Nanovibrational bioreactor for production of bone graft from mesenchymal stem cells

Studentship strategic priority area:Regenerative Medicine
Keywords: MSCs, mechanotransduction, nanokicking, osteogenesis

Abstract:
Mesenchymal stem cells (MSCs) are a promising resource for regenerative medicine. They can be obtained autologously and differentiate into tissues such as bone, fat, ligament and cartilage. They are of special interest in bone tissue engineering, as non-healing bone defects are commonly treated using autologous grafts, which are not always available and might result in damage to donor site. Using MSCs to produce lab grown bone grafts would allow to avoid the issues associated with bone autografts. To ensure the optimal safety of lab grown grafts, it is important to limit the use of animal products and excessive growth factors in their production. For this reason, strategies that employ mechanical stimulation to drive MSC osteogenesis are of key interest. Recently, it has been demonstrated that nanoscale vibration (named 'nanokicking') effectively promotes MSC osteogenesis in absence of any biochemical inducers. Applying nanokicking to 3D printed scaffolds seeded with autologously sourced MSCs could produce bone grafts tailored individually for each patient. Our aim is to find the optimal approach to applying nanovibrations to 3D printed constructs, evaluate the effectiveness of MSC osteogenic differentiation and identify some of the molecular pathways involved in sensing and response to nanokicking. In addition, once optimal procedure for bone formation is identified, we hope to use 3D printing to combine several materials and cell types to create complex tissue models. Modelling bone - soft tissue or bone - blood vessel interfaces would allow to determine the effects of nanokicking on the tissues surrounding the bone and inform the design of wearable nanokicking devices, which could potentially be used to prevent osteoporosis.