Volumetric muscle loss (VML) represents a clinical challenge due to the limited regenerative capacity of skeletal muscle. Most often, it results in scar tissue formation and loss of function, which cannot be prevented by current therapies. Decellularized extracellular matrix (DEM) has emerged as a native biomaterial for the enhancement of tissue repair. Here, we report the generation and characterization of hydrogels derived from DEM prepared from WT or thrombospondin (TSP)-2 null muscle tissue. TSP2-null hydrogels, when compared to WT, displayed altered architecture, protein composition, and biomechanical propertied and allowed enhanced invasion of C2C12 myocytes and chord formation by endothelial cells. They also displayed enhanced cell invasion, innervation, and angiogenesis following subcutaneous implantation. To evaluate their regenerative capacity, WT or TSP-2 null hydrogels were used to treat VML injury to tibialis anterior muscles and the latter induced greater recruitment of repair cells, innervation, and blood vessel formation and reduced inflammation. Taken together, these observations indicate that TSP2-null hydrogels enhance angiogenesis and promote muscle repair in a VML model.

中文翻译：

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新型肌肉源性细胞外基质水凝胶促进体积肌肉损失中的血管生成和神经发生

由于骨骼肌的再生能力有限，体积肌肉损失（VML）代表了临床挑战。最常见的是，它会导致疤痕组织形成和功能丧失，这是当前疗法无法预防的。脱细胞细胞外基质（DEM）已成为增强组织修复的天然生物材料。在这里，我们报告了由 WT 或血小板反应蛋白 (TSP)-2 无效肌肉组织制备的 DEM 衍生的水凝胶的生成和表征。与 WT 相比，无 TSP2 的水凝胶表现出改变的结构、蛋白质组成和生物力学特性，并增强了 C2C12 肌细胞的侵袭和内皮细胞的腱索形成。皮下植入后，它们还表现出增强的细胞侵袭、神经支配和血管生成。为了评估它们的再生能力，使用WT或TSP-2空水凝胶来治疗胫骨前肌的VML损伤，后者诱导更多的修复细胞募集、神经支配和血管形成并减少炎症。总而言之，这些观察结果表明，TSP2 缺失的水凝胶可增强 VML 模型中的血管生成并促进肌肉修复。