Inflammation-Responsive Drug-Loaded Hydrogels with Sequential Hemostasis, Antibacterial, and Anti-Inflammatory Behavior for Chronically Infected Diabetic Wound Treatment

被引:286
作者
Wang, Yu [1 ]
Wu, Ye [1 ]
Long, Linyu [2 ]
Yang, Li [2 ]
Fu, Daihua [2 ]
Hu, Cheng [2 ]
Kong, Qingquan [1 ,3 ]
Wang, Yunbing [2 ]
机构
[1] Sichuan Univ, West China Hosp, Dept Orthoped, Orthoped Res Inst, Chengdu 610041, Sichuan, Peoples R China
[2] Sichuan Univ, Natl Engn Res Ctr Biomat, Chengdu 610064, Sichuan, Peoples R China
[3] Sichuan Univ, Med X Ctr Mat, Chengdu 610064, Sichuan, Peoples R China
关键词
inflammation-responsive; hemostasis; antibacterial hybrid; drug-loaded micelles; wound healing; INJECTABLE HYDROGELS; IN-VITRO; NANOPARTICLES; GELATIN; NANOCLUSTERS; MECHANISMS; MICELLES; ALGINATE; DELIVERY; POLYMER;
D O I
10.1021/acsami.1c09889
中图分类号
TB3 [工程材料学];
学科分类号
0805 ; 080502 ;
摘要
Stimuli-responsive hydrogels possess unique advantages in drug delivery due to their variable performance and status based on the external environment. In the present study, a dual-responsive (pH and reactive oxygen species (ROS)) hydrogel was prepared to realize drug release properties under inflammatory stimulation. By grafting 3-carboxy-phenylboronic acid to the gelatin molecular backbone and cross-linking with poly(vinyl alcohol), we successfully synthesized the inflammation-responsive drug-loaded hydrogels after encapsulation with vancomycin-conjugated silver nanoclusters (VAN-AgNCs) and pH-sensitive micelles loaded with nimesulide (NIM). This novel design not only retained the dynamic functions of hydrogels, such as injectability, self-healing, and remodeling, but also realized sequential and on-demand drug delivery at diabetic-infected wound sites. In this work, we found that the hydrogel exhibited excellent biocompatibility and hemostasis properties owing to the enhanced cell-adhesive property of the gelatin component. The significant antibacterial and anti-inflammatory effect of the hydrogel was demonstrated in an in vitro experiment. Moreover, in the in vivo experiment, the hydrogel was found to play a role in promoting infected wound healing through sequential hemostasis and anti-bacterial and anti-inflammatory processes. Collectively, this inflammation-responsive hydrogel design containing VAN-AgNCs and NIM-loaded micelles has great potential in the application of chronically infected diabetic wound treatment, as well as in other inflammatory diseases.
引用
收藏
页码:33584 / 33599
页数:16
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