Heat-treated BMP-2 depots release BMP-2 in its bioactive form

Small depots of locally fixed bone morphogenetic protein-2 (BMP-2), which were dried onto biocompatible carriers and afterwards heat-treated, induce a local differentiation of contacting osteoblastic cells. Here we investigate whether such depots may act via a release of bioactive BMP-2. For in vivo experiments we employed a modified gap-healing approach using dump bell-shaped implants made from titanium plasma-sprayed Ti-6Al-4V, which were coated with BMP-2 at only one side. Four weeks after implantation into the cancellous bone of the lateral femur condylus of adult sheep we observed a polar formation of new trabecular bone close to the side where BMP-2 had been immobilized. We also tested whether BMP-2 depots stimulate remote cells under cell culture conditions and found, that alkaline phosphatase (ALP) of MC3T3-E1 cells was induced over a distance of several millimetres. Experiments show that BMP-2 at least in part desorbs from air-dried and heat-treated BMP-2 depots in its bioactive form. Local depots of BMP-2 may therefore allow to improve bone formation next to metal implants at predefined sites.