Structure–Biofunction Relationships in Nanoparticle-Reinforced PVA/Alginate Hydrogels for Infection-Controlled Tissue-Contact Applications

Abstract Poly(vinyl alcohol)/sodium alginate (PVA/SA) hydrogels are promising tissue-contact biomaterials; however, the comparative effects of different reinforcing nanoparticles within the same polymer matrix remain insufficiently clarified. This study aimed to compare the structural and biological performance of PVA/SA hydrogel scaffolds reinforced with zinc oxide nanoparticles (ZnONPs), hydroxyapatite (HAp), and graphene oxide nanosheets (GONs) under identical preparation conditions. PVA/SA-based hydrogels were prepared using freeze–thaw processing and evaluated by electron microscopy, EDXS, FT-IR, and Raman spectroscopy. Their swelling behavior, in vitro mass loss in PBS, antibacterial activity, L929 fibroblast cytocompatibility, hemolytic activity, and blood clotting index (BCI) were also examined. The maximum swelling ratios were 3.70 for PVA/SA, 2.46 for PVA/SA/ZnONPs, 3.39 for PVA/SA/HAp, and 3.20 for PVA/SA/GONs. After 28 days, mass loss reached 13.1% for PVA/SA, 15.9% for PVA/SA/ZnONPs, 10.5% for PVA/SA/HAp, and 10.1% for PVA/SA/GONs. The MTT assay showed acceptable cytocompatibility in all groups, with L929 cell viability of 91.74 ± 3.49% for PVA/SA, 84.35 ± 2.68% for PVA/SA/ZnONPs, 95.28 ± 2.28% for PVA/SA/HAp, and 78.55 ± 6.15% for PVA/SA/GONs after 48 h. ZnO produced the most pronounced antibacterial effect, although the activity was moderate in absolute terms, reducing S. aureus by 34.6% and K. pneumoniae by 18.5%, while other formulations showed only marginal reductions (≤7%). Hemolysis values were 3.4% for PVA/SA, 1.8% for PVA/SA/ZnONPs, 1.9% for PVA/SA/HAp, and 6.3% for PVA/SA/GONs. At 5 min, BCI values were 34.22%, 54.89%, 52.74%, and 8.7%, respectively. Overall, ZnONPs improved antibacterial activity, HAp provided the most favorable cytocompatibility and stability profile, while GONs showed a comparatively higher hemolytic response. These findings highlight the importance of nanoparticle selection in designing PVA/SA hydrogel scaffolds for tissue-contact applications.