Bone morphogenetic protein-2 sustained delivery by hydrogels with microspheres repairs rabbit mandibular defects

Abstract

Mandible defect is a difficult issue in dental surgery owing to limited therapeutic options. Recombinant human bone morphogenetic protein-2 (rhBMP2) is osteoinductive in bone regeneration. This article prepared chitosan/collagen hydrogels with rhBMP2-incorporated gelatin microsphere (GMs) for a sustained release of rhBMP2 to induce bone regeneration in rabbits. In experiments, mandibular defects of 8 mm in diameter and 3 mm in depth were surgically prepared on the right cheek of 27 rabbits. Either chitosan/collagen hydrogels alone, rhBMP2-incorporated hydrogels, or hydrogels with rhBMP2-incorporated GMs were implanted to the defect sites. The animals were euthanized at 2, 6, 12 weeks following surgery. In results, scanning electronic microscope images revealled spherical GMs. The complex delivery systems, hydrogels with rhBMP2-incorporated GMs, exhibited ideal release profiles in vitro. The complex delivery systems resulted in apparent new bone formation within 12 weeks, as evidenced by computed tomography and histological observations. All these results demonstrated that the chitosan/collagen hydrogels with rhBMP2-incorporated GMs had a better capacity to heal mandible defects than other two hydrogel scaffolds. Chitosan/collagen hydrogels with rhBMP2-incorporated GMs might be potential carriers of rhBMP2 for accelerating the repair of mandibular defects.

Keywords: Bone morphogenetic protein-2; Bone substitutes; Dental implants; Hydrogel; Microsphere.