Bone tissue engineering (BTE) emerged ?30 years ago and is based on seeding the artificial scaffold with stem cells, which are then differentiated into bone tissue. This approach in principle allows one to restore damaged or fractured bones and can be used in bone surgery. After the formation of bone, there is no need for the scaffold and in most cases, it can be surgically removed or (preferentially) degraded without additional surgery. Ideally, the scaffold degradation should be synchronized with the bone tissue regeneration rate. Because bones support important mechanical loads, the scaffolds for bone surgery need to have high mechanical strength. This is the main reason why bone surgery fixation devices are currently made of metals. However, metals normally require extraction surgery to be removed from the body, while bioresorbable polymers, which would be more beneficial in this respect, cannot be used due to their poor mechanical properties. Also, the chemical properties of the scaffolds are important to decrease immune response and minimize other adverse effects. Superior hardness and Young’s modulus of ND, as well as rich surface chemistry and chemical stability of the ND core, are advantageneous for enhancing the mechanical and chemical properties of bioresorbable polymer scaffolds. It was described that octadecylamine(ODA) functionalized NDs embedded in poly L-lactic acid (PLLA) resulted in 200% higher Young’s modulus and 800% higher hardness compared to neat PLLA. Murine osteoblast growth was demonstrated on the ND-ODA/PLLA matrix for up to one week. The solubility of ND-ODA in organic solvent (e.g. chloroform) facilitates the dispersion of the nanofiller in the hydrophobic PLLA matrix. The ND-adsorbed phospholipid complex was used to aquire a stable dispersion of ND particles in poly(lactic-co-glycolic acid) (PLGA) as compared to neat PLGA, 10 wt% ND/PLGA showed 100% increase in Young’s modulus and 550% increase in hardness. Besides, the ND inclusion into PLGA matrix slowed down its biodegradation in vivo, thus enabling a robust growth of hFOB1.19 osteoblasts.
The in vivo testing of ND/PLGA matrix over eight weeks has shown acceptable immune response and no toxicity. Stem cells differentiation towards osteoblasts is controlled by growth factors. One of them, bone morphogenetic protein (BMP), has been broadly used in BTE, however,concerns regarding its tumorigenic potential have recently been raised. The improved delivery system based on poly(L-lactide)-co-(?-caprolactone)(PLCL) scaffold and ND has been demonstrated to release BMP-2 locally. Authors claim that the ND surface chemistry plays an important role in sustained release of low doses of adsorbed BMP-2. The ND/ PLCL implant degrades in vivo over six months to 10% of its initial weight while minimizing anti-inflammatory response due to its low toxicity. ND/PLCL scaffolds have been recently reported to decrease the tumorigenic potential of early neoplastic dysplastic oral keratinocytes. The anticancer activity was associated with the presence of ND in these scaffolds through the mechanisms, which are currently under investigation. This result is a spectacular demonstration of anticancer activity of ND containing bone implants.