title: Improving bone formation in a rat femur segmental defect by controlling bone morphogenetic protein-2 release.
abstract: 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.
authors.affiliation: Extremity Trauma and Regenerative Medicine Task Area, United States Army Institute of Surgical Research, San Antonio, Texas 78234, USA.
authors.forename: Kate V
authors.initials: KV
authors.lastname: Brown
authors.forename: Bing
authors.initials: B
authors.lastname: Li
authors.forename: Teja
authors.initials: T
authors.lastname: Guda
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Perrien
authors.forename: Scott A
authors.initials: SA
authors.lastname: Guelcher
authors.forename: Joseph C
authors.initials: JC
authors.lastname: Wenke
mesh_terms: D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000494:pharmacology*; D001861:Bone Regeneration / Q000187:drug effects; D002417:Cattle; D003094:Collagen / Q000494:pharmacology; D005269:Femur / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000473:pathology*; D006801:Humans; D020007:Implants, Experimental; D007700:Kinetics; D019344:Lactic Acid / Q000494:pharmacology; D008863:Microspheres; D010012:Osteogenesis / Q000187:drug effects*; D011100:Polyglycolic Acid / Q000494:pharmacology; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011140:Polyurethanes / Q000494:pharmacology; D051381:Rats; D011994:Recombinant Proteins / Q000494:pharmacology; D054457:Tissue Scaffolds / Q000737:chemistry; D014057:Tomography, X-Ray Computed; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
chemical_list: D055396:Bone Morphogenetic Protein 2; D011140:Polyurethanes; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; C499469:recombinant human bone morphogenetic protein-2; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D003094:Collagen