Tissue engineering using 3D printed nano-bioactive glass loaded with NELL1 gene for repairing alveolar bone defects

The purposes of this study were to construct a novel tissue engineered bone composed of 3Dprinted bioactive glass block/chitosan nanoparticles(BD/CSn)composites loaded with Nel-like Type I molecular-1 DNA(pDNA-NELL1)and/or bone marrow mesenchymal stem cells(BMSCs),and study their osteogenic activities by repairing bone defects in rhesus monkeys.CSn with NELL1 gene plasmid and rhesus monkey BMSCs were composited with a BD scaffold to prepare the tissue-engineered bone.Four adult female rhesus monkeys with 10-to 12-years old and 5-7 kg in weight were used in animal experiments.The first and second premolar teeth from four regions of each monkey were removed to form bone defects with size of 10×10×5 mm,which were then implanted with above-mentioned tissue engineered bone.At 12 weeks after the implantation,gross observations,X-ray and micro-CT observations revealed that the new bone was extremely close to normal bone in mass,density,hardness,and structure.The bony cortex was smooth and closely connected to the surrounding normal bone.Histological observations revealed moderate inflammation in the repair area,and the new bone tissues were similar to normal ones.In conclusion,tissue engineered bone of this study exhibited good osteoconductivity for promoting the formation of new alveolar bone tissue,and NELL1 gene played a promotional role in bone regeneration.