Triphasic Release Model for Multilayered Gelatin Coatings That Can Recreate Growth Factor Profiles During Wound Healing

Abstract

Multilayered gelatin coatings were created to mimic growth factor profiles that normally occur during fracture healing. A model was developed to relate crosslinking and loading of individual layers to protein release. Modeling was simplified by dividing release profiles into three phases. The diffusion-controlled phase was determined by calculating periods of constant diffusivity for each homogeneous layer within devices. Diffusivity was a power law function of crosslinking. Fick's second law of diffusion was then used to determine release during the diffusion-controlled phase. Secondary diffusivity was determined by summing resistances of each successive homogeneous layer. The initial burst phase was defined as events proceeding the diffusion-controlled phase. Percentage of drug burst was a linear function of crosslinking. Release during the degradation-controlled phase, events following diffusion-controlled phase, was estimated based on first order hydrolysis of crosslinks. The model predicted time-variant release of differently labeled protein measured experimentally, and it can be used to design coatings to recreate the cascade of biomolecules that determine natural bone repair.