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. To address the unmet need for bone augmentation, tissue engineering and regenerative medicine have come to the fore in recent years with new approaches for de novo skeletal tissue formation. Typically, these approaches seek to harness stem cells, innovative scaffolds and biological factors that promise enhanced and more reliable bone formation strategies to improve the quality of life for many. This review provides an overview of recent developments in bone tissue engineering focusing on skeletal stem cells, vascular development, bone formation and the translation from preclinical in vivo models to clinical delivery.

Targeting and differentiating stem cells at sites of injury and repair is an exciting and promising area for disease treatment and reparative medicine. We have investigated remote magnetic field activation of magnetic nanoparticle-tagged mechanosensitive receptors on the cell membrane of human bone marrow stromal cells (HBMSCs) for use in osteoprogenitor cell delivery systems and activation of differentiation in vitro and in vivo toward an osteochondral lineage. HBMSC-labeled with magnetic beads coated with antibodies or peptides to the transmembrane ion channel stretch activated potassium channel (TREK-1) or arginine–glycine–aspartic acid were cultured in monolayer or encapsulated into polysaccharide alginate/chitosan microcapsules. Upregulation in gene expression was measured in magnetic particle-labeled HBMSCs in response to TREK-1 activation over a short period (7 days) with an increase in mRNA levels of Sox9, core binding factor alpha1 (Cbfa1), and osteopontin. Magnetic particle-labeled HBMSCs encapsulated into alginate chitosan capsules were exposed to magnetic forces both in vitro and in vivo intermittently for 21 days. After 21 days the encapsulated, magnetic particle-labeled HBMSCs in vivo were viable as evidenced by extensive cell tracker green fluorescence. The mechanical stimulation of HBMSCs labeled with TREK-1 magnetic nanoparticle receptors enhanced expression of type-1 collagen in vitro with increases in proteoglycan matrix, core binding factor alpha1 (Cbfa1) and collagen synthesis, and extracellular matrix production and elevated the expression of type-1 and type-2 collagen in vivo. Additionally, the magnetically remote stimulation of HBMSCs labeled with magnetic nanoparticle arginine–glycine–aspartic acid considerably enhanced proteoglycan and collagen synthesis and extracellular matrix production and elevated the expression of type-1 and type-2 collagen in vivo and in vitro. Osteogenic mechanosensitive receptor manipulation by magnetic nanotechnology can induce the differentiation of osteoprogenitor cell populations toward an osteogenic lineage. These cell manipulation strategies offer tremendous therapeutic opportunities in soft and hard tissue repair.