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Palmosi T, Tolomeo AM, Cirillo C, Sandrin D, Sciro M, Negrisolo S, Todesco M, Caicci F, Santoro M, Dal Lago E, Marchesan M, Modesti M, Bagno A, Romanato F, Grumati P, Fabozzo A, Gerosa G. Small intestinal submucosa-derived extracellular matrix as a heterotopic scaffold for cardiovascular applications. Front Bioeng Biotechnol 2022; 10:1042434. [PMID: 36578513 PMCID: PMC9792098 DOI: 10.3389/fbioe.2022.1042434] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2022] [Accepted: 11/22/2022] [Indexed: 12/14/2022] Open
Abstract
Structural cardiac lesions are often surgically repaired using prosthetic patches, which can be biological or synthetic. In the current clinical scenario, biological patches derived from the decellularization of a xenogeneic scaffold are gaining more interest as they maintain the natural architecture of the extracellular matrix (ECM) after the removal of the native cells and remnants. Once implanted in the host, these patches can induce tissue regeneration and repair, encouraging angiogenesis, migration, proliferation, and host cell differentiation. Lastly, decellularized xenogeneic patches undergo cell repopulation, thus reducing host immuno-mediated response against the graft and preventing device failure. Porcine small intestinal submucosa (pSIS) showed such properties in alternative clinical scenarios. Specifically, the US FDA approved its use in humans for urogenital procedures such as hernia repair, cystoplasties, ureteral reconstructions, stress incontinence, Peyronie's disease, penile chordee, and even urethral reconstruction for hypospadias and strictures. In addition, it has also been successfully used for skeletal muscle tissue reconstruction in young patients. However, for cardiovascular applications, the results are controversial. In this study, we aimed to validate our decellularization protocol for SIS, which is based on the use of Tergitol 15 S 9, by comparing it to our previous and efficient method (Triton X 100), which is not more available in the market. For both treatments, we evaluated the preservation of the ECM ultrastructure, biomechanical features, biocompatibility, and final bioinductive capabilities. The overall analysis shows that the SIS tissue is macroscopically distinguishable into two regions, one smooth and one wrinkle, equivalent to the ultrastructure and biochemical and proteomic profile. Furthermore, Tergitol 15 S 9 treatment does not modify tissue biomechanics, resulting in comparable to the native one and confirming the superior preservation of the collagen fibers. In summary, the present study showed that the SIS decellularized with Tergitol 15 S 9 guarantees higher performances, compared to the Triton X 100 method, in all the explored fields and for both SIS regions: smooth and wrinkle.
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Affiliation(s)
- Tiziana Palmosi
- Laboratory of Cardiovascular Medicine, Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padova, Padua, Italy,L.i.f.e.L.a.b. Program, Consorzio per la Ricerca Sanitaria (CORIS), Veneto Region Padua, Italy
| | - Anna Maria Tolomeo
- Laboratory of Cardiovascular Medicine, Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padova, Padua, Italy,L.i.f.e.L.a.b. Program, Consorzio per la Ricerca Sanitaria (CORIS), Veneto Region Padua, Italy
| | - Carmine Cirillo
- Telethon Institute of Genetics and Medicine (TIGEM), Pozzuoli, Italy
| | - Debora Sandrin
- L.i.f.e.L.a.b. Program, Consorzio per la Ricerca Sanitaria (CORIS), Veneto Region Padua, Italy,Optics and Bioimaging Lab, Department of Physics and Astronomy, Fondazione Istituto di Ricerca Pediatrica Città della Speranza, University of Padova, Padua, Italy
| | | | - Susanna Negrisolo
- Laboratory of Immunopathology and Molecular Biology of the Kidney, Department of Women’s and Children’s Health, University of Padova, Padua, Italy
| | - Martina Todesco
- L.i.f.e.L.a.b. Program, Consorzio per la Ricerca Sanitaria (CORIS), Veneto Region Padua, Italy,Department of Industrial Engineering, University of Padova, Padua, Italy
| | | | - Michele Santoro
- Telethon Institute of Genetics and Medicine (TIGEM), Pozzuoli, Italy
| | - Eleonora Dal Lago
- Department of Industrial Engineering, University of Padova, Padua, Italy
| | | | - Michele Modesti
- Department of Industrial Engineering, University of Padova, Padua, Italy
| | - Andrea Bagno
- L.i.f.e.L.a.b. Program, Consorzio per la Ricerca Sanitaria (CORIS), Veneto Region Padua, Italy,Department of Industrial Engineering, University of Padova, Padua, Italy
| | - Filippo Romanato
- L.i.f.e.L.a.b. Program, Consorzio per la Ricerca Sanitaria (CORIS), Veneto Region Padua, Italy,Department of Physics and Astronomy “G. Galilei”, University of Padova, Padua, Italy
| | - Paolo Grumati
- Telethon Institute of Genetics and Medicine (TIGEM), Pozzuoli, Italy,Department of Clinical Medicine and Surgery, University of Napoli Federico II, Naples, Italy
| | - Assunta Fabozzo
- L.i.f.e.L.a.b. Program, Consorzio per la Ricerca Sanitaria (CORIS), Veneto Region Padua, Italy,Cardiac Surgery Unit, Hospital University of Padova, Padua, Italy,*Correspondence: Assunta Fabozzo,
| | - Gino Gerosa
- Laboratory of Cardiovascular Medicine, Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padova, Padua, Italy,L.i.f.e.L.a.b. Program, Consorzio per la Ricerca Sanitaria (CORIS), Veneto Region Padua, Italy,Cardiac Surgery Unit, Hospital University of Padova, Padua, Italy
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Surgical Treatment of Short Bowel Syndrome—The Past, the Present and the Future, a Descriptive Review of the Literature. CHILDREN 2022; 9:children9071024. [PMID: 35884008 PMCID: PMC9322125 DOI: 10.3390/children9071024] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/13/2022] [Revised: 06/26/2022] [Accepted: 07/07/2022] [Indexed: 12/27/2022]
Abstract
Short bowel syndrome (SBS) is a devastating disorder with both short- and long-term implications for patients. Unfortunately, the prevalence of SBS has doubled over the past 40 years. Broadly speaking, the etiology of SBS can be categorized as congenital or secondary, the latter typically due to extensive small bowel resection following diseases of the small intestine, e.g., necrotizing enterocolitis, Hirschsprung’s disease or intestinal atresia. As of yet, no cure exists, thus, conservative treatment, primarily parenteral nutrition (PN), is the first-line therapy. In some cases, weaning from PN is not possible and operative therapy is required. The invention of the longitudinal intestinal lengthening and tailoring (LILT or Bianchi) procedure in 1980 was a major step forward in patient care and spawned further techniques that continue to improve lives for patients with severe SBS (e.g., double barrel enteroplasty, serial transverse enteroplasty, etc.). With this review, we aim to provide an overview of the clinical implications of SBS, common conservative therapies and the development of operative techniques over the past six decades. We also provide a short outlook on the future of operative techniques, specifically with respect to regenerative medicine.
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Collier CA, Mendiondo C, Raghavan S. Tissue engineering of the gastrointestinal tract: the historic path to translation. J Biol Eng 2022; 16:9. [PMID: 35379299 PMCID: PMC8981633 DOI: 10.1186/s13036-022-00289-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2022] [Accepted: 03/08/2022] [Indexed: 11/15/2022] Open
Abstract
The gastrointestinal (GI) tract is imperative for multiple functions including digestion, nutrient absorption, and timely waste disposal. The central feature of the gut is peristalsis, intestinal motility, which facilitates all of its functions. Disruptions in GI motility lead to sub-optimal GI function, resulting in a lower quality of life in many functional GI disorders. Over the last two decades, tissue engineering research directed towards the intestine has progressed rapidly due to advances in cell and stem-cell biology, integrative physiology, bioengineering and biomaterials. Newer biomedical tools (including optical tools, machine learning, and nuanced regenerative engineering approaches) have expanded our understanding of the complex cellular communication within the GI tract that lead to its orchestrated physiological function. Bioengineering therefore can be utilized towards several translational aspects: (i) regenerative medicine to remedy/restore GI physiological function; (ii) in vitro model building to mimic the complex physiology for drug and pharmacology testing; (iii) tool development to continue to unravel multi-cell communication networks to integrate cell and organ-level physiology. Despite the significant strides made historically in GI tissue engineering, fundamental challenges remain including the quest for identifying autologous human cell sources, enhanced scaffolding biomaterials to increase biocompatibility while matching viscoelastic properties of the underlying tissue, and overall biomanufacturing. This review provides historic perspectives for how bioengineering has advanced over time, highlights newer advances in bioengineering strategies, and provides a realistic perspective on the path to translation.
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Affiliation(s)
- Claudia A Collier
- Department of Biomedical Engineering, Texas A&M University, Emerging Technologies Building, 3120 TAMU, College Station, TX, 77843, USA
| | - Christian Mendiondo
- Department of Biomedical Engineering, Texas A&M University, Emerging Technologies Building, 3120 TAMU, College Station, TX, 77843, USA
| | - Shreya Raghavan
- Department of Biomedical Engineering, Texas A&M University, Emerging Technologies Building, 3120 TAMU, College Station, TX, 77843, USA.
- Department of Nanomedicine, Houston Methodist Research Institute, Houston, TX, USA.
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Tuveri M, Paiella S, Boschi F, Luchini C, Perri G, Gasparini C, Aresta A, Scarpa A, Salvia R, Bassi C. Evidence of glucose absorption in a neoformed intestine. Updates Surg 2022; 74:1705-1713. [PMID: 35050488 PMCID: PMC9481485 DOI: 10.1007/s13304-022-01241-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2021] [Accepted: 01/08/2022] [Indexed: 12/04/2022]
Abstract
Recent advances in the field of tissue regeneration are offering promising therapeutic options for the treatment of short bowel syndrome. This study aimed to evaluate the glucose absorptive capacity of a neoformed intestine obtained from a biological scaffold in a rodent model and the steadiness of the engrafted segment area. Twenty-four male Sprague–Dawley rats were used for this study. Under anesthesia, a patch of biological material (2.2 × 1.5 cm) was engrafted in the anti-mesenteric border of the small bowels of 12 rats. Twelve rats were sham-operated. Animals were studied at 4, 8, and 10 months postengraftment. Functional and histological analyses were performed. The functional analysis was performed using an 18F-FDG analog as a probe and the results were acquired with an optical imager. The intensity of the fluorescent signal emitted by the neointestine was comparable with that emitted by the native intestine in all animals and was visible after injection in the preserved mesentery. The mean intestinal volume at time of engraftment and after 10 months was 4.08 cm3 (95% CI [3.58–4.58]) and 3.26 cm3 (CI 95% [3.23–3.29]), respectively, with a mean shrinkage of 17.3% (range 10.6–23.8%), without any evidence of stenosis. Morphological analysis revealed the progression of the biological material toward a neoformed intestine similar to the native intestine, especially at 8 and 10 months. In a rodent model, we demonstrated that a neointestine, obtained from a biological scaffold showed glucose absorption and a durable increase in diameter.
