Impaired wound healing in traumatic skin injuries remains a severe clinical challenge due to impaired re-vascularization, harmful bacteria infection, and inflammation dysregulation. Macrophages are recognized as prominent immune cells in tissue regeneration and wound healing. Consequently, the modulation of macrophages provides a promising therapeutic target for wound healing disorders. Here, we aimed to explore whether a novel constructed combination of thermosensitive hydrogel Pluronic F-127 (PF-127) and phillyrin (PH, the main active compound of forsythia suspensa) could improve skin wound healing. Firstly, the biological effects of pH on the phenotype and inflammation of macrophages were assessed by flow cytometry and ELISA. The biocompatibility of the PF-127 plus PH combination was investigated on keratinocytes and red blood cells. The biological effect of PF-127/PH hydrogel on the migratory ability of keratinocytes was evaluated using the scratch and transwell migration assays. In addition,S. aureusandE. coliwere employed to test the antibacterial properties of the PF-127 plus PH combination. Finally, PF-127 plus PH scaffold was appliedto the full-thickness skin defect in mice. Histomorphological evaluation and immunochemistry were performed to explore the wound-healing activity of PF-127/PH hydrogel. PH can promote the polarization of macrophages from the M1 (pro-inflammatory) phenotype to the M2 (anti-inflammatory) phenotype. The PF-127/PH hydrogel was highly biocompatible and showed a potent stimulative effect on the migration of keratinocytesin vitro. The combination of PF-127 and PH exerted a pronounced antibacterial activity onS. aureusandE. coli in vitro.PF-127/PH hydrogel potently accelerates the healing of full-thickness skin defects by promoting skin cell proliferation, accelerating angiogenesis, and inhibiting inflammation. Our study suggests that PF-127/PH hydrogel has excellent potential for treating traumatic skin defects.

中文翻译：

---

负载连翘苷的热敏水凝胶调节巨噬细胞可促进小鼠皮肤伤口愈合

由于血运重建受损、有害细菌感染和炎症失调，创伤性皮肤损伤中的伤口愈合受损仍然是一个严峻的临床挑战。巨噬细胞被认为是组织再生和伤口愈合中重要的免疫细胞。因此，巨噬细胞的调节为伤口愈合障碍提供了有希望的治疗靶点。在这里，我们旨在探索热敏水凝胶 Pluronic F-127 (PF-127) 和连翘苷（PH，连翘的主要活性化合物）的新型组合是否可以改善皮肤伤口愈合。首先，通过流式细胞术和ELISA评估pH对巨噬细胞表型和炎症的生物学影响。研究了 PF-127 加 PH 组合对角质形成细胞和红细胞的生物相容性。使用划痕和跨孔迁移测定评估 PF-127/PH 水凝胶对角质形成细胞迁移能力的生物学效应。此外，S. 金黄色葡萄球菌和E. 使用大肠杆菌来测试 PF-127 加 PH 组合的抗菌特性。最后将PF-127加PH支架应用于小鼠全层皮肤缺损。通过组织形态学评估和免疫化学来探讨 PF-127/PH 水凝胶的伤口愈合活性。PH可促进巨噬细胞从M1（促炎）表型向M2（抗炎）表型极化。PF-127/PH水凝胶具有高度的生物相容性，并且在体外对角质形成细胞的迁移表现出有效的刺激作用。PF-127 和 PH 的组合对 S. 发挥了显着的抗菌活性。金黄色葡萄球菌和E. 体外大肠杆菌。PF-127/PH 水凝胶通过促进皮肤细胞增殖、加速血管生成和抑制炎症，有效加速全层皮肤缺损的愈合。我们的研究表明 PF-127/PH 水凝胶具有治疗创伤性皮肤缺陷的巨大潜力。