Repaire of Large Segmental Bone Defects by Marrow Stromal Cells Transplant with Demineralized Bone Matrix

Abstract

The aim of this study was to determine the healing potential of large segmental bone defects using tissue-engineered constructs in a large animal model before it can be introduced into a clinical trial. Isolated Autologous marrow stromal cells (aMSCs) were cultured in vitro, then seeded into allogenic demineralized bone matrix (aDBM) and co-cultivated for 7 days to construct DBM-MSCs complex. 24 goats were randomly divided into three groups (8 in each), on which 3 cm diaphyseal femoral defects were created unilaterally and subsequently filled with the DBM-MSCs complex, DBM alone and untreated control, respectively. A semiquantitative grading score was applied for radiological analysis after 12 weeks and 24 weeks. DBM-MSCs group increased the radiological scoring and biomechanical strength significantly and superiored over DBM only group. The animals in DBM-MSCs group total bone regeneration was observed in X-ray, whereas most of animal of DBM only group showed partial bone regeneration, while untreated showed no defect healing. Bone regeneration of DBM-MSCs group was histologically better than in DBM only controls and failed in untreated group. In summary, this study confirmed that the goat critical size defect was appropriate in size to produce large defect nonunions model, and our results strongly encourage the application of the transplantation of bone marrow stromal cells within demineralized bone matrix for bone regeneration of large segmental bone defects.