Controlled release of bioactive TGF-β1 from microspheres embedded within biodegradable hydrogels

Transforming growth factor-β1 (TGF-β1) is of great relevance to cartilage development and regeneration. A delivery system for controlled release of growth factors such as TGF-β1 may be therapeutic for cartilage repair. We have encapsulated TGF-β1 into poly(dl-lactide-co-glycolide) (PLGA) microspheres, and subsequently incorporated the microspheres into biodegradable hydrogels. The hydrogels are poly(ethylene glycol) based, and the degradation rate of the hydrogels is controlled by the non-toxic cross-linking reagent, genipin. Release kinetics of TGF-β1 were assessed using ELISA and the bioactivity of the released TGF-β1 was evaluated using a mink lung cell growth inhibition assay. The controlled release of TGF-β1 encapsulated within microspheres embedded in scaffolds is better controlled when compared to delivery from microspheres alone. ELISA results indicated that TGF-β1 was released over 21 days from the delivery system, and the burst release was decreased when the microspheres were embedded in the hydrogels. The concentration of TGF-β1 released from the gels can be controlled by both the mass of microspheres embedded in the gel, and by the concentration of genipin. Additionally, the scaffold permits containment and conformation of the spheres to the defect shape. Based on these in vitro observations, we predict that we can develop a microsphere-loaded hydrogel for controlled release of TGF-β1 to a cartilage wound site.