Structurally interlinked multi-crosslinking bioactive hydrogel network with enhanced antioxidant, antibiofilm, and antibacterial functionalities

Abstract

Recent advances in designing effective multifunctional hydrogel materials have attracted remarkable attention for their biomedical applications, particularly in controlled drug delivery, regenerative medicine, antibiofilm, and broad-spectrum antibacterial therapies. However, over the period we have gained a deep understanding of the structural design of novel smart hydrogels by employing their crosslinking methods, including physical, chemical, and metal coordination. Still designing a multifunctional hydrogel matrix with good mechanical strength, sustained drug release profile, and substantial stability in a biological microenvironment is challenging. In this report, a novel multifaceted and mechanically robust therapeutic hydrogel material has been developed involving multiple chemical and physical crosslinking approaches. Starting material N-acetyl-L-cysteine (NAC) crosslinked with silver salt and further stabilized by chemical crosslinking matrix of polyethylene glycol diacrylate (PEGDA). The fundamental therapeutic composition of hydrogel relies on metal-thiolate coordination, which imparts enhanced antibacterial properties. The incorporation of NAC further provides intrinsic antioxidant activity. To improve stability, antibacterial and antioxidant properties, tannic acid (TA) was integrated into the hydrogel as a bioactive agent. Modulating the PEGDA crosslinking density allowed for fine-tuning the TA release profile, ensuring stability and controlled therapeutic delivery. The combined incorporation of NAC, Ag, PEGDA, and TA in the NAPT hydrogel significantly enhances its antioxidant, antibacterial, and in-vitro biocompatibility properties, making it a highly promising material for advanced biomedical applications.