The wound-healing effect of insulin is well studied and reported. However, prolonged topical application of insulin without compromising its biological activity is still a challenge. In this study, the effect of topically delivered insulin on promoting wound healing in diabetic animals was evaluated. Alginate diamine PEG-g-poly(PEGMA) (ADPM2S2) was the material used for the topical delivery of insulin. ADPM2S2 hydrogels release insulin and strontium ions, and they synergistically act to regulate different phases of wound healing. Insulin was released from the ADPM2S2 hydrogel for a period of 48 h, maintaining its structural stability and biological activity. In vitro studies were performed under high-glucose conditions to evaluate the wound-healing potential of insulin. Insulin-loaded ADPM2S2 hydrogels showed significant improvement in cell migration, proliferation, and collagen deposition, compared to control cells under high-glucose conditions. Immunostaining studies in L929 cells showed a reduction in phospho Akt expression under high-glucose conditions, and in the presence of insulin, the expression increased. The gene expression studies revealed that insulin plays an important role in regulating the inflammatory phase and macrophage polarization, which favors accelerated wound closure. In vivo experiments in diabetic rat excision wounds treated with insulin-loaded ADPM2S2 showed 95% wound closure within 14 days compared with 82% in control groups. Thus, both the in vitro and in vivo results signify the therapeutic potential of topically delivered insulin in wound management under high-glucose conditions.

中文翻译：

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负载胰岛素的锶交联海藻酸盐水凝胶在糖尿病大鼠体内的伤口愈合功效

胰岛素的伤口愈合作用已得到充分研究和报道。然而，长期局部应用胰岛素而不损害其生物活性仍然是一个挑战。在这项研究中，评估了局部输送胰岛素对促进糖尿病动物伤口愈合的作用。海藻酸二胺PEG- g-聚(PEGMA) (ADPM2S2)是用于局部递送胰岛素的材料。 ADPM2S2 水凝胶释放胰岛素和锶离子，它们协同作用来调节伤口愈合的不同阶段。胰岛素从 ADPM2S2 水凝胶中释放 48 小时，保持其结构稳定性和生物活性。在高血糖条件下进行体外研究，以评估胰岛素的伤口愈合潜力。与高葡萄糖条件下的对照细胞相比，加载胰岛素的 ADPM2S2 水凝胶在细胞迁移、增殖和胶原沉积方面显示出显着改善。 L929 细胞的免疫染色研究表明，在高葡萄糖条件下，磷酸化 Akt 表达减少，而在胰岛素存在下，表达增加。基因表达研究表明，胰岛素在调节炎症阶段和巨噬细胞极化方面发挥着重要作用，这有利于加速伤口闭合。用负载胰岛素的 ADPM2S2 治疗糖尿病大鼠切除伤口的体内实验显示，14 天内伤口闭合率为 95%，而对照组为 82%。因此，体外和体内结果都表明局部递送胰岛素在高血糖条件下伤口处理中的治疗潜力。