Bone morphogenetic protein but not transforming growth factor-beta enhances bone formation in canine diaphyseal nonunions implanted with a biodegradable composite polymer

Background: The purpose of the present study was to create an effective bon e-graft substitute for the treatment of a diaphyseal nonunion. Methods: A standardized nonunion was established in the midportion of the r adial diaphysis in thirty mongrel dogs by creating a three-millimeter segme ntal bone defect (at least 2 percent of the total length of the bone). The nonunion was treated with implantation of a carrier comprised of poly(DL-la ctic acid) and polyglycolic acid copolymer (50:50 polglactic acid-polyglyco lic acid [PLG50]) containing canine purified bone morphogenetic protein (BM P) or recombinant human transforming growth factor-beta (TGF-beta 1), or bo th, or the carrier without BMP or TGF-beta 1, Five groups, consisting of si s dogs each, were treated with implantation of the carrier alone, implantat ion of the carrier with fifteen milligrams of BR IP, implantation of the ca rrier with 1.5 milligrams of BR IP, implantation of the carrier with fiftee n milligrams of BMP and ten nanograms of TGF-beta 1, or implantation of the carrier,vith ten nanograms of TGF-beta 1, At twelve weeks after implantati on, the radii were examined radiographically and the sites of nonunion were examined histomorphometrically. Results: We found that implantation of the polylactic acid-polyglycolic aci d carrier alone or in combination with ten nanograms of TGF-beta 1 failed t o induce significant radiographic or histomorphometric evidence of healing at the site of the nonunion. The radii treated with the carrier enriched,vi th either 1.5 or fifteen milligrams of BMP showed significantly increased p eriosteal and endosteal bone formation on histomorphometric (p < 0.05) and radiographic (p < 0.02) analysis. Conclusions: Bone formation in a persistent osseous defect that is similar to an ununited diaphyseal fracture is increased when species-specific BMP i ncorporated into a polylactic acid-polyglycolic acid carrier is implanted a t the site of the nonunion. TGF-beta 1 at a dose of ten nanograms per impla nt did not induce a similar degree of bone formation or potentiate the effe ct of BMP in this model. Clinical Relevance: The biodegradable implant containing BMP that was used in the present study to treat diaphyseal nonunion is an effective bone-graf t substitute.