Healing of bone defects in a rodent calvarial defect model using strong porous bioactive glass (13-93) scaffolds

"The main objective of this project was to evaluate the capacity of strong porous silicate (13-93) bioactive glass scaffolds prepared by a robocasting technique to regenerate bone and stimulate angiogenesis in a rat calvarial defect model. The scaffolds were created with the same grid-like microstructure but in a variety of formulations: (i) as-fabricated, (ii) pretreated in an aqueous phosphate solution to convert the glass surface to hydroxyapatite, (iii) loaded with bone morphogenetic protein-2 (BMP2) (1 µg per scaffold), and (iv) doped with copper (0.4-2.0 wt. % CuO). When compared to the as-fabricated scaffolds, the pretreated scaffolds enhanced bone regeneration at 6 weeks but not at 12 or 24 weeks. In comparison, the BMP2-loaded scaffolds enhanced bone regeneration at all three implantation times and they were almost completely infiltrated with lamellar bone within 12 weeks. Doping the as-fabricated scaffolds with 0.4 and 0.8 wt. % CuO did not affect the response of preosteoblastic MC3T3-E1 cells in vitro and bone regeneration in vivo. In comparison, the scaffolds doped with 2.0 wt. % CuO were toxic to the cells in vitro and significantly inhibited bone regeneration at 6 weeks post-implantation. The area of new blood vessels in the new bone that infiltrated the scaffolds at 6 weeks post-implantation was significantly enhanced by the BMP2 loading but not by CuO dopant concentrations of 0.4 and 0.8 wt. %. The fibrous tissue that infiltrated the scaffolds doped with 2.0 wt. % CuO showed a significantly higher blood vessel area than the as-fabricated scaffolds. Loading silicate 13-93 bioactive glass scaffolds with BMP2 significantly improved their capacity to regenerate bone in rat calvarial defects at 6 weeks post-implantation when compared to doping the glass with copper"--Abstract, page iv.