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

Potentiation of Osteo- and Angiogenesis in Vivo after Implantation of Hydroxyapatite Combined with Autogenous Growth Factors

Olaf Kilian, MD; Sabine Wenisch; Ingo Flesch; Reinhard Schnettler; Department of Trauma Surgery, University of Giessen, Giessen, Germany

Purpose: There is accumulating evidence that growth factors accelerate wound healing by stimulating matrix production and potentiating angiogenesis. Use of hydroxyapatite (HA) combined with autogenous growth factors purified from pig platelets was investigated to determine whether analogous effects of growth factors could be observed during early phases of fracture healing.

Methods: In the experimental procedure, two cylindrical defects were created within the intercondylar region of the pig femoral condylus. The proximal defect was filled with HA and the distal, with HA enriched with growth factors.

Results: Ten and 20 days after surgery the specimens were examined immunohistochemically and ultrastructurally. Antibodies to factor VIII, ED-A, and ED-B fibronectin, and to alpha smooth muscle actin have been used to study angio- and osteogenesis, especially the formation of granulation tissue. Even after 10 days, comparative immunohistochemical data revealed distinct differences between the use of HA and HA in combination with growth factors. There was a significant increase of neovascularization >from the application of growth factors, as demonstrated with factor VIII and ED-B fibronectin antibodies. Moreover, granulation tissue formation was accelerated. After 10 days, intense labeling for alpha smooth muscle actin and ED-A fibronectin could be observed only in combination with growth factors.

Discussion: Fibronectin expression precedes alpha smooth muscle actin deposition. Due to the effects of growth factors there is activation of resident fibroblasts to synthesize ED-A fibronectin necessary for the induction of myofibroblasts or pericytes by growth factors. Additionally, a few ED-B positive areas of woven bone, including osteoblasts, could be identified within the defect area after 10 days of local treatment with growth factors. This finding was confirmed ultrastructurally. It could be shown that the cells responsible for accelerated degradation of the implant enriched with growth factors were multinucleated giant cells.