and replacement by osseous tissue.
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Affiliation(s)
- Sang Jin Lee
- Biomaterials Laboratory, Korea Research Institute of Chemical Technology, Yuseong, Daejeon 305-600, South Korea
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Extracellular matrix as an inductive template for temporomandibular joint meniscus reconstruction: a pilot study. J Oral Maxillofac Surg 2012; 69:e488-505. [PMID: 21684655 DOI: 10.1016/j.joms.2011.02.130] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2010] [Revised: 02/18/2011] [Accepted: 02/27/2011] [Indexed: 11/20/2022]
Abstract
PURPOSE A device consisting of powdered porcine urinary bladder extracellular matrix (UBM-ECM) encapsulated within sheets of the same material was investigated as a scaffold for temporomandibular joint (TMJ) meniscus reconstruction. MATERIALS AND METHODS Five dogs underwent unilateral resection of the native meniscus and replacement with a UBM-ECM device. Necropsies were performed at 3, 4, 8, 12, and 24 weeks. Two additional dogs underwent bilateral resection of the meniscus with replacement with a UBM-ECM device on 1 side, leaving the contralateral side empty as a control. Necropsies were performed at 24 weeks for bilaterally treated animals. RESULTS Macroscopically, the UBM-ECM implants were remodeled rapidly and were indistinguishable from newly deposited host tissue at all time points. Microscopically, remodeling was characterized by a dense infiltration of predominantly CD68(+) mononuclear cells and smooth muscle actin-positive fibroblast-like cells at early time points changing with time to a sparse population of smooth muscle actin-negative spindle-shaped cells resembling those of the native fibrocartilaginous TMJ meniscus. Furthermore, the remodeling process showed deposition of predominantly type I collagen, the density and organization of which resembled those of the native meniscus by the 24-week time point. Ingrowth of calsequestrin-positive skeletal muscle tissue was also observed at the periphery of the remodeled UBM-ECM device and was similar to that found at the attachment site of the native meniscus to the surrounding soft tissues. Histologic results were identical for samples excised from both unilaterally and bilaterally treated animals. No adverse changes in the articulating surfaces of the condyle or fossa were observed in UBM-ECM-implanted joints. In the bilaterally treated animals, the unimplanted control side was characterized by degeneration and pitting of the articulating surfaces of both the condyle and the fossa, with disorganized bands of fibrous connective tissue observed within the joint space. CONCLUSION Results of this study suggest that the UBM-ECM device provides an effective interpositional material while serving as an inductive template for reconstruction of the TMJ meniscus.
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Turner NJ, Badylak JS, Weber DJ, Badylak SF. Biologic scaffold remodeling in a dog model of complex musculoskeletal injury. J Surg Res 2011; 176:490-502. [PMID: 22341350 DOI: 10.1016/j.jss.2011.11.1029] [Citation(s) in RCA: 91] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2011] [Revised: 11/08/2011] [Accepted: 11/23/2011] [Indexed: 02/03/2023]
Abstract
BACKGROUND Current treatment principles for muscle injuries with volumetric loss have been largely derived from empirical observations. Differences in severity or anatomic location have determinant effects on the tissue remodeling outcome. Biologic scaffolds composed of extracellular matrix (ECM) have been successfully used to restore vascularized, innervated, and contractile skeletal muscle in animal models but limited anatomic locations have been evaluated. The aim of this study was to determine the ability of a xenogeneic ECM scaffold to restore functional skeletal muscle in a canine model of a complex quadriceps injury involving bone, tendon, and muscle. MATERIALS AND METHODS Sixteen dogs were subjected to unilateral resection of the distal third of the vastus lateralis and medial half of the distal third of the vastus medialis muscles including the proximal half of their associated quadriceps tendon. This defect was replaced with a biologic scaffold composed of small intestinal submucosa extracellular matrix (SIS-ECM) and the remodeling response was evaluated at 1, 2, 3, and 6 mo (N = 4 per group). RESULTS The initial remodeling process followed a similar pattern to other studies of ECM-mediated muscle repair with rapid vascularization and migration of myoblasts into the defect site. However, over time the remodeling response resulted in the formation of dense collagenous tissue with islands of muscle in the segments of the scaffold not in contact with bone, and foci of bone and cartilage in the segments that were adjacent to the underlying bone. CONCLUSIONS SIS-ECM was not successful at restoring functional muscle tissue in this model. However, the results also suggest that SIS-ECM may have potential to promote integration of soft and boney tissues when implanted in close apposition to bone.
