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Song YT, Liu PC, Zhou XL, Chen YM, Wu W, Zhang JY, Li-Ling J, Xie HQ. Extracellular matrix-based biomaterials in burn wound repair: A promising therapeutic strategy. Int J Biol Macromol 2024; 283:137633. [PMID: 39549816 DOI: 10.1016/j.ijbiomac.2024.137633] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2024] [Revised: 11/11/2024] [Accepted: 11/12/2024] [Indexed: 11/18/2024]
Abstract
Burns are common traumatic injuries affecting many people worldwide. Development of specialized burn units, advances in acute care modalities, and burn prevention programs have successfully reduced the mortality rate of severe burns. Autologous skin grafting has been considered as the gold standard for wound coverage after the removal of burned skin. For full-thickness burns of a larger scale, however, the autograft donor site may be quickly exhausted, so that alternative skin coverage is necessary. Although rapid progress has been made in the development of skin substitutes for burn wounds during the last decade, no skin substitute has fulfilled the criteria as a perfect replacement for the damaged skin. Extracellular matrix (ECM) derived components have emerged as a source for the engineering of biomaterials capable of inducing desirable cell-specific responses and one of the most promising biomaterials for burn wound healing. Among these, acellular dermal matrix, small intestinal submucosa, and amniotic membrane have been applied to treat burn wounds with acceptable outcomes. This review has explored the use of biomaterials derived from naturally occurring ECM and their derivatives for approaches aiming to promote burn wound healing, and summarized the ECM-based wound dressings products applicable in burn wound and postburn scar contracture to date.
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Affiliation(s)
- Yu-Ting Song
- Department of Orthopedic Surgery and Orthopedic Research Institute, Stem Cell and Tissue Engineering Research Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
| | - Peng-Cheng Liu
- Department of Orthopedic Surgery and Orthopedic Research Institute, Stem Cell and Tissue Engineering Research Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China; Department of Burn and Plastic Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
| | - Xing-Li Zhou
- Department of Orthopedic Surgery and Orthopedic Research Institute, Stem Cell and Tissue Engineering Research Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China; Department of Dermatology, Rare Diseases Center, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
| | - Yan-Ming Chen
- Department of Orthopedic Surgery and Orthopedic Research Institute, Stem Cell and Tissue Engineering Research Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
| | - Wu Wu
- Department of Orthopedic Surgery and Orthopedic Research Institute, Stem Cell and Tissue Engineering Research Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China; Department of Burn and Plastic Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
| | - Ji-Ye Zhang
- Department of Orthopedic Surgery and Orthopedic Research Institute, Stem Cell and Tissue Engineering Research Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
| | - Jesse Li-Ling
- Department of Orthopedic Surgery and Orthopedic Research Institute, Stem Cell and Tissue Engineering Research Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China; Frontier Medical Center, Tianfu Jincheng Laboratory, Chengdu, Sichuan 610212, China
| | - Hui-Qi Xie
- Department of Orthopedic Surgery and Orthopedic Research Institute, Stem Cell and Tissue Engineering Research Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China; Frontier Medical Center, Tianfu Jincheng Laboratory, Chengdu, Sichuan 610212, China.
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Starup-Hansen J, Williams SC, Valetopoulou A, Khan DZ, Horsfall HL, Moudgil-Joshi J, Burton O, Kanona H, Saeed SR, Muirhead W, Marcus HJ, Grover P. Skull Base Repair following Resection of Vestibular Schwannoma: A Systematic Review (Part 2: The Translabyrinthine Approach). J Neurol Surg B Skull Base 2024; 85:e131-e144. [PMID: 39444760 PMCID: PMC11495917 DOI: 10.1055/a-2222-0016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2023] [Accepted: 11/25/2023] [Indexed: 10/25/2024] Open
Abstract
Objectives Despite advances in skull base reconstruction techniques, cerebrospinal fluid (CSF) leaks remain a relatively common complication after translabyrinthine (TL) vestibular schwannoma (VS) surgery. We conducted a systematic review to synthesize the repair techniques and materials used in TL VS surgery to prevent CSF leaks. Design A systematic review of studies published since 2000 reporting techniques to prevent CSF leaks during adult TL VS surgery was conducted. A narrative synthesis of primary repair protocols was produced, and a taxonomy was established. Additionally, the advantages, disadvantages, and associated CSF leak rates of different repair protocols were extracted. Results All 43 studies were case series, and 39 were retrospective. Repair strategies included heterogeneous combinations of autografts, xenografts, and synthetic materials. A taxonomy was produced, classifying repairs into seven distinct stages, including approaches to the dura, middle ear cleft, air cells, TL bony defect, extra-cranial soft tissue, postoperative dressings, and CSF diversion. The median postoperative incidence of CSF leaks was 6% (interquartile range: 0-10%). Conclusions This systematic review reveals substantial inter-institutional heterogeneity in intraoperative strategies to prevent CSF leaks following TL VS surgery. However, comparing these techniques is challenging due to the multiple predictive factors for CSF leaks and their inconsistent reporting. We propose a taxonomy of seven stages to classify operative techniques and materials aimed at preventing CSF leaks. We recommend that future evaluations should adopt a prospective approach encompassing data collection strategies that considers all operative stages described by our taxonomy.
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Affiliation(s)
- Joachim Starup-Hansen
- Victor Horsley Department of Neurosurgery, The National Hospital for Neurology and Neurosurgery, University College London NHS Trust, London, United Kingdom
- Wellcome/EPSRC Centre for Interventional and Surgical Sciences, University College London, London, United Kingdom
| | - Simon C. Williams
- Wellcome/EPSRC Centre for Interventional and Surgical Sciences, University College London, London, United Kingdom
- Department of Neurosurgery, The Royal London Hospital, London United Kingdom
| | - Alexandra Valetopoulou
- Victor Horsley Department of Neurosurgery, The National Hospital for Neurology and Neurosurgery, University College London NHS Trust, London, United Kingdom
- Wellcome/EPSRC Centre for Interventional and Surgical Sciences, University College London, London, United Kingdom
| | - Danyal Z. Khan
- Victor Horsley Department of Neurosurgery, The National Hospital for Neurology and Neurosurgery, University College London NHS Trust, London, United Kingdom
- Wellcome/EPSRC Centre for Interventional and Surgical Sciences, University College London, London, United Kingdom
| | - Hugo Layard Horsfall
- Victor Horsley Department of Neurosurgery, The National Hospital for Neurology and Neurosurgery, University College London NHS Trust, London, United Kingdom
- Wellcome/EPSRC Centre for Interventional and Surgical Sciences, University College London, London, United Kingdom
| | - Jigishaa Moudgil-Joshi
- Victor Horsley Department of Neurosurgery, The National Hospital for Neurology and Neurosurgery, University College London NHS Trust, London, United Kingdom
- Wellcome/EPSRC Centre for Interventional and Surgical Sciences, University College London, London, United Kingdom
| | - Oliver Burton
- Victor Horsley Department of Neurosurgery, The National Hospital for Neurology and Neurosurgery, University College London NHS Trust, London, United Kingdom
- Wellcome/EPSRC Centre for Interventional and Surgical Sciences, University College London, London, United Kingdom
| | - Hala Kanona
- Victor Horsley Department of Neurosurgery, The National Hospital for Neurology and Neurosurgery, University College London NHS Trust, London, United Kingdom
- The Royal National Throat, Nose and Ear Hospital, London, United Kingdom
| | - Shakeel R. Saeed
- Victor Horsley Department of Neurosurgery, The National Hospital for Neurology and Neurosurgery, University College London NHS Trust, London, United Kingdom
- The Royal National Throat, Nose and Ear Hospital, London, United Kingdom
- University College London Ear Institute, London, United Kingdom
| | - William Muirhead
- Victor Horsley Department of Neurosurgery, The National Hospital for Neurology and Neurosurgery, University College London NHS Trust, London, United Kingdom
- Wellcome/EPSRC Centre for Interventional and Surgical Sciences, University College London, London, United Kingdom
| | - Hani J. Marcus
- Victor Horsley Department of Neurosurgery, The National Hospital for Neurology and Neurosurgery, University College London NHS Trust, London, United Kingdom
- Wellcome/EPSRC Centre for Interventional and Surgical Sciences, University College London, London, United Kingdom
| | - Patrick Grover
- Victor Horsley Department of Neurosurgery, The National Hospital for Neurology and Neurosurgery, University College London NHS Trust, London, United Kingdom
- Wellcome/EPSRC Centre for Interventional and Surgical Sciences, University College London, London, United Kingdom
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Stöth M, Mineif AT, Sauer F, Meyer TJ, Mueller-Diesing F, Haug L, Scherzad A, Steinke M, Rossi A, Hackenberg S. A Tissue Engineered 3D Model of Cancer Cell Invasion for Human Head and Neck Squamous-Cell Carcinoma. Curr Issues Mol Biol 2024; 46:4049-4062. [PMID: 38785518 PMCID: PMC11119844 DOI: 10.3390/cimb46050250] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2024] [Revised: 04/23/2024] [Accepted: 04/25/2024] [Indexed: 05/25/2024] Open
Abstract
Head and neck squamous-cell carcinoma (HNSCC) is associated with aggressive local invasiveness, being a main reason for its poor prognosis. The exact mechanisms underlying the strong invasive abilities of HNSCC remain to be elucidated. Therefore, there is a need for in vitro models to study the interplay between cancer cells and normal adjacent tissue at the invasive tumor front. To generate oral mucosa tissue models (OMM), primary keratinocytes and fibroblasts from human oral mucosa were isolated and seeded onto a biological scaffold derived from porcine small intestinal submucosa with preserved mucosa. Thereafter, we tested different methods (single tumor cells, tumor cell spots, spheroids) to integrate the human cancer cell line FaDu to generate an invasive three-dimensional model of HNSCC. All models were subjected to morphological analysis by histology and immunohistochemistry. We successfully built OMM tissue models with high in vivo-in vitro correlation. The integration of FaDu cell spots and spheroids into the OMM failed. However, with the integration of single FaDu cells into the OMM, invasive tumor cell clusters developed. Between segments of regular epithelial differentiation of the OMM, these clusters showed a basal membrane penetration and lamina propria infiltration. Primary human fibroblasts and keratinocytes seeded onto a porcine carrier structure are suitable to build an OMM. The HNSCC model with integrated FaDu cells could enable subsequent investigations into cancer cell invasiveness.
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Affiliation(s)
- Manuel Stöth
- Department of Otorhinolaryngology, Plastic, Aesthetic and Reconstructive Head and Neck Surgery, University Hospital Würzburg, 97080 Würzburg, Germany; (M.S.); (T.J.M.); (F.M.-D.); (A.S.); (M.S.)
| | - Anna Teresa Mineif
- Chair of Tissue Engineering and Regenerative Medicine, University Hospital Würzburg, 97070 Würzburg, Germany; (A.T.M.)
| | - Fabian Sauer
- Chair of Tissue Engineering and Regenerative Medicine, University Hospital Würzburg, 97070 Würzburg, Germany; (A.T.M.)
| | - Till Jasper Meyer
- Department of Otorhinolaryngology, Plastic, Aesthetic and Reconstructive Head and Neck Surgery, University Hospital Würzburg, 97080 Würzburg, Germany; (M.S.); (T.J.M.); (F.M.-D.); (A.S.); (M.S.)
| | - Flurin Mueller-Diesing
- Department of Otorhinolaryngology, Plastic, Aesthetic and Reconstructive Head and Neck Surgery, University Hospital Würzburg, 97080 Würzburg, Germany; (M.S.); (T.J.M.); (F.M.-D.); (A.S.); (M.S.)
| | - Lukas Haug
- Institute of Pathology, University of Würzburg, 97080 Würzburg, Germany;
| | - Agmal Scherzad
- Department of Otorhinolaryngology, Plastic, Aesthetic and Reconstructive Head and Neck Surgery, University Hospital Würzburg, 97080 Würzburg, Germany; (M.S.); (T.J.M.); (F.M.-D.); (A.S.); (M.S.)
| | - Maria Steinke
- Department of Otorhinolaryngology, Plastic, Aesthetic and Reconstructive Head and Neck Surgery, University Hospital Würzburg, 97080 Würzburg, Germany; (M.S.); (T.J.M.); (F.M.-D.); (A.S.); (M.S.)
