Tailoring hydroxyethyl cellulose-based SIPN hydrogels: 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. We designed biocompatible SIPNs by entangling linear hydroxyethyl cellulose (HEC) macromolecules within a covalently cross-linked poly(2-hydroxyethyl methacrylate-co-methacrylic acid) matrix. We investigate the roles of different crosslinkers and the impact of accelerator amounts on the swelling behavior and mechanical performance. The hydrogels exhibit a strong pH-dependent response, with a maximum swelling capacity (%Qmax) reaching 2570% in neutral media, while showing significant deswelling at pH < 4. We find that maximum swelling decreases with increasing crosslinker concentration, which is paralleled by a significant increase in hydrogel stiffness. Interestingly, higher accelerator concentrations simultaneously increase both the swelling capacity and mechanical robustness under shear. The microstructure is investigated via histological techniques, and cell viability is tested using fibroblasts on optimal formulations. Significant cell viability, attachment, and migration were achieved by optimizing methacrylic acid (MAA) concentration to prevent medium acidification. 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 properties. To evaluate biomedical utility, pH-triggered doxycycline release was characterized, achieving a 82% encapsulation efficiency. In gastrointestinal simulations, the SIPN protected the drug at gastric pH and triggered a fast, extensive release (89%) upon transition to intestinal conditions.