Entropy-Regulated Swelling as the Mechanistic Driver of Drug Diffusion in a Mechanically Robust Hydroxyapatite/PVA Hybrid Hydrogel.

Hydrogels exhibit excellent permeability for solute transport, with their degree of swelling directly modulating drug diffusion through their polymer network. This dynamic hinders the quantitative prediction of the swelling mechanisms of these materials, owing to a decrease in configurational entropy resulting from the extension of polymer chains during water absorption. This study provides important insights into transport phenomena in a hydroxyapatite (HAp)-poly-(vinyl alcohol) (PVA) hydrogel by considering the thermodynamic principles governing molecular diffusion up to equilibrium and elucidating mechanisms relevant to drug delivery. HAp shows a hexagonal phase, and its unit cell volume increases by ∼2% after vinyl functionalization (HAp-π). PVA was converted to a chemically cross-linkable polymer and subsequently reacted with HAp-π to form a hybrid hydrogel network. The resulting system exhibits mechanical robustness resulting not only from chemical cross-links but also from noncovalent network constraints, which cooperatively give rise to a high density of effective cross-linking points. The hydrogel absorbs water and releases the drug slowly due to strong constraints imposed by the polymer structure. Despite these restrictions, molecular diffusion remains thermodynamically spontaneous (Δ