- Chair of Tissue Engineering and Regenerative Medicine, University Hospital Würzburg, 97070 Würzburg, Germany; (A.T.M.)
- Fraunhofer Institute for Silicate Research ISC, 97082 Würzburg, Germany;
| | - Angela Rossi
- Fraunhofer Institute for Silicate Research ISC, 97082 Würzburg, Germany;
| | - Stephan Hackenberg
- Department of Otorhinolaryngology, Plastic, Aesthetic and Reconstructive Head and Neck Surgery, University Hospital Würzburg, 97080 Würzburg, Germany; (M.S.); (T.J.M.); (F.M.-D.); (A.S.); (M.S.)
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Harmon KA, Burnette MD, Avery JT, Kimmerling KA, Mowry KC. Varying Properties of Extracellular Matrix Grafts Impact Their Durability and Cell Attachment and Proliferation in an In Vitro Chronic Wound Model. J Tissue Eng Regen Med 2024; 2024:6632276. [PMID: 40225755 PMCID: PMC11918773 DOI: 10.1155/2024/6632276] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2023] [Revised: 02/28/2024] [Accepted: 03/27/2024] [Indexed: 04/15/2025]
Abstract
While acute wounds typically progress through the phases of wound healing, chronic wounds often stall in the inflammatory phase due to elevated levels of matrix metalloproteinases (MMPs) and proinflammatory cytokines. Dysregulated expression of MMPs can result in the breakdown of extracellular matrix (ECM) formed during the wound healing process, resulting in stalled wounds. Native collagen-based wound dressings offer a potential wound management option to sequester excess MMPs and support cellular interactions that allow wound progression through the natural healing process. Herein, we utilized commercially available ECM matrices, two derived from porcine small intestinal submucosa (PCMP, 2 layers; PCMP-XT, 5 layers) and one derived from propria submucosa (ovine forestomach matrix, OFM, 1 layer), to demonstrate the impact of processing methodologies (e.g., layering and crosslinking) on functional characteristics needed for the management of chronic wounds. Grafts were evaluated for structural composition using scanning electron microscopy and histology, ability to reduce MMPs using fluorometric assays, and durability in an in vitro degradation chronic wound model. Both intact (nondegraded) and partially degraded grafts were assessed for their ability to serve as a functional cell scaffold using primary human fibroblasts. Grafts differed in matrix substructure and composition. While all grafts demonstrated attenuation of MMP activity, PCMP and PCMP-XT showed larger reductions of MMP levels. OFM rapidly degraded in the in vitro degradation model (<3 hours), while PCMP and PCMP-XT were significantly more durable (>7 days). The ability of PCMP and PCMP-XT to serve as scaffolds for cellular attachment was not impacted by degradation in vitro. Three ECM grafts with varying structural and functional characteristics exhibited differential durability when degraded in a simulated chronic wound model. Those that withstood rapid degradation maintained their ability to function as a scaffold to support attachment and proliferation of fibroblasts, a cell type important for wound healing.
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Affiliation(s)
- Katrina A. Harmon
- Organogenesis, 2 Perimeter Park South, Suite 310E, Birmingham, AL 35243, USA
| | - Miranda D. Burnette
- Organogenesis, 2 Perimeter Park South, Suite 310E, Birmingham, AL 35243, USA
| | - Justin T. Avery
- Organogenesis, 2 Perimeter Park South, Suite 310E, Birmingham, AL 35243, USA
| | - Kelly A. Kimmerling
- Organogenesis, 2 Perimeter Park South, Suite 310E, Birmingham, AL 35243, USA
| | - Katie C. Mowry
- Organogenesis, 2 Perimeter Park South, Suite 310E, Birmingham, AL 35243, USA
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Fu TS, Chen WC, Wang YC, Chang CW, Lin TY, Wong CB. Biomimetic vascularized adipose-derived mesenchymal stem cells bone-periosteum graft enhances angiogenesis and osteogenesis in a male rabbit spine fusion model. Bone Joint Res 2023; 12:722-733. [PMID: 38052231 PMCID: PMC10697772 DOI: 10.1302/2046-3758.1212.bjr-2023-0013.r1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/07/2023] Open
Abstract
Aims Several artificial bone grafts have been developed but fail to achieve anticipated osteogenesis due to their insufficient neovascularization capacity and periosteum support. This study aimed to develop a vascularized bone-periosteum construct (VBPC) to provide better angiogenesis and osteogenesis for bone regeneration. Methods A total of 24 male New Zealand white rabbits were divided into four groups according to the experimental materials. Allogenic adipose-derived mesenchymal stem cells (AMSCs) were cultured and seeded evenly in the collagen/chitosan sheet to form cell sheet as periosteum. Simultaneously, allogenic AMSCs were seeded onto alginate beads and were cultured to differentiate to endothelial-like cells to form vascularized bone construct (VBC). The cell sheet was wrapped onto VBC to create a vascularized bone-periosteum construct (VBPC). Four different experimental materials - acellular construct, VBC, non-vascularized bone-periosteum construct, and VBPC - were then implanted in bilateral L4-L5 intertransverse space. At 12 weeks post-surgery, the bone-forming capacities were determined by CT, biomechanical testing, histology, and immunohistochemistry staining analyses. Results At 12 weeks, the VBPC group significantly increased new bone formation volume compared with the other groups. Biomechanical testing demonstrated higher torque strength in the VBPC group. Notably, the haematoxylin and eosin, Masson's trichrome, and immunohistochemistry-stained histological results revealed that VBPC promoted neovascularization and new bone formation in the spine fusion areas. Conclusion The tissue-engineered VBPC showed great capability in promoting angiogenesis and osteogenesis in vivo. It may provide a novel approach to create a superior blood supply and nutritional environment to overcome the deficits of current artificial bone graft substitutes.
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Affiliation(s)
- Tsai-Sheng Fu
- Department of Orthopaedic Surgery, Chang Gung Memorial Hospital, School of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Wei-Chuan Chen
- Graduate School of Biotechnology and Bioengineering, Yuan Ze University, Taoyuan, Taiwan
| | - Ying-Chih Wang
- Department of Orthopaedic Surgery, Chang Gung Memorial Hospital, School of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Chia-Wei Chang
- Department of Orthopaedic Surgery, Chang Gung Memorial Hospital, School of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Tung-yi Lin
- Department of Orthopaedic Surgery, Chang Gung Memorial Hospital, School of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Chak-Bor Wong
- Department of Orthopaedic Surgery, Chang Gung Memorial Hospital, School of Medicine, Chang Gung University, Taoyuan, Taiwan
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Sharma A, Sharma D, Zhao F. Updates on Recent Clinical Assessment of Commercial Chronic Wound Care Products. Adv Healthc Mater 2023; 12:e2300556. [PMID: 37306401 PMCID: PMC11932735 DOI: 10.1002/adhm.202300556] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2023] [Revised: 06/01/2023] [Indexed: 06/13/2023]
Abstract
Impaired wound healing after trauma, disorders, and surgeries impact millions of people globally every year. Dysregulation in orchestrated healing mechanisms and underlying medical complications make chronic wound management extremely challenging. Besides standard-of-care treatments including broad spectrum antibiotics and wound-debridement, novel adjuvant therapies are clinically tested and commercialized. These include topical agents, skin substitutes, growth factor delivery, and stem cell therapies. With a goal to overcome factors playing pivotal role in delayed wound healing, researchers are exploring novel approaches to elicit desirable healing outcomes in chronic wounds. Although recent innovations in wound care products, therapies, and devices are extensively reviewed in past, a comprehensive review summarizing their clinical outcomes is surprisingly lacking. Herein, this work reviews the commercially available wound care products and their performance in clinical trials to provide a statistically comprehensive understanding of their safety and efficacy. The performance and suitability of various commercial wound care platforms, including xenogeneic and allogenic products, wound care devices, and novel biomaterials, are discussed for chronic wounds. The current clinical evaluation will provide a comprehensive understanding of the benefits and drawbacks of the most-recent approaches and will enable researchers and healthcare providers to develop next-generation technologies for chronic wound management.
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Affiliation(s)
- Archita Sharma
- Department of Biomedical Engineering, Texas A&M University, College Station, TX, 77840, USA
| | - Dhavan Sharma
- Department of Biomedical Engineering, Texas A&M University, College Station, TX, 77840, USA
| | - Feng Zhao
- Department of Biomedical Engineering, Texas A&M University, College Station, TX, 77840, USA
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Oliveira C, Sousa D, Teixeira JA, Ferreira-Santos P, Botelho CM. Polymeric biomaterials for wound healing. Front Bioeng Biotechnol 2023; 11:1136077. [PMID: 37576995 PMCID: PMC10415681 DOI: 10.3389/fbioe.2023.1136077] [Citation(s) in RCA: 18] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2023] [Accepted: 06/19/2023] [Indexed: 08/15/2023] Open
Abstract
Skin indicates a person's state of health and is so important that it influences a person's emotional and psychological behavior. In this context, the effective treatment of wounds is a major concern, since several conventional wound healing materials have not been able to provide adequate healing, often leading to scar formation. Hence, the development of innovative biomaterials for wound healing is essential. Natural and synthetic polymers are used extensively for wound dressings and scaffold production. Both natural and synthetic polymers have beneficial properties and limitations, so they are often used in combination to overcome overcome their individual limitations. The use of different polymers in the production of biomaterials has proven to be a promising alternative for the treatment of wounds, as their capacity to accelerate the healing process has been demonstrated in many studies. Thus, this work focuses on describing several currently commercially available solutions used for the management of skin wounds, such as polymeric biomaterials for skin substitutes. New directions, strategies, and innovative technologies for the design of polymeric biomaterials are also addressed, providing solutions for deep burns, personalized care and faster healing.
