|Titel på arbejdet||Stimulation of orthopaedic implant fixation. Investigations of osteogenic growth factors and topical delivery systems|
|Afdeling / Sted||Ortopædkirurgisk Afd. E, Aarhus Universitetshospital, og Interdisciplinary Nanoscience Center, AU|
|Abstract / Summary|
The long term survival of cementless orthopedic implants relies on a rapid bony osseointegration, as early implant migration has shown to be a strong predictor of early loosening. The challenge of facilitating a solid bony fixation of an implant is greatest in settings where bone stock is diminished and healing potential reduced. Since adjuvant therapies for implant fixation using osteogenic growth factors have been introduced, applications employing one growth factor have been extensively investigated. Applications combining two or more growth factors may be more favorable due to additive or synergistic effects on bone. We investigated the combination of Transforming Growth Factor beta one (TGF-β1) and Insulin-Like Growth factor one (IGF-1) as those two growth factors are highly expressed during bone growth. We investigated the growth factor combination administered topically to the implant surface by a biodegradable polymer. Furthermore we investigated the possibility of using chitosan, a ubiquitous polymer found in the exoskeletons of crustaceans, insects, fungal cell walls and plankton, as a drug carrier for implant applications.
This thesis is based on three papers. Studies I and II investigate the effect of the combination of TGF-β1 and IGF-1 coated onto the implant surface in Poly (D,L-lactide)(PDLLA), a biodegradable carrier. Study III investigates the effect of chitosan applied to an implant as a scaffold.
In study I the growth factor coating was applied on the surface of a porous coated titanium alloy implant and compared with a porous coated titanium alloy implant not coated with the growth factors. The implant model was an unloaded gap model, and situated in the proximal humerus of mature dogs. The observation period was 4 weeks, and the bone-implant specimens were evaluated by mechanical and histomorphometric tests. The fixation of the growth factor coated implants was two-fold higher than the fixation of the control implants without the growth factor coating. There was 2,5 times more bone on the surface of the growth factor implants than the controls, a 30 % median raise in inner zone gap healing and a 2-fold raise in outer zone gap healing. No fibrous tissue was found on the growth factor treated implants.
In study II the growth factor coated implants were used in a loaded gap model in the distal femurs of mature dogs. Similar implants with an additional hydroxyapatite coating was used as controls. As in study I, the observation period was 4 weeks, and the bone-implant specimens were evaluated by mechanical and histomorphometric tests. The mechanical test found all implants to be well fixed without any statistically significant differences in any of the three mechanical parameters. In contrast to the push-out test, the histomorphometric analysis found differences in tissue distribution around the implants. Bone ongrowth to the implants was 3 fold higher for HA coated implants. There was a little fibrous tissue ongrowth in 4 of the 10 HA coated implants, and no fibrous tissue on the growth factor coated implants. In the inner half of the gap, the bone volume fraction was 26% higher in the growth factor coated implant group. In the outer half of the gap, the bone volume fraction was 28% higher in the growth factor coated implant group. There were no signs of residual polymer on the implant surfaces.
In study III a porous chitosan scaffold was produced on titanium alloy implants. A standard porous coated titanium alloy implant without chitosan was used as control. The implants were inserted in the proximal tibia of dogs for 4 weeks, in an unloaded gap model. We evaluated the effect by mechanical push out test and histomorphometry. The chitosan scaffold was converted to a thick fibrous membrane that caused the implants to be fixated very poorly compared with the uncoated controls. There was 3-fold more bone around the chitosan coated implants outside of the fibrous membrane compared with the controls.
In conclusion the combination of TGF-β1 and IGF-1 coated onto the implant surface in a biodegradable carrier facilitated a markedly improved fixation and osseointegration of the porous coated titanium implants. The results with the growth factor coating are very encouraging, especially for situations were the host bone and healing potential is compromised. Further investigations are warranted to determine the best use of this promising adjuvant therapy.
The chitosan scaffold coated on the titanium implants proved to be useless for implant applications in the present form. There was however a great increase in gap healing of bone in the outer gap of the chitosan implants, and this justifies further investigation to establish whether chitosan has a potential for implant drug delivery applications.