Institute of Biomedical Engineering, University of Toronto, Toronto, ON, M5S 3G9, Canada.
Faculty of Kinesiology and Physical Education, University of Toronto, Toronto, ON, M5S 3G9, Canada.
Biomaterials. 2021 Aug;275:120909. doi: 10.1016/j.biomaterials.2021.120909. Epub 2021 May 24.
Volumetric muscle loss (VML) impairs the regenerative ability of skeletal muscle resulting in scar tissue formation and loss of function. Current treatments are of limited efficacy as they do not fully restore function, i.e., force generation. Regenerative biomaterials, such as those containing methacrylic-acid (MAA), are proposed as a novel approach to enhancing muscle regeneration without added cells, growth factors or drugs. Here, the regenerative effects of two hydrogels were investigated: MAA-poly(ethylene glycol) (MAA-PEG) and MAA-collagen. These hydrogels were used to treat VML injuries in murine tibialis anterior muscles. The MAA-collagen hydrogel significantly increased regenerating muscle fiber size and muscle force production. While both hydrogels increased vascularization, only the MAA-collagen hydrogel increased apparent muscle innervation. The MAA-collagen hydrogel also significantly reduced a pro-inflammatory macrophage (MHCII+CD206-) population. Furthermore, the hydrogels had distinct gene expression profiles indicating that their regenerative abilities were carrier dependent. Overall, this study suggests MAA-collagen as a cell-free and drug-free approach to enhancing skeletal muscle regeneration after traumatic injury.
体积性肌肉损失 (VML) 削弱了骨骼肌的再生能力,导致疤痕组织形成和功能丧失。目前的治疗方法效果有限,因为它们不能完全恢复功能,即产生力量。再生生物材料,如含有甲基丙烯酸 (MAA) 的生物材料,被提议作为一种增强肌肉再生的新方法,而无需添加细胞、生长因子或药物。在这里,研究了两种水凝胶的再生效果:MAA-聚乙二醇 (MAA-PEG) 和 MAA-胶原。这些水凝胶用于治疗小鼠胫骨前肌的 VML 损伤。MAA-胶原水凝胶显著增加了再生肌纤维的大小和肌肉力量的产生。虽然两种水凝胶都增加了血管生成,但只有 MAA-胶原水凝胶增加了明显的肌肉神经支配。MAA-胶原水凝胶还显著减少了促炎巨噬细胞 (MHCII+CD206-) 群。此外,水凝胶具有不同的基因表达谱,表明它们的再生能力取决于载体。总的来说,这项研究表明,MAA-胶原是一种无细胞和无药物的方法,可以增强创伤后骨骼肌的再生。