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Affiliation(s)
- Cristiana Oliveira
- CEB—Centre of Biological Engineering, University of Minho, Campus de Gualtar, Braga, Portugal
- LABBELS—Associate Laboratory, Braga, Portugal
| | - Diana Sousa
- CEB—Centre of Biological Engineering, University of Minho, Campus de Gualtar, Braga, Portugal
- LABBELS—Associate Laboratory, Braga, Portugal
| | - José A. Teixeira
- CEB—Centre of Biological Engineering, University of Minho, Campus de Gualtar, Braga, Portugal
- LABBELS—Associate Laboratory, Braga, Portugal
| | - Pedro Ferreira-Santos
- CEB—Centre of Biological Engineering, University of Minho, Campus de Gualtar, Braga, Portugal
- LABBELS—Associate Laboratory, Braga, Portugal
- Department of Chemical Engineering, Faculty of Science, University of Vigo, Ourense, Spain
| | - Claudia M. Botelho
- CEB—Centre of Biological Engineering, University of Minho, Campus de Gualtar, Braga, Portugal
- LABBELS—Associate Laboratory, Braga, Portugal
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Afzal Z, Huguet EL. Bioengineering liver tissue by repopulation of decellularised scaffolds. World J Hepatol 2023; 15:151-179. [PMID: 36926238 PMCID: PMC10011915 DOI: 10.4254/wjh.v15.i2.151] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/26/2022] [Revised: 11/22/2022] [Accepted: 02/15/2023] [Indexed: 02/24/2023] Open
Abstract
Liver transplantation is the only curative therapy for end stage liver disease, but is limited by the organ shortage, and is associated with the adverse consequences of immunosuppression. Repopulation of decellularised whole organ scaffolds with appropriate cells of recipient origin offers a theoretically attractive solution, allowing reliable and timely organ sourcing without the need for immunosuppression. Decellularisation methodologies vary widely but seek to address the conflicting objectives of removing the cellular component of tissues whilst keeping the 3D structure of the extra-cellular matrix intact, as well as retaining the instructive cell fate determining biochemicals contained therein. Liver scaffold recellularisation has progressed from small rodent in vitro studies to large animal in vivo perfusion models, using a wide range of cell types including primary cells, cell lines, foetal stem cells, and induced pluripotent stem cells. Within these models, a limited but measurable degree of physiologically significant hepatocyte function has been reported with demonstrable ammonia metabolism in vivo. Biliary repopulation and function have been restricted by challenges relating to the culture and propagations of cholangiocytes, though advances in organoid culture may help address this. Hepatic vasculature repopulation has enabled sustainable blood perfusion in vivo, but with cell types that would limit clinical applications, and which have not been shown to have the specific functions of liver sinusoidal endothelial cells. Minority cell groups such as Kupffer cells and stellate cells have not been repopulated. Bioengineering by repopulation of decellularised scaffolds has significantly progressed, but there remain significant experimental challenges to be addressed before therapeutic applications may be envisaged.
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Affiliation(s)
- Zeeshan Afzal
- Department of Surgery, Addenbrookes Hospital, NIHR Comprehensive Biomedical Research and Academic Health Sciences Centre; Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, United Kingdom
| | - Emmanuel Laurent Huguet
- Department of Surgery, Addenbrookes Hospital, NIHR Comprehensive Biomedical Research and Academic Health Sciences Centre; Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, United Kingdom
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Song YT, Dong L, Hu JG, Liu PC, Jiang YL, Zhou L, Wang M, Tan J, Li YX, Zhang QY, Zou CY, Zhang XZ, Zhao LM, Nie R, Zhang Y, Li-Ling J, Xie HQ. Application of genipin-crosslinked small intestine submucosa and urine-derived stem cells for the prevention of intrauterine adhesion in a rat model. COMPOSITES PART B: ENGINEERING 2023; 250:110461. [DOI: 10.1016/j.compositesb.2022.110461] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 08/25/2024]
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Simman R. Role of small intestinal submucosa extracellular matrix in advanced regenerative wound therapy. J Wound Care 2023; 32:S3-S10. [PMID: 36724085 DOI: 10.12968/jowc.2023.32.sup2.s3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/02/2023]
Abstract
Advanced regenerative therapies using cellular and tissue-based products (CTPs) can play an important role in effective management of hard-to-heal wounds. CTPs derived from allogenic or xenogenic tissues use an extracellular matrix (ECM) to provide a therapeutic ECM scaffold in the wound bed to facilitate tissue regeneration. One such example is OASIS Extracellular Matrix (Cook Biotech Incorporated), a porcine small intestinal submucosa extracellular matrix (SIS-ECM) that preclinical and clinical data have shown to be tolerable and effective in promoting tissue regeneration in hard-to-heal wounds.
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Affiliation(s)
- Richard Simman
- Professor of Plastic Surgery, University of Toledo College of Medicine and Life Sciences, and Jobst Vascular Institute, ProMedica Health Network, Toledo, Ohio, US
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Simman R. Role of small intestinal submucosa extracellular matrix in advanced regenerative wound therapy. J Wound Care 2023; 32:S3-S10. [PMID: 36744603 DOI: 10.12968/jowc.2023.32.sup1a.s3] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Advanced regenerative therapies using cellular and tissue-based products (CTPs) can play an important role in effective management of hard-to-heal wounds. CTPs derived from allogenic or xenogenic tissues use an extracellular matrix (ECM) to provide a therapeutic ECM scaffold in the wound bed to facilitate tissue regeneration. One such example is OASIS Extracellular Matrix (Cook Biotech Incorporated), a porcine small intestinal submucosa extracellular matrix (SIS-ECM) that preclinical and clinical data have shown to be tolerable and effective in promoting tissue regeneration in hard-to-heal wounds.
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Affiliation(s)
- Richard Simman
- Professor of Plastic Surgery, University of Toledo College of Medicine and Life Sciences, and Jobst Vascular Institute, ProMedica Health Network, Toledo, Ohio, US
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Qian H, He L, Ye Z, Wei Z, Ao J. Decellularized matrix for repairing intervertebral disc degeneration: Fabrication methods, applications and animal models. Mater Today Bio 2022; 18:100523. [PMID: 36590980 PMCID: PMC9800636 DOI: 10.1016/j.mtbio.2022.100523] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2022] [Revised: 12/14/2022] [Accepted: 12/16/2022] [Indexed: 12/23/2022] Open
Abstract
Intervertebral disc degeneration (IDD)-induced low back pain significantly influences the quality of life, placing a burden on public health systems worldwide. Currently available therapeutic strategies, such as conservative or operative treatment, cannot effectively restore intervertebral disc (IVD) function. Decellularized matrix (DCM) is a tissue-engineered biomaterial fabricated using physical, chemical, and enzymatic technologies to eliminate cells and antigens. By contrast, the extracellular matrix (ECM), including collagen and glycosaminoglycans, which are well retained, have been extensively studied in IVD regeneration. DCM inherits the native architecture and specific-differentiation induction ability of IVD and has demonstrated effectiveness in IVD regeneration in vitro and in vivo. Moreover, significant improvements have been achieved in the preparation process, mechanistic insights, and application of DCM for IDD repair. Herein, we comprehensively summarize and provide an overview of the roles and applications of DCM for IDD repair based on the existing evidence to shed a novel light on the clinical treatment of IDD.
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Key Words
- (3D), three-dimensional
- (AF), annular fibers
- (AFSC), AF stem cells
- (APNP), acellular hydrogel descendent from porcine NP
- (DAF-G), decellularized AF hydrogel
- (DAPI), 4,6-diamidino-2-phenylindole
- (DCM), decellularized matrix
- (DET), detergent-enzymatic treatment
- (DWJM), Wharton's jelly matrix
- (ECM), extracellular matrix
- (EVs), extracellular vesicles
- (Exos), exosome
- (IDD), intervertebral disc degeneration
- (IVD), intervertebral disc
- (LBP), Low back pain
- (NP), nucleus pulposus
- (NPCS), NP-based cell delivery system
- (PEGDA/DAFM), polyethylene glycol diacrylate/decellularized AF matrix
- (SD), sodium deoxycholate
- (SDS), sodium dodecyl sulfate
- (SIS), small intestinal submucosa
- (TGF), transforming growth factor
- (bFGF), basic fibroblast growth factor
- (hADSCs), human adipose-derived stem cells
- (hDF), human dermal fibroblast
- (iAF), inner annular fibers
- (oAF), outer annular fibers
- (sGAG), sulfated glycosaminoglycan
- Decellularized matrix
- Intervertebral disc degeneration
- Regenerative medicine
- Tissue engineering
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Affiliation(s)
- Hu Qian
- Department of Orthopaedic Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, China
| | - Li He
- Department of Orthopaedic Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, China
| | - Zhimin Ye
- Department of Pathology, School of Basic Medical Sciences, Central South University, Changsha, China
- Corresponding author. Department of Pathology, School of Basic Medical Sciences, Central South University, Changsha, 410000, China.
| | - Zairong Wei
- Department of Burns and Plastic Surgery, The Affiliated Hospital of Zunyi Medical College, Zunyi, China
| | - Jun Ao
- Department of Orthopaedic Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, China
- Corresponding author. Department of Orthopaedic Surgery, Affiliated Hospital of Zunyi Medical University, 149 Dalian Road, Zunyi, 563000, China.
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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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Outcome of a novel porcine-derived UBM/SIS composite biological mesh in a rabbit vaginal defect model. Int Urogynecol J 2022:10.1007/s00192-022-05400-5. [DOI: 10.1007/s00192-022-05400-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2022] [Accepted: 10/10/2022] [Indexed: 12/13/2022]
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Chen Y, Lu X, Luo H, Kassab GS. Aortic Leaflet Stresses Are Substantially Lower Using Pulmonary Visceral Pleura Than Pericardial Tissue. Front Bioeng Biotechnol 2022; 10:869095. [PMID: 35557866 PMCID: PMC9086238 DOI: 10.3389/fbioe.2022.869095] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2022] [Accepted: 03/17/2022] [Indexed: 12/05/2022] Open
Abstract
Background: Porcine heart and bovine pericardium valves, which are collagen-based with relatively little elastin, have been broadly utilized to construct bioprosthetic heart valves (BHVs). With a larger proportion of elastin, the pulmonary visceral pleura (PVP) has greater elasticity and could potentially serve as an advantageous biomaterial for the construction/repair of BHVs. The question of how the aortic valve’s performance is affected by its bending rigidity has not been well studied. Methods: Based on the stress–strain relationships of the pericardium and PVP determined by planar uni-axial tests, a three-dimensional (3D) computational fluid–structure interaction (FSI) framework is employed to numerically investigate the aortic valve’s performance by considering three different cases with Young’s modulus as follows: E=375, 750, and 1500 kPa, respectively. Results: The stroke volumes are 112, 99.6, and 91.4 ml as Young’s modulus increases from 375 to 750 and 1500 kPa, respectively. Peak geometric opening area (GOA) values are 2.3, 2.2, and 2.0 cm2 for E=375, 750, and 1500 kPa, respectively. The maximum value of the aortic leaflet stress is about 271 kPa for E=375 kPa, and it increases to about 383 and 540 kPa for E=750 and 1500 kPa in the belly region at the peak systole, while it reduces from 550 kPa to 450 and 400 kPa for E=375, 750, and 1500 kPa, respectively, at the instant of peak “water-hammer”. Conclusion: A more compliant PVP aortic leaflet valve with a smaller Young’s modulus, E, has a higher cardiac output, larger GOA, and lower hemodynamic resistance. Most importantly, the aortic leaflet stresses are substantially lower in the belly region within the higher compliance PVP aortic valve tissue during the systole phase, even though some stress increase is also found during the fast-closing phase due to the “water-hammer” effect similar to that in the pericardial tissue. Future clinical studies will be conducted to test the hypothesis that the PVP-based valve leaflets with higher compliance will have lower fatigue or calcification rates due to the overall lower stress.