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Affiliation(s)
- Massimiliano Tuveri
- General and Pancreatic Surgery Unit, Pancreas Institute, University of Verona, P.le L.A. Scuro n° 10, 37134 Verona, Italy
| | - Salvatore Paiella
- General and Pancreatic Surgery Unit, Pancreas Institute, University of Verona, P.le L.A. Scuro n° 10, 37134 Verona, Italy
| | - Federico Boschi
- Department of Computer Science, University of Verona, Verona, Italy
| | - Claudio Luchini
- Section of Pathology, Department of Diagnostics and Public Health, Pancreas Institute, University of Verona, Verona, Italy
| | - Giampaolo Perri
- General and Pancreatic Surgery Unit, Pancreas Institute, University of Verona, P.le L.A. Scuro n° 10, 37134 Verona, Italy
| | - Clizia Gasparini
- Radiology Unit, Pancreas Institute, University of Verona, Verona, Italy
| | - Alex Aresta
- Section of Pathology, Department of Diagnostics and Public Health, Pancreas Institute, University of Verona, Verona, Italy
| | - Aldo Scarpa
- Section of Pathology, Department of Diagnostics and Public Health, Pancreas Institute, University of Verona, Verona, Italy
- ARC-Net Research Center, University of Verona, Verona, Italy
| | - Roberto Salvia
- General and Pancreatic Surgery Unit, Pancreas Institute, University of Verona, P.le L.A. Scuro n° 10, 37134 Verona, Italy
| | - Claudio Bassi
- General and Pancreatic Surgery Unit, Pancreas Institute, University of Verona, P.le L.A. Scuro n° 10, 37134 Verona, Italy
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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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Pompili S, Latella G, Gaudio E, Sferra R, Vetuschi A. The Charming World of the Extracellular Matrix: A Dynamic and Protective Network of the Intestinal Wall. Front Med (Lausanne) 2021; 8:610189. [PMID: 33937276 PMCID: PMC8085262 DOI: 10.3389/fmed.2021.610189] [Citation(s) in RCA: 66] [Impact Index Per Article: 16.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2020] [Accepted: 03/22/2021] [Indexed: 02/06/2023] Open
Abstract
The intestinal extracellular matrix (ECM) represents a complex network of proteins that not only forms a support structure for resident cells but also interacts closely with them by modulating their phenotypes and functions. More than 300 molecules have been identified, each of them with unique biochemical properties and exclusive biological functions. ECM components not only provide a scaffold for the tissue but also afford tensile strength and limit overstretch of the organ. The ECM holds water, ensures suitable hydration of the tissue, and participates in a selective barrier to the external environment. ECM-to-cells interaction is crucial for morphogenesis and cell differentiation, proliferation, and apoptosis. The ECM is a dynamic and multifunctional structure. The ECM is constantly renewed and remodeled by coordinated action among ECM-producing cells, degrading enzymes, and their specific inhibitors. During this process, several growth factors are released in the ECM, and they, in turn, modulate the deposition of new ECM. In this review, we describe the main components and functions of intestinal ECM and we discuss their role in maintaining the structure and function of the intestinal barrier. Achieving complete knowledge of the ECM world is an important goal to understand the mechanisms leading to the onset and the progression of several intestinal diseases related to alterations in ECM remodeling.
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Affiliation(s)
- Simona Pompili
- Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy
| | - Giovanni Latella
- Department of Life, Health and Environmental Sciences, Gastroenterology Unit, University of L'Aquila, L'Aquila, Italy
| | - Eugenio Gaudio
- Department of Anatomical, Histological, Forensic Medicine, and Orthopedic Sciences, Sapienza University of Rome, Rome, Italy
| | - Roberta Sferra
- Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy
| | - Antonella Vetuschi
- Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy
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Human Bronchial Epithelial Cell Growth on Homologous Versus Heterologous Tissue Extracellular Matrix. J Surg Res 2021; 263:215-223. [PMID: 33691244 DOI: 10.1016/j.jss.2021.01.040] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2020] [Revised: 01/19/2021] [Accepted: 01/26/2021] [Indexed: 12/12/2022]
Abstract
BACKGROUND Extracellular matrix (ECM) bioscaffolds produced by decellularization of source tissue have been effectively used for numerous clinical applications. However, decellularized tracheal constructs have been unsuccessful due to the immediate requirement of a functional airway epithelium on surgical implantation. ECM can be solubilized to form hydrogels that have been shown to support growth of many different cell types. The purpose of the present study is to compare the ability of airway epithelial cells to attach, form a confluent monolayer, and differentiate on homologous (trachea) and heterologous (urinary bladder) ECM substrates for potential application in full tracheal replacement. MATERIALS AND METHODS Porcine tracheas and urinary bladders were decellularized. Human bronchial epithelial cells (HBECs) were cultured under differentiation conditions on acellular tracheal ECM and urinary bladder matrix (UBM) bioscaffolds and hydrogels and were assessed by histology and immunolabeling for markers of ciliation, goblet cell formation, and basement membrane deposition. RESULTS Both trachea and urinary bladder tissues were successfully decellularized. HBEC formed a confluent layer on both trachea and UBM scaffolds and on hydrogels created from these bioscaffolds. Cells grown on tracheal and UBM hydrogels, but not on bioscaffolds, showed positive-acetylated tubulin staining and the presence of mucus-producing goblet cells. Collagen IV immunolabeling showed basement membrane deposition by these cells on the surface of the hydrogels. CONCLUSIONS ECM hydrogels supported growth and differentiation of HBEC better than decellularized ECM bioscaffolds and show potential utility as substrates for promotion of a mature respiratory epithelium for regenerative medicine applications in the trachea.
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Effect of PDGF-B Gene-Activated Acellular Matrix and Mesenchymal Stem Cell Transplantation on Full Thickness Skin Burn Wound in Rat Model. Tissue Eng Regen Med 2020; 18:235-251. [PMID: 33145744 DOI: 10.1007/s13770-020-00302-3] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2020] [Revised: 08/10/2020] [Accepted: 09/16/2020] [Indexed: 10/23/2022] Open
Abstract
BACKGROUND Full thickness burn wounds are lack of angiogenesis, cell migration, epithelialisation and finally scar tissue formation. Tissue engineered composite graft can provide sustained release of growth factor and promote the wound healing by cell migration, early angiogenesis and proliferation of extracellular matrix and wound remodeling. The objective of this study was to evaluate the gene embedded (pDNA-platelet-derived growth factor, PDGF-B) porcine acellular urinary bladder matrix with transfected mesenchymal stem cells (rBMSC) on healing of full thickness burn wound in rat model. METHODS Full thickness burn wound of 2 × 2 cm size was created in dorsum of rat model under general anesthesia. Burn wounds were treated with silver sulfadiazine; porcine acellular urinary bladder matrix (PAUBM); PAUBM transfected with pDNA-PDGF-B; PAUBM seeded with rBMSC; PAUBM seeded with rBMSC transfected with pDNA-PDGF-B in groups A, B, C, D and E respectively. The wound healing was assessed based on clinical, macroscopically, immunologically, histopathological and RT-qPCR parameters. RESULTS Wound was significantly healed in group E and group D with early extracellular matrix deposition, enhanced granulation tissue formation and early angiogenesis compared to all other groups. The immunologic response against porcine acellular matrix showed that PDGF-B gene activated matrix along with stem cell group showed less antibody titer against acellular matrix than other groups in all intervals. PDGF gene activated matrix releasing the PDGF-B and promote the healing of full thickness burn wound with neovascularization and neo tissue formation. PDGF gene also enhances secretion of other growth factors results in PDGF mediated regenerative activities. This was confirmed in RT-qPCR at various time intervals. CONCLUSION Gene activated matrix encoded for PDGF-B protein transfected stem cells have been clinically proven for early acceleration of angiogenesis and tissue regeneration in burn wounds in rat models. Evaluation of PDGF-B gene-activated acellular matrix and mesenchymal stem cell in full thickness skin burn wound in rat.
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Xing H, Lee H, Luo L, Kyriakides TR. Extracellular matrix-derived biomaterials in engineering cell function. Biotechnol Adv 2020; 42:107421. [PMID: 31381963 PMCID: PMC6995418 DOI: 10.1016/j.biotechadv.2019.107421] [Citation(s) in RCA: 162] [Impact Index Per Article: 32.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2018] [Revised: 07/12/2019] [Accepted: 07/31/2019] [Indexed: 12/11/2022]
Abstract
Extracellular matrix (ECM) derived components are emerging sources for the engineering of biomaterials that are capable of inducing desirable cell-specific responses. This review explores the use of biomaterials derived from naturally occurring ECM proteins and their derivatives in approaches that aim to regulate cell function. Biomaterials addressed are grouped into six categories: purified single ECM proteins, combinations of purified ECM proteins, cell-derived ECM, tissue-derived ECM, diseased and modified ECM, and ECM-polymer coupled biomaterials. Purified ECM proteins serve as a material coating for enhanced cell adhesion and biocompatibility. Cell-derived and tissue-derived ECM, generated by cell isolation and decellularization technologies, can capture the native state of the ECM environment and guide cell migration and alignment patterns as well as stem cell differentiation. We focus primarily on recent advances in the fields of soft tissue, cardiac, and dermal repair, and explore the utilization of ECM proteins as biomaterials to engineer cell responses.
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Affiliation(s)
- Hao Xing
- Department of Biomedical Engineering, Yale University, United States of America
| | - Hudson Lee
- Department of Molecular Biophysics and Biochemistry, Yale University, United States of America
| | - Lijing Luo
- Department of Pathology, Yale University, United States of America
| | - Themis R Kyriakides
- Department of Biomedical Engineering, Yale University, United States of America; Department of Pathology, Yale University, United States of America.
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10
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Mendibil U, Ruiz-Hernandez R, Retegi-Carrion S, Garcia-Urquia N, Olalde-Graells B, Abarrategi A. Tissue-Specific Decellularization Methods: Rationale and Strategies to Achieve Regenerative Compounds. Int J Mol Sci 2020; 21:E5447. [PMID: 32751654 PMCID: PMC7432490 DOI: 10.3390/ijms21155447] [Citation(s) in RCA: 152] [Impact Index Per Article: 30.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2020] [Revised: 07/25/2020] [Accepted: 07/28/2020] [Indexed: 02/07/2023] Open
Abstract
The extracellular matrix (ECM) is a complex network with multiple functions, including specific functions during tissue regeneration. Precisely, the properties of the ECM have been thoroughly used in tissue engineering and regenerative medicine research, aiming to restore the function of damaged or dysfunctional tissues. Tissue decellularization is gaining momentum as a technique to obtain potentially implantable decellularized extracellular matrix (dECM) with well-preserved key components. Interestingly, the tissue-specific dECM is becoming a feasible option to carry out regenerative medicine research, with multiple advantages compared to other approaches. This review provides an overview of the most common methods used to obtain the dECM and summarizes the strategies adopted to decellularize specific tissues, aiming to provide a helpful guide for future research development.
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Affiliation(s)
- Unai Mendibil
- Center for Cooperative Research in Biomaterials (CIC biomaGUNE), Basque Research and Technology Alliance (BRTA), 20014 Donostia-San Sebastian, Spain; (U.M.); (R.R.-H.); (S.R.-C.)
- TECNALIA, Basque Research and Technology Alliance (BRTA), 20009 Donostia-San Sebastian, Spain; (N.G.-U.); (B.O.-G.)
| | - Raquel Ruiz-Hernandez
- Center for Cooperative Research in Biomaterials (CIC biomaGUNE), Basque Research and Technology Alliance (BRTA), 20014 Donostia-San Sebastian, Spain; (U.M.); (R.R.-H.); (S.R.-C.)
| | - Sugoi Retegi-Carrion
- Center for Cooperative Research in Biomaterials (CIC biomaGUNE), Basque Research and Technology Alliance (BRTA), 20014 Donostia-San Sebastian, Spain; (U.M.); (R.R.-H.); (S.R.-C.)
| | - Nerea Garcia-Urquia
- TECNALIA, Basque Research and Technology Alliance (BRTA), 20009 Donostia-San Sebastian, Spain; (N.G.-U.); (B.O.-G.)
| | - Beatriz Olalde-Graells
- TECNALIA, Basque Research and Technology Alliance (BRTA), 20009 Donostia-San Sebastian, Spain; (N.G.-U.); (B.O.-G.)
| | - Ander Abarrategi
- Center for Cooperative Research in Biomaterials (CIC biomaGUNE), Basque Research and Technology Alliance (BRTA), 20014 Donostia-San Sebastian, Spain; (U.M.); (R.R.-H.); (S.R.-C.)
