Cartilage-inspired biocompatible double network PVA based hydrogels: A critical comparison of the role of agarose, chitosan, and silk fibroin additives

Abstract

Biopolymer additives have long been recognized for enhancing the structural, mechanical, and functional properties of polyvinyl alcohol (PVA)-based hydrogels, thus enabling tailored performance for diverse biomedical applications. Although agarose, chitosan, and silk fibroin are routinely incorporated into PVA hydrogels – especially in cartilage tissue engineering – their specific contributions have not been systematically compared under consistent fabrication and testing conditions. In this study, we unveil the distinct roles of these biopolymers in modulating the properties of PVA-based double-network (DN) hydrogels, providing critical insights into their advantages and drawbacks for tissue engineering applications. Agarose enhances compressive strength and facilitates macroporous structures, ideal for load-bearing applications. Chitosan delivers superior elastic recovery and tribological performance, while silk fibroin exhibits exceptional water retention and energy dissipation properties. A multilayer (ML) hydrogel design combining agarose and chitosan demonstrates synergistic effects, integrating structural reinforcement with enhanced elasticity. Additionally, all hydrogels exhibited high water content (>80 %), favorable swelling behavior, and interconnected porous structures, which are essential for mimicking cartilage's extracellular matrix. Preliminary biocompatibility studies confirmed minimal cytotoxic effects, further supporting their potential for cartilage repair and other biomedical applications. The findings underscore the versatility of PVA hydrogels as a platform for engineering biomaterials with finely tunable mechanical and functional properties. Through a systematic evaluation of biopolymer additive effects, this work establishes a solid foundation for the rational optimization of hydrogel designs tailored to diverse biomedical applications.