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Affiliation(s)
- Ye Chen
- California Medical Innovations Institute, San Diego, CA, United States
| | - Xiao Lu
- California Medical Innovations Institute, San Diego, CA, United States
| | - Haoxiang Luo
- Department of Mechanical Engineering, Vanderbilt University, Nashville, TN, United States
| | - Ghassan S. Kassab
- California Medical Innovations Institute, San Diego, CA, United States
- *Correspondence: Ghassan S. Kassab,
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Lu X, Han L, Kassab GS. Pulmonary Visceral Pleura Biomaterial: Elastin- and Collagen-Based Extracellular Matrix. Front Bioeng Biotechnol 2022; 10:796076. [PMID: 35433658 PMCID: PMC9006517 DOI: 10.3389/fbioe.2022.796076] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2021] [Accepted: 02/28/2022] [Indexed: 12/17/2022] Open
Abstract
Objective: The goal of the study is to determine the structural characteristics, mechanical properties, cytotoxicity, and biocompatibility of the pulmonary visceral pleura (PVP).Background: Collagen and elastin are the major components of the extracellular matrix. The PVP has an abundance of elastin and collagen that can serve as a potential biomaterial for clinical repair and reconstructions.Methods: The PVP was processed from swine and bovine lungs. Chemical analyses were used to determine collagen and elastin contents in the PVPs. Immunofluorescence microscopy was used to analyze the structure of the PVP. The stress–strain relationships and stress relaxation were determined by using the planar uniaxial test. The cytotoxicity of the PVP was tested in cultured cells. In in vivo evaluations, the PVP was implanted in the sciatic nerve and skin of rats.Results: Collagen and elastin contents are abundant in the PVP with larger proportions of elastin than in the bovine pericardium and porcine small intestinal submucosa. A microstructural analysis revealed that the elastin fibers were distributed throughout the PVP and the collagen was distributed mainly in the mesothelial basal lamina. The incremental moduli in stress–strain curves and relaxation moduli in the Maxwell–Wiechert model of PVP were approximately one-tenth of the bovine pericardium and small intestinal submucosa. The minimal cytotoxicity of the PVP was demonstrated. The axons proliferated in the PVP conduit guidance from proximal to distal sciatic nerves of rats. The neo-skin regenerated under the PVP skin substitute within 4 weeks.Conclusions: The PVP is composed of abundant collagen and elastin. The structural characteristics and mechanical compliance of the PVP render a suitable biological material for repair/reconstruction.
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Design by Nature: Emerging Applications of Native Liver Extracellular Matrix for Cholangiocyte Organoid-Based Regenerative Medicine. Bioengineering (Basel) 2022; 9:bioengineering9030110. [PMID: 35324799 PMCID: PMC8945468 DOI: 10.3390/bioengineering9030110] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2022] [Revised: 02/25/2022] [Accepted: 03/04/2022] [Indexed: 12/14/2022] Open
Abstract
Organoid technology holds great promise for regenerative medicine. Recent studies show feasibility for bile duct tissue repair in humans by successfully transplanting cholangiocyte organoids in liver grafts during perfusion. Large-scale expansion of cholangiocytes is essential for extending these regenerative medicine applications. Human cholangiocyte organoids have a high and stable proliferation capacity, making them an attractive source of cholangiocytes. Commercially available basement membrane extract (BME) is used to expand the organoids. BME allows the cells to self-organize into 3D structures and stimulates cell proliferation. However, the use of BME is limiting the clinical applications of the organoids. There is a need for alternative tissue-specific and clinically relevant culture substrates capable of supporting organoid proliferation. Hydrogels prepared from decellularized and solubilized native livers are an attractive alternative for BME. These hydrogels can be used for the culture and expansion of cholangiocyte organoids in a clinically relevant manner. Moreover, the liver-derived hydrogels retain tissue-specific aspects of the extracellular microenvironment. They are composed of a complex mixture of bioactive and biodegradable extracellular matrix (ECM) components and can support the growth of various hepatobiliary cells. In this review, we provide an overview of the clinical potential of native liver ECM-based hydrogels for applications with human cholangiocyte organoids. We discuss the current limitations of BME for the clinical applications of organoids and how native ECM hydrogels can potentially overcome these problems in an effort to unlock the full regenerative clinical potential of the organoids.
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Wang X, Shi C, Hou X, Song S, Li C, Cao W, Chen W, Li L. Application of biomaterials and tissue engineering in bladder regeneration. J Biomater Appl 2022; 36:1484-1502. [DOI: 10.1177/08853282211048574] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
The primary functions of the bladder are storing urine under low and stable pressure and micturition. Various forms of trauma, tumors, and iatrogenic injuries can cause the loss of or reduce bladder function or capacity. If such damage is not treated in time, it will eventually lead to kidney damage and can even be life-threatening in severe cases. The emergence of tissue engineering technology has led to the development of more possibilities for bladder repair and reconstruction, in which the selection of scaffolds is crucial. In recent years, a growing number of tissue-engineered bladder scaffolds have been constructed. Therefore, this paper will discuss the development of tissue-engineered bladder scaffolds and will further analyze the limitations of and challenges encountered in bladder reconstruction.
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Affiliation(s)
- Xiaoya Wang
- Department of Human Anatomy, Histology and Embryology, School of Basic Medicine, Qingdao University, Qingdao, Shandong, China
| | - Chunying Shi
- Department of Human Anatomy, Histology and Embryology, School of Basic Medicine, Qingdao University, Qingdao, Shandong, China
| | - Xianglin Hou
- Institute of genetics and developmental biology, Chinese Academy of Sciences, Beijing, China
| | - Siqi Song
- Department of Human Anatomy, Histology and Embryology, School of Basic Medicine, Qingdao University, Qingdao, Shandong, China
| | - Chenglin Li
- Department of Human Anatomy, Histology and Embryology, School of Basic Medicine, Qingdao University, Qingdao, Shandong, China
| | - Wenxuan Cao
- Department of Human Anatomy, Histology and Embryology, School of Basic Medicine, Qingdao University, Qingdao, Shandong, China
| | - Wei Chen
- Department of Urology, Xinqiao Hospital, Army Medical University, Chongqing, China
| | - Ling Li
- Department of Human Anatomy, Histology and Embryology, School of Basic Medicine, Qingdao University, Qingdao, Shandong, China
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Histopathological Analysis of Decellularized Porcine Small Intestinal Submucosa after Treatment of Skin Ulcer. PLASTIC AND RECONSTRUCTIVE SURGERY-GLOBAL OPEN 2021; 9:e3967. [PMID: 34938643 PMCID: PMC8687724 DOI: 10.1097/gox.0000000000003967] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2021] [Accepted: 10/04/2021] [Indexed: 11/25/2022]
Abstract
Background: Decellularized porcine small intestinal submucosa (SIS), commercialized as an extracellular matrix rich in cell-inducing substrates and factors, has been clinically applied to treat intractable skin ulcers and has shown therapeutic effects. The SIS reportedly induces cell infiltration and integrates with the ulcer bed after 3–7 days of application. The attached SIS degenerates over time, and the remaining mass appears as slough, below which is granulation tissue that is essential for healing. This study aimed to determine whether the slough should be removed in clinical settings. Methods: Five patients with intractable skin ulcers were included in this case series. Seven days after applying a two-layer fenestrated-type SIS to the ulcer, the removed slough was histopathologically examined. Results: The collagen fibers of the SIS somewhat degenerated, and inflammatory cell infiltration was observed from the ulcer side to the surface side of the SIS. Neovascularization was similarly observed on the ulcer side. The degree of inflammatory cell infiltration decreased from the ulcer side to the surface side, whereas pus (ie, aggregates of neutrophils) was observed on the surface and ulcer edges. Additionally, the removed slough contained regenerative epithelium on the ulcer side of the remaining collagen fibers. Conclusions: After treating intractable skin ulcers using SIS, we recommend removal of the upper surface and ulcer edge of the degenerated SIS or slough to prevent infection and preservation of the lower side of the degenerated SIS to maintain the granulation tissue and regenerative epithelium.
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Totten DJ, Manzoor NF, Yancey KL, Yawn RJ, Haynes DS, Rivas A. Comparison of Small Intestinal Submucosal Graft and Autologous Tissue in Prevention of CSF leak after Posterior Fossa Craniotomy. J Neurol Surg B Skull Base 2021; 82:695-699. [PMID: 34745839 DOI: 10.1055/s-0040-1713772] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2019] [Accepted: 04/27/2020] [Indexed: 10/21/2022] Open
Abstract
Objective To compare the use of porcine small intestinal submucosal grafts (SISG) and standard autologous material (fascia) in prevention of cerebrospinal fluid (CSF) leak and pseudomeningocele formation after translabyrinthine resection. Setting Set at the tertiary skull base center. Methods This is a retrospective chart review. After Institutional Review Board approval, we performed a retrospective cohort study evaluating CSF leak in patients who underwent resection of lateral skull base defects with multilayered reconstruction using either fascia autograft or porcine SISGs. Demographics were summarized with descriptive statistics. Logistic regression was used to compare autograft and xenograft cohorts in terms of CSF complications. Results Seventy-seven patients underwent lateral skull base resection, followed by reconstruction of the posterior cranial fossa. Of these patients, 21 (27.3%) underwent multilayer repair using SISG xenograft. There were no significant differences in leak-associated complications between autograft and xenograft cohorts. Ventriculoperitoneal shunt was necessary in one (1.8%) autograft and one (4.8) xenograft cases ( p = 0.49). Operative repair to revise surgical defect was necessary in three (5.4%) autograft cases and none in xenograft cases. Conclusion The use of SISG as a component of complex skull base reconstruction after translabyrinthine tumor resection may help reduce CSF leak rates and need for further intervention.
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Affiliation(s)
- Douglas J Totten
- Vanderbilt University School of Medicine, Nashville, Tennessee, United States
| | - Nauman F Manzoor
- Department of Otolaryngology-Head and Neck Surgery, Vanderbilt University Medical Center, Nashville, Tennessee, United States
| | - Kristen L Yancey
- Department of Otolaryngology-Head and Neck Surgery, Vanderbilt University Medical Center, Nashville, Tennessee, United States
| | - Robert J Yawn
- Department of Otolaryngology-Head and Neck Surgery, Vanderbilt University Medical Center, Nashville, Tennessee, United States
| | - David S Haynes
- Department of Otolaryngology-Head and Neck Surgery, Vanderbilt University Medical Center, Nashville, Tennessee, United States
| | - Alejandro Rivas
- Department of Otolaryngology-Head and Neck Surgery, Vanderbilt University Medical Center, Nashville, Tennessee, United States
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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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Zhou XB, Xu SW, Ye LP, Mao XL, Chen YH, Wu JF, Cai Y, Wang Y, Wang L, Li SW. Progress of esophageal stricture prevention after endoscopic submucosal dissection by regenerative medicine and tissue engineering. Regen Ther 2021; 17:51-60. [PMID: 33997185 PMCID: PMC8100352 DOI: 10.1016/j.reth.2021.01.003] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2020] [Revised: 11/17/2020] [Accepted: 01/11/2021] [Indexed: 01/10/2023] Open
Abstract
Endoscopic submucosal dissection (ESD) has been widely accepted as an effective treatment for early esophageal cancer. However, post-ESD esophageal stricture remains a thorny issue. We herein review many strategies for preventing post-ESD esophageal stricture, as well as discuss their strengths and weaknesses. These strategies include pharmacological prophylaxis, esophageal stent and tissue engineering and regenerative medicine treatment. In this review, we summarize these studies and discuss the underlying progress and future directions of tissue engineering and regenerative medicine treatment.
