Zhang Kunbao, Yang Chao, Cheng Chuanxu, Shi Chengxin, Sun Madi, Hu Hanze, Shi Tongfei, Chen Xuenian, He Xuan, Zheng Xiao, Li Mingqiang, Shao Dan
School of Biomedical Sciences and Engineering, South China University of Technology, Guangzhou International Campus, Guangzhou, Guangdong 511442, China.
National Engineering Research Center for Tissue Restoration and Reconstruction, South China University of Technology, Guangdong 510006, China.
ACS Appl Mater Interfaces. 2022 Jun 1. doi: 10.1021/acsami.2c04300.
Chronic diabetic wound healing remains a challenge due to the existence of excessive danger molecules and bacteria in the inflammatory microenvironment. There is an urgent need for advanced wound dressings that target both inflammation and infection. Here, a bioactive hydrogel without loading any anti-inflammatory ingredients is rationally designed to achieve a "Pull-Push" approach for efficient and safe bacteria-infected diabetic wound healing by integrating danger molecule scavenging (Pull) with antibiotic delivery (Push) in the inflammatory microenvironment. The cationic hydrogel, termed the OCMC-Tob/PEI hydrogel, is fabricated by the conjugation of polyethylenimine (PEI) and tobramycin (Tob) on an oxidized carboxymethyl cellulose (OCMC) backbone via the Schiff base reaction with injectable, self-healing, and biocompatible properties. The OCMC-Tob/PEI hydrogel not only displays the remarkable capability of capturing multiple negatively charged danger molecules (e.g., cell-free DNA, lipopolysaccharides, and tumor necrosis factor-α) to ameliorate anti-inflammation effects but also achieves controllable long-term antibacterial activity by the pH-sensitive release of Tob. Consequently, this multifunctional hydrogel greatly expedites the wound closure rate with combined anti-inflammation and anti-infection effects on -infected diabetic wounds. Our work provides a highly versatile treatment approach for chronic diabetic wounds and a promising dressing for regenerative medicine.
由于炎症微环境中存在过多的危险分子和细菌，慢性糖尿病伤口的愈合仍然是一项挑战。迫切需要同时针对炎症和感染的先进伤口敷料。在此，我们合理设计了一种未负载任何抗炎成分的生物活性水凝胶，通过在炎症微环境中将危险分子清除（拉）与抗生素递送（推）相结合，实现一种“拉 - 推”方法，用于高效且安全地促进细菌感染的糖尿病伤口愈合。这种阳离子水凝胶被称为OCMC - Tob/PEI水凝胶，它是通过聚乙烯亚胺（PEI）和妥布霉素（Tob）在氧化羧甲基纤维素（OCMC）主链上通过席夫碱反应共轭而成，具有可注射、自愈和生物相容性等特性。OCMC - Tob/PEI水凝胶不仅展现出捕获多种带负电荷危险分子（如游离DNA、脂多糖和肿瘤坏死因子 - α）以改善抗炎效果的卓越能力，还通过Tob的pH敏感释放实现可控的长期抗菌活性。因此，这种多功能水凝胶通过对感染的糖尿病伤口产生联合抗炎和抗感染作用，极大地加快了伤口闭合速度。我们的工作为慢性糖尿病伤口提供了一种高度通用的治疗方法，并为再生医学提供了一种有前景的敷料。
