Teng Ying-Ying, Zou Ming-Li, Liu Si-Yu, Jia Yuan, Zhang Kai-Wen, Yuan Zheng-Dong, Wu Jun-Jie, Ye Jun-Xing, Yu Shun, Li Xia, Zhou Xiao-Jin, Yuan Feng-Lai
Institute of Integrated Chinese and Western Medicine, The Hospital Affiliated to Jiangnan University, Wuxi, China.
Wuxi Clinical Medicine School of Integrated Chinese and Western Medicine, Nanjing University of Chinese Medicine, Wuxi, China.
Front Bioeng Biotechnol. 2022 Jun 27;10:902894. doi: 10.3389/fbioe.2022.902894. eCollection 2022.
Bone morphogenetic protein (BMP) pathway is essential for M2 macrophage polarization and hair-follicle neogenesis. Icariin, a flavonoid derived from , is a mediator of the BMP pathway. Here, we develop a hydrogel formulation functionalized with icariin for regulation of macrophage polarization to accelerate wound healing and hair-follicle neogenesis. Compared to skin defects without icariin treatment, those treated with icariin+PEG hydrogel healed faster and had new hair follicles. Results showed that icariin+PEG hydrogel induced a higher level of M2 phenotypic transformation of macrophages. Moreover, icariin+PEG hydrogel significantly accelerated wound-repair process by reducing the invasion of inflammation, excessive deposition of collagen, immoderate activation of myofibroblasts, and increasing the regeneration of hair follicles. Furthermore, studies demonstrated that the icariin+PEG hydrogel induced macrophages to polarize to the M2 phenotype and dermal papilla cell to hair follicles. Finally, molecular analysis demonstrated that the icariin+PEG hydrogel increased the expression of BMP4 and Smad1/5 phosphorylation in skin wounds. These results demonstrate the therapeutic potential of icariin-containing thermosensitive hydrogels for inducing M2 macrophage polarization to accelerate wound healing and promote hair-follicle neogenesis by regulating the BMP pathway.
骨形态发生蛋白（BMP）信号通路对于M2巨噬细胞极化和毛囊新生至关重要。淫羊藿苷是一种从中提取的黄酮类化合物，是BMP信号通路的介导因子。在此，我们开发了一种用淫羊藿苷功能化的水凝胶制剂，用于调节巨噬细胞极化，以加速伤口愈合和毛囊新生。与未用淫羊藿苷处理的皮肤缺损相比，用淫羊藿苷+聚乙二醇（PEG）水凝胶处理的皮肤缺损愈合更快，且有新的毛囊形成。结果显示，淫羊藿苷+PEG水凝胶诱导巨噬细胞发生更高水平的M2表型转化。此外，淫羊藿苷+PEG水凝胶通过减少炎症侵袭、胶原蛋白过度沉积、肌成纤维细胞过度活化以及增加毛囊再生，显著加速了伤口修复过程。此外，研究表明淫羊藿苷+PEG水凝胶诱导巨噬细胞向M2表型极化，并诱导真皮乳头细胞形成毛囊。最后，分子分析表明，淫羊藿苷+PEG水凝胶增加了皮肤伤口中BMP4的表达以及Smad1/5的磷酸化。这些结果证明了含淫羊藿苷的热敏水凝胶通过调节BMP信号通路诱导M2巨噬细胞极化以加速伤口愈合和促进毛囊新生的治疗潜力。
