Xing Chao, Zhu Hanting, Dou Xiaoqiu, Gao Laiben, Baddi Sravan, Zou Yunqing, Zhao Changli, Peng Yinbo, Fang Yong, Feng Chuan-Liang
State Key Lab of Metal Matrix Composites, Shanghai Key Laboratory for Molecular Engineering of Chiral Drugs School of Pharmacy, School of Materials Science and Engineering, Shanghai Jiao Tong University, Shanghai 200240, China.
Department of Burns and Plastic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 201900, China.
ACS Nano. 2023 Apr 11;17(7):6275-6291. doi: 10.1021/acsnano.2c10039. Epub 2023 Mar 22.
Revascularization plays a critical role in the healing of diabetic wounds. Accumulation of advanced glycation end products (AGEs) and refractory multidrug resistant bacterial infection are the two major barriers to revascularization, directly leading to impaired healing of diabetic wounds. Here, an artfully designed chiral gel dressing is fabricated (named as HA-LM2-RMR), which consists of l-phenylalanine and cationic hexapeptide coassembled helical nanofibers cross-linked with hyaluronic acid via hydrogen bonding. This chiral gel possesses abundant chiral and cationic sites, not only effectively reducing AGEs via stereoselective interaction but also specifically killing multidrug resistant bacteria rather than host cells since cationic hexapeptides selectively interact with negatively charged microbial membrane. Surprisingly, the HA-LM2-RMR fibers present an attractive ability to activate sprouted angiogenesis of Human Umbilical Vein Endothelial Cells by upregulating VEGF and OPA1 expression. In comparison with clinical Prontosan Wound Gel, the HA-LM2-RMR gel presents superior healing efficiency in the infected diabetic wound with respect to angiogenesis and re-epithelialization, shortening the healing period from 21 days to 14 days. These findings for chiral wound dressing provide insights for the design and construction of diabetic wound dressings that target revascularization, which holds great potential to be utilized in tissue regenerative medicine.
血管再生在糖尿病伤口愈合中起着关键作用。晚期糖基化终产物（AGEs）的积累和难治性多重耐药细菌感染是血管再生的两大障碍，直接导致糖尿病伤口愈合受损。在此，制备了一种精心设计的手性凝胶敷料（命名为HA-LM2-RMR），它由L-苯丙氨酸和阳离子六肽共组装的螺旋纳米纤维通过氢键与透明质酸交联而成。这种手性凝胶具有丰富的手性和阳离子位点，不仅通过立体选择性相互作用有效减少AGEs，而且由于阳离子六肽与带负电荷的微生物膜选择性相互作用，能特异性杀死多重耐药细菌而不损伤宿主细胞。令人惊讶的是，HA-LM2-RMR纤维具有通过上调VEGF和OPA1表达来激活人脐静脉内皮细胞血管生成的诱人能力。与临床使用的普朗托散伤口凝胶相比，HA-LM2-RMR凝胶在感染性糖尿病伤口的血管生成和再上皮化方面表现出更高的愈合效率，将愈合时间从21天缩短至14天。这些关于手性伤口敷料的发现为靶向血管再生的糖尿病伤口敷料的设计和构建提供了思路，在组织再生医学中具有巨大的应用潜力。
