Abstract：
Chronic wounds are a major healthcare challenge owing to their complex healing mechanism and number of impediments to the healing process, like infections, unregulated inflammation, impaired cellular functions, poor angiogenesis, and enhanced protease activity. Current topical care strategies, such as surgical debridement, absorption of exudates, drug-loaded hydrogels for infection and inflammation management, and exogenous supply of growth factors for angiogenesis and cell proliferation, slow the progression of wounds and reduce patient suffering but suffer from low overall cure rates. Therefore, we have developed a proteolytically stable, multifunctional nanoparticle loaded-peptide gel with inherent anti-inflammatory, antibacterial, and pro-angiogenic properties to provide a favorable wound healing milieu by restoring impaired cellular functions. We have fabricated a self-assembled, lauric acid-peptide conjugate gel, LA-LLys-DPhe-LLys-NH2, loaded with yttrium oxide (Y2O3) nanoparticles (NLG). Gel formed a nanofibrous structure, and nanoparticles were passively entrapped within the network. The surface morphology, stability, viscoelastic, and self-healing characteristics of gels were characterized. It showed a high stability against degradation by proteolytic enzymes and highly potent antibacterial activities against E. coli and S. aureus due to the presence of positively charged side chains of lysine in the peptide chain. It also exhibited an excellent antioxidant activity as well as ability to stimulate cell proliferation in murine fibroblast (L929) cells and human umbilical vein endothelial cells (HUVECs). The incorporation of nanoparticles promoted angiogenesis by upregulating pro-angiogenic genes, vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF2), and epidermal growth factor (EGFR), and the gel caused complete wound closure in cells. In summary, the Y2O3 nanoparticle-loaded lauric acid-peptide conjugate gel is able to elicit the desired tissue regeneration responses and, therefore, has a strong potential as a matrix for the treatment of chronic wounds.
摘要：
慢性伤口由于其复杂的愈合机制和愈合过程的许多障碍而成为主要的医疗保健挑战。比如感染，不受调节的炎症，细胞功能受损，血管生成不良，和增强的蛋白酶活性。当前的局部护理策略，如手术清创术，渗出液的吸收，用于感染和炎症管理的载药水凝胶，以及用于血管生成和细胞增殖的生长因子的外源供应，减缓伤口的进展，减少患者的痛苦，但总体治愈率低。因此,我们开发了一种蛋白水解稳定的，多功能纳米粒子负载肽凝胶具有固有的抗炎，抗菌，和促血管生成特性，以通过恢复受损的细胞功能来提供有利的伤口愈合环境。我们制造了一个自组装的，月桂酸-肽偶联凝胶,LA-LLys-DPhe-LLys-NH2,负载有氧化钇(Y2O3)纳米颗粒(NLG)。凝胶形成了纳米纤维结构，和纳米粒子被被动地捕获在网络中。表面形貌,稳定性,粘弹性,并对凝胶的自愈特性进行了表征。由于肽链中赖氨酸的带正电荷的侧链的存在,其显示出抗蛋白水解酶降解的高稳定性和抗大肠杆菌和金黄色葡萄球菌的高效抗菌活性。它还表现出优异的抗氧化活性以及刺激鼠成纤维细胞（L929）细胞和人脐静脉内皮细胞（HUVEC）细胞增殖的能力。纳米颗粒的掺入通过上调促血管生成基因促进血管生成，血管内皮生长因子（VEGF），成纤维细胞生长因子（FGF2），和表皮生长因子（EGFR），凝胶导致细胞伤口完全闭合。总之,负载Y2O3纳米颗粒的月桂酸-肽偶联凝胶能够引起所需的组织再生反应，因此,具有作为治疗慢性伤口的基质的强大潜力。
