A subcutaneous pancreatic islet transplantation platform using a clinically applicable, biodegradable Vicryl mesh scaffold - an experimental study
Pancreatic islet transplantation into the liver is an effective treatment for type 1 diabetes but has some critical limitations. The subcutaneous site is a potential alternative transplant site, requiring minimally invasive procedures and allowing frequent graft monitoring; however, hypoxia is a major drawback. Our previous study without scaffolding demonstrated post‐transplant graft aggregation in the subcutaneous site, which theoretically exacerbates lethal intra‐graft hypoxia. In this study, we introduce a clinically applicable subcutaneous islet transplantation platform using a biodegradable Vicryl mesh scaffold to prevent aggregation in a diabetic rat model. Islets were sandwiched between layers of clinically proven Vicryl mesh within thrombin‐fibrin gel. In vitro, the mesh prevented islet aggregation and intra‐islet hypoxia, which significantly improved islet viability. In vivo rat syngeneic islet transplantations into a prevascularized subcutaneous pocket demonstrated that the mesh significantly enhanced engraftment, as measured by assays for graft survival and function. Histological examination at six weeks showed well‐vascularized grafts sandwiched in a flat shape between the mesh layers. The biodegradable mesh was fully absorbed by three months, which alleviated chronic foreign body reaction and fibrosis, and supported long‐term graft maintenance. This simple graft shape modification approach is an effective and clinically applicable strategy for improved subcutaneous islet transplantation.
Additional Information© 2020 Steunstichting ESOT. Published by John Wiley & Sons Ltd. Issue Online: 27 June 2020; Version of Record online: 14 April 2020; Accepted manuscript online: 21 March 2020; Manuscript accepted: 17 March 2020; Manuscript revised: 27 December 2019; Manuscript received: 07 December 2019. Funding Information: Nora Eccles Treadwell Foundation.
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