In Vivo Stable Allogenic Cartilage Regeneration in a Goat Model Based on Immunoisolation Strategy Using Electrospun Semipermeable Membranes

基于电纺半透膜免疫隔离策略的山羊体内稳定同种异体软骨再生模型

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作者:Yingying Huo, Baoshuai Bai, Rui Zheng, Yuyan Sun, Yao Yu, Xin Wang, Hong Chen, Yujie Hua, Yixin Zhang, Guangdong Zhou, Xiaoyun Wang

Abstract

Tissue engineering is a promising strategy for cartilage defect repair. However, autologous cartilage regeneration is limited by additional trauma to the donor site and a long in vitro culture period. Alternatively, allogenic cartilage regeneration has attracted attention because of the unique advantages of an abundant donor source and immediate supply, but it will cause immune rejection responses (IRRs), especially in immunocompetent large animals. Therefore, a universal technique needs to be established to overcome IRRs for allogenic cartilage regeneration in large animals. In the current study, a hybrid synthetic-natural electrospun thermoplastic polyurethane/gelatin (TPU/GT) semipermeable membrane to explore the feasibility of stable allogenic cartilage regeneration by an immunoisolation strategy is developed. In vitro results demonstrated that the rationally designed electrospun TPU/GT membranes has ideal biocompatibility, semipermeability, and an immunoisolation function. In vivo results further showed that the semipermeable membrane (SPM) efficiently blocked immune cell attack, decreased immune factor production, and cell apoptosis of the regenerated allogenic cartilage. Importantly, TPU/GT-encapsulated cartilage-sheet constructs achieved stable allogeneic cartilage regeneration in a goat model. The current study provides a novel strategy for allogenic cartilage regeneration and supplies a new cartilage donor source to repair various cartilage defects.

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