Crosslinker-free in situ hydrogel induces self-aggregation of human dental pulp stem cells with enhanced antibacterial activity

Abstract

Recently, injectable hydrogels have garnered significant attention in tissue engineering due to their controlled flowability, strong plasticity, adaptability, and good biocompatibility. However, research on readily injectable in situ-forming hydrogels capable of forming functional three-dimensional (3D) tissue condensations remains limited. This study explores the development and evaluation of a carboxymethyl chitosan (CMCTS) / oxidized hyaluronic acid (oHA) hydrogel incorporated with silver sulfadiazine (AgSD) for tissue engineering applications with inherent antibacterial activity. Through physicochemical analysis, the optimal formulation of CMCTS/oHA hydrogels was established. The hydrogel demonstrated excellent injectability, enabling minimally invasive in situ delivery. In vitro cytotoxicity assays identified 0.1% AgSD as the optimal concentration, supporting cell proliferation while exhibiting antimicrobial efficacy against S. mutans and E. faecalis. In vivo studies revealed complete hydrogel degradation and good biocompatibility, with no adverse tissue reactions. The hydrogels ability to form 3D cell aggregates and support tissue regeneration underscores its potential for future 3D tissue engineering applications. Consequently, the injectable CMCTS/oHA/AgSD hydrogel developed in this study holds significant potential for application in a wide range of bioengineering fields, including antibacterial substance delivery systems and 3D tissue engineering, indicating potential for future clinical application.