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Affiliation(s)
- Neill J Turner
- McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania 15219, USA.
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Keane TJ, Londono R, Turner NJ, Badylak SF. Consequences of ineffective decellularization of biologic scaffolds on the host response. Biomaterials 2011; 33:1771-81. [PMID: 22137126 DOI: 10.1016/j.biomaterials.2011.10.054] [Citation(s) in RCA: 434] [Impact Index Per Article: 31.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2011] [Accepted: 10/20/2011] [Indexed: 11/17/2022]
Abstract
Biologic scaffold materials composed of extracellular matrix (ECM) are routinely used for a variety of clinical applications. Despite known variations in tissue remodeling outcomes, quantitative criteria by which decellularization can be assessed were only recently described and as a result, the amount of retained cellular material varies widely among commercial products. The objective of this study was to evaluate the consequences of ineffective decellularization on the host response. Three different methods of decellularization were used to decellularize porcine small intestinal ECM (SIS-ECM). The amount of cell remnants was quantified by the amount and fragmentation of DNA within the scaffold materials. The M1/M2 phenotypic polarization profile of macrophages, activated in response to these ECM scaffolds, was assessed in vitro and in vivo using a rodent model of body wall repair. The results show that, in vitro, more aggressive decellularization is associated with a shift in macrophage phenotype predominance from M1 to M2. While this shift was not quantitatively apparent in vivo, notable differences were found in the distribution of M1 vs. M2 macrophages within the various scaffolds. A clear association between macrophage phenotype and remodeling outcome exists and effective decellularization remains an important component in the processing of ECM-based scaffolds.
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Affiliation(s)
- Timothy J Keane
- McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA 15219, USA
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Zhao L, Zhao J, Wang S, Wang J, Liu J. Comparative study between tissue-engineered periosteum and structural allograft in rabbit critical-sized radial defect model. J Biomed Mater Res B Appl Biomater 2011; 97:1-9. [PMID: 21290569 DOI: 10.1002/jbm.b.31768] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2010] [Revised: 07/27/2010] [Accepted: 08/05/2010] [Indexed: 01/14/2023]
Abstract
The purpose of this study was to compare the efficacy of tissue-engineered periosteum (TEP) to allgeneic bone in repairing segmental bone defect. TEP was fabricated with osteoinduced rabbit bone marrow mesenchymal stem cells (MSCs) and porcine small intestinal submucosa (SIS). Allogrfats were cryopreserved radial segments of New Zealand Rabbits. Forty-eight radial critical-sized defects (CSD) were bilaterally produced in 24 rabbits. The defects were divided into three groups, group A, TEP implantation, group B, SIS implantation, and group C allograft. Bone defect reconstruction was kinetically analyzed at 4, 8, and 12 weeks by radiographic and histological scoring system. In group A, bone defects were radiographically and histologically healed with mature cortex and marrow cavity by 12 weeks, while none of the defects healed in group B. Group C showed a slow process of creeping substitution with lymphocyte infiltration. Statistical comparison confirmed that group A had a more efficient and rapid bone defect reparation as well as remodelling than Group B and C. In conclusion, TEP is superior to structural allograft in reconstruction of allogenic segmental bone defect. Pure SIS cannot guide bone regeneration in this rabbit model.
