Accession Number : ADA615487


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


Descriptive Note : Journal article


Corporate Author : ARMY INST OF SURGICAL RESEARCH FORT SAM HOUSTON TX


Personal Author(s) : Brown, Kate V ; Li, Bing ; Guda, Teja ; Perrien, Daniel S ; Guelcher, Scott A ; Wenke, Joseph C


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/a615487.pdf


Report Date : 01 Apr 2011


Pagination or Media Count : 13


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.


Descriptors :   *BONES , *PHARMACOKINETICS , *PROTEINS , COLLAGEN , COMPOSITE MATERIALS , COMPUTERIZED TOMOGRAPHY , HISTOLOGY , MORPHOGENESIS , POLYURETHANE RESINS , SPONGES , SURGERY , SYNTHESIS(CHEMISTRY)


Subject Categories : Biochemistry
      Anatomy and Physiology
      Medicine and Medical Research
      Pharmacology


Distribution Statement : APPROVED FOR PUBLIC RELEASE