Composite bilayered scaffolds with bio-functionalized ceramics for cranial bone defects: An in vivo evaluation

Despite having substantial regenerative capabilities, bone regeneration in critical injuries may be insufficient and require an additional intervention. With advancements in material science and production technology it is now possible to generate complex scaffolds with controlled architectures for repairing these injuries. Additionally, these materials can be functionalized with bioactive molecules to enhance osteoinductivity. In the present work, we developed a multifunctional composite bilayered scaffold (BS), integrating a ceramic nanocement (NC) and macroporous composite scaffold (CG) for cranial injuries, mimicking bone architecture. The scaffolds were functionalized with recombinant human bone morphogenetic protein-2 (rhBMP-2) (BMP) (2 μg/scaffold) and zoledronic acid (ZA) (10 μg/scaffold). We hypothesized that the composite scaffolds would support proliferation of osteoblast progenitor cells and provide controlled release of loaded bioactive molecules to induce bone regeneration. Higher amounts of mineralized tissue (MT) deposition was observed with functionalized scaffolds 12 weeks post in vivo implantation in 8.5 mm critical cranial defect in rats. Contrary to our expectations, BS + ZA functionalized scaffolds had highest MT deposition (13.9 mm3), followed by CG + ZA + BMP with 9.2 mm3 and BS + ZA + BMP with 7.6 mm3 of MT deposition, all significantly higher than non-functionalized CG (7.2 mm3) or BS (4.9 mm3) scaffolds and the empty [Teotia et al 2017 ACS Appl. Mater. Interfaces, 9, 6816–6828] groups. The results supported an osteopromotive multifunctional scaffold implantation in critical defects.