Natural bone inspired core-shell triple-layered gel/PCL/gel 3D printed scaffolds for bone tissue engineering

Despite technological advancements in bone tissue engineering, it is still a challenge to fabricate a scaffold with high bioactivity as well as high mechanical strength that can promote osteogenesis as well as bear load. Here we developed a 3D printed gel-polymer multi-layered hybrid scaffold. The innermost layer is porous gel-based framework made of gelatin/carboxymethyl-chitin/nano-hydroxyapatite and is cryogenically 3D printed. Further, the second and middle layer of micro-engineered polycaprolactone (PCL) is infused in the gel with controlled penetration and tuneable coating thickness. The PCL surface is further coated with a third and final thin layer of gel matrix used for the first layer. This triple-layered structure demonstrates compression strength and modulus of 13.07 ± 1.15 MPa and 21.8 ± 0.82 MPa, respectively, post 8 weeks degradation which is >3000% and >700% than gel scaffold. It also shows degradation of 6.84 ± 0.70% (83% reduction than gel scaffold) after 12 weeks and swelling of 69.09 ± 6.83% (81% reduction) as compared to gel scaffolds. Further, nearly 300%, 250%, 50%, and 440% increase in cellular attachment, proliferation, protein generation, and mineralization, respectively are achieved as compared to only PCL scaffolds. Thus, these hybrid scaffolds offer high mechanical strength, slow degradation rate, high bioactivity, and high osteoconductivity. These multifunctional scaffolds have potential for reconstructing non-load-bearing bone defects like sinus lift, jaw cysts, and moderate load-bearing like reconstructing hard palate, orbital palate, and other craniomaxillofacial bone defects.