Design and characterization of native and oxidized polyvinyl alcohol based devices for next-generation biomedical applications

Polyvinyl alcohol (PVA) and its oxidized derivative (OxPVA) have emerged as versatile biomaterials due to their biocompatibility, high water content, tunable mechanical properties, and low friction coefficient. This thesis investigates their potential in two clinically relevant areas with regulatory approval and commercial interest: articular cartilage replacement and tissue engineering, and peripheral nerve regeneration. PVA hydrogels were fabricated via physical freeze–thawing (FT) cycles, avoiding chemical crosslinkers that could compromise biocompatibility. FT parameters, including cycle duration, temperature, and number of cycles, were optimized for each application and hydrogel dimension. Key properties of PVA hydrogels, including long-term mechanical stability and nutrient/protein diffusivity (via Fluorescence Recovery After Photobleaching, FRAP), were assessed to guide design and scale-up. Tensile stiffness increased during the first week of frozen storage due to the micro-crystallite growth and hydrogen-bond consolidation, then reached a plateau. FRAP confirmed PVA capability for effective transport of nutrients, proteins, and bioactive molecules. PVA hydrogels were studied as artificial cartilage models to reproduce the tribological and mechanical behavior of native tissue for viscosupplementation testing, in collaboration with IBSA Farmaceutici Italia S.r.l.. Hydrogels at 20% polymer concentration exhibited compressive stiffness within the cartilage physiological range and a friction coefficient of 0.14 ± 0.01. Tribological testing showed that hyaluronic acid reduced friction to 0.02–0.06 across all concentrations, closely mimicking the human cartilage behavior. To enhance bioactivity, decellularized human cartilage matrix (acellular cartilage, AC) was incorporated in bilayer or blend configurations, providing spatially defined or homogeneously distributed cues. The PVA/AC bilayer scaffold offered the best compromise between biological and mechanical properties, supporting long-term cartilage restoration. Two additional cartilage tissue engineering studies were conducted. Composite scaffolds combining a 20% PVA support with gelatin/alginate/fibrinogen (G/A/F) hydrogels were developed for 3D bioprinting in collaboration with the University of Montpellier. These scaffolds enhanced mechanical stability, comparing to the G/A/F hydrogel alone, and supported cell viability, proliferation, and osteogenic differentiation. Optimized 3D bioprinting replicated the zonal organization of native hyaline cartilage, reinforcing biomimetic potential for regenerative therapies. OxPVA-based porous scaffolds fabricated via particle leaching, with or without decellularized ECM, demonstrated enhanced bioactivity, highlighting their potential for cartilage regeneration. Mechanical limitations of PVA hydrogels were addressed through modified FT protocols and thermal post-treatments, including drying and annealing, improving stiffness without triggering chemical toxicity. For peripheral nerve regeneration, OxPVA conduits were explored as ready-on-the-bench alternatives to autologous grafts, which are the current gold standard. Incorporation of water-soluble multiwalled carbon nanotubes (MWCNT-S) enhanced surface conductivity. The composite conduits supported axonal regeneration in a 5 mm animal nerve defect model over six weeks, demonstrating functional, histological, and mechanical recovery. Overall, this work highlights the versatility of PVA and OxPVA hydrogels for diverse biomedical applications. By combining tunable mechanical and diffusive properties with bioactive modifications, these materials can enhance tissue integration and regenerative outcomes, providing a framework for further optimization, industrial translation, and clinical application.