PAPER 22: THE EFFECTS OF RECOMBINANT HUMAN BONE MORPHOGENIC PROTEIN-2 (RHBMP-2) ON NON-CRITICAL SIZE SEGMENTAL DEFECT HEALING IN DIABETIC RATS

Abstract

Introduction/Background: This study was designed to determine the osteoinductive capacity of rhBMP-2 in a non-critical size femoral defect in normal rats and rats with diabetes mellitus (DM). It was hypothesized that DM would result in impaired bone regeneration in the femoral non-critical size defects due to reduced bone formation and local delivery of rhBMP-2 would accelerate non-DM healing and normalize impaired bone healing in DM rats to the levels of Non-DM bone healing.

Materials/Methods: A total of 80 BB Wistar rats were used in the project. A 3mm defect was created during surgery and stabilized with a polyimide plate and either a 0.05cc/11μg dose of rhBMP-2 or buffer in a collagen sponge was implanted into the defect. Microradiographs were taken on the day of sacrifice and processing of samples for PECAM-1 immunohistochemistry, histomorphometry, and mechanical testing was performed.

Results: Both Non-DM and DM groups treated with rhBMP-2 demonstrated significantly higher radiographic scoring, total new bone formation, BV quantification, and mechanical testing parameters compared to those treated with buffer at all timepoints with no significance noted between Non-DM and DM groups treated with rhBMP-2.

Discussion/Conclusions: This study reveals decreased amount of new bone formation in DM animals compared to Non-DM animals, showing the detrimental effects of DM upon bone healing. A single application of rhBMP-2 resulted in new bone formation in DM animals similar to Non-DM animals, suggesting a critical role for rhBMP-2 in ameliorating the deleterious effects of DM on bone regeneration and formation.

Besides these groups 15 more DM rats were used for PECAM-1 staining for angiogenesis (7 with 1 loss at a 3 week time point) and mechanical testing (8 at a 9 week time point).