Session I - Combined Session (International Society for Fracture Repair)

*BMP-2 Coating of Titanium Implants Increases Biomechanical Strength and Accelerates Bone Remodeling in Fracture Treatment: A Biomechanical and Histological Study on Rats

Gerhard Schmidmaier, MD; Britt Wildemann, MD; Felix Cromme, MD; F. Kandziora, MD; Norbert P. Haas, MD; Michael Raschke, MD; Trauma and Reconstructive Surgery-Charité, Campus Virchow, Humboldt-University of Berlin, Berlin, Germany (a-Charitè Hospital Research Support)

Purpose: Bone morphogenetic protein-2 (BMP-2), a member of the TGF-beta superfamily, is known to stimulate osteogenic cells. In vivo studies have shown that BMP-2 delivered from collagen sponges enhances healing of fractures [Welch RD, J Bone Miner Res 1998, 13:1483-1490]. This application technique requires opening of the fracture and may have possible side effects due to the use of bovine collagen. A newly developed coating method for implants based on biodegradable poly(D,L-lactide) allows the incorporation of growth factors and the controlled release of these factors during the healing process without the need for further devices. The effect of BMP-2 (5% weight-to-volume ratio) locally released from coated intramedullary implants on fracture healing was investigated with biomechanical and histologic analysis in rats.

Methods: A standardized closed fracture of the right tibiae of 5-month old Sprague Dawley rats (N = 80) was performed with a fracture device (impulse p = 1.12 Ns). The fractures were intramedullarly stabilized with uncoated versus coated titanium K-wires. The following groups were examined: group I, implant uncoated, 28 days (N = 20); group II, implant coated with PDLLA + rh-BMP-2, 28 days (N = 20); group III, implant uncoated, 42 days (N = 20); and group IV, implant coated with PDLLA + rh-BMP-2, 42 days (N = 20).

After fracture of the right tibiae, x-ray examinations (posteroanterior and lateral) were performed throughout the experimental period. After sacrifice of the animals, both tibiae were dissected for biomechanical torsional testing using a material testing machine (Zwick 1455, Ulm, Germany). For histologic and histomorphometric analyses, the tibiae were fixed and embedded in methylmetacrylate; 5-µm sections were prepared and stained with Safranin O/light green and v. Kossa. The histomorphometry of the calli was analyzed using an image analyzing system (Zeiss KS 400).

Results: A progressed callus consolidation was demonstrated in the BMP-2-treated groups compared with the uncoated groups at both time points. The histomorphometric analysis demonstrated a progressed callus remodeling with significantly higher mineralization of the cortices and higher mineralization and less cartilage of the periosteal callus. After 4 and 6 weeks, the local application of BMP-2 demonstrated a significantly (t-test, P <0.05) higher maximum load and torsional stiffness in the biomechanical testing compared with controls.

Discussion: The results clearly demonstrated that the local application of BMP-2 from PDLLA-coated implants significantly accelerated fracture healing. Two time points were investigated to analyze the effect of the BMP-2 coating on the healing process. The biomechanical torsional testing after 28 and 42 days revealed a higher torsional stability compared with that of the control groups. These data were supported by the histomorphometric results. The callus treated with BMP-2 demonstrated a progressed remodeling with significantly higher mineralization and less cartilage compared with controls.

Conclusion: These results are in accordance with other studies investigating the effect of BMP-2 on fracture healing. However, local administration of growth factors from coated osteosynthetic implants could reduce clinical problems in fracture treatment without opening of the fracture, implantation of further devices, injections with the risk of infection, or side effects caused by the carrier.