- Ikerbasque, Basque Foundation for Science, 48013 Bilbao, Spain
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11
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Whole Organ Engineering: Approaches, Challenges, and Future Directions. APPLIED SCIENCES-BASEL 2020. [DOI: 10.3390/app10124277] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
End-stage organ failure remains a leading cause of morbidity and mortality across the globe. The only curative treatment option currently available for patients diagnosed with end-stage organ failure is organ transplantation. However, due to a critical shortage of organs, only a fraction of these patients are able to receive a viable organ transplantation. Those patients fortunate enough to receive a transplant must then be subjected to a lifelong regimen of immunosuppressant drugs. The concept of whole organ engineering offers a promising alternative to organ transplantation that overcomes these limitations. Organ engineering is a discipline that merges developmental biology, anatomy, physiology, and cellular interactions with enabling technologies such as advanced biomaterials and biofabrication to create bioartificial organs that recapitulate native organs in vivo. There have been numerous developments in bioengineering of whole organs over the past two decades. Key technological advancements include (1) methods of whole organ decellularization and recellularization, (2) three-dimensional bioprinting, (3) advanced stem cell technologies, and (4) the ability to genetically modify tissues and cells. These advancements give hope that organ engineering will become a commercial reality in the next decade. In this review article, we describe the foundational principles of whole organ engineering, discuss key technological advances, and provide an overview of current limitations and future directions.
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12
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Qi D, Shi W, Black AR, Kuss MA, Pang X, He Y, Liu B, Duan B. Repair and regeneration of small intestine: A review of current engineering approaches. Biomaterials 2020; 240:119832. [PMID: 32113114 DOI: 10.1016/j.biomaterials.2020.119832] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2018] [Revised: 01/21/2020] [Accepted: 01/25/2020] [Indexed: 02/06/2023]
Abstract
The small intestine (SI) is difficult to regenerate or reconstruct due to its complex structure and functions. Recent developments in stem cell research, advanced engineering technologies, and regenerative medicine strategies bring new hope of solving clinical problems of the SI. This review will first summarize the structure, function, development, cell types, and matrix components of the SI. Then, the major cell sources for SI regeneration are introduced, and state-of-the-art biofabrication technologies for generating engineered SI tissues or models are overviewed. Furthermore, in vitro models and in vivo transplantation, based on intestinal organoids and tissue engineering, are highlighted. Finally, current challenges and future perspectives are discussed to help direct future applications for SI repair and regeneration.
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Affiliation(s)
- Dianjun Qi
- Department of General Practice, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning, China; Mary & Dick Holland Regenerative Medicine Program, University of Nebraska Medical Center, Omaha, NE, USA; Division of Cardiology, Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE, USA
| | - Wen Shi
- Mary & Dick Holland Regenerative Medicine Program, University of Nebraska Medical Center, Omaha, NE, USA; Division of Cardiology, Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE, USA
| | - Adrian R Black
- Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE, USA
| | - Mitchell A Kuss
- Mary & Dick Holland Regenerative Medicine Program, University of Nebraska Medical Center, Omaha, NE, USA; Division of Cardiology, Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE, USA
| | - Xining Pang
- Department of General Practice, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning, China; Department of Academician Expert Workstation and Liaoning Province Human Amniotic Membrane Dressings Stem Cells and Regenerative Medicine Engineering Research Center, Shenyang Amnion Biological Engineering Technology Research and Development Center Co., Ltd, Shenyang, Liaoning, China
| | - Yini He
- Department of General Practice, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning, China
| | - Bing Liu
- Department of Anorectal Surgery, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning, China
| | - Bin Duan
- Mary & Dick Holland Regenerative Medicine Program, University of Nebraska Medical Center, Omaha, NE, USA; Division of Cardiology, Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE, USA; Department of Surgery, University of Nebraska Medical Center, Omaha, NE, USA; Department of Mechanical and Materials Engineering, University of Nebraska-Lincoln, Lincoln, NE, USA.
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13
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Wang RM, Duran P, Christman KL. Processed Tissues. Biomater Sci 2020. [DOI: 10.1016/b978-0-12-816137-1.00027-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2022]
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14
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Liao J, Xu B, Zhang R, Fan Y, Xie H, Li X. Applications of decellularized materials in tissue engineering: advantages, drawbacks and current improvements, and future perspectives. J Mater Chem B 2020; 8:10023-10049. [PMID: 33053004 DOI: 10.1039/d0tb01534b] [Citation(s) in RCA: 64] [Impact Index Per Article: 12.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
Decellularized materials (DMs) are attracting more and more attention in tissue engineering because of their many unique advantages, and they could be further improved in some aspects through various means.
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Affiliation(s)
- Jie Liao
- Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education
- School of Biological Science and Medical Engineering
- Beijing Advanced Innovation Center for Biomedical Engineering
- Beihang University
- Beijing 100083
| | - Bo Xu
- Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education
- School of Biological Science and Medical Engineering
- Beijing Advanced Innovation Center for Biomedical Engineering
- Beihang University
- Beijing 100083
| | - Ruihong Zhang
- Department of Research and Teaching
- the Fourth Central Hospital of Baoding City
- Baoding 072350
- China
| | - Yubo Fan
- Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education
- School of Biological Science and Medical Engineering
- Beijing Advanced Innovation Center for Biomedical Engineering
- Beihang University
- Beijing 100083
| | - Huiqi Xie
- Laboratory of Stem Cell and Tissue Engineering
- State Key Laboratory of Biotherapy and Cancer Center
- West China Hospital
- Sichuan University and Collaborative Innovation Center of Biotherapy
- Chengdu 610041
| | - Xiaoming Li
- Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education
- School of Biological Science and Medical Engineering
- Beijing Advanced Innovation Center for Biomedical Engineering
- Beihang University
- Beijing 100083
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15
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Murawski A, Diaz R, Inglesby S, Delabar K, Quirino RL. Synthesis of Bio-based Polymer Composites: Fabrication, Fillers, Properties, and Challenges. LECTURE NOTES IN BIOENGINEERING 2019. [DOI: 10.1007/978-3-030-04741-2_2] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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16
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Ji Y, Zhou J, Sun T, Tang K, Xiong Z, Ren Z, Yao S, Chen K, Yang F, Zhu F, Guo X. Diverse preparation methods for small intestinal submucosa (SIS): Decellularization, components, and structure. J Biomed Mater Res A 2018; 107:689-697. [PMID: 30468308 DOI: 10.1002/jbm.a.36582] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2018] [Revised: 10/16/2018] [Accepted: 11/15/2018] [Indexed: 11/10/2022]
Abstract
The native extracellular matrix (ECM) biomaterial derived from small intestinal submucosa (SIS) is widely applied in tissue engineering for tissue repair and regeneration. SIS ECM is obtained through physical and chemical methods to remove the intrinsic cells, which would otherwise cause adverse immune reactions when the SIS ECM is implanted into the host body. Several research teams have reported diverse SIS decellularization methods. However, there was no consensus on the criteria to be used for the decellularization methods for SIS and further research on the mechanism action of SIS is needed for comprehensive detection of the biological composition. In this present study, we used three reported methods to prepare SIS and compared their effects on decellularization and the remaining biological components, microstructure and cytocompatibility. SIS prepared by the three kinds of decellularization methods all achieved the recommended criteria, had good biocompatibility and retained most active components. Nevertheless, regardless of which decellularization method was used, the microstructure and bioactive components of the prepared SIS were damaged in varying degrees. We recommend that researchers need to select a decellularization method that would be appropriate to use according to their research purposes. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 689-697, 2019.
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Affiliation(s)
- Yanhui Ji
- Department of Orthopaedics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.,Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Jinge Zhou
- Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Tingfang Sun
- Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Kai Tang
- Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Zekang Xiong
- Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Zhengwei Ren
- Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Sheng Yao
- Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Kaifang Chen
- Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Fan Yang
- Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Fengzhao Zhu
- Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
| | - Xiaodong Guo
- Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
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17
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Iop L, Palmosi T, Dal Sasso E, Gerosa G. Bioengineered tissue solutions for repair, correction and reconstruction in cardiovascular surgery. J Thorac Dis 2018; 10:S2390-S2411. [PMID: 30123578 PMCID: PMC6081367 DOI: 10.21037/jtd.2018.04.27] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2018] [Accepted: 04/02/2018] [Indexed: 01/06/2023]
Abstract
The treatment of cardiac alterations is still nowadays a dramatic issue in the cardiosurgical practice. Synthetic materials applied in this surgery have failed in their long-term therapeutic efficacy due to low biocompatibility and compliance, especially when used in contractile sites. In order to overcome these treatment pitfalls, novel solutions have been developed based on biological tissues. Patches in pericardium, small intestinal submucosa, as well as engineered tissues of myocardium, heart valves and blood vessels have undergone a large preclinical investigation in regenerative medicine studies. Clinical translation has been started or reached by several of these new bioengineered treatment alternatives. This review will describe the preclinical and clinical experiences realized so far with the application of biological tissues in cardiovascular surgery. It will depict the progressive steps realized in the evolution of this research, as well as it will point out the challenges yet to face in order to generate the ideal biomaterial for cardiovascular repair, corrective and reconstructive surgery.
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Affiliation(s)
- Laura Iop
- Cardiovascular Regenerative Medicine, Department of Cardiac, Thoracic and Vascular Surgery, University of Padua and Venetian Institute of Molecular Medicine (VIMM), Padua, Italy
| | - Tiziana Palmosi
- Cardiovascular Regenerative Medicine, Department of Cardiac, Thoracic and Vascular Surgery, University of Padua and Venetian Institute of Molecular Medicine (VIMM), Padua, Italy
| | - Eleonora Dal Sasso
- Cardiovascular Regenerative Medicine, Department of Cardiac, Thoracic and Vascular Surgery, University of Padua and Venetian Institute of Molecular Medicine (VIMM), Padua, Italy
| | - Gino Gerosa
- Cardiovascular Regenerative Medicine, Department of Cardiac, Thoracic and Vascular Surgery, University of Padua and Venetian Institute of Molecular Medicine (VIMM), Padua, Italy
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18
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Górski A, Jończyk-Matysiak E, Międzybrodzki R, Weber-Dąbrowska B, Łusiak-Szelachowska M, Bagińska N, Borysowski J, Łobocka MB, Węgrzyn A, Węgrzyn G. Phage Therapy: Beyond Antibacterial Action. Front Med (Lausanne) 2018; 5:146. [PMID: 29876350 PMCID: PMC5974148 DOI: 10.3389/fmed.2018.00146] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2018] [Accepted: 04/30/2018] [Indexed: 12/12/2022] Open
Abstract
Until recently, phages were considered as mere “bacteria eaters” with potential for use in combating antimicrobial resistance. The real value of phage therapy assessed according to the standards of evidence-based medicine awaits confirmation by clinical trials. However, the progress in research on phage biology has shed more light on the significance of phages. Accumulating data indicate that phages may also interact with eukaryotic cells. How such interactions could be translated into advances in medicine (especially novel means of therapy) is discussed herein.
