Cellulose Nanocrystal-Reinforced Poly(vinyl alcohol) Barrier Membranes Leveraging Hydroxy-Functionalized Surfaces to Promote Guided Bone Regeneration

Biomolecular hydrogels demonstrate potential for bone regeneration because of their aqueous biocompatibility and low toxicity; however, their mechanical fragility and insufficient bioactivity significantly constrain osteogenic application. Herein, cellulose nanocrystals (CNCs) were introduced into poly(vinyl alcohol) (PVA) hydrogels to improve their mechanical properties and osteogenic regeneration potential. The hydroxyl-rich structure of CNCs facilitates dynamic hydrogen bonds that increase mechanical strength and stabilize the porous matrix, thereby augmenting the barrier function against fibroblasts. The mechanical reinforcement and high density of surface hydroxyl groups conferred by CNCs markedly promote bone tissue regeneration. PVA hydrogels were prepared via a freeze-thaw process, incorporating different CNCs concentrations to evaluate their effects on tensile and compressive strength. PVA/CNC2 and PVA/CNC5 hydrogels, which exhibited mechanical adaptability, were selected for further investigation. We studied the proliferation and osteogenic differentiation of MC3T3-E1 cells in response to these hydrogels. Moreover, the bone healing performance of the PVA/CNCs hydrogels was assessed using a rat critical-sized calvarial defect model. We also conducted transcriptomic sequencing to investigate the osteogenic mechanisms of the PVA/CNCs hydrogels. This study demonstrates how hydroxyl-enriched surfaces facilitate bone tissue regeneration, emphasizing a dynamic hydrogen bond-mediated cross-linking strategy to enhance hydrogel mechanical properties. The findings offer a theoretical framework and technical guidance for the development of advanced hydrogel-based biomaterials with tailored mechanical properties and regenerative capabilities.