PDGF Modulates Demineralized Bone Matrix-Induced Cartilage and Bone Formation

Objectives: Because platelet derived growth factor (PDGF) has been proposed as a therapeutic agent to promote bone healing, this study was undertaken to examine the effect of platelet derived growth factor (PDGF) on the ability of human demineralized bone matrix (DBM) to induce bone formation in the nude mouse muscle implantation model. Methods: Human DBM, previously shown to be osteoinductive in nude mouse calf muscle, was mixed with PDGF-BB (0, 0.1, 1, and 10 µg/10 mg DBM) and implanted bilaterally in the calf muscles of immunocompromised (Nu/Nu) mice (6 mice/group). Implanted tissue was harvested at 14, 28, and 56 days post-surgery and processed for histology. Osteoinduction was assessed using a qualitative scoring system and quantitative histomorphometry. Results: Cartilage was present at 14 days in all implanted tissues, but the amount decreased with increasing PDGF concentration. By 28 days no cartilage was present in tissue with low PDGF concentrations, but cartilage remained when the high PDGF dose was used. New bone formation was present at 28 days and to a similar or greater extent at 56 days. PDGF (10 µg) reduced bone formation at 28 days, but this effect was resolved by 56 days. Histomorphometry showed that the amount of new cartilage at 14 days, and of new bone and new bone marrow at 28 days were reduced in the presence of 1 µg PDGF, although the number of osteoinductive sites remained high. In sites treated with 10 µg PDGF, new bone area was decreased by 67% and area of bone marrow was reduced by 80% at 28 and 56 days. In another phase of this study, platelet rich plasma, which contains enriched PDGF, was found to reduce the osteoinductivity of DBM in the mouse model. Conclusions: Our results show that PDGF modulates intramuscular osteoinduction by DBM in immunocompromised mice.