A 'toolbox' for bone regeneration
Bone engineering relies on the use of 3D lattices together with appropriate growth factors and stem cells to construct bone in the laboratory. The polymeric scaffold provides the required support for the growth and differentiation of stem cells into bone. The use of biodegradable polymers allows for the 'artificial' bone to become fully incorporated once placed into the site of the patient's bone injury. The goal of the EU-funded project VASCUBONE (Construction kit for tailor-made vascularized bone implants) was to optimise the methods and components required for bone engineering. The consortium tailored a combination of advanced biomaterials, adult stem cells and imaging methods to enhance bone regeneration based on the patient's needs. Researchers first tested the biocompatibility as well as the osteoconductive and osteoinductive properties of a number of biomaterials. Particular attention was given to improving their hydrophilicity and the active surface area of the materials used. Therefore, scientists exploited functionalised nano-sized diamond particles (nDPs) to increase the area of contact with the bio-entities. This extracellular matrix when combined with certain binding growth factors can simulate the bone conditions and maximise mesenchymal stem cell differentiation to bone. Project partners also investigated the control and monitoring of the cell seeding of the scaffolds, and the analysis of differentiation processes and cell-matrix interactions. A defined oscillatory flow was shown to be the most efficient means of incorporating cells in the porous scaffold system. The VASCUBONE systems were tested in animal models with bone defects and new bone formation was evaluated through histology and radiography. Polymeric scaffolds inoculated with bone morphogenetic protein 2 demonstrated the highest bone formation rate. The optimisation of magnetic resonance imaging improved imaging and assessment of the new bone implants. The new materials were tested and found to be non-cytotoxic and biocompatible, and an intravenous dose toxicity study of the nDPs showed they were safe. VASCUBONE also developed new tools to control and ensure safety, immunological acceptance and efficacy of new implants. Furthermore, a successful design was established to investigate in vivo environmentally induced carcinogenesis and to monitor implanted materials/scaffolds using bioluminescence. This was done to overcome the limitations of long-term rodent assays. Finally, all these new models were validated using in vitro-in vivo correlation studies. The new biomaterials contained within the VASCUBONE toolbox will help to reduce the level of disability and therefore significantly benefit patients and health services.
Keywords
Bone implants, polymeric scaffold, stem cells, VASCUBONE, biomaterials
