In vivo engineered extracellular matrix scaffolds with instructive niches for oriented tissue regeneration

体内工程化细胞外基质支架,具有定向组织再生的指导性功能

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作者:Meifeng Zhu, Wen Li, Xianhao Dong, Xingyu Yuan, Adam C Midgley, Hong Chang, Yuhao Wang, Haoyu Wang, Kai Wang, Peter X Ma, Hongjun Wang, Deling Kong

Abstract

Implanted scaffolds with inductive niches can facilitate the recruitment and differentiation of host cells, thereby enhancing endogenous tissue regeneration. Extracellular matrix (ECM) scaffolds derived from cultured cells or natural tissues exhibit superior biocompatibility and trigger favourable immune responses. However, the lack of hierarchical porous structure fails to provide cells with guidance cues for directional migration and spatial organization, and consequently limit the morpho-functional integration for oriented tissues. Here, we engineer ECM scaffolds with parallel microchannels (ECM-C) by subcutaneous implantation of sacrificial templates, followed by template removal and decellularization. The advantages of such ECM-C scaffolds are evidenced by close regulation of in vitro cell activities, and enhanced cell infiltration and vascularization upon in vivo implantation. We demonstrate the versatility and flexibility of these scaffolds by regenerating vascularized and innervated neo-muscle, vascularized neo-nerve and pulsatile neo-artery with functional integration. This strategy has potential to yield inducible biomaterials with applications across tissue engineering and regenerative medicine.

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