Diabetic wound healing encounters numerous challenges including bacterial infection, macrophage dysfunction, excessive inflammation, and oxidative stress, causing delays in the overlapping processes of inflammation, proliferation, and remodeling and thus imposing a high burden on patients. Platelet-rich plasma (PRP) has demonstrated significant potential for diabetic wound treatment by promoting granulation tissue formation, collagen deposition, re-epithelialization, and angiogenesis. However, the underlying molecular and cellular mechanisms remain unclear. Here, immunomodulatory hydrogel co-networks based on PRP, with strong hemostatic, antibacterial, and free radical scavenging effects, are developed for diabetic wound treatment. In vitro and in vivo, the hydrogels can reduce endothelial cell apoptosis and promote tube formation by regulating the oxidative stress microenvironment. For anti-inflammatory and tissue repair, the hydrogels can facilitate the M2 macrophage polarization by inhibiting phosphorylation of p-IκBα and p-P65 in the NF-κB signaling pathway. Through increasing the expression of key angiogenic factors (HIF-1α, VEGF, and FGF2), the hydrogels can significantly promote angiogenesis and the formation of endothelial cell tubular structures. These findings offer new insight into the synergistic regulatory contributions of the PRP-based therapy throughout multiple stages of healing, thereby establishing a biomolecular and cellular foundation for advanced diabetic wound management.

中文翻译：

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富血小板血浆/壳聚糖/硫酸软骨素免疫调节水凝胶共网络用于糖尿病伤口修复：功能和分子机制


糖尿病伤口愈合面临细菌感染、巨噬细胞功能障碍、过度炎症和氧化应激等诸多挑战，导致炎症、增殖和重塑的重叠过程延迟，从而给患者带来沉重负担。富血小板血浆 (PRP) 通过促进肉芽组织形成、胶原蛋白沉积、上皮再形成和血管生成，在糖尿病伤口治疗方面显示出巨大的潜力。然而，潜在的分子和细胞机制仍不清楚。在此，开发了基于 PRP 的免疫调节水凝胶共网络，具有强大的止血、抗菌和自由基清除作用，用于糖尿病伤口治疗。在体外和体内，水凝胶可以通过调节氧化应激微环境来减少内皮细胞凋亡并促进管形成。对于抗炎和组织修复，水凝胶可以通过抑制 NF-κB 信号通路中 p-IκBα 和 p-P65 的磷酸化来促进 M2 巨噬细胞极化。通过增加关键血管生成因子（HIF-1α、VEGF和FGF2）的表达，水凝胶可以显着促进血管生成和内皮细胞管状结构的形成。这些发现为基于 PRP 的疗法在多个愈合阶段的协同调节贡献提供了新的见解，从而为高级糖尿病伤口管理奠定了生物分子和细胞基础。