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Key Words
- 5-FU, 5-Fluorouracil
- ADSC, Autologous adipose-derived stem cells
- ASGS, autologous skin graft surgery
- ChST15, carbohydrate sulfotransferase 15
- EBD, endoscopic balloon dilation
- ECM, extracellular matrix
- ESD, endoscopic submucosal dissection
- Endoscopic submucosal dissection
- Esophageal stricture
- FCMS, fully covered metal stent
- OMECs, oral mucosal epithelial cell sheets
- PGAs, polyglycolic acid sheet
- PIPAAm, poly(N-isopropylacrylamide)
- Regenerative medicine
- SESCNs, superficial esophageal squamous cell neoplasms
- SIS, small intestinal submucosa
- SeMS, self-expandable metal stents
- TA, triamcinolone acetonide
- TS-PGA, triamcinolone-soaked polyglycolic acid sheet
- Tissue engineering
- Tβ4, Thymosin β4
- ccESTD, complete circular endoscopic submucosal tunnel dissection
- siRNA, small interfering RNA
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Affiliation(s)
- Xian-bin Zhou
- Department of Gastroenterology, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, LinHai, Zhejiang, China
| | - Shi-wen Xu
- Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Li-ping Ye
- Department of Gastroenterology, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, LinHai, Zhejiang, China
| | - Xin-li Mao
- Department of Gastroenterology, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, LinHai, Zhejiang, China
| | - Ya-hong Chen
- Health Management Center, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Linhai, Zhejiang, China
| | - Jian-fen Wu
- Department of Gastroenterology, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, LinHai, Zhejiang, China
| | - Yue Cai
- Department of Gastroenterology, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, LinHai, Zhejiang, China
| | - Yi Wang
- Department of Gastroenterology, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, LinHai, Zhejiang, China
| | - Li Wang
- College of Basic Medicine, Inner Mongolia Medical University, Hohhot, Inner Mongolia, China
| | - Shao-wei Li
- Department of Gastroenterology, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, LinHai, Zhejiang, China
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Pendolino AL, Unadkat S, Navaratnam AV, Randhawa PS, Andrews PJ. A Single-Center 5-Year Experience Using the Triple-Layer Technique for Surgical Repair of Nasal Septal Perforations. Facial Plast Surg Aesthet Med 2021; 24:326-327. [PMID: 33847509 DOI: 10.1089/fpsam.2020.0623] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Affiliation(s)
- Alfonso Luca Pendolino
- Department of ENT, Royal National ENT and Eastman Dental Hospitals, London, United Kingdom
- Ear Institute, UCL, London, United Kingdom
| | - Samit Unadkat
- Department of ENT, Royal National ENT and Eastman Dental Hospitals, London, United Kingdom
| | - Annakan V Navaratnam
- Department of ENT, Royal National ENT and Eastman Dental Hospitals, London, United Kingdom
| | - Premjit S Randhawa
- Department of ENT, Royal National ENT and Eastman Dental Hospitals, London, United Kingdom
| | - Peter J Andrews
- Department of ENT, Royal National ENT and Eastman Dental Hospitals, London, United Kingdom
- Ear Institute, UCL, London, United Kingdom
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25
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Qiu S, Liang L, Zou P, Chen Q. Decellularized small intestine submucosa/polylactic-co-glycolic acid composite scaffold for potential application in hypopharyngeal and cervical esophageal tissue repair. Regen Biomater 2021; 8:rbaa061. [PMID: 33738114 PMCID: PMC7955713 DOI: 10.1093/rb/rbaa061] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2020] [Revised: 11/01/2020] [Accepted: 12/18/2020] [Indexed: 11/14/2022] Open
Abstract
There has been an increase in the incidence of hypopharyngeal and cervical esophageal cancer worldwide, and hence growing needs for hypopharyngeal and cervical esophageal tissue repair. This work produced a bi-layer composite scaffold with decellularized small intestine submucosa and polylactic-co-glycolic acid, which resembled the layered architectures of its intended tissues. The decellularized small intestine submucosa contained minimal residual DNA (52.5 ± 1.2 ng/mg) and the composite scaffold exhibited satisfactory mechanical properties (a tensile modulus of 21.1 ± 4.8 MPa, an ultimate tensile strength of 14.0 ± 2.9 MPa and a failure strain of 26.9 ± 5.1%). The interactions between cells and the respective layers of the scaffold were characterized by CCK-8 assays, immunostaining and Western blotting. Desirable cell proliferation and phenotypic behaviors were observed. These results have provided an important basis for the next-step in vivo studies of the scaffold, and bode well for its future clinical applications.
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Affiliation(s)
- Shijie Qiu
- Department of Otorhinolaryngology-Head and Neck Surgery, The First Affiliated Hospital of Zhejiang University, 79 Qingchun Road, Hangzhou, 310003, People's Republic of China.,Department of Otorhinolaryngology-Head and Neck Surgery, Lihuili Hospital of Ningbo University, 57 Xingning Road, Ningbo, 315041, People's Republic of China
| | - Lijin Liang
- Ningbo Regen Biotech Co., Ltd, 199 East Hexiao Road, Ningbo, 315157, People's Republic of China
| | - Peng Zou
- Ningbo Regen Biotech Co., Ltd, 199 East Hexiao Road, Ningbo, 315157, People's Republic of China
| | - Qi Chen
- Ningbo Regen Biotech Co., Ltd, 199 East Hexiao Road, Ningbo, 315157, People's Republic of China
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26
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Material Characterisation and Stratification of Conjunctival Epithelial Cells on Electrospun Poly(ε-Caprolactone) Fibres Loaded with Decellularised Tissue Matrices. Pharmaceutics 2021; 13:pharmaceutics13030318. [PMID: 33671006 PMCID: PMC7997349 DOI: 10.3390/pharmaceutics13030318] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2021] [Revised: 02/17/2021] [Accepted: 02/24/2021] [Indexed: 12/16/2022] Open
Abstract
The conjunctiva, an under-researched yet incredibly important tissue, plays key roles in providing protection to the eye and maintaining homeostasis of its ocular surface. Multiple diseases can impair conjunctival function leading to severe consequences that require surgical intervention. Small conjunctival defects can be repaired relatively easily, but larger defects rely on tissue grafts which generally do not provide adequate healing. A tissue engineering approach involving a biomaterial substrate capable of supporting a stratified epithelium with embedded, mucin-secreting goblet cells offers a potential solution. As a first step, this study aimed to induce stratification of human conjunctival epithelial cells cultured on electrospun scaffolds composed from poly(ε-caprolactone) (PCL) and decellularised tissue matrix (small intestinal submucosa (SIS) or urinary bladder matrix (UBM)) and held at the air/liquid interface. Stratification, up to 5 cell layers, occurred more frequently on scaffolds containing PCL + UBM. Incorporation of these decellularised tissue matrices also impacted material properties, with significant changes occurring to their fibre diameter, tensile properties, and chemical composition throughout the scaffold structure compared to PCL alone. These matrix containing scaffolds warrant further long-term investigation as a potential advanced therapy medicinal product for conjunctiva repair and regeneration.
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27
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Singh H, Purohit SD, Bhaskar R, Yadav I, Bhushan S, Gupta MK, Gautam S, Showkeen M, Mishra NC. Biomatrix from goat-waste in sponge/gel/powder form for tissue engineering and synergistic effect of nanoceria. Biomed Mater 2021; 16:025008. [PMID: 33440366 DOI: 10.1088/1748-605x/abdb74] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
For tissue engineering (TE), decellularized matrices gained huge potential as they consist of natural biomolecules which help in cell attachment and proliferation. Among various animal tissues, goat tissue has gained least attention in spite of the fact that goat tissue is less susceptible to disease transmission as compared to cadaveric porcine and bovine tissue. In this study, goat small intestine submucosa (G-SIS) was isolated from goat small intestine (G-SI), a waste from goat-slaughterhouse, and decellularized to obtain decellularized G-SIS (DG-SIS) biomatrix in the form of powder, gel and sponge form, so that it can be used for healing various types of wounds. Further, nanoceria (NC), owing to its free radical scavenging, anti-inflammatory, antibacterial and angiogenic properties, was incorporated in the DG-SIS in to fabricate DG-SIS/NC nanobiocomposite scaffold, which may exhibit synergistic effects to accelerate tissue regeneration. The scaffolds were found to be hydrophilic, biodegradable, haemocompatible, biocompatible, antibacterial and showed free radical scavenging capability. The scaffold containing NC concentration (500 µg ml-1) depicted highest cell (fibroblast cells) adhesion, MTT activity and free radical scavenging as compared to the DG-SIS and other nanobiocomposite scaffolds. Thus, DG-SIS/NC3 (NC with concentration 500 µg ml-1) scaffold could be a potential scaffold biomaterial for skin TE application.
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Affiliation(s)
- Hemant Singh
- Department of Polymer and Process Engineering, Indian Institute of Technology Roorkee, Roorkee, India
| | - Shiv Dutt Purohit
- Department of Polymer and Process Engineering, Indian Institute of Technology Roorkee, Roorkee, India
| | - Rakesh Bhaskar
- Department of Biotechnology and Medical Engineering, National Institute of Technology Rourkela, Rourkela, India
| | - Indu Yadav
- Department of Polymer and Process Engineering, Indian Institute of Technology Roorkee, Roorkee, India
| | - Sakchi Bhushan
- Department of Polymer and Process Engineering, Indian Institute of Technology Roorkee, Roorkee, India
| | - Mukesh Kumar Gupta
- Department of Biotechnology and Medical Engineering, National Institute of Technology Rourkela, Rourkela, India
| | - Sneh Gautam
- Molecular Biology and Genetic Engineering, G.B. Pant University of Agriculture and Technology, Pantnagar, India
| | - Muzamil Showkeen
- Division of Veterinary Biochemistry, Sher-e-Kashmir University of Agricultural Sciences and Technology, Srinagar, India
| | - Narayan Chandra Mishra
- Department of Polymer and Process Engineering, Indian Institute of Technology Roorkee, Roorkee, India
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28
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Oualla-Bachiri W, Fernández-González A, Quiñones-Vico MI, Arias-Santiago S. From Grafts to Human Bioengineered Vascularized Skin Substitutes. Int J Mol Sci 2020; 21:E8197. [PMID: 33147759 PMCID: PMC7662999 DOI: 10.3390/ijms21218197] [Citation(s) in RCA: 41] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2020] [Revised: 10/27/2020] [Accepted: 10/29/2020] [Indexed: 12/18/2022] Open
Abstract
The skin plays an important role in the maintenance of the human's body physiological homeostasis. It acts as a coverage that protects against infective microorganism or biomechanical impacts. Skin is also implied in thermal regulation and fluid balance. However, skin can suffer several damages that impede normal wound-healing responses and lead to chronic wounds. Since the use of autografts, allografts, and xenografts present source limitations and intense rejection associated problems, bioengineered artificial skin substitutes (BASS) have emerged as a promising solution to address these problems. Despite this, currently available skin substitutes have many drawbacks, and an ideal skin substitute has not been developed yet. The advances that have been produced on tissue engineering techniques have enabled improving and developing new arising skin substitutes. The aim of this review is to outline these advances, including commercially available skin substitutes, to finally focus on future tissue engineering perspectives leading to the creation of autologous prevascularized skin equivalents with a hypodermal-like layer to achieve an exemplary skin substitute that fulfills all the biological characteristics of native skin and contributes to wound healing.
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Affiliation(s)
- Wasima Oualla-Bachiri
- Cell Production and Tissue Engineering Unit, Virgen de las Nieves University Hospital, 18014 Granada, Spain; (W.O.-B.); (M.I.Q.-V.); (S.A.-S.)
