Key Laboratory of Textile Science & Technology, Ministry Education, College of Textiles, Donghua University, No. 2999 North Renmin Road, Songjiang, Shanghai 201620, China.
Key Laboratory of Textile Science & Technology, Ministry Education, College of Textiles, Donghua University, No. 2999 North Renmin Road, Songjiang, Shanghai 201620, China.
Acta Biomater. 2018 Jan;65:305-316. doi: 10.1016/j.actbio.2017.08.048. Epub 2017 Sep 1.
A multi-functional hybrid hydrogel P(M-Arg/NIPAAm) with temperature response, anti-protein adsorption and antibacterial properties was prepared and applied as wound dressing. The hydrogel was carried out by free radical copolymerization of methacrylate arginine (M-Arg) and N-isopropyl acrylamide (NIPAAm) monomers using N,N'-methylene bisacrylamide as a crosslinker, and ammonium persulfate/N,N,N', N'-tetramethylethylenediamine as the redox initiator. To endow the antimicrobial property, chlorhexidine diacetate (CHX) was preloaded into the hydrogel and polyhexamethylene guanidine phosphate (PHMG) was grafted on the hydrogel surface, respectively. The antimicrobial property of two series of hydrogels was evaluated and compared. The successful synthesis of M-Arg, PHMG and hydrogels was proved by C NMR, H NMR and FTIR spectroscopy. The hydrogel morphology characterized by scanning electron microscopy confirmed that the homogeneous porous and interconnected structures of the hydrogels. The swelling, protein adsorption property, in vitro release of CHX, antimicrobial assessment, cell viability as well as in vivo wound healing in a mouse model were studied. The results showed the nontoxicity and antimicrobial P(M-Arg/NIPAAm) hydrogel accelerated the full-thickness wound healing process and had the potential application in wound dressing.
Despite the zwitterionic characteristic and biocompatible property of arginine based hydrogels, the brittle behavior and non-transparency still remain as a significant problem for wound dressing. Furthermore promoting the antibacterial property of the zwitterionic hydrogel is also necessary to prevent the bacterial colonization and subsequent wound infection. Therefore, we created a hybrid hydrogel combined methacrylate arginine (M-Arg) and N-isopropyl acrylamide (NIPAAm). NIPAAm improves transparency and mechanical property as well as acts as a temperature-response drug release system. Additionally, chlorhexidine (CHX) was preloaded into the hydrogels and polyhexamethylene guanidine phosphate (PHMG) was grafted on the hydrogel surface, respectively, which make the hydrogel useful as a favorable antibacterial dressing. The hybrid hydrogel has a combination effect of biocompatibility, environmentally responsive transformation behavior, biodegradability, anti-protein adsorption and antimicrobial properties. This report proposes the preparation of P(M-Arg/NIPAAm) hydrogel that has a great potential for wound healing.
一种具有温度响应、抗蛋白吸附和抗菌性能的多功能杂化水凝胶 P（M-Arg/NIPAAm）被制备并用作伤口敷料。该水凝胶通过甲基丙烯酰精氨酸（M-Arg）和 N-异丙基丙烯酰胺（NIPAAm）单体的自由基共聚反应进行，使用 N，N'-亚甲基双丙烯酰胺作为交联剂，过硫酸铵/N，N，N'，N'-四甲基乙二胺作为氧化还原引发剂。为了赋予抗菌性能，分别将洗必泰二乙酸（CHX）预载入水凝胶中和将聚六亚甲基胍磷酸盐（PHMG）接枝到水凝胶表面。评估和比较了这两个系列水凝胶的抗菌性能。通过 C NMR、H NMR 和 FTIR 光谱证明了 M-Arg、PHMG 和水凝胶的成功合成。扫描电子显微镜对水凝胶形貌的表征证实了水凝胶具有均匀的多孔和互联结构。研究了水凝胶的溶胀、蛋白质吸附性能、CHX 的体外释放、抗菌评估、细胞活力以及小鼠模型中的体内伤口愈合。结果表明，非毒性和抗菌性 P（M-Arg/NIPAAm）水凝胶加速了全厚度伤口愈合过程，具有在伤口敷料中应用的潜力。
尽管基于精氨酸的水凝胶具有两性离子特性和生物相容性，但脆性和不透明性仍然是伤口敷料的一个重大问题。此外，促进两性离子水凝胶的抗菌性能也是防止细菌定植和随后伤口感染所必需的。因此，我们创建了一种杂化水凝胶，结合了甲基丙烯酰精氨酸（M-Arg）和 N-异丙基丙烯酰胺（NIPAAm）。NIPAAm 提高了透明度和机械性能，并充当温度响应的药物释放系统。此外，分别将洗必泰（CHX）预载入水凝胶中和将聚六亚甲基胍磷酸盐（PHMG）接枝到水凝胶表面，使水凝胶可用作一种有利的抗菌敷料。杂化水凝胶具有生物相容性、环境响应转化行为、生物降解性、抗蛋白吸附和抗菌性能的综合作用。本报告提出了制备 P（M-Arg/NIPAAm）水凝胶的方法，该水凝胶在伤口愈合方面具有很大的潜力。
