Persistent inflammation and disrupted immunoregulation are critical factors in impeding diabetic wound healing. While immunoregulatory hydrogel dressings hold significant promise for clinical applications in diabetic wound healing, the current application often demands intricate interventions and high-cost treatments involving cytokines and cell therapies. The development of single component immunoregulatory hydrogels remains a complex challenge. To address this issue, an active peptide hydrogel with immunoregulatory properties targeting the TLR4/NF-kB pathway, aiming to promote rapid diabetic wound healing, is engineered. The hydrogel sequence comprises naphthalene derivative, phenylalanine, and glycine to modulate hydrophilic/hydrophobic characteristics. The amino group on arginine contributes to tissue adhesion and regulation of intermolecular forces, ultimately yielding stable gels. The results underscore the formation of the peptide hydrogel (NFA) via the physical crosslinking of self-assembled nanofibers in water, thereby affording both excellent injectability and tissue adhesion. Notably, NFA demonstrates significant potential in promoting wound healing in a mouse model with full-thickness wounds by regulating macrophage responses in the inflammatory microenvironment through the TLR4/NF-kB pathway.

中文翻译：

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一种靶向 TLR4 的生物活性肽水凝胶，可调节糖尿病伤口修复的免疫微环境

持续的炎症和免疫调节紊乱是阻碍糖尿病伤口愈合的关键因素。虽然免疫调节水凝胶敷料在糖尿病伤口愈合的临床应用中具有广阔的前景，但目前的应用通常需要复杂的干预措施和涉及细胞因子和细胞疗法的高成本治疗。单组分免疫调节水凝胶的开发仍然是一个复杂的挑战。为了解决这个问题，我们设计了一种具有针对 TLR4/NF-kB 通路的免疫调节特性的活性肽水凝胶，旨在促进糖尿病伤口快速愈合。水凝胶序列包含萘衍生物、苯丙氨酸和甘氨酸以调节亲水/疏水特性。精氨酸上的氨基有助于组织粘附和分子间力的调节，最终产生稳定的凝胶。结果强调了通过水中自组装纳米纤维的物理交联形成肽水凝胶（NFA），从而提供优异的可注射性和组织粘附性。值得注意的是，NFA 通过 TLR4/NF-kB 途径调节炎症微环境中的巨噬细胞反应，在全层伤口小鼠模型中显示出促进伤口愈合的巨大潜力。