- Biosanitary Institute of Granada (ibs. GRANADA), 18014 Granada, Spain
- Andalusian Network of Design and Translation of Advanced Therapies, 41092 Sevilla, Spain
| | - Ana Fernández-González
- Cell Production and Tissue Engineering Unit, Virgen de las Nieves University Hospital, 18014 Granada, Spain; (W.O.-B.); (M.I.Q.-V.); (S.A.-S.)
- Biosanitary Institute of Granada (ibs. GRANADA), 18014 Granada, Spain
- Andalusian Network of Design and Translation of Advanced Therapies, 41092 Sevilla, Spain
| | - María I. Quiñones-Vico
- Cell Production and Tissue Engineering Unit, Virgen de las Nieves University Hospital, 18014 Granada, Spain; (W.O.-B.); (M.I.Q.-V.); (S.A.-S.)
- Biosanitary Institute of Granada (ibs. GRANADA), 18014 Granada, Spain
- Andalusian Network of Design and Translation of Advanced Therapies, 41092 Sevilla, Spain
| | - Salvador Arias-Santiago
- Cell Production and Tissue Engineering Unit, Virgen de las Nieves University Hospital, 18014 Granada, Spain; (W.O.-B.); (M.I.Q.-V.); (S.A.-S.)
- Biosanitary Institute of Granada (ibs. GRANADA), 18014 Granada, Spain
- Andalusian Network of Design and Translation of Advanced Therapies, 41092 Sevilla, Spain
- Dermatology Department, Virgen de las Nieves University Hospital, 18014 Granada, Spain
- Dermatology Department, School of Medicine, Granada University, 18016 Granada, Spain
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Norris EG, Dalecki D, Hocking DC. Using Acoustic Fields to Fabricate ECM-Based Biomaterials for Regenerative Medicine Applications. RECENT PROGRESS IN MATERIALS 2020; 2:1-24. [PMID: 33604591 PMCID: PMC7889011 DOI: 10.21926/rpm.2003018] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Ultrasound is emerging as a promising tool for both characterizing and fabricating engineered biomaterials. Ultrasound-based technologies offer a diverse toolbox with outstanding capacity for optimization and customization within a variety of therapeutic contexts, including improved extracellular matrix-based materials for regenerative medicine applications. Non-invasive ultrasound fabrication tools include the use of thermal and mechanical effects of acoustic waves to modify the structure and function of extracellular matrix scaffolds both directly, and indirectly via biochemical and cellular mediators. Materials derived from components of native extracellular matrix are an essential component of engineered biomaterials designed to stimulate cell and tissue functions and repair or replace injured tissues. Thus, continued investigations into biological and acoustic mechanisms by which ultrasound can be used to manipulate extracellular matrix components within three-dimensional hydrogels hold much potential to enable the production of improved biomaterials for clinical and research applications.
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Affiliation(s)
- Emma G Norris
- Department of Pharmacology and Physiology, University of Rochester, Rochester, New York, USA
| | - Diane Dalecki
- Department of Biomedical Engineering, University of Rochester, Rochester, New York, USA
| | - Denise C Hocking
- Department of Pharmacology and Physiology, University of Rochester, Rochester, New York, USA
- Department of Biomedical Engineering, University of Rochester, Rochester, New York, USA
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30
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Wang X, Majumdar S, Soiberman U, Webb JN, Chung L, Scarcelli G, Elisseeff JH. Multifunctional synthetic Bowman's membrane-stromal biomimetic for corneal reconstruction. Biomaterials 2020; 241:119880. [PMID: 32097748 PMCID: PMC7236884 DOI: 10.1016/j.biomaterials.2020.119880] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2019] [Revised: 01/23/2020] [Accepted: 02/10/2020] [Indexed: 12/21/2022]
Abstract
As the outermost layer of the eye, the cornea is vulnerable to physical and chemical trauma, which can result in loss of transparency and lead to corneal blindness. Given the global corneal donor shortage, there is an unmet need for biocompatible corneal substitutes that have high transparency, mechanical integrity and regenerative potentials. Herein we engineered a dual-layered collagen vitrigel containing biomimetic synthetic Bowman's membrane (sBM) and stromal layer (sSL). The sBM supported rapid epithelial cell migration, maturation and multilayer formation, and the sSL containing tissue-derived extracellular matrix (ECM) microparticles presented a biomimetic lamellar ultrastructure mimicking the native corneal stroma. The incorporation of tissue-derived microparticles in sSL layer significantly enhanced the mechanical properties and suturability of the implant without compromising the transparency after vitrification. In vivo performance of the vitrigel in a rabbit anterior lamellar keratoplasty model showed full re-epithelialization within 14 days and integration of the vitrigel with the host tissue stroma by day 30. The migrated epithelial cells formed functional multilayer with limbal stem cell marker p63 K14 expressed in the lower layer, epithelial marker K3 and K12 expressed through the layers and tight junction protein ZO-1 expressed by the multilayers. Corneal fibroblasts migrated into the implants to facilitate host/implant integration and corneal stromal regeneration. In summary, these results suggest that the multi-functional layers of this novel collagen vitrigel exhibited significantly improved biological performance as corneal substitute by harnessing a fast re-epithelialization and stromal regeneration potential.
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Affiliation(s)
- Xiaokun Wang
- Translational Tissue Engineering Center, Wilmer Eye Institute, Johns Hopkins School of Medicine, Baltimore, MD, USA
| | - Shoumyo Majumdar
- Translational Tissue Engineering Center, Wilmer Eye Institute, Johns Hopkins School of Medicine, Baltimore, MD, USA
| | - Uri Soiberman
- Department of Ophthalmology, Johns Hopkins Hospital, Baltimore, MD, USA
| | - Joshua N Webb
- A. James Clark School of Bioengineering, University of Maryland, College Park, MD, USA
| | - Liam Chung
- Translational Tissue Engineering Center, Wilmer Eye Institute, Johns Hopkins School of Medicine, Baltimore, MD, USA
| | - Giuliano Scarcelli
- A. James Clark School of Bioengineering, University of Maryland, College Park, MD, USA
| | - Jennifer H Elisseeff
- Translational Tissue Engineering Center, Wilmer Eye Institute, Johns Hopkins School of Medicine, Baltimore, MD, USA.
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31
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Fey C, Betz J, Rosenbaum C, Kralisch D, Vielreicher M, Friedrich O, Metzger M, Zdzieblo D. Bacterial nanocellulose as novel carrier for intestinal epithelial cells in drug delivery studies. MATERIALS SCIENCE & ENGINEERING. C, MATERIALS FOR BIOLOGICAL APPLICATIONS 2020; 109:110613. [DOI: 10.1016/j.msec.2019.110613] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/21/2019] [Revised: 12/21/2019] [Accepted: 12/26/2019] [Indexed: 01/14/2023]
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32
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Assessment of Biocompatibility and Local Action of Biomaterial for Production of an Envelope for Implanted Heart Electronic Devices. Bull Exp Biol Med 2020; 168:375-377. [PMID: 31938920 DOI: 10.1007/s10517-020-04712-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2019] [Indexed: 10/25/2022]
Abstract
We studied a biomaterial for a new domestic product, a biological envelope for implantation of cardiac electronic devices. The product is designed to prevent complications after pacemaker implantation and to facilitate the reimplantation procedure. By chemical and biological processing of raw materials (submucosa of porcine small intestine), an acellular extracellular collagen matrix was obtained. The biocompatibility of the material was tested in vitro using stem cell cultures. The biomaterial for fabrication of the envelope is not cytotoxic, biocompatible, and represents a suitable substrate for attachment, growth, and reproduction of stem cells. The biological effect of the material was studied in vivo on the model of heterotopic implantation in small laboratory animals. The biomaterial did not induce inflammation and tissue reaction and was completely transformed into healthy vascularized tissue without scars in 90 days after implantation.
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El-Taliawi OG, Taguchi T, Dong F, Battig J, Griffon DJ. Biocompatibility of allogenic canine fascia lata: In vitro evaluation and small case series. Vet Surg 2019; 49:310-320. [PMID: 31863601 DOI: 10.1111/vsu.13358] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2019] [Revised: 10/06/2019] [Accepted: 10/30/2019] [Indexed: 12/01/2022]
Abstract
OBJECTIVE To evaluate the biocompatibility of canine fascia lata (FL) in vitro and after FL allograft implantation in dogs with clinical disease. STUDY DESIGN In vitro experiment and small case series. SAMPLE POPULATION Six dogs treated with allogenic freeze-dried FL. METHODS Fibroblasts were cultured on disks of FL, polypropylene mesh (PM; negative control), and porcine small intestinal submucosa (SIS; positive control). Constructs were compared at 3, 7, and 14 days for water content, DNA amounts, scanning electron microscopy, and histology. Records of dogs treated with FL allografts with follow-up examination were reviewed for signalment, indication for surgery, surgical procedure, and outcomes. All owners were invited to complete a standardized questionnaire for long-term follow-up. RESULTS Water content was greater in FL and SIS than in PM (P = .03). Fascia lata constructs contained more DNA compared with PM constructs at days 7 and 14 (P < .05), whereas SIS constructs did not differ from FL or PM. Fibroblasts appeared spherical and distributed throughout FL constructs, whereas they appeared stellate and remained on the surface of SIS and PM. Fascia lata allografts were implanted in six dogs with surgical conditions. No incisional complications were noted. All dogs had good to excellent long-term outcomes, except one that experienced recurrence of a perineal hernia 2 years after repair. CONCLUSION In vitro, canine FL allowed attachment and proliferation of fibroblasts throughout layers of the graft. Canine allogenic FL was clinically well tolerated in this small population of dogs. CLINICAL SIGNIFICANCE Allogenic FL is biocompatible and can be considered an alternative to SIS for soft tissue augmentation in dogs.
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Affiliation(s)
| | - Takashi Taguchi
- Western University of Health Sciences, College of Veterinary Medicine, Pomona, California
| | - Fanglong Dong
- Western University of Health Sciences, Graduate College of Biomedical Sciences, Pomona, California
| | - Jean Battig
- Animal Dental Clinic NW, Lake Oswego, Oregon
| | - Dominique J Griffon
- Western University of Health Sciences, College of Veterinary Medicine, Pomona, California
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34
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Tavelli L, McGuire MK, Zucchelli G, Rasperini G, Feinberg SE, Wang HL, Giannobile WV. Extracellular matrix-based scaffolding technologies for periodontal and peri-implant soft tissue regeneration. J Periodontol 2019; 91:17-25. [PMID: 31475361 DOI: 10.1002/jper.19-0351] [Citation(s) in RCA: 105] [Impact Index Per Article: 17.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2019] [Revised: 08/03/2019] [Accepted: 08/10/2019] [Indexed: 12/26/2022]
Abstract
The present article focuses on the properties and indications of scaffold-based extracellular matrix (ECM) technologies as alternatives to autogenous soft tissue grafts for periodontal and peri-implant plastic surgical reconstruction. The different processing methods for the creation of cell-free constructs resulting in preservation of the extracellular matrices influence the characteristics and behavior of scaffolding biomaterials. The aim of this review is to discuss the properties, clinical application, and limitations of ECM-based scaffold technologies in periodontal and peri-implant soft tissue augmentation when used as alternatives to autogenous soft tissue grafts.