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Affiliation(s)
- Andrzej Górski
- Bacteriophage Laboratory, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wrocław, Poland.,Phage Therapy Unit, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wrocław, Poland.,Department of Clinical Immunology, Transplantation Institute, Medical University of Warsaw, Warsaw, Poland
| | - Ewa Jończyk-Matysiak
- Bacteriophage Laboratory, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wrocław, Poland
| | - Ryszard Międzybrodzki
- Bacteriophage Laboratory, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wrocław, Poland.,Phage Therapy Unit, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wrocław, Poland.,Department of Clinical Immunology, Transplantation Institute, Medical University of Warsaw, Warsaw, Poland
| | - Beata Weber-Dąbrowska
- Bacteriophage Laboratory, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wrocław, Poland.,Phage Therapy Unit, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wrocław, Poland
| | - Marzanna Łusiak-Szelachowska
- Bacteriophage Laboratory, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wrocław, Poland
| | - Natalia Bagińska
- Bacteriophage Laboratory, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wrocław, Poland
| | - Jan Borysowski
- Department of Clinical Immunology, Transplantation Institute, Medical University of Warsaw, Warsaw, Poland
| | - Małgorzata B Łobocka
- Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Warsaw, Poland.,Autonomous Department of Microbial Biology, Faculty of Agriculture and Biology, Warsaw University of Life Sciences, Warsaw, Poland
| | - Alicja Węgrzyn
- Laboratory of Molecular Biology, Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Gdańsk, Poland
| | - Grzegorz Węgrzyn
- Department of Molecular Biology, University of Gdańsk, Gdańsk, Poland
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19
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Colorectal wall regeneration resulting from the association of chitosan hydrogel and stromal vascular fraction from adipose tissue. J Biomed Mater Res A 2017; 106:460-467. [DOI: 10.1002/jbm.a.36243] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2016] [Revised: 06/28/2017] [Accepted: 09/19/2017] [Indexed: 12/13/2022]
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20
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Trecartin A, Grikscheit T. Tissue Engineering Functional Gastrointestinal Regions: The Importance of Stem and Progenitor Cells. Cold Spring Harb Perspect Med 2017; 7:cshperspect.a025700. [PMID: 28320829 DOI: 10.1101/cshperspect.a025700] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
The intestine shows extraordinary regenerative potential that might be harnessed to alleviate numerous morbid and lethal human diseases. The intestinal stem cells regenerate the epithelium every 5 days throughout an individual's lifetime. Understanding stem-cell signaling affords power to influence the niche environment for growing intestine. The manifold approaches to tissue engineering may be organized by variations of three basic components required for the transplantation and growth of stem/progenitor cells: (1) cell delivery materials or scaffolds; (2) donor cells including adult stem cells, induced pluripotent stem cells, and in vitro expansion of isolated or cocultured epithelial, smooth muscle, myofibroblasts, or nerve cells; and (3) environmental modulators or biopharmaceuticals. Tissue engineering has been applied to the regeneration of every major region of the gastrointestinal tract from esophagus to colon, with scientists around the world aiming to carry these techniques into human therapy.
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Affiliation(s)
- Andrew Trecartin
- Department of Pediatric Surgery, Children's Hospital Los Angeles, Los Angeles, California 90027
| | - Tracy Grikscheit
- Department of Pediatric Surgery, Children's Hospital Los Angeles, Los Angeles, California 90027
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21
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Hussey GS, Cramer MC, Badylak SF. Extracellular Matrix Bioscaffolds for Building Gastrointestinal Tissue. Cell Mol Gastroenterol Hepatol 2017; 5:1-13. [PMID: 29276748 PMCID: PMC5736871 DOI: 10.1016/j.jcmgh.2017.09.004] [Citation(s) in RCA: 45] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/24/2017] [Accepted: 09/08/2017] [Indexed: 12/14/2022]
Abstract
Regenerative medicine is a rapidly advancing field that uses principles of tissue engineering, developmental biology, stem cell biology, immunology, and bioengineering to reconstruct diseased or damaged tissues. Biologic scaffolds composed of extracellular matrix have shown great promise as an inductive substrate to facilitate the constructive remodeling of gastrointestinal (GI) tissue damaged by neoplasia, inflammatory bowel disease, and congenital or acquired defects. The present review summarizes the preparation and use of extracellular matrix scaffolds for bioengineering of the GI tract, identifies significant advances made in regenerative medicine for the reconstruction of functional GI tissue, and describes an emerging therapeutic approach.
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Affiliation(s)
- George S. Hussey
- McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania
- Department of Surgery, School of Medicine, University of Pittsburgh Medical Center Presbyterian Hospital, University of Pittsburgh, Pittsburgh, Pennsylvania
| | - Madeline C. Cramer
- McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania
- Department of Bioengineering, 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, School of Medicine, University of Pittsburgh Medical Center Presbyterian Hospital, University of Pittsburgh, Pittsburgh, Pennsylvania
- Correspondence Address correspondence to: Stephen F. Badylak, DVM, PhD, MD, McGowan Institute for Regenerative Medicine, University of Pittsburgh, 450 Technology Drive, Suite 300, Pittsburgh, Pennsylvania 15219-3110. fax: (412) 624-5256.McGowan Institute for Regenerative MedicineUniversity of Pittsburgh450 Technology Drive, Suite 300PittsburghPennsylvania15219-3110
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22
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The extracellular matrix of the gastrointestinal tract: a regenerative medicine platform. Nat Rev Gastroenterol Hepatol 2017; 14:540-552. [PMID: 28698662 DOI: 10.1038/nrgastro.2017.76] [Citation(s) in RCA: 53] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
The synthesis and secretion of components that constitute the extracellular matrix (ECM) by resident cell types occur at the earliest stages of embryonic development, and continue throughout life in both healthy and diseased physiological states. The ECM consists of a complex mixture of insoluble and soluble functional components that are arranged in a tissue-specific 3D ultrastructure, and it regulates numerous biological processes, including angiogenesis, innervation and stem cell differentiation. Owing to its composition and influence on embryonic development, as well as cellular and organ homeostasis, the ECM is an ideal therapeutic substrate for the repair of damaged or diseased tissues. Biologic scaffold materials that are composed of ECM have been used in various surgical and tissue-engineering applications. The gastrointestinal (GI) tract presents distinct challenges, such as diverse pH conditions and the requirement for motility and nutrient absorption. Despite these challenges, the use of homologous and heterologous ECM bioscaffolds for the focal or segmental reconstruction and regeneration of GI tissue has shown promise in early preclinical and clinical studies. This Review discusses the importance of tissue-specific ECM bioscaffolds and highlights the major advances that have been made in regenerative medicine strategies for the reconstruction of functional GI tissues.
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23
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Kremer A, Ribitsch I, Reboredo J, Dürr J, Egerbacher M, Jenner F, Walles H. Three-Dimensional Coculture of Meniscal Cells and Mesenchymal Stem Cells in Collagen Type I Hydrogel on a Small Intestinal Matrix—A Pilot Study Toward Equine Meniscus Tissue Engineering. Tissue Eng Part A 2017; 23:390-402. [DOI: 10.1089/ten.tea.2016.0317] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/01/2023] Open
Affiliation(s)
- Antje Kremer
- Department of Tissue Engineering and Regenerative Medicine (TERM), University Hospital Wuerzburg, Wuerzburg, Germany
- Translational Center Wuerzburg ‘Regenerative therapies,’ Wuerzburg Branch of the Fraunhofer IGB, Wuerzburg, Germany
| | - Iris Ribitsch
- Vienna Equine Tissue Engineering and Regenerative Medicine, Equine Clinic, University of Veterinary Medicine Vienna, Vienna, Austria
- Department of Companion Animals and Horses, University of Veterinary Medicine Vienna, Vienna, Austria
| | - Jenny Reboredo
- Department of Tissue Engineering and Regenerative Medicine (TERM), University Hospital Wuerzburg, Wuerzburg, Germany
- Translational Center Wuerzburg ‘Regenerative therapies,’ Wuerzburg Branch of the Fraunhofer IGB, Wuerzburg, Germany
| | - Julia Dürr
- Department of Pathobiology, Institute of Histology & Embryology, University of Veterinary Medicine Vienna, Vienna, Austria
| | - Monika Egerbacher
- Department of Pathobiology, Institute of Histology & Embryology, University of Veterinary Medicine Vienna, Vienna, Austria
| | - Florien Jenner
- Vienna Equine Tissue Engineering and Regenerative Medicine, Equine Clinic, University of Veterinary Medicine Vienna, Vienna, Austria
- Department of Companion Animals and Horses, University of Veterinary Medicine Vienna, Vienna, Austria
| | - Heike Walles
- Department of Tissue Engineering and Regenerative Medicine (TERM), University Hospital Wuerzburg, Wuerzburg, Germany
- Translational Center Wuerzburg ‘Regenerative therapies,’ Wuerzburg Branch of the Fraunhofer IGB, Wuerzburg, Germany
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24
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Keane TJ, Dziki J, Sobieski E, Smoulder A, Castleton A, Turner N, White LJ, Badylak SF. Restoring Mucosal Barrier Function and Modifying Macrophage Phenotype with an Extracellular Matrix Hydrogel: Potential Therapy for Ulcerative Colitis. J Crohns Colitis 2017; 11:360-368. [PMID: 27543807 DOI: 10.1093/ecco-jcc/jjw149] [Citation(s) in RCA: 37] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/06/2016] [Accepted: 07/13/2016] [Indexed: 01/21/2023]
Abstract
BACKGROUND AND AIMS Despite advances in therapeutic options, more than half of all patients with ulcerative colitis [UC] do not achieve long-term remission, many require colectomy, and the disease still has a marked negative impact on quality of life. Extracellular matrix [ECM] bioscaffolds facilitate the functional repair of many soft tissues by mechanisms that include mitigation of pro-inflammatory macrophage phenotype and mobilization of endogenous stem/progenitor cells. The aim of the present study was to determine if an ECM hydrogel therapy could influence outcomes in an inducible rodent model of UC. METHODS The dextran sodium sulphate [DSS]-colitis model was used in male Sprague Dawley rats. Animals were treated via enema with an ECM hydrogel and the severity of colitis was determined by clinical and histological criteria. Lamina propria cells were isolated and the production of inflammatory mediators was quantified. Mucosal permeability was assessed in vivo by administering TRITC-dextran and in vitro using transepithelial electrical resistance [TEER]. RESULTS ECM hydrogel therapy accelerated healing and improved outcome. The hydrogel was adhesive to colonic tissue, which allowed for targeted delivery of the therapy, and resulted in a reduction in clinical and histological signs of disease. ECM hydrogel facilitated functional improvement of colonic epithelial barrier function and the resolution of the pro-inflammatory state of tissue macrophages. CONCLUSIONS The present study shows that a non-surgical and non-pharmacological ECM-based therapy can abate DSS-colitis not by immunosuppression but by promoting phenotypic change in local macrophage phenotype and rapid replacement of the colonic mucosal barrier.
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Affiliation(s)
- Timothy J Keane
- McGowan Institute for Regenerative Medicine, Pittsburgh, PA, USA
- Department of Bioengineering, University of Pittsburgh, Pittsburgh, USA
| | - Jenna Dziki
- McGowan Institute for Regenerative Medicine, Pittsburgh, PA, USA
- Department of Bioengineering, University of Pittsburgh, Pittsburgh, USA
| | - Eric Sobieski
- McGowan Institute for Regenerative Medicine, Pittsburgh, PA, USA
- Department of Bioengineering, University of Pittsburgh, Pittsburgh, USA
| | - Adam Smoulder
- McGowan Institute for Regenerative Medicine, Pittsburgh, PA, USA
- Department of Bioengineering, University of Pittsburgh, Pittsburgh, USA
| | - Arthur Castleton
- McGowan Institute for Regenerative Medicine, Pittsburgh, PA, USA
| | - Neill Turner
- McGowan Institute for Regenerative Medicine, Pittsburgh, PA, USA
- Department of Surgery, University of Pittsburgh, Pittsburgh, PA, USA
| | - Lisa J White
- McGowan Institute for Regenerative Medicine, Pittsburgh, PA, USA
- School of Pharmacy, University of Nottingham, Nottingham, UK
| | - Stephen F Badylak
- McGowan Institute for Regenerative Medicine, Pittsburgh, PA, USA
- Department of Bioengineering, University of Pittsburgh, Pittsburgh, USA
- Department of Surgery, University of Pittsburgh, Pittsburgh, PA, USA
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25
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Rosen M, Roselli EE, Faber C, Ratliff NB, Ponsky JL, Smedira NG. Small Intestinal Submucosa Intracardiac Patch: An Experimental Study. Surg Innov 2016; 12:227-31. [PMID: 16224643 DOI: 10.1177/155335060501200307] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
In this experimental study, small intestinal submucosa was implanted as an atrial prosthesis in calves. Echocardiography and histology showed this to be an impermeable prosthesis that develops a neointimal nonthrombogenic surface making it safe for repair of defects in a low-pressure system. Further study with small intestinal submucosa in an intracardiac position is warranted.
