Shi Liyang, Zhao Yannan, Xie Qifan, Fan Caixia, Hilborn Jöns, Dai Jianwu, Ossipov Dmitri A
Department of Chemistry-Ångström, Division of Polymer Chemistry, Uppsala University, Uppsala, 75121, Sweden.
Center for Regenerative Medicine, State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, 100190, P. R. China.
Adv Healthc Mater. 2018 Mar;7(5). doi: 10.1002/adhm.201700973. Epub 2017 Dec 27.
Biomaterial-based regenerative approaches would allow for cost-effective off-the-shelf solution for the treatment of wounds. Hyaluronan (HA)-based hydrogel is one attractive biomaterial candidate because it is involved in natural healing processes, including inflammation, granulation, and reepithelialization. Herein, dynamic metal-ligand coordination bonds are used to fabricate moldable supramolecular HA hydrogels with self-healing properties. To achieve reversible crosslinking of HA chains, the biopolymer is modified with pendant bisphosphonate (BP) ligands using carbodiimide coupling and chemoselective "click" reactions. Hydrogel is formed immediately after simple addition of silver (Ag ) ions to the solution of HA containing BP groups (HA-BP). Compared with previous HA-based wound healing hydrogels, the HA-BP·Ag hydrogel is highly suitable for clinical use as it can fill irregularly shaped wound defects without the need for premolding. The HA-BP·Ag hydrogel shows antimicrobial properties to both Gram-positive and Gram-negative bacterial strains, enabling prevention of infections in wound care. In vivo evaluation using a rat full-thickness skin wound model shows significantly lower wound remaining rate and a thicker layer of regenerated epidermis as compared with the group left without treatment. The presented moldable and self-healing supramolecular HA hydrogel with "ready-to-use" properties possesses a great potential for regenerative wound treatment.
基于生物材料的再生方法将为伤口治疗提供经济高效的现成解决方案。基于透明质酸（HA）的水凝胶是一种有吸引力的生物材料候选物，因为它参与自然愈合过程，包括炎症、肉芽形成和再上皮化。在此，利用动态金属-配体配位键制备具有自愈合特性的可成型超分子HA水凝胶。为了实现HA链的可逆交联，使用碳二亚胺偶联和化学选择性“点击”反应，用侧链双膦酸盐（BP）配体对生物聚合物进行修饰。在向含有BP基团的HA（HA-BP）溶液中简单添加银（Ag⁺）离子后，立即形成水凝胶。与先前基于HA的伤口愈合水凝胶相比，HA-BP·Ag水凝胶非常适合临床使用，因为它可以填充不规则形状的伤口缺损，而无需预成型。HA-BP·Ag水凝胶对革兰氏阳性和革兰氏阴性细菌菌株均具有抗菌特性，能够在伤口护理中预防感染。使用大鼠全层皮肤伤口模型进行的体内评估显示，与未治疗组相比，伤口残留率显著降低，再生表皮层更厚。所呈现的具有“即用型”特性的可成型且自愈合的超分子HA水凝胶在再生伤口治疗方面具有巨大潜力。
