Microsphere-based bioresorbable structures loaded with proteins for tissue regeneration applications

Novel bioresorbable fiber/microsphere composite structures loaded with proteins were developed and studied. These unique polymeric structures are designed to combine good mechanical properties with a desired controlled protein-release profile, in order to serve as scaffolds for tissue regeneration applications. The composite fiber structures were formed by "coating" poly(L-lactic acid) fibers with protein-containing poly(DL-lactic-co-glycolic acid) microspheres. The microspheres were prepared by a double emulsion technique and were loaded with the model enzyme horseradish peroxidase (HRP). The present study focused on the effect of the double emulsion's composition and processing conditions on the microsphere structure and on the resulting cumulative protein release for 90 days. The release profiles generally exhibited an initial burst effect, a lag period and an increased release rate after 2 months. HRP release from these structures was governed by diffusion, rather than by degradation. A decrease in the emulsion's mixing rate significantly improved the release profile through unique matrix-like structures. The initial burst effect can be reduced by decreasing the internal phase quantity and its protein content, or by adding a surfactant to the internal emulsion. Proper selection of the double emulsion formulation and processing conditions can yield fiber microsphere structures with the desired protein release behavior.