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Affiliation(s)
- Lin Zhao
- Department of Orthopaedic Surgery, Orthopaedic Institute of the 2nd Hospital of Lanzhou University, 730030, Lanzhou City, People's Republic of China.
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Mondalek FG, Ashley RA, Roth CC, Kibar Y, Shakir N, Ihnat MA, Fung KM, Grady BP, Kropp BP, Lin HK. Enhanced angiogenesis of modified porcine small intestinal submucosa with hyaluronic acid-poly(lactide-co-glycolide) nanoparticles: from fabrication to preclinical validation. J Biomed Mater Res A 2010; 94:712-9. [PMID: 20213816 DOI: 10.1002/jbm.a.32748] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/17/2023]
Abstract
Hyaluronic acid-poly(de-co-glycolide) nanoparticles (HA-PLGA NPs) were synthesized to stabilize the porous structure of porcine small intestinal submucosa (SIS), to improve surface biocompatibility and to enhance performance in tissue regeneration. HA-PLGA NPs were characterized for size, zeta potential, surface morphology, and HA loading. Human microvascular endothelial cells responded to HA-PLGA NPs and HA-PLGA modified SIS (HA-PLGA-SIS) with elevated cell proliferation. HA-PLGA-SIS significantly enhanced neo-vascularization in an in ovo chorioallantoic membrane angiogenesis model. The angiogenic capability of the newly fabricated HA-PLGA-SIS was tested in a canine bladder augmentation model. Urinary bladder augmentation was performed in beagle dogs following hemi-cystectomy using HA-PLGA-SIS. The regenerated bladder was harvested at 10 weeks post augmentation and vascularization was evaluated using CD31 immunohistochemical staining. Bladder regenerated with HA-PLGA-SIS had significantly higher vascular ingrowth compared to unmodified SIS. This study shows that HA-PLGA NPs may represent a new approach for modifying naturally derived SIS biomaterials in regenerative medicine.
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Affiliation(s)
- Fadee G Mondalek
- Department of Chemical, Biological and Materials Engineering, University of Oklahoma, Norman, Oklahoma 73019, USA
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Shekaran A, García AJ. Extracellular matrix-mimetic adhesive biomaterials for bone repair. J Biomed Mater Res A 2010; 96:261-72. [PMID: 21105174 DOI: 10.1002/jbm.a.32979] [Citation(s) in RCA: 151] [Impact Index Per Article: 10.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2010] [Revised: 09/07/2010] [Accepted: 09/08/2010] [Indexed: 01/12/2023]
Abstract
Limited osseointegration of current orthopedic biomaterials contributes to the failure of implants such as arthroplasties, bone screws, and bone grafts, which present a large socioeconomic cost within the United States. These implant failures underscore the need for biomimetic approaches that modulate host cell-implant material responses to enhance implant osseointegration and bone formation. Bioinspired strategies have included functionalizing implants with extracellular matrix (ECM) proteins or ECM-derived peptides or protein fragments, which engage integrins and direct osteoblast adhesion and differentiation. This review discusses (1) bone ECM composition and key integrins implicated in osteogenic differentiation, (2) the use of implants functionalized with ECM-mimetic peptides/protein fragments, and (3) growth factor-derived peptides to promote the mechanical fixation of implants to bone and to enhance bone healing within large defects.
