Institute of Biomaterials and Biomedical Engineering, 164 College Street, Suite 407, Toronto, Ontario, M5S 3G9, Canada.
Institute of Biomaterials and Biomedical Engineering, 164 College Street, Suite 407, Toronto, Ontario, M5S 3G9, Canada; Department of Chemical Engineering and Applied Chemistry, University of Toronto, 164 College Street, Suite 407, Toronto, Ontario, M5S 3G9, Canada.
Biomaterials. 2019 Dec;223:119477. doi: 10.1016/j.biomaterials.2019.119477. Epub 2019 Sep 5.
After severe trauma, skeletal muscle cannot repair itself leading to scar tissue formation and functional impairment. A novel approach to overcome this issue is to alter the fibrotic response in muscle using regenerative biomaterials, such as those containing methacrylic acid (MAA). In the skin, MAA-based materials have been shown to promote wound healing and new vessel formation, through endogenous mechanisms, including macrophage polarization; however, MAA has yet to be studied outside the skin. To study the innate immune response to MAA in skeletal muscle, MAA-poly(ethylene glycol) (MAA-PEG) hydrogels were synthesized with degradation rates of either 2 (fast-degrading) or 7 days (slow-degrading). When injected into the tibialis anterior muscle of mice, both slow- and fast-degrading MAA hydrogels increased the expression of Il-10, Tnfα and M2 macrophage markers (Fizz1 and Arg for slow-and fast-degrading, respectively). Moreover, the slow degrading MAA hydrogel decreased the number of pro-inflammatory MHCII+ macrophages. An unbiased t-distributed stochastic neighbor embedding (tSNE) analysis suggested the involvement of other immune cells beyond just macrophages in the effect of MAA on skeletal muscle. Overall, this study shows that MAA hydrogels bias macrophages towards a pro-regenerative phenotype.
在严重创伤后，骨骼肌无法自我修复，导致形成疤痕组织和功能障碍。一种克服这个问题的新方法是使用再生生物材料改变肌肉中的纤维变性反应，例如含有甲基丙烯酸（MAA）的生物材料。在皮肤中，已经证明基于 MAA 的材料通过内源性机制（包括巨噬细胞极化）促进伤口愈合和新血管形成；然而，MAA 尚未在皮肤以外的地方进行研究。为了研究 MAA 在骨骼肌中的固有免疫反应，合成了降解速率分别为 2 天（快速降解）和 7 天（缓慢降解）的 MAA-聚（乙二醇）（MAA-PEG）水凝胶。当将其注射到小鼠的胫骨前肌中时，缓慢和快速降解的 MAA 水凝胶均增加了 Il-10、Tnfα 和 M2 巨噬细胞标志物（Fizz1 和 Arg 分别用于缓慢和快速降解）的表达。此外，缓慢降解的 MAA 水凝胶减少了促炎 MHCII+巨噬细胞的数量。无偏 t 分布随机邻嵌入（tSNE）分析表明，除了巨噬细胞之外，MAA 对骨骼肌的影响还涉及其他免疫细胞。总的来说，这项研究表明 MAA 水凝胶使巨噬细胞偏向于再生表型。
