Combination of Bone Marrow and TGF-β1 Augment the Healing of Critical-Sized bone Defects

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Abstract
A 1.5 cm segmental defect in the radius of rabbits was used to compare healing at sites administered TGF-beta, with or without autologous bone marrow, to autogenous cortical bone graft. The carrier for TGF-beta consisted of tricalcium phosphate (TCP) granules and hetastarch. The efficacy of TGF-beta formulations and bone marrow (BM) was compared to autogenous bone, carrier control, and untreated defect sites. Bone measurements taken at necropsy included the anterior-posterior (AP) diameter and medial to lateral (LAT) diameter of the defect; the AP and LAT diameters of both radii measured 1 cm proximal to the distal epiphysis, and the AP and LAT diameters of the mid-shaft of the femora. The bones from each group were subdivided for either histological evaluation or for mechanical testing. Strength (maximum torque), energy, angle of rotation and stiffness were determined for both the treated and contralateral radii. Results of the radiographic, necropsy, and mechanical data for defects administered 1.0 microgram of TGF-beta1 + BM or autogenous cortical bone were similar and indicated superior healing compared to defects left blank or administered the carrier control with or without bone marrow. Defects administered 1.0 microgram of TGF-beta1 + BM or autogenous cortical bone had high mechanical strength relative to the control groups and were characterized histologically as healed primarily with lamellar bone. The results from the defects left blank or administered carrier control were similar and generally characterized by poor healing or nonunion. This study demonstrated substantial equality of healing between 1.0 microgram of TGF-beta1 + BM and autograft indicating that this formulation could function as a substitute for autologous grafts.