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Affiliation(s)
- Asha Shekaran
- Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, Georgia, USA
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Repairing critical-sized rat calvarial defects with a periosteal cell-seeded small intestinal submucosal layer. Plast Reconstr Surg 2010; 122:400-409. [PMID: 18626355 DOI: 10.1097/prs.0b013e31817d6206] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
Abstract
BACKGROUND Small intestinal submucosa was evaluated as a bioscaffold candidate for periosteum-derived osteoblasts, and its suitability as a bone replacement material for cranial defects was investigated. METHODS In the in vitro phase, osteoblasts were expanded in osteogenic medium and were then seeded onto small intestinal submucosa. To confirm osteoblast phenotype, they were tested for alkaline phosphatase, collagen type 1, and calcium expression. In the in vivo phase, calvarial critical-sized defects were created in 35 rats. The defects were either left untreated for surgical control (group 1), treated with small intestinal submucosa alone (group 2), treated with an osteoblast-embedded construct (group 3), or treated with an autogenous bone graft (group 4). The results were evaluated 12 weeks after surgery with radiopacity measurements and with stereologic analysis. RESULTS Periosteal cells grew successfully in vitro. The percentage radiopaque area at the defect was measured to be 42, 74, 76, and 89 percent for groups 1, 2, 3, and 4, respectively. The pixel intensity of the same site was 36.4, 48.1, 47.5, and 54.5 for the same groups, respectively. Tissue-engineered constructs did not achieve enough bone formation and calcification to be effective as autogenous bone grafts and were not superior to the small intestinal submucosa alone. However, both small intestinal submucosa and cell-seeded small intestinal submucosa showed significantly more bone formation compared with the untreated group. CONCLUSIONS Although it was demonstrated that the small intestinal submucosa itself has osteogenic properties, it was not significantly increased by adding periosteum-derived osteoblasts to it. The osteogenic properties of small intestinal submucosa are promising, and its role as a scaffold should be investigated further.
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Yang Z, Jin F, Zhang X, Ma D, Han C, Huo N, Wang Y, Zhang Y, Lin Z, Jin Y. Tissue engineering of cementum/periodontal-ligament complex using a novel three-dimensional pellet cultivation system for human periodontal ligament stem cells. Tissue Eng Part C Methods 2010; 15:571-81. [PMID: 19534606 DOI: 10.1089/ten.tec.2008.0561] [Citation(s) in RCA: 71] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
Limitations of conventional regeneration modalities underscore the necessity of recapitulating development for periodontal tissue engineering. In this study, we proposed a novel three-dimensional pellet cultivation system for periodontal ligament stem cells (PDLSCs) to recreate the biological microenvironment similar to those of a regenerative milieu. Monodispersed human PDLSCs were cultured in medium with ascorbic acid and conditioned medium from developing apical tooth germ cells and were subsequently harvested from culture plate as a contiguous cell sheet with abundant extracellular matrix. The detached cell-matrix membrane spontaneously contracted to produce a single-cell pellet. The PDLSCs embedded within this cell-matrix complex exhibited several phenotypic characteristics of cementoblast lineages, as indicated by upregulated alkaline phosphatase activity, accelerated mineralization, and the expression of bone sialoprotein and osteocalcin genes. When this PDLSC pellets were transplanted into immunocompromised mice, a regular aligned cementum/PDL-like complex was formed. These results suggest that the combination of apical tooth germ cell-conditioned medium and endogenous extracellular matrix could maximally mimic the microenvironment of root/periodontal tissue development and enhance the reconstruction of physiological architecture of a cementum/PDL-like complex in a tissue-mimicking way; on the other hand, such PDLSC pellet may also be a promising alternative to promote periodontal defect repair for future clinical applications.
