The Degradation Rate and Osteoinductive Efficacy of BMP-2-Bearing Biomimetic Coatings Vary as a Function of the Drug Delivery Mode

摘要

We have investigated the osteoinductive efficacy of various types of BMP-2-containing biomimetic calcium phosphate coating. The criterion for an optimal system is that it elicits a high osteogenic activity at a low drug dose within a short period of time. Four different drug delivery modes were investigated at an ectopic (subcutaneous) ossification site in rats: (ⅰ) naked titanium-alloy implants bearing adsorbed BMP-2 at three different loading doses (2.5 μg, 5.0 ug and 7.5 μg per implant); (ⅱ) titanium-alloy implants coated with a crystalline layer of calcium phosphate bearing adsorbed BMP-2 at three different loading doses (2.5 μg, 5.0 μg and 7.5 μg per implant); (ⅲ) titanium-alloy implants coated with a crystalline layer of calcium phosphate bearing incorporated BMP-2 at three different doses (0.56 μg, 0.61 μg and 1.7 μg per implant); and (ⅳ) a hybrid system, consisting of titanium-alloy implants coated with a layer of crystalline calcium phosphate bearing incorporated BMP-2 at three different concentrations (as mentioned above) and adsorbed BMP-2 at a fixed dose (7.5 μg per implant). The implanted samples were retrieved at various times between 1 and 5 weeks after surgery, and then analyzed histologically and histomorphometrically. Two weeks after surgery, the amount of bone deposited around calcium phosphate coatings bearing the highest dose of incorporated BMP-2 (1.7 μg per implant) was almost 3-fold greater than that associated with coatings bearing adsorbed BMP-2 at a 3-fold higher dose (5.0 μg per implant), namely, 5.83 mm~3 of bone tissue vs. 1.98 mm~3 of bone tissue per implant. A positive correlation existed between the rate of coating degradation and the rate of ectopic bone formation. Using the hybrid system, coating degradation and osteoinductive efficacy were further potentiated, in a manner that was proportional to the incorporated dose of BMP-2. We conclude that the rate of coating degration and the osteoinductive efficacy of BMP-2 can be modulated by the mode of drug delivery.