Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Tissue Engineering, Shanghai, 200011, PR China.
National Tissue Engineering Center of China, Shanghai, 200241, PR China.
Adv Healthc Mater. 2023 May;12(13):e2203084. doi: 10.1002/adhm.202203084. Epub 2023 Feb 26.
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.
组织工程是一种很有前途的软骨缺损修复策略。然而，自体软骨再生受到供体部位额外创伤和体外培养时间长的限制。相比之下，同种异体软骨再生因其丰富的供体来源和即时供应的独特优势而受到关注，但它会引起免疫排斥反应（IRR），特别是在免疫功能正常的大动物中。因此，需要建立一种通用技术来克服大动物同种异体软骨再生的 IRR。在本研究中，开发了一种混合合成-天然电纺热塑性聚氨酯/明胶（TPU/GT）半渗透膜，以探索通过免疫隔离策略实现稳定的同种异体软骨再生的可行性。体外结果表明，合理设计的电纺 TPU/GT 膜具有理想的生物相容性、半透性和免疫隔离功能。体内结果进一步表明，半渗透膜（SPM）有效地阻止了免疫细胞的攻击，减少了免疫因子的产生和再生同种异体软骨的细胞凋亡。重要的是，TPU/GT 包裹的软骨片构建体在山羊模型中实现了稳定的同种异体软骨再生。本研究为同种异体软骨再生提供了一种新策略，并为修复各种软骨缺损提供了新的软骨供体来源。
