COMBINATION OF BONE-MARROW AND TGF-BETA-1 AUGMENT THE HEALING OF CRITICAL-SIZED BONE DEFECTS

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 bo ne 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 me asurements taken at necropsy included the anterior-posterior (AP) diam eter and medial to lateral (LAT) diameter of the defect; the AP and LA T diameters of both radii measured 1 cm proximal to the distal epiphys is, and the AP and LAT diameters of the mid-shaft of the femora. The b ones from each group were subdivided for either histological evaluatio n or for mechanical testing. Strength (maximum torque), energy, angle of rotation and stiffness were determined for both the treated and con tralateral radii. Results of the radiographic, necropsy, and mechanica l data for defects administered 1.0 mu g of TGF-beta 1 + BM or autogen ous cortical bone were similar and indicated superior healing compared to defects left blank or administered the carrier control with or wit hout bone marrow. Detects administered 1.0 mu g of TGF-beta 1 + BM or autogenous cortical bane had high mechanical strength relative to the control groups and were characterized histologically as healed primari ly with lamellar bone. The results from the defects left blank or admi nistered carrier control were similar and generally characterized by p oor healing or nonunion. This study demonstrated substantial equality of healing between 1.0 mu g of TGF-beta 1 + BM and autograft indicatin g that this formulation could function as a substitute for autologous grafts.