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Affiliation(s)
- Michael Rosen
- Cleveland Clinic Foundation Department of General Surgery, Cleveland, OH 44195, USA
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26
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27
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Shirafkan A, Montalbano M, McGuire J, Rastellini C, Cicalese L. New approaches to increase intestinal length: Methods used for intestinal regeneration and bioengineering. World J Transplant 2016; 6:1-9. [PMID: 27011901 PMCID: PMC4801784 DOI: 10.5500/wjt.v6.i1.1] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/01/2015] [Revised: 12/01/2015] [Accepted: 01/11/2016] [Indexed: 02/05/2023] Open
Abstract
Inadequate absorptive surface area poses a great challenge to the patients suffering a variety of intestinal diseases causing short bowel syndrome. To date, these patients are managed with total parenteral nutrition or intestinal transplantation. However, these carry significant morbidity and mortality. Currently, by emergence of tissue engineering, anticipations to utilize an alternative method to increase the intestinal absorptive surface area are increasing. In this paper, we will review the improvements made over time in attempting elongating the intestine with surgical techniques as well as using intestinal bioengineering. Performing sequential intestinal lengthening was the preliminary method applied in humans. However, these methods did not reach widespread use and has limited outcome. Subsequent experimental methods were developed utilizing scaffolds to regenerate intestinal tissue and organoids unit from the intestinal epithelium. Stem cells also have been studied and applied in all types of tissue engineering. Biomaterials were utilized as a structural support for naive cells to produce bio-engineered tissue that can achieve a near-normal anatomical structure. A promising novel approach is the elongation of the intestine with an acellular biologic scaffold to generate a neo-formed intestinal tissue that showed, for the first time, evidence of absorption in vivo. In the large intestine, studies are more focused on regeneration and engineering of sphincters and will be briefly reviewed. From the review of the existing literature, it can be concluded that significant progress has been achieved in these experimental methods but that these now need to be fully translated into a pre-clinical and clinical experimentation to become a future viable therapeutic option.
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28
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Hendow EK, Guhmann P, Wright B, Sofokleous P, Parmar N, Day RM. Biomaterials for hollow organ tissue engineering. FIBROGENESIS & TISSUE REPAIR 2016; 9:3. [PMID: 27014369 PMCID: PMC4806416 DOI: 10.1186/s13069-016-0040-6] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 01/29/2016] [Accepted: 03/15/2016] [Indexed: 12/14/2022]
Abstract
Tissue engineering is a rapidly advancing field that is likely to transform how medicine is practised in the near future. For hollow organs such as those found in the cardiovascular and respiratory systems or gastrointestinal tract, tissue engineering can provide replacement of the entire organ or provide restoration of function to specific regions. Larger tissue-engineered constructs often require biomaterial-based scaffold structures to provide support and structure for new tissue growth. Consideration must be given to the choice of material and manufacturing process to ensure the de novo tissue closely matches the mechanical and physiological properties of the native tissue. This review will discuss some of the approaches taken to date for fabricating hollow organ scaffolds and the selection of appropriate biomaterials.
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Affiliation(s)
- Eseelle K. Hendow
- Applied Biomedical Engineering Group, Division of Medicine, University College London, 21 University Street, London, UK
| | - Pauline Guhmann
- Applied Biomedical Engineering Group, Division of Medicine, University College London, 21 University Street, London, UK
| | - Bernice Wright
- Applied Biomedical Engineering Group, Division of Medicine, University College London, 21 University Street, London, UK
| | - Panagiotis Sofokleous
- Applied Biomedical Engineering Group, Division of Medicine, University College London, 21 University Street, London, UK
| | - Nina Parmar
- Applied Biomedical Engineering Group, Division of Medicine, University College London, 21 University Street, London, UK
| | - Richard M. Day
- Applied Biomedical Engineering Group, Division of Medicine, University College London, 21 University Street, London, UK
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Keane TJ, Dziki J, Castelton A, Faulk DM, Messerschmidt V, Londono R, Reing JE, Velankar SS, Badylak SF. Preparation and characterization of a biologic scaffold and hydrogel derived from colonic mucosa. J Biomed Mater Res B Appl Biomater 2015; 105:291-306. [DOI: 10.1002/jbm.b.33556] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2015] [Revised: 08/28/2015] [Accepted: 10/11/2015] [Indexed: 12/30/2022]
Affiliation(s)
- Timothy J. Keane
- McGowan Institute for Regenerative Medicine; Pittsburgh Pennsylvania 15219
- Department of Bioengineering; University of Pittsburgh; Pittsburgh Pennsylvania 15213
| | - Jenna Dziki
- McGowan Institute for Regenerative Medicine; Pittsburgh Pennsylvania 15219
- Department of Bioengineering; University of Pittsburgh; Pittsburgh Pennsylvania 15213
| | - Arthur Castelton
- McGowan Institute for Regenerative Medicine; Pittsburgh Pennsylvania 15219
| | - Denver M. Faulk
- McGowan Institute for Regenerative Medicine; Pittsburgh Pennsylvania 15219
- Department of Bioengineering; University of Pittsburgh; Pittsburgh Pennsylvania 15213
| | | | - Ricardo Londono
- McGowan Institute for Regenerative Medicine; Pittsburgh Pennsylvania 15219
| | - Janet E. Reing
- McGowan Institute for Regenerative Medicine; Pittsburgh Pennsylvania 15219
| | - Sachin S. Velankar
- Department of Chemical and Petroleum Engineering; University of Pittsburgh; Pittsburgh Pennsylvania 15213
| | - Stephen F. Badylak
- McGowan Institute for Regenerative Medicine; Pittsburgh Pennsylvania 15219
- Department of Bioengineering; University of Pittsburgh; Pittsburgh Pennsylvania 15213
- Department of Surgery; University of Pittsburgh; Pittsburgh Pennsylvania 15219
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Yang M, Zhou G, Castano-Izquierdo H, Zhu Y, Mao C. Biomineralization of Natural Collagenous Nanofibrous Membranes and Their Potential Use in Bone Tissue Engineering. J Biomed Nanotechnol 2015; 11:447-56. [PMID: 25883539 DOI: 10.1166/jbn.2015.2038] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Small intestinal submucosa (SIS) membranes as a decellularized tissue are known to be a natural nanofibrous biomaterial mainly made of type I collagen fibers and containing some growth factors (fibroblast growth factor 2 and transforming growth factor β) desired in tissue engineering. Here we show that the SIS membranes can promote the formation of bone mineral hydroxylapatite (HAP) crystals along the collagen fibers constituting the membranes from a HAP-supersaturated solution. The resultant biomineralized HAP-SIS scaffolds were found to promote the attachment, growth and osteogenic differentiation of mesenchymal stem cells (MSCs) in both basal and osteogenic media by the evaluation of osteogenic marker formation. More importantly, the HAP-SIS scaffolds could induce the osteogenic differentiation in the basal media without osteogenic supplements due to the presence of HAP crystals in the scaffolds. Histological characterization of the MSC-seeded scaffolds showed that HAP-SIS scaffolds are biocompatible and promote the formation of new tissue in vitro. The biomineralized SIS membranes mimic some aspects of natural bone in terms of the composition and nanostructures and can find potential use in bone tissue engineering.
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Rego SL, Zakhem E, Orlando G, Bitar KN. Bioengineering functional human sphincteric and non-sphincteric gastrointestinal smooth muscle constructs. Methods 2015; 99:128-34. [PMID: 26314281 DOI: 10.1016/j.ymeth.2015.08.014] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2015] [Revised: 06/29/2015] [Accepted: 08/23/2015] [Indexed: 01/04/2023] Open
Abstract
Digestion and motility of luminal content through the gastrointestinal (GI) tract are achieved by cooperation between distinct cell types. Much of the 3 dimensional (3D) in vitro modeling used to study the GI physiology and disease focus solely on epithelial cells and not smooth muscle cells (SMCs). SMCs of the gut function either to propel and mix luminal contents (phasic; non-sphincteric) or to act as barriers to prevent the movement of luminal materials (tonic; sphincteric). Motility disorders including pyloric stenosis and chronic intestinal pseudoobstruction (CIPO) affect sphincteric and non-sphincteric SMCs, respectively. Bioengineering offers a useful tool to develop functional GI tissue mimics that possess similar characteristics to native tissue. The objective of this study was to bioengineer 3D human pyloric sphincter and small intestinal (SI) constructs in vitro that recapitulate the contractile phenotypes of sphincteric and non-sphincteric human GI SMCs. Bioengineered 3D human pylorus and circular SI SMC constructs were developed and displayed a contractile phenotype. Constructs composed of human pylorus SMCs displayed tonic SMC characteristics, including generation of basal tone, at higher levels than SI SMC constructs which is similar to what is seen in native tissue. Both constructs contracted in response to potassium chloride (KCl) and acetylcholine (ACh) and relaxed in response to vasoactive intestinal peptide (VIP). These studies provide the first bioengineered human pylorus constructs that maintain a sphincteric phenotype. These bioengineered constructs provide appropriate models to study motility disorders of the gut or replacement tissues for various GI organs.
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Affiliation(s)
- Stephen L Rego
- Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, NC, United States.
| | - Elie Zakhem
- Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, NC, United States; Department of Molecular Medicine and Translational Sciences, Wake Forest School of Medicine, Winston-Salem, NC, United States.
| | - Giuseppe Orlando
- Department of General Surgery, Wake Forest School of Medicine, Winston-Salem, NC, United States.
| | - Khalil N Bitar
- Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, NC, United States; Department of Molecular Medicine and Translational Sciences, Wake Forest School of Medicine, Winston-Salem, NC, United States; Virginia Tech-Wake Forest School of Biomedical Engineering and Sciences, Winston-Salem, NC, United States.
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Kajbafzadeh AM, Khorramirouz R, Akbarzadeh A, Sabetkish S, Sabetkish N, Saadat P, Tehrani M. A novel technique for simultaneous whole-body and multi-organ decellularization: umbilical artery catheterization as a perfusion-based method in a sheep foetus model. Int J Exp Pathol 2015; 96:116-32. [PMID: 26031202 DOI: 10.1111/iep.12124] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2014] [Accepted: 02/09/2015] [Indexed: 01/19/2023] Open
Abstract
The aim of this study was to develop a method to generate multi-organ acellular matrices. Using a foetal sheep model have developed a method of systemic pulsatile perfusion via the umbilical artery which allows for simultaneous multi-organ decellularization. Twenty sheep foetuses were systemically perfused with Triton X-100 and sodium dodecyl sulphate. Following completion of the whole-body decellularization, multiple biopsy samples were taken from different parts of 21 organs to ascertain complete cell component removal in the preserved extracellular matrices. Both the natural and decellularized organs were subjected to several examinations. The samples were obtained from the skin, eye, ear, nose, throat, cardiovascular, respiratory, gastrointestinal, urinary, musculoskeletal, central nervous and peripheral nervous systems. The histological results depicted well-preserved extracellular matrix (ECM) integrity and intact vascular structures, without any evidence of residual cellular materials, in all decellularized bioscaffolds. Scanning electron microscope (SEM) and biochemical properties remained intact, similar to their age-matched native counterparts. Preservation of the collagen structure was evaluated by a hydroxyproline assay. Dense organs such as bone and muscle were also completely decellularized, with a preserved ECM structure. Thus, as shown in this study, several organs and different tissues were decellularized using a perfusion-based method, which has not been previously accomplished. Given the technical challenges that exist for the efficient generation of biological scaffolds, the current results may pave the way for obtaining a variety of decellularized scaffolds from a single donor. In this study, there have been unique responses to the single acellularization protocol in foetuses, which may reflect the homogeneity of tissues and organs in the developing foetal body.
