Comparison of Cellular Response to Anorganic Bone Matrix/Cell Binding Peptide and Allogenic Cranial Bone After Sinus Augmentation in Rhesus Monkeys
This study compared cellular responses of maxillary sinuses after augmentation with anorganic bovine-derived hydroxyapatite matrix linked to the cell binding polypeptide P-15 (ABM/P-15) or PepGen P-15 and allogenic freeze-dried cranial bone slabs. Five adult Macaque fascicularis monkeys were used. On one side, the floor of the sinus was augmented with ABM/P-15, while the other side was augmented with 2 cranial bone slabs. Trephine bone biopsies were obtained 6, 12, and 24 weeks postgrafting. Animals were sacrificed 8 months after grafting. Soft X-ray microradiography was used to determine bone density. The volume fraction (Vv) of regenerated bone, the number of mesenchymal cells, and the numbers of proliferating cell nuclear antigen (PCNA)- and alkaline phosphatase–positive cells at different augmentation sites were measured and compared. Basal bone heights were calculated at surgery and compared with total heights of the augmented sinus floors 8 months postgrafting. Bone formation, number of mesenchymal cells, PCNA index, and alkaline phosphatase index were significantly higher for the ABM/P-15 side than for the allogenic bone–augmented side. Both sides ended with a significant increase in bone height. The PCNA index decreased significantly over time (P < .05), while the alkaline phosphatase index increased significantly (P < .05) over time on both sides. Both graft materials have led to significant augmentation of the floor of the maxillary sinus with new bone; however, new bone formation and maturation were faster on the ABM/P-15 sites.Abstract

Figure 1. Creation of an oval window osteotomy in the lateral wall of the maxillary sinus.
Figure 2. Measuring alveolar bone height from the floor of the sinus to the crest of the ridge using a caliber before grafting.
Figure 3. ABM/P-15 (PepGen P-15) placed under the sinus membrane.
Figure 4. Two full-thickness slabs of allogenic freeze-dried calvarial bone were trimmed to fit in the sinus floor. The slabs were fixed to the host bone with a titanium screw.
Figure 5. A 2-mm-diameter trephine bur was inserted directly through the gingiva into the grafted area to obtain the bone core.
Figure 6. Showing the consistency of one of the bone cores (ABM/P-15 side). The lower picture shows the contact soft X-ray microradiogram.

Figure 7. Contact soft X-ray microradiogram of one of the ABM/P-15–grafted sinuses showing the graft materials surrounded by less-dense regenerated bone.
Figure 8. Contact soft X-ray microradiogram of coronal section of maxillary sinus showing the cranial bone slabs surrounded by regenerating bone.
Figure 9. Comparison of final bone heights (in mm) 8 months following bone augmentation of the floor of the maxillary sinus vs basal bone heights before grafting.

Figure 10. Bone core 6 weeks postgrafting (20 × 1.25): Woven bone with large number of osteocytes surrounds the ABM/P-15 particles.
Figure 11. Bone core 12 weeks postgrafting (20 × 1.25): The newly formed bone appears as mature lamellae around the ABM particle.
Figure 12. Bone core 12 weeks postgrafting (20 × 1.25): Evidence of ABM graft resorption by multinucleated cells (arrow) was seen.
Figure 13. Bone core 24 weeks postgrafting with ABM/P-15 (20 × 1.25): Note the presence of more mature lamellar bone at this stage than in earlier biopsies.

Figure 14. Floor of maxillary sinus 8 months postgrafting with ABM/P-15 (20 × 1.25, hematoxylin & eosin): Graft particles invaded by connective tissue can be seen under the sinus membrane (arrows). Most of the particles are completely encased in new bone.
Figure 15. Calcified section stained with modified Mason stain (20 × 1.25) of sinus floor 8 months postgrafting with ABM/P-15: Mineralized bone stains blue, and osteoid stains red. The presence of osteoid under the osteoblasts is indicative of active osteogenesis.
Figure 16. Floor of the sinus 8 months after augmentation with allogenic cranial bone (20 × 1.25, hematoxylin & eosin): The graft (BG) appears to undergo remodeling and is being replaced with host vital bone (VB). Note the presence of resting lines between the graft and the newly formed bone (arrows).
Figure 17. Calcified section stained with modified Mason stain (20 × 1.25) of the sinus floor 8 months postgrafting with allogenic cranial bone. A layer of osteoid (stained red) lines the inner surface of a remodeling tunnel, which is cutting through cranial bone graft, indicative of creeping substitution of the cranial bone with vital host bone.

Figure 18. Number of mesenchymal cells per unit area.
Figure 19. Proliferating cell nuclear antigen (PCNA)-positive cells in a core bone biopsy 6 weeks postgrafting with allogenic cranial bone.
Figure 20. Proliferating cell nuclear antigen (PCNA) index.
Figure 21. Alkaline phosphatase–positive cells (osteoblasts) (arrow) in the floor of the sinus 8 months postgrafting with ABM/P-15. New bone (B) and ABM particles (ABM) are seen.

Figure 22. Alkaline phosphatase index.
Figure 23. Volume fraction of new bone (Vv).
Figure 24. Densitometry of basal bones and grafted areas.
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