Tailoring SIPN Hydrogels from Biocompatible Polymers: Optimizing Physico-Chemical and Biocompatibility Properties

Semi-Interpenetrating Polymer Network (SIPN) hydrogels are promising soft materials for numerous applications, owing to their enhanced robustness and high swelling capacity. Many SIPN hydrogels rely on non-biocompatible polymers (<i>e.g.</i>, polyacrylamide) or lack adequate porosity, which hinders optimal cell proliferation and limits their applied potential. In this work, we design novel, biocompatible SIPN hydrogels composed of linear hydroxyethyl cellulose and cross-linked poly(acrylic acid-co-2-hydroxyethyl methacrylate). We systematically investigate the roles of different crosslinkers, their concentrations, and the impact of accelerator amounts on the swelling behavior and mechanical performance. We find that maximum swelling decreases with increasing crosslinker concentration, which is paralleled by a significant increase in hydrogel toughness. Interestingly, the addition of higher accelerator concentrations increases both the swelling capacity and mechanical robustness, suggesting complex structural interactions within the network. The hydrogel microstructure is investigated via histological techniques, and cell viability is tested using fibroblasts on optimal formulations. We find that to achieve excellent cell viability, with fibroblasts displaying proliferation, attachment, spreading, and active intra-scaffold migration, the concentration of methacrylic acid (MA) needs to be optimized. Indeed, high concentrations of MA result in poor cell viability due to the highly acidic environment. Our results demonstrate the remarkable tunability of these SIPN hydrogels, a key advantage for applications ranging from soft robotics to tissue engineering. Furthermore, this work clearly illustrates the complex requirements for successful cell proliferation in hydrogels, emphasizing the need for not only biocompatible polymers, but also for optimal mechanical and precise microstructural and chemical properties.