Polymer–Ceramic Gelatin Hydrogels with Tunable Transport: Physicochemical Characterization and Insights into Network Structure–Molecular Mobility for pH-Responsive Methylcobalamin Delivery

Abstract Gelatin-based hydrogels are promising platforms for controlled drug delivery but are often limited by poor mechanical stability and rapid dissolution under physiological conditions. Here, a pH-responsive polymer–ceramic hybrid hydrogel was engineered through the covalent coupling of vinyl-functionalized gelatin (Gel–MAL) with vinyl groups grafted onto the hydroxyapatite surface (HAp-F) during network formation. The chemical structure and physicochemical properties of the resulting materials were characterized by 1H NMR, FTIR, and X-ray diffraction (XRD). The influence of network composition and pH on swelling, mechanical performance, and methylcobalamin (MeB12) release was investigated. All hydrogels exhibited rapid initial hydration followed by equilibrium swelling, with water uptake governed by network architecture. Incorporation of HAp-F altered the mechanical response and swelling behavior of the hydrogels, with formulation- and pH-dependent effects on network expansion and MeB12 release. Kinetic analysis provided a phenomenological description of the release profiles, enabling comparison of the apparent contributions of diffusional transport and macromolecular relaxation under different pH conditions. The apparent Gibbs free-energy terms associated with these effective transport contributions were consistently higher for macromolecular relaxation than for diffusion, indicating greater apparent resistance associated with the relaxation contribution within the applied phenomenological framework. This study provides insight into how molecular composition governs swelling and mechanical properties and how these characteristics relate to macromolecular mobility and release kinetics, offering a structure–property–transport perspective on pH-responsive MeB12 delivery from polymer–ceramic hydrogels.