The repair of spinal cord injury (SCI) highly relies on microenvironment remodeling and facilitating the recruitment and neuronal differentiation of endogenous stem/progenitor cells. Decellularized tissue matrices (DTMs) have shown their unique and beneficial characteristics in promoting neural tissue regeneration, especially those derived from the nervous system. Herein, we present a comparative analysis of a DTM hydrogel derived from spinal cord (DSCM-gel) and a decellularized matrix hydrogel derived from peripheral nerves (DNM-gel). The tissue-specificity of DSCM-gel was evaluated both in vitro, using neural stem/progenitor cell (NSPC) culture, and in vivo, using various materials and biological analyses, including transcriptome and proteomics. It was found that DSCM-gel retained an extracellular matrix-like nanofibrous structure but exhibited higher porosity than DNM-gel, which potentiated NSPCs viability, proliferation, and migration in the early stage of 3D culturing, followed by facilitation of the NSPCs differentiation into neurons. Transcriptome analysis indicated that DSCM-gel regulates NSPCs behavior by modulating integrin α2, α9, and β1 expression profiles along with AKT/ERK related signaling pathways. Proteomics analyses suggest that DSCM specific extracellular matrix proteins, such as the tenascin family (TNC) and some soluble growth factor (FGF2) may contribute to these regulations. Furthermore, in vivo assessments confirmed that DSCM-gel provides a suitable microenvironment for endogenous stem/progenitor cell recruitment and axonal regeneration for bridging the lesion site after a completely transected SCI. Thus, this systematic study provides key insights useful for the development of the tissue-specific DTM biomaterials for translational microenvironment replacement therapies and tissue repair.

脊髓损伤（SCI）的修复高度依赖于微环境重塑并促进内源性干/祖细胞的募集和神经元分化。去细胞组织基质（DTM）在促进神经组织再生方面，特别是从神经系统衍生的组织中，已显示出其独特而有益的特性。在本文中，我们对源自脊髓的DTM水凝胶（DSCM-gel）和源自周围神经的脱细胞基质水凝胶（DNM-gel）进行了比较分析。在体外，使用神经干/祖细胞（NSPC）培养和体内评估DSCM-gel的组织特异性，使用各种材料和生物学分析，包括转录组和蛋白质组学。发现DSCM凝胶保留了细胞外基质样的纳米纤维结构，但显示出比DNM凝胶更高的孔隙率，从而在3D培养的早期增强了NSPC的活力，增殖和迁移，随后促进了NSPC分化为神经元。 。转录组分析表明，DSCM-gel通过调节整联蛋白α2，α9和β1表达谱以及与AKT / ERK相关的信号通路来调节NSPC的行为。蛋白质组学分析表明，DSCM特异的细胞外基质蛋白，例如腱糖蛋白家族（TNC）和某些可溶性生长因子（FGF2），可能有助于这些调节。此外，体内评估证实，DSCM-gel为内源性干/祖细胞募集和轴突再生提供了合适的微环境，以在完全横切SCI后桥接病变部位。因此，这项系统的研究提供了关键见解，可用于开发针对组织的DTM生物材料，用于翻译微环境替代疗法和组织修复。