Enhancement of osteogenesis and stem cell differentiation by injectable nanocomposite and dynamic acoustic radiation force stimulation

Osteopenia affects mineral density, microstructure, and integrity of bone, leading to increased risk of fractures, as well as high rates of non-union, which affect patients’ quality of life. Current treatments are ineffective, requiring invasive surgeries and/or long-term drug therapy. The objective of this study was to develop a novel noninvasive biomimetic treatment for rapid regeneration to promote cell differentiation and osteogenesis. An injectable orthopedic implant was designed by developing a thermosensitive scaffold incorporating carbon nanotubes and chitosan-β glycerophosphate hydrogels. An innovative biophysical stimulation using dynamic ultrasound radiation force (ARF) was used to induce carbon nanotube resonance for regulating osteogenic differentiation of stem cells. An assay on activity of ALP, a biomarker of osteogenesis, and a fluorescence-based live/dead cell assay were conducted to determine the best treatment for inducing rapid cell formation. The single-walled carbon nanotube scaffold and 60 mW/cm2 ARF group was the best treatment, and enhanced ALP activity and stem cell differentiation by 430%. Cell viability was increased by 65% through the ARF treatment. This study developed a novel treatment for regulating cell proliferation using single-walled carbon nanotube nanocomposite implants and synergistic stimulation of stem cells with ultrasound. This rapid, noninvasive, cost-effective treatment may provide an innovative alternative for osteoporotic treatment and rapid fracture healing.