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Affiliation(s)
- Abdol-Mohammad Kajbafzadeh
- Pediatric Urology Research Center, Section of Tissue Engineering and Stem Cells Therapy, Children's Hospital Medical Center, Tehran University of Medical Sciences, Tehran, Iran (IRI)
| | - Reza Khorramirouz
- Pediatric Urology Research Center, Section of Tissue Engineering and Stem Cells Therapy, Children's Hospital Medical Center, Tehran University of Medical Sciences, Tehran, Iran (IRI)
| | - Aram Akbarzadeh
- Pediatric Urology Research Center, Section of Tissue Engineering and Stem Cells Therapy, Children's Hospital Medical Center, Tehran University of Medical Sciences, Tehran, Iran (IRI)
| | - Shabnam Sabetkish
- Pediatric Urology Research Center, Section of Tissue Engineering and Stem Cells Therapy, Children's Hospital Medical Center, Tehran University of Medical Sciences, Tehran, Iran (IRI)
| | - Nastaran Sabetkish
- Pediatric Urology Research Center, Section of Tissue Engineering and Stem Cells Therapy, Children's Hospital Medical Center, Tehran University of Medical Sciences, Tehran, Iran (IRI)
| | - Paria Saadat
- Pediatric Urology Research Center, Section of Tissue Engineering and Stem Cells Therapy, Children's Hospital Medical Center, Tehran University of Medical Sciences, Tehran, Iran (IRI)
| | - Mona Tehrani
- Pediatric Urology Research Center, Section of Tissue Engineering and Stem Cells Therapy, Children's Hospital Medical Center, Tehran University of Medical Sciences, Tehran, Iran (IRI)
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Denost Q, Adam JP, Pontallier A, Montembault A, Bareille R, Siadous R, Delmond S, Rullier E, David L, Bordenave L. Colorectal tissue engineering: A comparative study between porcine small intestinal submucosa (SIS) and chitosan hydrogel patches. Surgery 2015; 158:1714-23. [PMID: 26275832 DOI: 10.1016/j.surg.2015.06.040] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2015] [Revised: 05/14/2015] [Accepted: 06/03/2015] [Indexed: 12/16/2022]
Abstract
OBJECTIVE Tissue engineering may provide new operative tools for colorectal surgery in elective indications. The aim of this study was to define a suitable bioscaffold for colorectal tissue engineering. METHODS We compared 2 bioscaffolds with in vitro and in vivo experiments: porcine small intestinal submucosa (SIS) versus chitosan hydrogel matrix. We assessed nontoxicity of the scaffold in vitro by using human adipose-derived stem cells (hADSC). In vivo, a 1 × 2-cm colonic wall defect was created in 16 rabbits. Animals were divided randomly into 2 groups according to the graft used, SIS or chitosan hydrogel. Graft area was explanted at 4 and 8 weeks. The end points of in vivo experiments were technical feasibility, behavior of the scaffold, in situ putative inflammatory effect, and the quality of tissue regeneration, in particular smooth muscle layer regeneration. RESULTS In vitro, hADSC attachment and proliferation occurred on both scaffolds without a substantial difference. After proliferation, hADSCs kept their mesenchymal stem cell characteristics. In vivo, one animal died in each group. Eight weeks after implantation, the chitosan scaffold allowed better wound healing compared with the SIS scaffold, with more effective control of inflammatory activity and an integral regeneration of the colonic wall including the smooth muscle cell layer. CONCLUSION The outcomes of in vitro experiments did not differ greatly between the 2 groups. Macroscopic and histologic findings, however, revealed better wound healing of the colonic wall in the chitosan group suggesting that the chitosan hydrogel could serve as a better scaffold for colorectal tissue engineering.
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Affiliation(s)
- Quentin Denost
- Department of Digestive Surgery, CHU de Bordeaux, University of Bordeaux, Bordeaux, France; Bioingénierie tissulaire, University of Bordeaux, Bordeaux, France; INSERM, Bioingenierie tissulaire, U1026, Bordeaux, France; CHU de Bordeaux, CIC 1401, Bordeaux, France.
| | - Jean-Philippe Adam
- Department of Digestive Surgery, CHU de Bordeaux, University of Bordeaux, Bordeaux, France; Bioingénierie tissulaire, University of Bordeaux, Bordeaux, France; INSERM, Bioingenierie tissulaire, U1026, Bordeaux, France
| | - Arnaud Pontallier
- Department of Digestive Surgery, CHU de Bordeaux, University of Bordeaux, Bordeaux, France; Bioingénierie tissulaire, University of Bordeaux, Bordeaux, France; INSERM, Bioingenierie tissulaire, U1026, Bordeaux, France
| | | | - Reine Bareille
- Bioingénierie tissulaire, University of Bordeaux, Bordeaux, France; INSERM, Bioingenierie tissulaire, U1026, Bordeaux, France
| | - Robin Siadous
- Bioingénierie tissulaire, University of Bordeaux, Bordeaux, France; INSERM, Bioingenierie tissulaire, U1026, Bordeaux, France
| | | | - Eric Rullier
- Department of Digestive Surgery, CHU de Bordeaux, University of Bordeaux, Bordeaux, France
| | - Laurent David
- Université de Lyon, Université Claude Bernard Lyon 1, Villeurbanne Cedex, France
| | - Laurence Bordenave
- Bioingénierie tissulaire, University of Bordeaux, Bordeaux, France; INSERM, Bioingenierie tissulaire, U1026, Bordeaux, France; CHU de Bordeaux, CIC 1401, Bordeaux, France
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Welman T, Michel S, Segaren N, Shanmugarajah K. Bioengineering for Organ Transplantation: Progress and Challenges. Bioengineered 2015; 6:257-61. [PMID: 26259720 DOI: 10.1080/21655979.2015.1081320] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/28/2023] Open
Abstract
Organ transplantation can offer a curative option for patients with end stage organ failure. Unfortunately the treatment is severely limited by the availability of donor organs. Organ bioengineering could provide a solution to the worldwide critical organ shortage. The majority of protocols to date have employed the use of decellularization-recellularization technology of naturally occurring tissues and organs with promising results in heart, lung, liver, pancreas, intestine and kidney engineering. Successful decellularization has provided researchers with suitable scaffolds to attempt cell reseeding. Future work will need to focus on the optimization of organ specific recellularization techniques before organ bioengineering can become clinically translatable. This review will examine the current progress in organ bioengineering and highlight future challenges in the field.
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Affiliation(s)
- Ted Welman
- a Ashford and St Peter's Hospitals NHS Foundation Trust ; Chertsey, Surrey , United Kingdom
| | - Sebastian Michel
- b Department of Cardiac Surgery ; Ludwig-Maximilians-Universtät München ; Munich , Germany
| | - Nicholas Segaren
- c Department of Plastic Surgery ; Addenbrooke's Hospital ; Cambridge , United Kingdom
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Naji M, Rasouli J, Shakhssalim N, Dehghan MM, Soleimani M. Supportive features of a new hybrid scaffold for urothelium engineering. Arch Med Sci 2015; 11:438-45. [PMID: 25995764 PMCID: PMC4424262 DOI: 10.5114/aoms.2015.50977] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/23/2013] [Revised: 03/12/2013] [Accepted: 05/18/2013] [Indexed: 11/17/2022] Open
Abstract
INTRODUCTION Different clinical conditions can compromise the urinary bladder function and structure. Routine regenerative practices in urology for bladder augmentation have been associated with diverse side effects. The internal lining of the bladder, the urothelium, plays an integral role in normal bladder function. Tissue engineering has provided novel therapeutic strategies through scaffolding and cell transplantation. Nano-scale surface features of scaffolds are valuable parameters for enhancement of cell behavior and function. MATERIAL AND METHODS We fabricated a new hybrid scaffold of poly ɛ-caprolactone (PCL) and poly-L-lactide acid (PLLA) using an electrospinning system to exploit each polymer's advantages at nano-scale in the same scaffold. Dog urothelial cells were isolated, characterized by immunocytochemistry, and expanded for loading on the scaffold. Cell viability and proliferation on the scaffold surface were assessed by 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Furthermore, cytoarchitecture, distribution and detailed morphology of cells, and expression of cell specific markers were examined using hematoxylin and eosin (H + E) staining, scanning electron microscopy (SEM), and immunohistochemistry, respectively. RESULTS According to MTT results, the scaffold did not exert any cytotoxic effect, and also supported cell proliferation and viability for 14 days of culture, which led to a significant increase in the number of cells. Scanning electron microscopy images revealed evenly distributed and normal appearing colonies of urothelial cells. A well-defined layer of cells was observed using H + E staining, which preserved their markers (pan-cytokeratin and uroplakin III) while growing on the scaffold. CONCLUSIONS Our findings confirmed favorable properties of PCL/PLLA regarding biocompatibility and applicability for upcoming new methods of bladder augmentation and engineering.
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Affiliation(s)
- Mohammad Naji
- Urology and Nephrology Research Center (UNRC), Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Javad Rasouli
- Urology and Nephrology Research Center (UNRC), Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Nasser Shakhssalim
- Urology and Nephrology Research Center (UNRC), Shahid Labbafinejad Medical Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohammad Mehdi Dehghan
- Department of Clinical Sciences, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran
| | - Masoud Soleimani
- Tarbiat Modares University, School of Medical Science, Hematology Department and Stem Cell Technology Research Center, UNRC, Tehran, Iran
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Nakao M, Ueno T, Oga A, Kuramitsu Y, Nakatsu H, Oka M. Proposal of intestinal tissue engineering combined with Bianchi's procedure. J Pediatr Surg 2015; 50:573-80. [PMID: 25840066 DOI: 10.1016/j.jpedsurg.2014.11.035] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/27/2013] [Revised: 10/02/2014] [Accepted: 11/05/2014] [Indexed: 12/16/2022]
Abstract
AIM The aim of this study is to examine the feasibility of the small intestinal submucosa (SIS) when the longitudinal staples during Bianchi's procedure are replaced with SIS graft. METHODS The mesentery of the bowel was separated based on the bifurcated vessels in five beagles. A 2×7-cm longitudinal half of the bowel was excised and the defect was repaired using SIS with similar blood supply in Bianchi's operation. Six months later, intestinal motility in the SIS-grafted area was recorded. Tissue preparations were obtained from the reorganized area. An organ bath technique with electrical field stimulation was applied. Both the native small intestine and grafted area were morphologically investigated using immunohistochemistry. MAIN RESULTS All dogs survived and thrived with no anastomotic leakage. Isoperistaltic migrating contractility during fasting was observed through the grafted segment including the reorganized area. The SIS-reorganized tissue contracted in response to an acetylcholine agonist and electrical field stimulation. The mucosa was covered with normal epithelium. Reorganization of neural and smooth muscle cells was observed. CONCLUSIONS SIS has the potential for use as a scaffold that promotes the formation of a physical and physiological neointestine. Our present proposal approaches a novel surgical treatment in patients with short bowel syndrome.
