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

• Published in: ACS applied materials & interfaces Vol. 13; no. 28; pp. 33584 - 33599
• Main Authors: Wang, Yu, Wu, Ye, Long, Linyu, Yang, Li, Fu, Daihua, Hu, Cheng, Kong, Qingquan, Wang, Yunbing
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 21-07-2021
• Subjects: Animals; Anti-Bacterial Agents - therapeutic use; Anti-Inflammatory Agents - therapeutic use; Applications of Polymer, Composite, and Coating Materials; Boronic Acids - chemistry; Diabetes Mellitus, Experimental - complications; Drug Carriers - chemistry; Gelatin - chemistry; Hemostasis - drug effects; Hemostatics - therapeutic use; Hydrogels - chemistry; Hydrogen-Ion Concentration; Male; Metal Nanoparticles - chemistry; Metal Nanoparticles - therapeutic use; Polyvinyl Alcohol - chemistry; Rats; Rats, Sprague-Dawley; Silver - chemistry; Silver - therapeutic use; Staphylococcal Infections - drug therapy; Staphylococcal Infections - etiology; Staphylococcus aureus - drug effects; Sulfonamides - therapeutic use; Swine; Vancomycin - therapeutic use; Wound Healing - drug effects; inflammation-responsive; wound healing; antibacterial hybrid; hemostasis; drug-loaded micelles
• ISSN: 1944-8244; 1944-8252
• DOI: 10.1021/acsami.1c09889

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 antibacterial 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.