Osteogenic Effect of a Bioactive Calcium Alkali Phosphate Bone Substitute in Humans

Abstract

(1) Background: The desire to avoid autograft harvesting in implant dentistry has prompted an ever-increasing quest for bioceramic bone substitutes, which stimulate osteogenesis while resorbing in a timely fashion. Consequently, a highly bioactive silicon containing calcium alkali orthophosphate (Si-CAP) material was created, which previously was shown to induce greater bone cell maturation and bone neo-formation than β-tricalcium phosphate (β-TCP) in vivo as well as in vitro. Our study tested the hypothesis that the enhanced effect on bone cell function in vitro and in sheep in vivo would lead to more copious bone neoformation in patients following sinus floor augmentation (SFA) employing Si-CAP when compared to β-TCP. (2) Methods: The effects of Si-CAP on osteogenesis and Si-CAP resorbability were evaluated in biopsies harvested from 38 patients six months after SFA in comparison to β-TCP employing undecalcified histology, histomorphometry, and immunohistochemical analysis of osteogenic marker expression. (3) Results: Si-CAP as well as β-TCP supported matrix mineralization and bone formation. Apically furthest away from the original bone tissue, Si-CAP induced significantly higher bone formation, bone-bonding (bone-bioceramic contact), and granule resorption than β-TCP. This was in conjunction with a higher expression of osteogenic markers. (4) Conclusions: Si-CAP induced higher and more advanced bone formation and resorbability than β-TCP, while β-TCP's remarkable osteoconductivity has been widely demonstrated. Hence, Si-CAP constitutes a well-suited bioactive graft choice for SFA in the clinical arena.

Keywords: bioactive bone grafting material; bioactivity; bioceramics; bone regeneration; calcium alkali orthophosphate materials; osteogenesis; silicon release; sinus floor augmentation.

Figure 1

(a) Scanning electron micrograph of the Si-CAP (Osseolive^®) particulate bone grafting material. Bar = 500 µm. (b) Scanning electron micrographs of the Ceros^® Β-TCP particulate bone grafting material. Bar = 500 µm.

Figure 2

Schematic illustrating the biopsy sampling from patients six months after grafting of the sinus floor utilizing a calcium phosphate bone grafting material as well as the respective histomicrograph with its anatomical orientation and the ROIs.

Figure 3

(a) Cone beam CT (CBCT) acquired postoperatively in a patient, in whom Si-CAP granules were used for SFA; (b) panoramic radiographs taken at preparation of the implant bed 6 months after utilizing Si-CAP granules for sinus floor grafting; (c) CBCT acquired subsequent to implant surgery 6 months after bilateral sinus floor grafting using Si-CAP; (d) CBCT acquired after implant placement 6 months after SFA with β-TCP granules: residual bone grafting material is clearly visible (green arrow).

Figure 4

Histograms depicting the results of the histomorphometric analysis: bone area fraction, bioceramic granule area fraction, and bone-bioceramic contact of (a) the central ROI and (b) the apical ROI in hard tissue sections of either Si-CAP biopsy specimens or β-TCP biopsy samples, which were harvested six months after sinus floor grafting. All values are the mean + standard deviation of 19 measurements.

Figure 5

Biopsy sampled 6 months after implanting Si-CAP for sinus floor grafting: (a) macroscopic photograph; (b,c) synchrotron microtomographical image (bone—red; residual grafting materials—grey); (d–h) histomicrographs of undecalcified hard tissue section with immunodetection of OCN (osteocalcin). Excellent trabecular bone formation is visible after sinus floor grafting. A few highly leached and degraded fragments of the Si-CAP granules are embedded in these newly formed trabeculae. Extensive bone ingrowth into the pores of these residues, which feature excellent bone bonding, is present (d,e) (yellow arrows); OS—osteoid. At the degrading Si-CAP granule surface, active matrix mineralization and osseous tissue formation with strong OCN expression are visible in the apical region of the biopsies in close proximity to the bordering sinus mucosa (d–g) (green arrows). As such, progressing bone formation is in tandem with the continuously progressing degradation of the residual Si-CAP granules, which are gradually replaced by the new bone tissue ((e–g) black arrows; (d,h) blue arrows); (i) histomicrograph of 5 µm undecalcified section immunohistochemically stained for von Willebrand factor: visualization of capillary formation (orange arrows) in bone tissue formed in the pores of a degrading Si-CAP granule six months after sinus floor grafting (bar = 20 µm).

Figure 6

Biopsy harvested 6 months after SFA with β-TCP: (a) macroscopic photograph; (b) synchrotron microtomographical image (bone—red; residual grafting material—white); (c–e) histomicrographs of undecalcified hard tissue sections with immunodetection of collagen I (d); osteocalcin (e). A greater amount of residual β-TCP bone substitute material is visible (c–e) (yellow arrows) in comparison to Si-CAP biopsy samples. The β-TCP granules display excellent bone-bioceramic contact in the central ROI (d) (black arrowheads) with bone ingrowth into the pores of the β-TCP granules. OS—osteoid; B—mineralized bone tissue; M—osteogenic mesenchyme. (e) Histomicrograph with β-TCP bone grafting material in the apical ROI. Commencing bone formation (black arrows) at the bioceramic surface (yellow arrows) and osteoblasts with strong staining for OCN (green arrowhead) are present in combination with moderate OCN staining of the osteogenic mesenchyme indicating active matrix mineralization (orange arrows).