Osteoinductive hydroxyapatite-coated titanium implants

Previous studies have shown that heterotopic induction of bone formation by calcium phosphate-based macroporous constructs is set into motion by the geometry of the implanted substrata, i.e. a sequence of repetitive concavities assembled within the macroporous spaces. The aim of this study was to construct osteoinductive titanium implants that per se, and without the exogenous application of the osteogenic soluble molecular signals of the transforming growth factor-β supergene family, would initiate the induction of bone formation. To generate intrinsically osteoinductive titanium implants for translation in clinical contexts, titanium grade Ti-6A1-4V cylinders of 15 mm in length and 3.85 mm in diameter, with or without concavities, were plasma sprayed with crystalline hydroxyapatite resulting in a uniform layer of 30 μm in thickness. Before coating, experimental titanium implants were prepared with a sequence of 36 repetitive concavities 1600 μm in diameter and 800 μm in depth, spaced a distance of 1000 μm apart. Mandibular molars and premolars were extracted to prepare edentulous mandibular ridges for later implantation. Planar and geometric hydroxyapatite-coated titanium constructs were implanted in the left and right edentulized hemi-mandibles, respectively, after a healing period of 7–8 months, 3 per hemi-mandible. Three planar and three geometric implants were implanted in the left and right tibiae, respectively; additionally, planar and geometric constructs were also inserted in the rectus abdominis muscle. Six animals were euthanized at 30 and 90 days after implantation; one animal had to be euthanized 5 days after surgery and the remaining animal was euthanized 31 months after implantation. Undecalcified longitudinal sections were precision-sawed, ground and polished to 40–60 μm; all sections were stained with a modified Goldner’s trichrome. Undecalcified specimen block preparation was performed using the EXAKT precision cutting and grinding system. Histomorphometric analyses of bone in contact (BIC) showed that on day 30 there was no difference between the geometric vs. planar control implants; on day 90, the ratio of BIC to surface within the geometric implants was greater than on the standard planar implants in both mandibular and tibial sites; 31 months after implantation, selected concavities cut into the geometric implants harvested from the rectus abdominis muscle showed the spontaneous induction of bone formation with mineralized bone surfaced by osteoid seams. These data in non-human primates indicate that geometrically-constructed plasma-sprayed titanium implants are per se osteogenic, the concavities providing a unique microenvironment to initiate bone differentiation by induction.