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Affiliation(s)
- Lorenzo Tavelli
- Department of Periodontics & Oral Medicine, University of Michigan, School of Dentistry, Ann Arbor, MI, USA
| | - Michael K McGuire
- Department of Periodontics & Oral Medicine, University of Michigan, School of Dentistry, Ann Arbor, MI, USA.,Private practice, Houston, TX, USA.,Department of Periodontics, University of Texas, Dental Branch Houston and Health Science Center, San Antonio, TX, USA
| | - Giovanni Zucchelli
- Department of Periodontics & Oral Medicine, University of Michigan, School of Dentistry, Ann Arbor, MI, USA.,Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy
| | - Giulio Rasperini
- Department of Periodontics & Oral Medicine, University of Michigan, School of Dentistry, Ann Arbor, MI, USA.,Department of Biomedical, Surgical and Dental Sciences, University of Milan, Foundation IRCCS Ca' Granda Policlinic, Milan, Italy
| | - Stephen E Feinberg
- Department of Oral and Maxillofacial Surgery, University of Michigan, Ann Arbor, MI, USA
| | - Hom-Lay Wang
- Department of Periodontics & Oral Medicine, University of Michigan, School of Dentistry, Ann Arbor, MI, USA
| | - William V Giannobile
- Department of Periodontics & Oral Medicine, University of Michigan, School of Dentistry, Ann Arbor, MI, USA.,Department of Biomedical Engineering & Biointerfaces Institute, College of Engineering, University of Michigan, Ann Arbor, MI, USA
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35
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Haldar S, Sharma A, Gupta S, Chauhan S, Roy P, Lahiri D. Bioengineered smart trilayer skin tissue substitute for efficient deep wound healing. MATERIALS SCIENCE & ENGINEERING. C, MATERIALS FOR BIOLOGICAL APPLICATIONS 2019; 105:110140. [PMID: 31546402 DOI: 10.1016/j.msec.2019.110140] [Citation(s) in RCA: 27] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/03/2019] [Revised: 08/11/2019] [Accepted: 08/26/2019] [Indexed: 01/13/2023]
Abstract
Skin substitutes for deep wound healing require meticulous designing and fabrication to ensure proper structural and functional regeneration of the tissue. Range of physical and mechanical properties conducive for regeneration of different layers of skin is a prerequisite of an ideal scaffold. However, single or bilayer substitutes, lacking this feature, fail to heal full thickness wound. Complete scar free regeneration of skin is still a big challenge. This study reports fabrication of a trilayer scaffold, from biodegradable polymers that can provide the right ambience for simultaneous regeneration of all the three layers of skin. The scaffold was developed through optimization of different fabrication techniques, namely, casting, electrospinning and lyophilisation, for obtaining a tailored trilayer structure. It has mechanical strength similar to skin layers, can maintain a porosity-gradient and provides microenvironments suitable for simultaneous regeneration of epidermis, dermis and hypodermis. A co-culture model, of keratinocytes and dermal fibroblasts, confirms the efficiency of the scaffold in supporting proliferation and differentiation of different types of cells, into organized tissue. The scaffold showed improved and expedited wound healing in-vivo. Taken together, these compelling evidences successfully established the engineered trilayer scaffold as a promising template for skin tissue regeneration in case of deep wound.
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Affiliation(s)
- Swati Haldar
- Tissue Engineering Lab, Centre of Nanotechnology, IIT Roorkee, India; Biomaterials and Multiscale Mechanics Lab, Department of Metallurgical and Materials Engineering, IIT Roorkee, India; Molecular Endocrinology Lab, Department of Biotechnology, IIT Roorkee, Roorkee, Uttarakhand 247667, India
| | - Akriti Sharma
- Tissue Engineering Lab, Centre of Nanotechnology, IIT Roorkee, India; Biomaterials and Multiscale Mechanics Lab, Department of Metallurgical and Materials Engineering, IIT Roorkee, India
| | - Sumeet Gupta
- Department of Pharmacology, Maharishi Markandeshwar (Deemed to be University), Mullana, Ambala 133207, India
| | - Samrat Chauhan
- Department of Pharmacology, Maharishi Markandeshwar (Deemed to be University), Mullana, Ambala 133207, India
| | - Partha Roy
- Tissue Engineering Lab, Centre of Nanotechnology, IIT Roorkee, India; Molecular Endocrinology Lab, Department of Biotechnology, IIT Roorkee, Roorkee, Uttarakhand 247667, India
| | - Debrupa Lahiri
- Tissue Engineering Lab, Centre of Nanotechnology, IIT Roorkee, India; Biomaterials and Multiscale Mechanics Lab, Department of Metallurgical and Materials Engineering, IIT Roorkee, India.
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36
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Cao G, Huang Y, Li K, Fan Y, Xie H, Li X. Small intestinal submucosa: superiority, limitations and solutions, and its potential to address bottlenecks in tissue repair. J Mater Chem B 2019; 7:5038-5055. [PMID: 31432871 DOI: 10.1039/c9tb00530g] [Citation(s) in RCA: 60] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
Over the past few decades, small intestinal submucosa (SIS), a naturally occurring decellularized extracellular matrix (ECM), has attracted much attention in tissue repair because it can provide plentiful bioactive factors and a biomimetic three-dimensional microenvironment to induce desired cellular functions. In this article, the state-of-the-art research studies on SIS are reviewed, which are mainly centered on three aspects: (1) main superiority such as remarkable bioactivity, low immunogenicity, satisfactory resorbability and promising recellularization; (2) current efforts to overcome its limitations mainly focusing on reducing the naturally occurring heterogeneity, controlling the degradation rate and improving the mechanical properties; (3) great potential in solving the bottleneck problems encountered in repairing various tissues with particular emphasis on cardiovascular, urogenital, abdominal wall, skin, musculotendinous, gastrointestinal, vaginal, and bone tissues. In addition, future research trends are proposed in the conclusion and perspectives section.
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Affiliation(s)
- Guangxiu Cao
- Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education, School of Biological Science and Medical Engineering, Beihang University, Beijing 100083, China. and Beijing Advanced Innovation Center for Biomedical Engineering, Beihang University, Beijing 100083, China
| | - Yan Huang
- Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education, School of Biological Science and Medical Engineering, Beihang University, Beijing 100083, China. and Beijing Advanced Innovation Center for Biomedical Engineering, Beihang University, Beijing 100083, China
| | - Kun Li
- State Key Laboratory of Powder Metallurgy, Central South University, Changsha 410083, China
| | - Yubo Fan
- Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education, School of Biological Science and Medical Engineering, Beihang University, Beijing 100083, China. and Beijing Advanced Innovation Center for Biomedical Engineering, Beihang University, Beijing 100083, China
| | - 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, China.
| | - Xiaoming Li
- Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education, School of Biological Science and Medical Engineering, Beihang University, Beijing 100083, China. and Beijing Advanced Innovation Center for Biomedical Engineering, Beihang University, Beijing 100083, China
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37
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Shi L, Hu Y, Ullah MW, Ullah I, Ou H, Zhang W, Xiong L, Zhang X. Cryogenic free-form extrusion bioprinting of decellularized small intestinal submucosa for potential applications in skin tissue engineering. Biofabrication 2019; 11:035023. [PMID: 30943455 DOI: 10.1088/1758-5090/ab15a9] [Citation(s) in RCA: 41] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
A novel strategy of cryogenic 3D bioprinting assisted by free-from extrusion printing has been developed and applied to printing of a decellularized small intestinal submucosa (dSIS) slurry. The rheological properties, including kinetic viscosity, storage modulus (G'), and loss modulus (G″), were appropriate for free-from extrusion printing of dSIS slurry. Three different groups of scaffolds, including P500, P600, and P700, with filament distances of 500, 600, and 700 μm, respectively were fabricated at a 5 mm s-1 working velocity of the platform (V xy) and 25 kPa air pressure of the dispensing system (P) at -20 °C. The fabricated scaffolds were crosslinked via 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) which resulted in a polyporous microstructure. The variations in the filament diameter and pore size were evaluated in the initial frozen state after printing, the lyophilized state, and after immersion in a PBS solution. The Young's modulus of the P500, P600, and P700 scaffolds was measured in wet and dry states for EDC-crosslinked scaffolds. The cell experiment results showed improved cell adhesion, viability, and proliferation both on the surface and within the scaffold, indicating the biocompatibility and suitability of the scaffold for 3D cell models. Further, gene and protein expression of normal skin fibroblasts on dSIS scaffolds demonstrated their ability to promote the production of some extracellular matrix proteins (i.e. collagen I, collagen III, and fibronectin) in vitro. Overall, this study presents a new potential strategy, by combining cryogenic 3D bioprinting with decellularized extracellular matrix materials, to manufacture ideal scaffolds for skin tissue engineering applications.
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Affiliation(s)
- Lei Shi
- State Key Laboratory of Materials Processing and Die/Mold Technology, School of Materials Science and Engineering, Huazhong University of Science and Technology, Wuhan 430074, People's Republic of China
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Xin H, Wang Z, Wu S, Wang P, Tao X, Xu C, You L. Calcified decellularized arterial scaffolds impact vascular smooth muscle cell transformation via downregulating α-SMA expression and upregulating OPN expression. Exp Ther Med 2019; 18:705-710. [PMID: 31281450 DOI: 10.3892/etm.2019.7626] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2018] [Accepted: 03/26/2019] [Indexed: 02/06/2023] Open
Abstract
The underlying mechanisms of arterial remodeling (AR) remain unclear. Studies have indicated that decellularized scaffolds stimulate the differentiation of fibroblasts into myofibroblasts and promote the accumulation of the extracellular matrix (ECM). In the present study, the impact of ECM changes following AR on vascular smooth muscle cell (VSMC) phenotypes was investigated. VSMCs were co-cultured with normal or calcified decellularized arterial scaffolds. The expression levels of α-smooth muscle actin (α-SMA) and osteopontin (OPN) were measured at 2, 5, 10, 15 and 21 days following the establishment of the co-culture systems. The expression of α-SMA in the normal co-culture group was significantly increased compared with that in the calcified arterial decellularized scaffold co-culture group (P<0.05 and P<0.001). In addition, the expression of OPN in the AR co-culture group was significantly increased compared with the normal co-culture group (P<0.05 and P<0.001). To conclude, the calcified decellularized arterial scaffolds impact VSMC transformation by downregulating α-SMA expression and upregulating OPN expression (P<0.001). To the best of our knowledge, the present study is the first study that co-cultured VSMCs with normal or calcified decellularized arterial scaffolds.
