ABSTRACT
Allograft (Allo) incorporation in the presence of a systemic disease like diabetes mellitus (DM) is becoming a major issue in the orthopedic community. Mesenchymal stem cells (MSC) are multipotent stem cells that may be derived from adult, whole bone marrow and have been shown to induce bone formation in segmental defects when combined with the appropriate carrier/scaffold. The objectives of this study were to analyze the effect of DM upon Allo incorporation in a segmental rat femoral defect and to also investigate MSC augmentation of Allo incorporation. Segmental (5 mm) femoral defects were created in non-DM and DM rats and treated with Allo containing demineralized bone matrix (DBM) or DBM with MSC augmentation. Histological scoring at 4 weeks demonstrated less mature bone in the DM/DBM group compared to its non-DM counterpart (p < 0.001). However, there was significantly more mature bone in the DM/MSC group when compared to the DM/DBM group at both 4 and 8 weeks (p < 0.001 and p = 0.004). Furthermore, significantly more bone formation was observed in the DM/MSC group compared to the DM/DBM group at the 4-week time point (p < 0.001). The results of this study suggest that MSC are a potential adjunct for bone regeneration when implanted in an orthotopic site in the presence of DM.
Subject(s)
Bone Transplantation , Diabetes Mellitus, Type 1/physiopathology , Fractures, Bone/therapy , Graft Survival/physiology , Mesenchymal Stem Cell Transplantation , Animals , Bone Demineralization Technique , Diabetes Mellitus, Type 1/complications , Disease Models, Animal , Fracture Healing/physiology , Fractures, Bone/complications , Fractures, Bone/physiopathology , Male , Mesenchymal Stem Cells/physiology , Osteotomy , Rats , Rats, Inbred BB , Transplantation, HomologousABSTRACT
OBJECTIVE: Recombinant human bone morphogenetic protein-2 (rhBMP-2) has been shown to enhance new bone formation in fracture and bone defect models in both normal and diabetic rats. Effects of rhBMP-2 in a segmental femoral defect model in diabetes mellitus (DM) BB Wistar rats have not been reported. METHODS: Collagen sponge soaked with either buffer or rhBMP-2 was inserted in a mid-diaphyseal 3.0-mm defect fixed with polyimide plate and stainless steel screws, in 62 DM BB Wistar rats. Progress of new bone formation in the defect was monitored with serial radiographs every 2 weeks. Histomorphometric analysis of the new bone formation was done on undecalcified sections of the extracted femurs at 3 and 6 weeks post surgery. Further analysis of the new bone was done by assessment of neoangiogenesis using immunohistochemical staining for Platelet endothelial cell adhesion molecule-1. Mechanical testing was performed at 9 weeks to assess the new bone with respect to 4 different parameters of mechanical and structural properties of bone. RESULTS: Radiographs assessed over a 6-point grading system showed statistically significant improvement in scores in rhBMP-2-treated rats at 6 weeks (P < 0.001). Histomorphometric analysis showed statistically significant increase in area of new bone formation between rats treated with rhBMP-2 compared with buffer at both 3 and 6 weeks (P < 0.001). On Platelet endothelial cell adhesion molecule-1 staining at 3 weeks, the mean number of vessels in rhBMP-2-treated DM rats was 12.76 +/- 5.43/mm(2) compared with 4.49 +/- 1.89/mm(2) in buffer treated DM rats (P = 0.034). On mechanical testing, all 4 DM/buffer rats had nonunion. In DM/rhBMP-2 rats, the torque to failure and torsional rigidity values were 393.57 +/- 233.3 (P < 0.03) and 29,711 +/- 6224 (P < 0.002), respectively. CONCLUSIONS: Clearly, although DM has a known impact on osseous healing, its negative effects are ameliorated with the application of the rhBMP-2-collagen carrier and demonstrates the potential clinical role of this adjunct in the clinical arena.
Subject(s)
Bone Morphogenetic Proteins/administration & dosage , Diabetes Complications/drug therapy , Disease Models, Animal , Drug Implants/administration & dosage , Femoral Fractures/complications , Femoral Fractures/drug therapy , Fracture Healing/drug effects , Recombinant Proteins/administration & dosage , Transforming Growth Factor beta/administration & dosage , Animals , Bone Morphogenetic Protein 2 , Femoral Fractures/diagnosis , Humans , Male , Rats , Rats, Wistar , Treatment OutcomeABSTRACT
Many reconstructive options exist for symptomatic hindfoot and ankle problems. Hindfoot and tibiotalar fusions are reliable procedures with consistent results. Unfortunately, many potential complications have been cited throughout the literature. Although the most important aspect in any fusion surgery is meticulous technique, advances in technology, including PRP, bone stimulators, and BMPs seem to be useful additions in the quest to achieve solid fusions with decreased complications.
Subject(s)
Ankle Joint/surgery , Arthrodesis/methods , Foot Joints/surgery , Adult , Arthrodesis/adverse effects , Electric Stimulation Therapy , Female , Humans , Middle Aged , Platelet-Rich PlasmaABSTRACT
Patients with diabetic ankle fractures consistently are at greater risk of sustaining a complication during treatment than nondiabetics.other medical comorbidities, especially Charcot neuroarthropathy and peripheral vascular disease, play distinct roles in increasing these complication rates. Many options for nonoperative and operative treatment exist, but respect for soft tissue management and attention to stable, rigid fixation with prolonged immobilization and prolonged restricted weight bearing are paramount in trying to minimize problems and yield functions.