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Affiliation(s)
- Zhenhua Yang
- Department of Orthodontics, School of Stomatology, Fourth Military Medical University , Xi'an, People's Republic of China
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Kim KS, Lee JY, Kang YM, Kim E, Kim GH, Rhee SD, Cheon HG, Kim JH, Min BH, Lee HB, Kim MS. Small intestine submucosa sponge for in vivo support of tissue-engineered bone formation in the presence of rat bone marrow stem cells. Biomaterials 2010; 31:1104-13. [DOI: 10.1016/j.biomaterials.2009.10.020] [Citation(s) in RCA: 74] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2009] [Accepted: 10/08/2009] [Indexed: 10/20/2022]
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Tan Y, Zhang Y, Pei M. Meniscus Reconstruction Through Coculturing Meniscus Cells with Synovium-Derived Stem Cells on Small Intestine Submucosa—A Pilot Study to Engineer Meniscus Tissue Constructs. Tissue Eng Part A 2010; 16:67-79. [PMID: 19619075 DOI: 10.1089/ten.tea.2008.0680] [Citation(s) in RCA: 42] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023] Open
Affiliation(s)
- Yunbing Tan
- Tissue Engineering Laboratory, Department of Orthopaedics, West Virginia University, Morgantown, West Virginia
- Mechanical and Aerospace Engineering, West Virginia University, Morgantown, West Virginia
| | - Yuanyuan Zhang
- Institute for Regenerative Medicine, Wake Forest University Health Science, Winston-Salem, North Carolina
| | - Ming Pei
- Tissue Engineering Laboratory, Department of Orthopaedics, West Virginia University, Morgantown, West Virginia
- Mechanical and Aerospace Engineering, West Virginia University, Morgantown, West Virginia
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Taveau JW, Tartaglia M, Buchannan D, Smith B, Koenig G, Thomfohrde K, Stouch B, Jeck S, Greene CH. Regeneration of Uterine Horn Using Porcine Small Intestinal Submucosa Grafts in Rabbits. J INVEST SURG 2009; 17:81-92. [PMID: 15204714 DOI: 10.1080/08941930490422456] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2022]
Abstract
Tubal factor infertility may be reversed using porcine small-intestinal submucosa (SIS). The method uses as a model the New Zealand White rabbit uerine horn. In surgery, SIS grafts were prepared from porcine jejunum; the uterine horn segment was resected and a graft was placed; then the contralateral adnexa was resected. Fecundability was tested with natural mating. Three out of six rabbits became pregnant. Gross and microscopic examination confirmed regeneration of all tissue layers. Thus, this study determined that SIS facilitates successful regeneration of uterine horn morphology in a manner similar to that observed in other tissues and species.
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Affiliation(s)
- Jon W Taveau
- Department of Biomedical Sciences, Division of Physiology, Philadelphia College of Osteopathic Medicine, Philadelphia, Pennsylvania, USA
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Tan MY, Zhi W, Wei RQ, Huang YC, Zhou KP, Tan B, Deng L, Luo JC, Li XQ, Xie HQ, Yang ZM. Repair of infarcted myocardium using mesenchymal stem cell seeded small intestinal submucosa in rabbits. Biomaterials 2009; 30:3234-3240. [PMID: 19261327 DOI: 10.1016/j.biomaterials.2009.02.013] [Citation(s) in RCA: 94] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2008] [Accepted: 02/08/2009] [Indexed: 11/24/2022]
Abstract
Myocardial infarction (MI) remains a common and deadly disease. Using tissue-engineered cardiac grafts to repair infarcted myocrdium is considered to be a therapeutic approach. This study tested the feasibility of using MSCs-seeded SIS to repair chronic myocardial infarction in a rabbit model. MI in rabbits was created by ligation of the left anterior descending artery. BrdU-labeled mesenchymal stem cells (MSCs) were seeded on the small intestinal submucosa and cultured for 5-7 days prior to implantation. Four weeks after myocardial infarction, cardiac grafts were implanted onto the epicardial surface of infarcted myocardium. Four weeks after implantation of the membranes, a serial of tests including echocardiography, hemodynamics, histology and immunohistochemistry were undertaken to evaluate the effect of the implanted grafts on recovery of the infarcted myocardium. It was shown that left ventricular contractile function and dimension, the capillary density of the infarcted region, and myocardial pathological changes were significantly improved in rabbits implanted either SIS or MSCs-seeded SIS. But the MSCs-seeded SIS was more effective. Immunofluorescence staining demonstrated the migration of Brdu-labeled MSCs from the membrane into the infarcted area and their differentiation to cardiomyocytes and smooth muscle cells. Taken together, these results suggest that MSCs-seeded SIS can be used to repair chronic myocardial infarction, which enhances myocardial regeneration.
