This open access review looks over present work on the engineering of new bone tissue, created from a patient's own cells, and the state of progress towards clinical availability. For most people the greatest problem with bones is the loss of strength and resilience that occurs in later life. One can hope that work presently largely focused on regrowing bone lost to physical damage or surgery will lead to a much greater understanding of the relevant cellular biology along the way, which in turn will uncover ways to restore strength to bone tissue in the old.
Medical advances have led to a welcome increase in life expectancy. However, accompanying longevity introduces new challenges: increases in age-related diseases and associated reductions in quality of life. The loss of skeletal tissue that can accompany trauma, injury, disease or advancing years can result in significant morbidity and significant socio-economic cost and emphasise the need for new, more reliable skeletal regeneration strategies. Current approaches to replace or restore significant quantities of lost skeletal tissue come with substantial limitations and inherent disadvantages that may be harmful. Tissue engineering and regenerative medicine have come to the fore in recent years with new approaches for de novo skeletal tissue formation in an attempt to address the unmet need for bone augmentation and skeletal repair. These approaches seek to harness stem cells, innovative scaffolds and biological factors to create, ideally, robust, reproducible and enhanced bone formation strategies to improve the quality of life for an ageing population.
A wealth of in vitro data over the last four decades has elucidated invaluable information on the molecular and cellular mechanisms involved in osteogenic repair, and the more recent development of complex, multicellular, three-dimensional models has significantly enhanced our understanding of osteogenesis and bone healing. However, these techniques remain unable to mimic the cellular, molecular, physiological and biomechanical intricacies present at the whole organism level. Critical aspects in bone repair such as the presence of a vascular network and biomechanical stimulation have proven difficult to reproduce outside of the living organism.
To date, stem cell therapy is hampered predominantly by our limited understanding of skeletal stem cells. There is a need for facile, safe and efficacious protocols of stem cell isolation and expansion together with enhanced bioinformatics knowledge on the phenotypic 'fingerprint' of the skeletal stem cell at a single-cell resolution and the generation of skeletal cells from pluripotent stem cell sources. It is likely new cell approaches and the development of 'smart' hydrogels, able to temporally and spatially control growth factor release to render safe and efficacious growth factor use in stimulation of fracture healing and arthrodesis, are areas that will see significant development. The next 5 to 10 years will see intense interest in the potential of additive manufacture to produce synthetic multiphasic scaffolds in which the internal architecture and topography are analysed for cartilage and bone regeneration requirements.