Improving Bone Formation in a Rat Femur Segmental Defect by Controlling Bone Morphogenetic Protein-2 Release

• Published in: Tissue engineering. Part A 2011-07, Vol.17 (13-14), p.1735-1746
• Main Authors: Brown, Kate V., Li, Bing, Guda, Teja, Perrien, Daniel S., Guelcher, Scott A., Wenke, Joseph C.
• Format: Article
• Language: English
• Subjects: Animals; Bone density; Bone Morphogenetic Protein 2 - pharmacology; Bone morphogenetic proteins; Bone Regeneration - drug effects; Bones; Cattle; Collagen; Collagen - pharmacology; Femur - diagnostic imaging; Femur - drug effects; Femur - pathology; Growth; Humans; Implants, Experimental; Kinetics; Lactic Acid - pharmacology; Microspheres; Original Articles; Osteogenesis - drug effects; Physiological aspects; Polyglycolic Acid - pharmacology; Polyurethanes - pharmacology; Proteins; Rats; Recombinant Proteins - pharmacology; Tissue engineering; Tissue Scaffolds - chemistry; Tomography, X-Ray Computed; Transforming Growth Factor beta - pharmacology
• ISSN: 1937-3341; 1937-335X
• DOI: 10.1089/ten.tea.2010.0446

Nonunion is a common complication in open fractures and other severe bone injuries. Recombinant human bone morphogenetic protein-2 (rhBMP-2) delivered on a collagen sponge enhances healing of fractures. However, the burst release of rhBMP-2 necessitates supra-physiological doses of rhBMP-2 to achieve a robust osteogenic effect, which introduces risk of ectopic bone formation and severe inflammation and increases the cost. Although the concept that the ideal pharmacokinetics for rhBMP-2 includes both a burst and sustained release is generally accepted, investigations into the effects of the release kinetics on new bone formation are limited. In the present study, biodegradable polyurethane (PUR) and PUR/microsphere [PUR/poly(lactic- co -glycolic acid)] composite scaffolds with varying rhBMP-2 release kinetics were compared to the collagen sponge delivery system in a critical-sized rat segmental defect model. Microcomputed tomography analysis indicated that a burst followed by a sustained release of rhBMP-2 from the PUR scaffolds regenerated 50% more new bone than the collagen sponge loaded with rhBMP-2, whereas a sustained release without the burst did not form significantly more bone than the scaffold without rhBMP-2. This study demonstrated that the putative optimal release profile (i.e., burst followed by sustained release) for rhBMP-2 can be achieved using PUR scaffolds, and that this enhanced pharmacokinetics regenerated more bone than the clinically available standard of care in a critical-sized defect in rat femora.