Impact of pore size on the vascularization and osseointegration of ceramic bone substitutes in vivo

The repair of bone defects with biomaterials depends on a sufficient vascularization of the implantation site. We analyzed the effect of pore size on the vascularization and osseointegration of biphasic calcium phosphate particles, which were implanted into critical-sized cranial defects in Balb/c mice. Dense particles and particles with pore sizes in the ranges 40-70, 70-140, 140-210, and 210-280 mu m were tested (n = 6 animals per group). Angiogenesis, vascularization, and leukocyte-endothelium interactions were monitored for 28 days by intravital microscopy. The formation of new bone and the bone-interface contact (BIC) were determined histomorphometrically. Twenty-eight days after implantation, the functional capillary density was significantly higher with ceramic particles whose pore sizes exceeded 140 mu m [140-210 mu m: 6.6 (+/- 0.8) mm/mm; 210-280 mu m: 7.3 (+/- 0.6) mm/mm 21 than with those whose pore sizes were lesser than 140 mu m [40-70 mu m: 5.3 (+/- 0.4) mm/mm(2); 70-440 mu m: 5.6 (+/- 0.3) mm/mm(2)] or with dense particles [5.7 (+/-.8) mm/mm(2)]. The volume of newly-formed bone deposited within the implants increased as the pore size increased 40-70 mu m: 0.07 (+/- 0.02) mm(3); 70-140 mu m: 0.10 (+/- 0.06) min; 140-210 mu m: 0.13 (+/- 0.05) min 3; 210-280 mu m: 0.15 (+/- 0.06) mm(3)]. Similar results were observed for the BIC. The data demonstrates pore size to be a critical parameter governing the dynamic processes of vascularization and osseointegration of bone substitutes.