A Novel Human TGF-β1 Fusion Protein in Combination with rhBMP-2 Increases Chondro-Osteogenic Differentiation of Bone Marrow Mesenchymal Stem Cells
OBJECTIVE Transforming growth factor-beta 1 (TGF-beta 1) is a polyfunctional regulatory cytokine that has been shown to have roles in extracellular matrix interactions, soft tissue healing, and osteogenesis. This study was undertaken to determine the efficacy of TGF-beta 1 in the formation of functionally normal bone in tibial-diaphyseal defects. METHOD Seven hundred fifty micrograms of recombinant human TGF-beta 1 was added to a guanidine-extracted demineralised bone matrix (Gu-DBM) carrier and the implants were used to fill a 2.5 cm tibial diaphyseal defect in skeletally mature female sheep. The defects were allowed to heal over a 12-week period. After sacrifice, they were analyzed using four-point bending mechanical testing. RESULTS Implants with TGF-beta 1 showed complete bony bridging of the defect and stress-strain curves similar to the normal contralateral limb, while implants with the carrier alone failed to bridge the gap. CONCLUSIONS These results demonstrate the ability of TGF-beta 1 to induce new bone which has structural and functional characteristics similar to normal bone.