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Affiliation(s)
- Mei Yun Tan
- Division of Stem Cell and Tissue Engineering, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, PR China
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Pribitkin EA, Ambro BT, Bloeden E, O'Hara BJ. Rabbit Ear Cartilage Regeneration With a Small Intestinal Submucosa Graft. Laryngoscope 2009; 114:1-19. [PMID: 15475771 DOI: 10.1097/00005537-200409001-00001] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
OBJECTIVES/HYPOTHESIS The objective was to demonstrate that interpositional grafting with porcine small intestinal submucosa promotes cartilage regeneration following excision of rabbit auricular cartilage. STUDY DESIGN Blinded, controlled study. METHODS Eight New Zealand white rabbits underwent excision of auricular cartilage on two sites with and two sites without preservation of perichondrium. Porcine small intestinal submucosa was implanted into one site with and one site without intact perichondrium. Remaining sites served as control sites. Histological assessment was performed at 3 (n = 4) and 6 (n = 3) months and at 1 year (n = 1) after grafting. RESULTS Histological evaluation showed cartilage regeneration accompanied by chronic inflammation in areas in which porcine small intestinal submucosa was implanted between layers of intact perichondrium. Other sites failed to show significant cartilage regeneration. CONCLUSION The results of the study using porcine small intestinal submucosa as a bioscaffold for cartilage regeneration are promising and justify further animal and human studies.
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Affiliation(s)
- Edmund A Pribitkin
- Department of Otolaryngology-Head and Neck Surgery, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
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Sheahan DE, Gillian TD. Reconstructive cranioplasty using a porcine small intestinal submucosal graft. J Small Anim Pract 2008; 49:257-9. [PMID: 18373537 DOI: 10.1111/j.1748-5827.2007.00515.x] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
A six-year-old border collie was presented with a solid mass on the dorsal cranium. Histological examination showed the mass to be a multilobular tumour of bone. A magnetic resonance imaging scan confirmed deformation of the dorsal cranium with compression of the cerebral hemispheres. A craniotomy was performed to excise the mass and overlying skin, resulting in a substantial deficit of calvarium and skin. A cranioplasty using a small intestinal submucosal (SIS) graft was performed to reconstruct the calvarial defect. A local myocutaneous advancement flap was elevated and positioned over the cranioplasty to close the skin deficit. The outcome of this reconstruction was aesthetic and functional. The small intestinal submucosal graft provided satisfactory mechanical support and was a suitable physical barrier in place of the calvarial bone. Histological examination of the small intestinal submucosal graft 128 days after implantation showed that the graft had been replaced by a dense network of collagenous tissue, with small focal areas of partially mineralised woven bone merging with a fibrocartilaginous matrix of the deeper margin. Histological examination also confirmed regrowth of the multilobular tumour of bone in the region of the small intestinal submucosal graft indicating that it is only a suitable implant if adequate surgical margins are obtained.
