Session III - Polytrauma Fracture Healing

Friday, October 22, 1999 Session III, 4:38 pm

*The Local Application of Growth Factors like IGF-1 and TGF-ß1 from a Biodegradable Poly(D,L-Lactide) Coating of Implants Increases Fracture Healing

Gerhard Schmidaier, MD (a-DFG-German Society for Research); Michael Raschke, PD (a-DFG-German Society for Research); Hermann Bail, MD (a-DFG-German Society for Research); Stefan Kolbeck, MD (a-DFG-German Society for Research); Norbert P. Haas, MD (a-DFG-German Society for Research), Department of Trauma & Reconstructive Surgery, Charité, Humboldt-University, Berlin, Germany

Purpose: The local application of growth factors (IGF-I and TGF-ß1) >from a biodegradable poly D,L-lactide (PDLLA) coating of implants, could benefit the clinical outcome of fracture treatment.

Former in vitro studies investigated the properties of the PDLLA coating on metallic implants for the local application of drugs.

The coating can be performed under sterile conditions and has high mechanical stability. The incorporated growth factors demonstrated a continuous release of 80% from the PDLLA coating for at leased 6 weeks in vitro and in vivo.

Methods: We produced a standardized fracture of the right tibiae in five month old Sprague Dawley rats (n=144). The fractures were stabilized with coated versus uncoated titanium K-wires. Following groups were examined:

  • Group I: implant uncoated
  • Group II: implant coated with PDLLA
  • Group III: implant coated with PDLLA + IGF-I (5%) + TGF-b1 (1%)

    • After standardized fracture of the right tibiae, x-ray examinations were performed throughout the following four and six weeks. At four, or six weeks the animals were sacrificed. Both tibiae were dissected for biomechanical testing. The histomorphometric analyses of the calli and the radiological findings were quantified in an image analyzing system.

    Results: The x-ray examinations of group I showed incomplete consolidation of the fractured tibiae after four and six weeks. In group II we found good callus formation in comparison with the uncoated group I. The animals of group III demonstrated almost completely consolidated fractures after four and six weeks. Compared to the non fractured tibiae we found significantly (p<0.05) higher torsional stiffness (t-stiff) and maximum load (max.-load) of the PDLLA + IGF-I + TGF-ß1 coated group III versus the PDLLA coated group II and uncoated group I after 4 weeks and after 6 weeks. The uncoated group I showed significantly less torsional stability than the PDLLA - coated group II.

     Group III:
    4 weeks: 83% max.-load; 139% t-stiff /
    6 weeks: 121% max.-load; 170% t-stiff
     Group II:
    4 weeks: 63% max.-load; 85% t-stiff /
    6 weeks: 86% max.-load; 88% t-stiff
     Group I:
    4 weeks: 47% max.-load; 53% t-stiff /
    6 weeks: 51% max.-load; 61% t-stiff

    The histomorphometric analyses supported the findings of the x-ray examinations and the biomechanical testing. We found significantly (p<0.05) more fibroblasts and cartilage cells in group I (uncoated implants) than in group II and group III. Group II (PDLLA coated implants) showed good callus formation and progressed bone remodeling, with few cartilage and connective tissue cells. Group III, stabilized with implants coated with PDLLA, IGF-I and TGF-ß1, showed almost completely remodeled fractures.

    Discussion and Conclusion: The results of the x-ray examinations, the biomechanical testing and the histomorphometric analyses clearly demonstrated that a coating of PDLLA with IGF-I and TGF-ß1 stimulates fracture healing significantly. The carrier PDLLA itself has a positive effect on fracture healing. The reason for this phenomenon remains unclear and is the purpose of further examinations.

    The coating of implants with PDLLA and incorporated growth factors (IGF-I and TGF-ß1) accelerates fracture healing and could improve the clinical outcome in orthopaedic and trauma surgery.