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Affiliation(s)
- Huaping Xin
- Department of Geriatrics, The People's Hospital of Yichun City, Yichun, Jiangxi 336000, P.R. China
| | - Zhimin Wang
- Department of Neurology, Taizhou First People's Hospital, Taizhou, Zhejiang 318000, P.R. China
| | - Shuwu Wu
- Department of Geriatrics, The People's Hospital of Yichun City, Yichun, Jiangxi 336000, P.R. China
| | - Peng Wang
- Department of Neurology, Taizhou First People's Hospital, Taizhou, Zhejiang 318000, P.R. China
| | - Xiaoxiao Tao
- Department of Neurology, Taizhou First People's Hospital, Taizhou, Zhejiang 318000, P.R. China
| | - Chenhua Xu
- Department of Neurology, Taizhou First People's Hospital, Taizhou, Zhejiang 318000, P.R. China
| | - Liling You
- Department of Neurology, Taizhou First People's Hospital, Taizhou, Zhejiang 318000, P.R. China
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Adibfar A, Retrouvey H, Padeanu S, Jeschke MG, Shahrokhi S. Current State of Selected Wound Regeneration Templates and Temporary Covers. CURRENT TRAUMA REPORTS 2019. [DOI: 10.1007/s40719-019-00165-7] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
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40
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Bio-Based Covered Stents: The Potential of Biologically Derived Membranes. TISSUE ENGINEERING PART B-REVIEWS 2019; 25:135-151. [DOI: 10.1089/ten.teb.2018.0207] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
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41
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Small Intestinal Submucosa Matrix as a Novel Therapy for Wounds in Dystrophic Epidermolysis Bullosa. Dermatol Surg 2019; 45:863-864. [PMID: 30608297 DOI: 10.1097/dss.0000000000001731] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
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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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Tympanic Membrane Perforation Repair Using Porcine Small Intestinal Submucosal Grafting. Otol Neurotol 2018; 39:e332-e335. [DOI: 10.1097/mao.0000000000001792] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
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Ajalloueian F, Lemon G, Hilborn J, Chronakis IS, Fossum M. Bladder biomechanics and the use of scaffolds for regenerative medicine in the urinary bladder. Nat Rev Urol 2018; 15:155-174. [DOI: 10.1038/nrurol.2018.5] [Citation(s) in RCA: 43] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/16/2023]
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Abstract
Decellularization technology promises to overcome some of the significant limitations in the regenerative medicine field by providing functional biocompatible grafts. The technique involves removal of the cells from the biological tissues or organs for further use in tissue engineering and clinical interventions. There are significant differences between decellularization protocols due to the intrinsic properties of different tissue types and purpose of use. This multistep, chemical-solution-based protocol is optimized for the preparation of decellularized bovine small intestinal submucosa (SIS).
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Affiliation(s)
- Mahmut Parmaksiz
- Tissue Engineering, Biomaterials and Nanobiotechnology Laboratory, Ankara University Faculty of Science, and Ankara University Stem Cell Institute, Ankara, Turkey
| | - Ayşe Eser Elçin
- Tissue Engineering, Biomaterials and Nanobiotechnology Laboratory, Ankara University Faculty of Science, and Ankara University Stem Cell Institute, Ankara, Turkey
| | - Yaşar Murat Elçin
- Biovalda Health Technologies, Inc., Ankara, Turkey.
- Tissue Engineering, Biomaterials and Nanobiotechnology Laboratory, Ankara University Faculty of Science, Ankara, Turkey.
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Li N, Sui Z, Liu Y, Wang D, Ge G, Yang L. A fast screening model for drug permeability assessment based on native small intestinal extracellular matrix. RSC Adv 2018; 8:34514-34524. [PMID: 35548601 PMCID: PMC9086926 DOI: 10.1039/c8ra05992f] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2018] [Accepted: 09/18/2018] [Indexed: 11/25/2022] Open
Abstract
The Caco-2 cell monolayer model is widely utilized to predict drug permeability across human intestinal epithelial cells. However, at least 21 days is required for the formation and maturation of a well-tight Caco-2 cell monolayer, thereby restricting the throughput of the screening model during drug discovery. To address this challenge, a fast (7 days), and more physiologically relevant screening model integrating both the Caco-2 cell model and a small intestinal submucosa (SIS) hydrogel was developed in this study. The 7 day model exhibited desirable phenotype and functional similarity to the conventional 21 day Caco-2 model with respect to paracellular resistance, alkaline phosphatase (ALP) activities, and the mRNA expression level of three transporters (PEPT1, OATP1A2, and P-gp) as well as their mediated influx or efflux. Besides, the increased gene expression of two excretive transporters (BCRP, MRP2) and their enhanced functionality were observed in the current fast model compared to the traditional 21 day model. More importantly, a strong correlation (r2 = 0.9458) was obtained between the absorptive Papp values of 19 model compounds in the 7 day model and those in the conventional 21 day model. These results revealed the pivotal role of the native extracellular matrix (SIS) in facilitating the differentiation of Caco-2 cells, leading to the reconstruction of the accelerated 7 day model, which presents a promising tool for screening drug permeability in future drug discovery. Application of a native decellularized small intestinal extracellular matrix for the construction of a fast screening model for drug absorption evaluation.![]()
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Affiliation(s)
- Na Li
- Institute of Interdisciplinary Integrative Medicine Research
- Shanghai University of Traditional Chinese Medicine
- Shanghai 201203
- China
- Department of Biomedical Engineering
| | - Zhigang Sui
- Dalian Institute of Chemical Physics
- Chinese Academy of Sciences
- Dalian
- China
| | - Yong Liu
- School of Life Science and Medicine
- Dalian University of Technology
- Panjin
- China
| | - Dandan Wang
- Institute of Interdisciplinary Integrative Medicine Research
- Shanghai University of Traditional Chinese Medicine
- Shanghai 201203
- China
| | - Guangbo Ge
- Institute of Interdisciplinary Integrative Medicine Research
- Shanghai University of Traditional Chinese Medicine
- Shanghai 201203
- China
| | - Ling Yang
- Institute of Interdisciplinary Integrative Medicine Research
- Shanghai University of Traditional Chinese Medicine
- Shanghai 201203
- China
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Pal A, Pathak C, Vernon B. Synthesis, characterization and application of biodegradable polymer grafted novel bioprosthetic tissue. JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION 2017; 29:217-235. [PMID: 29161994 DOI: 10.1080/09205063.2017.1409046] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Abstract
Animal tissue has an extended history of clinical use in applications like heart valve bioprosthesis devices, cardiovascular surgical applications etc. but often does not last long after implantation in the body due to rapid unwanted degradation. The goal of this work is to develop novel composite biomaterials by grafting biological tissue with synthetic, biodegradable polymers. In the current research phase, porcine submucosa, ureter and bovine pericardial tissue are grafted with poly DL-lactide (PLA), poly glycolide (PGA) and poly DL-lactide glycolide (PLGA) copolymers. The grafted and control tissues are characterized by FTIR and SEM. The biodegradability of the tissue-graft composite materials is determined by pepsin and collagenase digestion assays, showing it can be tailored by varying the grafted polymer type and amount. The grafted tissues can be tuned for a particular clinical or tissue engineering applications including drug delivery with little or no burst release and sustained/controlled delivery.
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Affiliation(s)
- Amrita Pal
- a School of Biological and Health Systems Engineering , Arizona State University , Tempe , AZ , USA
| | - Chandrashekhar Pathak
- a School of Biological and Health Systems Engineering , Arizona State University , Tempe , AZ , USA
| | - Brent Vernon
- a School of Biological and Health Systems Engineering , Arizona State University , Tempe , AZ , USA
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Rashtbar M, Hadjati J, Ai J, Shirian S, Jahanzad I, Azami M, Asadpuor S, Sadroddiny E. Critical-sized full-thickness skin defect regeneration using ovine small intestinal submucosa with or without mesenchymal stem cells in rat model. J Biomed Mater Res B Appl Biomater 2017; 106:2177-2190. [DOI: 10.1002/jbm.b.34019] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2017] [Revised: 09/10/2017] [Accepted: 09/24/2017] [Indexed: 11/11/2022]
Affiliation(s)
- Morteza Rashtbar
- Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine; Tehran University of Medical Sciences; Tehran Iran
| | - Jamshid Hadjati
- Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine; Tehran University of Medical Sciences; Tehran Iran
- Department of Immunology, School of Medicine; Tehran University of Medical Sciences; Tehran Iran
| | - Jafar Ai
- Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine; Tehran University of Medical Sciences; Tehran Iran
| | - Sadegh Shirian
- Department of Pathology, School of Veterinary Medicine; Shahrekord University; Shahrekord Iran
- Shiraz Molecular Pathology Research Center, Dr. Daneshbod Pathology Laboratory; Shiraz Iran
| | - Issa Jahanzad
- Department of Pathology, Immunohistochemistry Laboratory; Cancer Institute of Iran, Tehran University of Medical Sciences; Tehran Iran
| | - Mahmoud Azami
- Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine; Tehran University of Medical Sciences; Tehran Iran
| | - Shiva Asadpuor
- 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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Turner NJ, Johnson SA, Foster LJR, Badylak SF. Sutureless nerve repair with ECM bioscaffolds and laser-activated chitosan adhesive. J Biomed Mater Res B Appl Biomater 2017; 106:1698-1711. [DOI: 10.1002/jbm.b.33975] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2017] [Revised: 06/21/2017] [Accepted: 07/29/2017] [Indexed: 01/18/2023]
Affiliation(s)
- Neill J. Turner
- McGowan Institute for Regenerative Medicine, University of Pittsburgh; Pittsburgh Pennsylvania 15219
- Department of Surgery; University of Pittsburgh; Pittsburgh Pennsylvania 15219
| | - Scott A. Johnson
- McGowan Institute for Regenerative Medicine, University of Pittsburgh; Pittsburgh Pennsylvania 15219
| | - Leslie J. R. Foster
- Biopolymer Research Group; School of Biotechnology and Bimolecular Sciences, The University of New South Wales; Sydney Australia
- Save Sight Institute, Faculty of Medicine, University of Sydney; Sydney Australia
| | - Stephen F. Badylak
- McGowan Institute for Regenerative Medicine, University of Pittsburgh; Pittsburgh Pennsylvania 15219
- Department of Surgery; University of Pittsburgh; Pittsburgh Pennsylvania 15219
- Department of Bioengineering; University of Pittsburgh; Pittsburgh Pennsylvania 15260
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First human use of hybrid synthetic/biologic mesh in ventral hernia repair: a multicenter trial. Surg Endosc 2017; 32:1123-1130. [PMID: 28726148 DOI: 10.1007/s00464-017-5715-6] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2017] [Accepted: 07/06/2017] [Indexed: 12/17/2022]
Abstract
BACKGROUND Mesh options for reinforcement of ventral/incisional hernia (VIH) repair include synthetic or biologic materials. While each material has known advantages and disadvantages, little is understood about outcomes when these materials are used in combination. This multicenter study reports on the first human use of a novel synthetic/biologic hybrid mesh (Zenapro® Hybrid Hernia Repair Device) for VIH repair. METHODS This prospective, multicenter post-market clinical trial enrolled consecutive adults who underwent elective VIH repair with hybrid mesh placed in the intraperitoneal or retromuscular/preperitoneal position. Patients were classified as Ventral Hernia Working Group (VHWG) grades 1-3 and had clean or clean-contaminated wounds. Outcomes of ventral and incisional hernia were compared using appropriate parametric tests. RESULTS In all, 63 patients underwent VIH repair with hybrid mesh. Most were females (54.0%), had a mean age of 54.8 ± 10.9 years and mean body mass index of 34.5 ± 7.8 kg/m2, and classified as VHWG grade 2 (87.3%). Most defects were midline (92.1%) with a mean area of 106 ± 155 cm2. Cases were commonly classified as clean (92.1%) and were performed laparoscopically (60.3%). Primary fascial closure was achieved in 82.5% with 28.2% requiring component separation. Mesh location was frequently intraperitoneal (69.8%). Overall, 39% of patients available for follow-up at 12 months suffered surgical site events, which were generally more frequent after incisional hernia repair. Of these, seroma (23.7%) was most common, but few (8.5%) required procedural intervention. Other surgical site events that required procedural intervention included hematoma (1.7%), wound dehiscence (1.7%), and surgical site infection (3.4%). Recurrence rate was 6.8% (95% CI 2.2-16.6%) at 12-months postoperatively. CONCLUSION Zenapro® Hybrid Hernia Repair Device is safe and effective in VHWG grade 1-2 patients with clean wounds out to 12 months. Short-term outcomes and recurrence rate are acceptable. This hybrid mesh represents a novel option for reinforcement during VIH repair.
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