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Affiliation(s)
- D E Sheahan
- Division of Small Animal Clinical Studies, Department of Veterinary Clinical Studies, University of Glasgow Veterinary School, Bearsden Road, Bearsden, Glasgow G61 1QH
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47
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Bertone AL, Goin S, Kamei SJ, Mattoon JS, Litsky AS, Weisbrode SE, Clarke RB, Plouhar PL, Kaeding CC. Metacarpophalangeal collateral ligament reconstruction using small intestinal submucosa in an equine model. J Biomed Mater Res A 2008; 84:219-29. [PMID: 17607764 DOI: 10.1002/jbm.a.31432] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022]
Abstract
Xenogeneic porcine small intestinal submucosa (SIS) is a natural, biodegradable matrix that has been successfully used as a scaffold for repair of tissue defects. The goal of this study was to compare a collateral ligament transection surgically reconstructed with an anchored SIS ligament to a sham-operated control procedure for the correction of joint laxity using an equine model. Ten metacarpophalangeal joints from 10 horses had complete transection of the lateral collateral ligament. In 6 horses, the collateral ligament was reconstructed with a multilaminate strip of SIS anchored with screws into bone tunnels proximal and distal to the joint. The sham controls had similar screws, but no SIS placed. Clinical compatibility and effectiveness were evaluated with lameness, incisional quality, and joint range of motion, circumference and laxity. Ligament structure and strength was quantified with serial high resolution ultrasound, histology, and mechanical testing at 8 weeks. Surgical repair with SIS eliminated joint laxity at surgery. SIS-treated joints had significantly less laxity than sham treatment at 8 weeks (p < 0.001). SIS-treated ligaments demonstrated a progressive increase in repair tissue density and fiber alignment that by week 8 were significantly greater than sham-treated ligament (p < 0.03). SIS-repaired ligament tended to have greater peak stress to failure than sham-treatment (p < 0.07). Cellularity within the ligament repair tissue and inflammation within the bone tunnel was significantly greater in the SIS-treated limbs (p < 0.017). Within the first 8 weeks of healing, SIS implanted to reinforce collateral ligament injury was biocompatible in the joint environment, restored initial loss of joint stability, and accelerated early repair tissue quality. SIS ligament reconstruction might provide benefit to early ligament healing and assist early joint stability associated with ligament injury.
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Affiliation(s)
- Alicia L Bertone
- Comparative Orthopaedic Research Laboratories, Department of Veterinary Clinical Sciences, The Ohio State University, Columbus, Ohio 43210, USA.
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48
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Liu W, Cao Y. Application of scaffold materials in tissue reconstruction in immunocompetent mammals: Our experience and future requirements. Biomaterials 2007; 28:5078-86. [PMID: 17669487 DOI: 10.1016/j.biomaterials.2007.07.028] [Citation(s) in RCA: 49] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2007] [Accepted: 07/17/2007] [Indexed: 11/25/2022]
Abstract
In spite of many researches on scaffold material design, fabrication and characterization, as well as cell-material interaction in vitro, in vivo study especially in large mammals should be an essential step towards practical application. In our center, different scaffold materials have been applied to the reconstruction of various types of tissues using immunocompetent mammals as major animal models, such as for reconstruction of bone, cartilage, tendon, skin, blood vessel and corneal stroma, etc. In this article, our experience, as well as encountered challenges in the application of scaffold materials, is introduced. Additionally, future requirements for scaffold application in tissue reconstruction and regeneration are proposed as well.
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Affiliation(s)
- Wei Liu
- Department of Plastic and Reconstructive Surgery, Shanghai 9th People's Hospital, Shanghai Jiao Tong University School of Medicine, National Tissue Engineering Center of China, 639 Zhi Zao Ju Road, Shanghai 200011, PR China
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49
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Suckow MA, Hodde JP, Wolter WR, Hiles MC. Repair of experimental Achilles tenotomy with porcine renal capsule material in a rat model. JOURNAL OF MATERIALS SCIENCE. MATERIALS IN MEDICINE 2007; 18:1105-10. [PMID: 17268862 DOI: 10.1007/s10856-007-0158-6] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/04/2005] [Accepted: 03/08/2006] [Indexed: 05/13/2023]
Abstract
Porcine small intestinal submucosa (SIS) is a collagenous acellular matrix which has found substantial utility as a tissue growth scaffold. In the present study, the utility of porcine renal capsule matrix (RCM) was compared to SIS in a rat Achilles tenotomy repair model. Groups of rats underwent surgical tenotomy followed by either no repair, repair with a SIS graft, or repair with a RCM graft. The weight-bearing ability of the manipulated limb was evaluated for 10 days following surgery using a subjective scale. Tenotomy sites sampled 28 days after surgery were numerically graded for degree of histologic change. There were no statistically significant differences between groups with respect to return to weight-bearing ability (p >or= 0.05) or degree of histologic change (p >or= 0.001); however, a non-significant trend suggested that rats treated with SIS or RCM experienced a faster return to limb function than untreated rats, and RCM-treated rats had slightly higher scores for degree of histologic change, suggesting a more rapid repair of the tenotomy site than in SIS-treated or untreated rats. The harvested tenotomy sites in all treatment groups were characterized by marked fibroplasia and presence of macrophages. Remnants of SIS surrounded by macrophages and multi-nucleated giant cells were still present in some rats, however remnants of RCM were not observed, suggesting more rapid incorporation of RCM. The results show that RCM is equivalent to SIS as a material for repair of Achilles tendon injury and merits further study in other tendon injury models.
