Porous hydroxyapatite scaffold with three-dimensional localized drug delivery system using biodegradable microspheres

Abstract

In this study, ionic immobilization of dexamethasone (DEX)-loaded poly(lactic-co-glycolic acid) (PLGA) microspheres was performed on the hydroxyapatite (HAp) scaffold surfaces. It was hypothesized that in vivo bone regeneration could be enhanced with HAp scaffolds containing DEX-loaded PLGA microspheres compared to the use of HAp scaffolds alone. In vitro drug release from the encapsulated microspheres was measured prior to the implantation in the femur defects of beagle dogs. It was observed that porous, interconnected HAp scaffolds as well as DEX-loaded PLGA microspheres were successfully fabricated in this study. Additionally, PEI was successfully coated on PLGA microsphere surfaces, resulting in a net positive-charged surface. With such modification of the PLGA microsphere surfaces, DEX-loaded PLGA microspheres were immobilized on the negatively charged HAp scaffold surfaces. Release profile of DEX over a 4 week immersion study indicated an initial burst release followed by a sustained release. In vivo evaluation of the defects filled with DEX-loaded HAp scaffolds indicated enhanced volume and quality of new bone formation when compared to defects that were either unfilled or filled with HAp scaffolds alone. This innovative platform for bioactive molecule delivery more potently induced osteogenesis in vivo, which may be exploited in implantable bone graft substitutes for stem cell therapy or improved in vivo performance. It was thus concluded that various bioactive molecules for bone regeneration might be efficiently incorporated with calcium phosphate-based bioceramics using biodegradable polymeric microspheres.