In this study we compared the effects of local release of TGF-β1 and IGF-1 with that of a hydroxyapatite coating on the fixation of weight-bearing implants surrounded by a circumferential gap. Although we did not find any difference in the mechanical fixation, the effect on the surrounding tissue was different with the two interventions. While the growth factors primarily stimulated bone in the gap, the HA coating had superior bone ongrowth.
We used an experimental animal model that attempts to mimic the cancellous bone fixation of clinical implants. The implants are weight-bearing and their intraarticular location results in a flow of synovial fluid along the implant interface. The main idea of this model is to test whether a treatment will enhance the initial implant fixation, and thus prevent early loosening. The observation period of 4 weeks has been shown to detect differences in early fixation in this model (Soballe et al. 2003
). We used a paired design, thus eliminating the inter-individual variation between animals.
As with all other experimental models, this model also has limitations. The loading is mainly in shear and does not include the rotational forces that also apply to human implants. The dog has a bone turnover which is 2–3 times higher than that in humans. This may influence the effect of certain treatments. Moreover, the implants are simplified in shape and size and do not include fixation points of both cancellous and cortical bone. However, this allows implantation in a highly controlled environment and permits unbiased histological evaluation.
The histological analysis showed that the solid fixation in both groups was obtained in a different way for each group: the HA-coated implants had a greater surface bone ongrowth, whereas the growth factor-coated Ti implants had greater new bone formation in the surrounding gap.
The effect of local release of TGF-β1 and IGF-1 on the tissue response was different than for HA. In accordance with previous studies (Lamberg et al. 2006
), no fibrous tissue ongrowth was found on any implant with TGF-β1 and IGF-1. Without adjuvant therapy, a high degree of fibrous tissue anchorage would be expected on titanium implants in this implant model (Soballe et al. 1992
, Elmengaard et al. 2005
). We believe that the elimination of fibrous tissue on the interface is not an effect related to the poly(D,L-lactide) scaffold. A parallel study has shown no difference in fibrous tissue ongrowth between poly(D,L-lactide)-coated and control titanium implants (unpublished data). To our knowledge, no other adjuvant treatment has been shown experimentally to stimulate gap healing around titanium implants better than HA.
We used a polymer for controlled release of the growth factors. The poly(D,L-lactide) has been used successfully as a drug carrier (Schmidmaier et al. 2001b
, Rose et al. 2004
). Polylactides are also used to make screws and plates for fracture treatment, and are generally considered safe. This delivery system has advantages over other methods such as simple surface adsorption of growth factors and collagen sponges, as it has been documented to be mechanically stable (Schmidmaier et al. 2001b
) and thereby able to resist the forces of implantation. In addition, it is generally accepted that the majority of the growth factors most likely remain in the scaffold until the bleeding from the bone has ceased. Elution studies have shown a release profile of 50% release within 48 h, with growth factors detectable for several weeks thereafter. In contrast to the studies of fracture healing in a rat model (Schmidmaier et al. 2001b
), there was no polymer left on our implants at the end of the observation period. The amount of growth factor used depends on the size of the implants, as the growth factors are administered in a specific w/w ratio to the poly(D,L-lactide) scaffold. The w/w ratio that we used was based on previous experience (Kandziora et al. 2003
, Lamberg et al. 2006
). It is possible that even better results would be obtained with different ratios, and this is the subject of further investigation.
The mechanical fixation obtained with local release of TGF-β1 and IGF-1 is comparable to that of an HA coating. The mechanical fixation was achieved in different ways, as HA stimulated bone ongrowth while TGF -β1 and IGF-1 significantly increased gap healing. The results of this study suggest that controlled local growth factor release has the potential to be used in clinical situations in which a more general stimulation of bone is required, e.g. in revision arthroplasties or pseudoarthrosis. Given their different effects, a combination of the two coatings would be an interesting subject for further investigation. It is necessary to keep in mind that hydroxyapatite has had a long and successful history of clinical implementation, while growth factors may have unknown side effects when used clinically.