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Affiliation(s)
- M A Suckow
- University of Notre Dame, 400 Freimann Life Science Center, Notre Dame, IN 46556, USA.
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50
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Su Y, Zeng BF, Zhang CQ, Zhang KG, Xie XT. Study of biocompatibility of small intestinal submucosa (SIS) with Schwann cells in vitro. Brain Res 2007; 1145:41-7. [PMID: 17367764 DOI: 10.1016/j.brainres.2007.01.138] [Citation(s) in RCA: 17] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2006] [Revised: 01/10/2007] [Accepted: 01/17/2007] [Indexed: 01/12/2023]
Abstract
No satisfactory method currently exists for repairing long peripheral nerve defects. Efforts have been made to fabricate bioactive artificial nerve conduits, comprised of a biomaterial pre-seeded with Schwann cells (SCs), which creating a favorable micro-environment for axonal regeneration, to be an alternative to autografting by means of tissue engineering. Small intestinal submucosa (SIS) possesses special biological characteristics and is comprehensively researched for tissue repairing at varied tissues and organs. This study investigated the biocompatibility of SIS with SCs in vitro. Cultured rat SCs were seeded on SIS. Cell morphology was observed by light microscopy, scanning electron microscopy and transmission electron microscope. The viability of SCs was measured by MTT assay. Secretion of NGF-beta and BDNF was quantitatively assessed by ELISA, and NGF-beta mRNA and BDNF mRNA were semi-quantitatively assessed by RT-PCR. The results indicated that SCs could adhere, migrate and proliferate on the surface of SIS in good condition with productive function of secreting growth factors. SIS has a good biocompatibility with SCs and SIS pre-seeded with SCs has potential to be an alternate candidate of autografting for repairing long peripheral nerve defects.
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MESH Headings
- Animals
- Animals, Newborn
- Biocompatible Materials/therapeutic use
- Brain-Derived Neurotrophic Factor/genetics
- Brain-Derived Neurotrophic Factor/metabolism
- Cell Adhesion/physiology
- Cell Movement/physiology
- Cell Proliferation
- Cell Survival/physiology
- Cells, Cultured
- Graft Survival/physiology
- Intestinal Mucosa/physiology
- Intestinal Mucosa/ultrastructure
- Intestine, Small/physiology
- Intestine, Small/ultrastructure
- Microscopy, Electron, Scanning
- Microscopy, Electron, Transmission
- Nerve Growth Factor/genetics
- Nerve Growth Factor/metabolism
- Nerve Regeneration/physiology
- Peripheral Nerves/cytology
- Peripheral Nerves/physiology
- Peripheral Nerves/surgery
- Peripheral Nervous System Diseases/therapy
- RNA, Messenger/metabolism
- Rats
- Rats, Sprague-Dawley
- Schwann Cells/metabolism
- Schwann Cells/ultrastructure
- Sus scrofa
- Tissue Engineering/methods
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Affiliation(s)
- Yan Su
- Department of Orthopaedics, The Sixth Affiliated People's Hospital, Shanghai Jiaotong University, 600 Yishan Road, Shanghai 200233, China
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