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Affiliation(s)
- Mitsuhiro Nakao
- Department of Digestive Surgery and Surgical Oncology (Department of Surgery II), Yamaguchi University Graduate School of Medicine, Yamaguchi, Japan
| | - Tomio Ueno
- Department of Digestive Surgery and Surgical Oncology (Department of Surgery II), Yamaguchi University Graduate School of Medicine, Yamaguchi, Japan.
| | - Atsunori Oga
- Department of Molecular Pathology, Yamaguchi University Graduate School of Medicine, Yamaguchi, Japan
| | - Yasuhiro Kuramitsu
- Department of Biochemistry and Functional Proteomics, Yamaguchi University Graduate School of Medicine, Yamaguchi, Japan
| | - Hiroki Nakatsu
- Department of Digestive Surgery and Surgical Oncology (Department of Surgery II), Yamaguchi University Graduate School of Medicine, Yamaguchi, Japan
| | - Masaaki Oka
- Department of Digestive Surgery and Surgical Oncology (Department of Surgery II), Yamaguchi University Graduate School of Medicine, Yamaguchi, Japan
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A review of: Application of synthetic scaffold in tissue engineering heart valves. MATERIALS SCIENCE & ENGINEERING. C, MATERIALS FOR BIOLOGICAL APPLICATIONS 2015; 48:556-65. [DOI: 10.1016/j.msec.2014.12.016] [Citation(s) in RCA: 59] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/04/2014] [Revised: 08/26/2014] [Accepted: 12/05/2014] [Indexed: 01/28/2023]
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Schumacher MA, Aihara E, Feng R, Engevik A, Shroyer NF, Ottemann KM, Worrell RT, Montrose MH, Shivdasani RA, Zavros Y. The use of murine-derived fundic organoids in studies of gastric physiology. J Physiol 2015; 593:1809-27. [PMID: 25605613 DOI: 10.1113/jphysiol.2014.283028] [Citation(s) in RCA: 88] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2014] [Accepted: 01/16/2015] [Indexed: 02/06/2023] Open
Abstract
KEY POINTS An in vitro approach to study gastric development is primary mouse-derived epithelium cultured as three-dimensional spheroids known as organoids. We have devised two unique gastric fundic-derived organoid cultures: model 1 for the expansion of gastric fundic stem cells, and model 2 for the maintenance of mature cell lineages. Organoids maintained in co-culture with immortalized stomach mesenchymal cells express robust numbers of surface pit, mucous neck, chief, endocrine and parietal cells. Histamine induced a significant decrease in intraluminal pH that was reversed by omeprazole in fundic organoids and indicated functional activity and regulation of parietal cells. Localized photodamage resulted in rapid cell exfoliation coincident with migration of neighbouring cells to the damaged area, sustaining epithelial continuity. We report the use of these models for studies of epithelial cell biology and cell damage and repair. ABSTRACT Studies of gastric function and disease have been limited by the lack of extended primary cultures of the epithelium. An in vitro approach to study gastric development is primary mouse-derived antral epithelium cultured as three-dimensional spheroids known as organoids. There have been no reports on the use of organoids for gastric function. We have devised two unique gastric fundic-derived organoid cultures: model 1 for the expansion of gastric fundic stem cells, and model 2 for the maintenance of mature cell lineages. Both models were generated from single glands dissociated from whole fundic tissue and grown in basement membrane matrix (Matrigel) and organoid growth medium. Model 1 enriches for a stem cell-like niche via simple passage of the organoids. Maintained in Matrigel and growth medium, proliferating organoids expressed high levels of stem cell markers CD44 and Lgr5. Model 2 is a system of gastric organoids co-cultured with immortalized stomach mesenchymal cells (ISMCs). Organoids maintained in co-culture with ISMCs express robust numbers of surface pit, mucous neck, chief, endocrine and parietal cells. Histamine induced a significant decrease in intraluminal pH that was reversed by omeprazole in fundic organoids and indicated functional activity and regulation of parietal cells. Localized photodamage resulted in rapid cell exfoliation coincident with migration of neighbouring cells to the damaged area, sustaining epithelial continuity. Thus, we report the use of these models for studies of epithelial cell biology and cell damage and repair.
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Affiliation(s)
- Michael A Schumacher
- Department of Molecular and Cellular Physiology, University of Cincinnati College of Medicine, Cincinnati, OH, USA
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Franck D, Chung YG, Coburn J, Kaplan DL, Estrada CR, Mauney JR. In vitro evaluation of bi-layer silk fibroin scaffolds for gastrointestinal tissue engineering. J Tissue Eng 2014; 5:2041731414556849. [PMID: 25396043 PMCID: PMC4228923 DOI: 10.1177/2041731414556849] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2014] [Accepted: 09/25/2014] [Indexed: 01/01/2023] Open
Abstract
Silk fibroin scaffolds were investigated for their ability to support attachment, proliferation, and differentiation of human gastrointestinal epithelial and smooth muscle cell lines in order to ascertain their potential for tissue engineering. A bi-layer silk fibroin matrix composed of a porous silk fibroin foam annealed to a homogeneous silk fibroin film was evaluated in parallel with small intestinal submucosa scaffolds. AlamarBlue analysis revealed that silk fibroin scaffolds supported significantly higher levels of small intestinal smooth muscle cell, colon smooth muscle cell, and esophageal smooth muscle cell attachment in comparison to small intestinal submucosa. Following 7 days of culture, relative numbers of each smooth muscle cell population maintained on both scaffold groups were significantly elevated over respective 1-day levels—indicative of cell proliferation. Real-time reverse transcription polymerase chain reaction and immunohistochemical analyses demonstrated that both silk fibroin and small intestinal submucosa scaffolds were permissive for contractile differentiation of small intestinal smooth muscle cell, colon smooth muscle cell, esophageal smooth muscle cell as determined by significant upregulation of α-smooth muscle actin and SM22α messenger RNA and protein expression levels following transforming growth factor-β1 stimulation. AlamarBlue analysis demonstrated that both matrix groups supported similar degrees of attachment and proliferation of gastrointestinal epithelial cell lines including colonic T84 cells and esophageal epithelial cells. Following 14 days of culture on both matrices, spontaneous differentiation of T84 cells toward an enterocyte lineage was confirmed by expression of brush border enzymes, lactase, and maltase, as determined by real-time reverse transcription polymerase chain reaction and immunohistochemical analyses. In contrast to small intestinal submucosa scaffolds, silk fibroin scaffolds supported spontaneous differentiation of esophageal epithelial cells toward a suprabasal cell lineage as indicated by significant upregulation of cytokeratin 4 and cytokeratin 13 messenger RNA transcript levels. In addition, esophageal epithelial cells maintained on silk fibroin scaffolds also produced significantly higher involucrin messenger RNA transcript levels in comparison to small intestinal submucosa counterparts, indicating an increased propensity for superficial, squamous cell specification. Collectively, these data provide evidence for the potential of silk fibroin scaffolds for gastrointestinal tissue engineering applications.
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Affiliation(s)
- Debra Franck
- Urological Diseases Research Center, Department of Urology, Boston Children's Hospital, Boston, MA, USA
| | - Yeun Goo Chung
- Urological Diseases Research Center, Department of Urology, Boston Children's Hospital, Boston, MA, USA ; Department of Surgery, Harvard Medical School, Boston, MA, USA
| | - Jeannine Coburn
- Department of Biomedical Engineering, Tufts University, Medford, MA, USA
| | - David L Kaplan
- Department of Biomedical Engineering, Tufts University, Medford, MA, USA
| | - Carlos R Estrada
- Urological Diseases Research Center, Department of Urology, Boston Children's Hospital, Boston, MA, USA ; Department of Surgery, Harvard Medical School, Boston, MA, USA
| | - Joshua R Mauney
- Urological Diseases Research Center, Department of Urology, Boston Children's Hospital, Boston, MA, USA ; Department of Surgery, Harvard Medical School, Boston, MA, USA
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Abstract
Regenerative medicine has recently been established as an emerging interdisciplinary field focused on the repair; replacement or regeneration of cells, tissues and organs. It involves various disciplines, which are focused on different aspects of the regeneration process such as cell biology, gene therapy, bioengineering, material science and pharmacology. In this article, we will outline progress on tissue engineering of specific tissues and organs relevant to paediatric surgery.
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Affiliation(s)
- Panagiotis Maghsoudlou
- Surgery Unit, Institute of Child Health and Great Ormond Street Hospital, University College London, 30 Guilford St, London WC1N 1EH, UK
| | - Luca Urbani
- Surgery Unit, Institute of Child Health and Great Ormond Street Hospital, University College London, 30 Guilford St, London WC1N 1EH, UK
| | - Paolo De Coppi
- Surgery Unit, Institute of Child Health and Great Ormond Street Hospital, University College London, 30 Guilford St, London WC1N 1EH, UK.
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Shim JB, Ankeny RF, Kim H, Nerem RM, Khang G. A study of a three-dimensional PLGA sponge containing natural polymers co-cultured with endothelial and mesenchymal stem cells as a tissue engineering scaffold. Biomed Mater 2014; 9:045015. [PMID: 25065725 DOI: 10.1088/1748-6041/9/4/045015] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022]
Abstract
The interaction between vascular endothelial cells (ECs) and vascular smooth muscle cells (VSMCs) in a complex hemodynamic and mechanical environment plays an important role in the control of blood vessel growth and function. Despite the importance of VSMCs, substitutes are needed for vascular therapies. A potential VSMC substitute is human adult bone marrow derived mesenchymal stem cells (hMSCs). In this study, the effect of poly(lactic-co-glycolic acid) (PLGA) scaffolds containing three natural polymers (demineralized bone particles, silk, and small intestine submucosa) on the phenotype of MSCs and SMCs cultured with or without ECs was investigated. The study objective was to create a media equivalent for a tissue engineered blood vessel using PLGA, natural polymers, and MSCs co-cultured with ECs. The PLGA containing the natural polymers silk and SIS showed increased proliferation and cell adhesion. The presence of silk and DBP promoted a MSC phenotype change into a SMC-like phenotype at the mRNA level; however these differences at the protein level were not seen. Additionally, PLGA containing SIS did not induce SMC gene or protein upregulation. Finally, the effect of ECs in combination with the natural polymers was tested. When co-cultured with ECs, the mRNA of SMC specific markers in MSCs and SMCs were increased when compared to SMCs or MSCs alone. However, MSCs, when co-cultured with ECs on PLGA containing silk, exhibited significantly increased α-SMA and calponin expression when compared to PLGA only scaffolds. These results indicate that the natural polymer silk in combination with the co-culture of endothelial cells was most effective at increasing cell viability and inducing a SMC-like phenotype at the mRNA and protein level in MSCs.
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Affiliation(s)
- Jung Bo Shim
- Department of BIN Fusion Technology & Polymer Fusion Research Center, Chonbuk National University, Jeonju, Republic of Korea
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Ding JX, Chen XJ, Zhang XY, Zhang Y, Hua KQ. Acellular porcine small intestinal submucosa graft for cervicovaginal reconstruction in eight patients with malformation of the uterine cervix. Hum Reprod 2014; 29:677-82. [DOI: 10.1093/humrep/det470] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022] Open
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Abstract
Tissue engineering is an emerging discipline that combines engineering principles and the biological sciences toward the development of functional replacement tissue. Virtually every tissue in the body has been investigated and tremendous advances have been made in many areas. This article focuses on the gastrointestinal tract and reviews the current status of bioengineering gastrointestinal tissues, including the esophagus, stomach, small intestine and colon. Although progress has been achieved, there continues to be significant challenges that need to be addressed.
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Affiliation(s)
- Rebecca A Penkala
- University of Washington, Department of Bioengineering, Seattle, WA, USA.
