Osteoblast Behaviors on Novel Self-assembled Helical Rosette Nanotubes and Hydrogel Composites for Bone Tissue Engineering

摘要

To date, although traditional autografts and allografts have been standard methods to treat bone fractures and defects, the formation of biocompatible and injectable scaffolds to induce new bone growth is still a promising method to repair bone defects considering their minimally invasive and osteoinductive features. In this study, a novel bone tissue engineering scaffold based on the self-assembled properties of helical rosette nanotubes (HRNs) and biocompatible hydrogels (specifically, poly(2-hydroxyethyl methacrylate)-pHEMA) was designed to fill bone fractures and repair bone defects. HRNs are a new class of organic nanotubes with a hollow core 11 A in diameter, which originate from the self-assembly of DNA base pair building blocks (guanine-cytosine) in aqueous solutions. Since HRNs can significantly change their aggregation state and become more viscous based on heating or when added to serum free medium at body temperature, HRNs may provide an exciting therapy to heal bone fractures as injectable bone substitutes. In addition, biocompatible hydrogels were used in conjunction with HRNs in this study to strengthen the bone substitutes and also to serve as a potential drug releasing carrier to stimulate new bone growth at such fracture sites. Two types of HRNs, one with a lysine side chain and the other conjugated to 1% and 10% RGD (arginine-glycine-aspartic acid) peptides on HRNs, were prepared and dispersed into hydrogels. Due to their nanometric features and the helical architecture of HRNs which biomimic collagen, results showed that these HRN hydrogel composites can significantly improve osteoblast adhesion compared to hydrogel controls. Furthermore, 0.01 mg/ml HRNs with RGD embedded in and coated on hydrogels can also enhance osteoblast attachment compared to 0.01 mg/ml HRNs with lysine side chains embedded in and coated on hydrogels. Results showed an increasing trend of osteoblast adhesion on these scaffolds with more RGD groups (10%) on HRNs. In this manner, nanostructured HRN hydrogel composites provide a promising alternative to repair bone defects considering the flexibility in the design of HRNs and their exceptional cytocompatibilty properties.