Introduction/Background: Diabetes Mellitus (DM) is a disease affecting over 21 million Americans resulting in numerous systemic effects, one of which is impaired bone healing. This study was designed to determine the osteoinductive capacity of MSC augmentation in allograft incorporation within a critical size femoral defect model in rats with DM.

Materials/Methods: A 5mm critical size defect was created in the right femur of 40 male DM BB Wistar. Groups: DM/Allograft(All)+DBM and Non-DM/All+DBM: In two groups, the defect was filled with an allograft from a normal non-DM donor rat filled with approximately 0.05mm3 of DBM. DM/All+DBM/MSCs: In the experimental group, the defect was filled with All+DBM, and loaded with 10×106 MSC/mL. Histomorphometry: Animals were sacrificed at 4 and 8 weeks post-surgery, the femurs were processed for undecalcified histomorphometry, and seven areas of interest were measured.

Results: At 4 and 8 weeks the average bone formation within the defect and total bone formation in the DM/All+DBM/MSC group and at 8 weeks the average total bone formation in the Non-DM/All+DBM group was significantly increased compared to the DM/All+DBM group. No significance was found comparing the Non-DM/All+DBM and DM/All+DBM/MSC groups.

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 allograft incorporation in a critical size defect. MSC augmentation resulted in new bone formation in DM animals similar to Non-DM animals, suggesting a potential role for MSC as an advjuvant during the process of allograft incorporation.

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).