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44
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Jwo SC, Chiu CH, Tang SJ, Hsieh MF. Tubular scaffolds of gelatin and poly(ε-caprolactone)-block-poly(γ-glutamic acid) blending hydrogel for the proliferation of the primary intestinal smooth muscle cells of rats. Biomed Mater 2013; 8:065002. [PMID: 24225182 DOI: 10.1088/1748-6041/8/6/065002] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022]
Abstract
The proper regeneration of intestinal muscle for functional peristalsis is the most challenging aspect of current small intestine tissue engineering. This study aimed to fabricate a hydrogel scaffold for the proliferation of intestinal smooth muscle cells (ISMCs). Tubular porous scaffolds of 10-20 wt% gelatin and 0.05-0.1 wt% poly(ε-caprolactone)-block-poly(γ-glutamic acid) blending hydrogel were cross-linked by carbodiimide and succinimide in an annular space of a glass mold. The scaffolds with higher gelatin contents degraded slower in the phosphate buffer solution. In rheological measurements, the hydrated scaffolds were elastic (all tangent delta <0.45); they responded differentially to frequency, indicating a complete viscoelastic property that is beneficial for soft tissue regeneration. Isolated rat ISMCs, with the characteristic biomarkers α-SMA, calponin and myh11, were loaded into the scaffolds by using either static or centrifugal methods. The average cell density inside the scaffolds increased in a time-dependent manner in most scaffolds of both seeding groups, although at early time points (seven days) the centrifugal seeding method trapped cells more efficiently and yielded a higher cell density than the static seeding method. The static seeding method increased the cell density from 7.5-fold to 16.3-fold after 28 days, whereas the centrifugal procedure produced a maximum increase of only 2.4-fold in the same period. In vitro degradation data showed that 50-80% of the scaffold was degraded by the 14th day. However, the self-secreted extracellular matrix maintained the integrity of the scaffolds for cell proliferation and spreading for up to 28 days. Confocal microscopic images revealed cell-cell contacts with the formation of a 3D network, demonstrating that the fabricated scaffolds were highly biocompatible. Therefore, these polymeric biomaterials hold great promise for in vivo applications of intestinal tissue engineering.
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Affiliation(s)
- Shyh-Chuan Jwo
- Division of General Surgery, Chang Gung Memorial Hospital, Keelung, and College of Medicine, Chang Gung University, Taoyuan, Taiwan, Republic of China. Institute of Bioscience and Biotechnology, National Taiwan Ocean University, Keelung, Taiwan, Republic of China
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Maghsoudlou P, Totonelli G, Loukogeorgakis SP, Eaton S, De Coppi P. A decellularization methodology for the production of a natural acellular intestinal matrix. J Vis Exp 2013. [PMID: 24145913 PMCID: PMC3923547 DOI: 10.3791/50658] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/03/2023] Open
Abstract
Successful tissue engineering involves the combination of scaffolds with appropriate cells in vitro or in vivo. Scaffolds may be synthetic, naturally-derived or derived from tissues/organs. The latter are obtained using a technique called decellularization. Decellularization may involve a combination of physical, chemical, and enzymatic methods. The goal of this technique is to remove all cellular traces whilst maintaining the macro- and micro-architecture of the original tissue. Intestinal tissue engineering has thus far used relatively simple scaffolds that do not replicate the complex architecture of the native organ. The focus of this paper is to describe an efficient decellularization technique for rat small intestine. The isolation of the small intestine so as to ensure the maintenance of a vascular connection is described. The combination of chemical and enzymatic solutions to remove the cells whilst preserving the villus-crypt axis in the luminal aspect of the scaffold is also set out. Finally, assessment of produced scaffolds for appropriate characteristics is discussed.
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Affiliation(s)
- Panagiotis Maghsoudlou
- Surgery Unit, Institute of Child Health and Great Ormond Street Hospital, University College London
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Nakatsu H, Ueno T, Oga A, Nakao M, Nishimura T, Kobayashi S, Oka M. Influence of mesenchymal stem cells on stomach tissue engineering using small intestinal submucosa. J Tissue Eng Regen Med 2013; 9:296-304. [PMID: 23913876 PMCID: PMC4409104 DOI: 10.1002/term.1794] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2012] [Revised: 05/12/2013] [Accepted: 06/12/2013] [Indexed: 12/23/2022]
Abstract
Small intestinal submucosa (SIS) is a biodegradable collagen-rich matrix containing functional growth factors. We have previously reported encouraging outcomes for regeneration of an artificial defect in the rodent stomach using SIS grafts, although the muscular layer was diminutive. In this study, we investigated the feasibility of SIS in conjunction with mesenchymal stem cells (MSCs) for regeneration of the gastrointestinal tract. MSCs from the bone marrow of green fluorescence protein (GFP)-transgenic Sprague-Dawley (SD) rats were isolated and expanded ex vivo. A 1 cm whole-layer stomach defect in SD rats was repaired using: a plain SIS graft without MSCs (group 1, control); a plain SIS graft followed by intravenous injection of MSCs (group 2); a SIS graft co-cultured with MSCs (group 3); or a SIS sandwich containing an MSC sheet (group 4). Pharmacological, electrophysiological and immunohistochemical examination was performed to evaluate the regenerated stomach tissue. Contractility in response to a muscarinic receptor agonist, a nitric oxide precursor or electrical field stimulation was observed in all groups. SIS grafts seeded with MSCs (groups 3 and 4) appeared to support improved regeneration compared with SIS grafts not seeded with MSCs (groups 1 and 2), by enabling the development of well-structured smooth muscle layers of significantly increased length. GFP expression was detected in the regenerated interstitial tissue, with fibroblast-like cells in the seeded-SIS groups. SIS potently induced pharmacological and electrophysiological regeneration of the digestive tract, and seeded MSCs provided an enriched environment that supported tissue regeneration by the SIS graft in the engineered stomach.
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Affiliation(s)
- Hiroki Nakatsu
- Department of Digestive Surgery and Surgical Oncology (Department of Surgery II), Yamaguchi University Graduate School of Medicine, Japan
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Greca FH, de Noronha L, Marcolini FRN, Verona A, Pereira IA, Bier RS. Small intestinal submucosa as a graft to increase rectum diameter. J Surg Res 2013; 183:503-8. [DOI: 10.1016/j.jss.2013.01.059] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2012] [Revised: 01/01/2013] [Accepted: 01/30/2013] [Indexed: 11/30/2022]
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Grimes J, Schmiedt C, Milovancev M, Radlinsky M, Cornell K. Efficacy of Serosal Patching in Dogs with Septic Peritonitis. J Am Anim Hosp Assoc 2013; 49:246-9. [DOI: 10.5326/jaaha-ms-5870] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
The objective of this study was to evaluate the correlation of serosal patching in dogs with existing septic peritonitis with continued postoperative septic peritonitis and death. Records were collected from dogs that underwent intestinal surgery from 1998 to 2007 at four veterinary teaching hospitals and one private referral clinic. Dogs were included if they were diagnosed with septic peritonitis and had subsequent surgery of either the small intestine or cecum. Eighty-two surgeries were evaluated. Eighteen dogs (22%) received a serosal patch during surgery. Of those, three dogs (16.7%) had septic peritonitis postoperatively. Sixty-four dogs (78%) did not receive a serosal patch, and 19 of those dogs (29.7%) had postoperative septic peritonitis (P = 0.27). Of the 18 cases with serosal patching, 6 (33.3%) died prior to discharge. Of the 63 cases that did not receive a patch and had information regarding survival, 14 (22.2%) died prior to discharge (P = 0.34). Use of a serosal patch did not protect dogs from either postoperative septic peritonitis or failure to survive.
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Affiliation(s)
- Janet Grimes
- Department of Small Animal Medicine and Surgery, College of Veterinary Medicine, University of Georgia, Athens, GA (J.G., C.S., M.R., K.C.); and Department of Clinical Sciences, College of Veterinary Medicine, Oregon State University, Corvallis, OR (M.M.)
| | - Chad Schmiedt
- Department of Small Animal Medicine and Surgery, College of Veterinary Medicine, University of Georgia, Athens, GA (J.G., C.S., M.R., K.C.); and Department of Clinical Sciences, College of Veterinary Medicine, Oregon State University, Corvallis, OR (M.M.)
| | - Milan Milovancev
- Department of Small Animal Medicine and Surgery, College of Veterinary Medicine, University of Georgia, Athens, GA (J.G., C.S., M.R., K.C.); and Department of Clinical Sciences, College of Veterinary Medicine, Oregon State University, Corvallis, OR (M.M.)
| | - MaryAnn Radlinsky
- Department of Small Animal Medicine and Surgery, College of Veterinary Medicine, University of Georgia, Athens, GA (J.G., C.S., M.R., K.C.); and Department of Clinical Sciences, College of Veterinary Medicine, Oregon State University, Corvallis, OR (M.M.)
| | - Karen Cornell
- Department of Small Animal Medicine and Surgery, College of Veterinary Medicine, University of Georgia, Athens, GA (J.G., C.S., M.R., K.C.); and Department of Clinical Sciences, College of Veterinary Medicine, Oregon State University, Corvallis, OR (M.M.)
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Abstract
So what is the "big deal" about engineering of collagen materials? It is certainly not enough to produce the familiar line about it being "more physiological." This phrase explains very little of the substance and gets nowhere near to the base of the question. We need to be clear about why this is important enough to justify a major new research investment.
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Affiliation(s)
- Robert A Brown
- Division of Surgery, UCL Centre for Tissue Regeneration Science, Institute of Orthopaedics, University College London, London, United Kingdom
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50
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Nowocin AK, Southgate A, Shurey S, Sibbons P, Gabe SM, Ansari T. The development and implantation of a biologically derived allograft scaffold. J Tissue Eng Regen Med 2013; 10:140-8. [PMID: 23554406 DOI: 10.1002/term.1722] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2012] [Revised: 07/18/2012] [Accepted: 01/08/2013] [Indexed: 11/12/2022]
Abstract
Biologically derived scaffolds are becoming viable treatment options for tissue/organ repair and regeneration. A continuing hurdle is the need for a functional blood supply to and from the implanted scaffold. We have addressed this problem by constructing an acellular ileal scaffold with an attached vascular network suitable for implantation and immediate reperfusion with the host's blood. Using a vascular perfusion approach, a segment of porcine ileum up to 30 cm long, together with its attached vasculature, was decellularized as a single entity. The quality of the decellularized scaffold was assessed histologically and using molecular tools. To establish vascular perfusion potentials of the scaffold, a right-sided nephrectomy and end-to-end anastomosis of the decellularized scaffold's vasculature to a renal artery and vein were performed in a pig of similar size to the donor animal. Lengths of ileal scaffold, together with its attached vasculature, were successfully decellularized, with no evidence of intact cells/nuclear material or collagen degradation. The scaffold's decellularized vascular network demonstrated optimum perfusion at 1, 2 and 24 h post-implantation and the mesenteric arcade remained patent throughout the assessment. The 1, 2 and 24 h explanted scaffolds demonstrated signs of cellular attachment, with cells positive for CD68 and CD133 on the vascular luminal aspect. It is possible to decellularize clinically relevant lengths of small intestine, together with the associated vasculature, as a single segment. The functional vascular network may represent a route for recellularization for future regeneration of bowel tissue for patients with short bowel syndrome.
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Affiliation(s)
- Anna K Nowocin
- Department of Surgical Research, NPIMR, Harrow, Middlesex, UK
| | - Aaron Southgate
- Department of Surgical Research, NPIMR, Harrow, Middlesex, UK
| | - Sandra Shurey
- Department of Surgical Research, NPIMR, Harrow, Middlesex, UK
| | - Paul Sibbons
- Department of Surgical Research, NPIMR, Harrow, Middlesex, UK
| | - Simon M Gabe
- Lennard-Jones Intestinal Failure Unit and Academic Institute, St Mark's Hospital, Harrow, UK.,Division of Surgery, Oncology, Reproductive Biology and Anaesthetics, Imperial College, London, UK
| | - Tahera Ansari
- Department of Surgical Research, NPIMR, Harrow, Middlesex, UK
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