Abstract
Bone regeneration is a complex, well-orchestrated physiological process of bone formation, which can be seen during normal fracture healing, and is involved in continuous remodelling throughout adult life. However, there are complex clinical conditions in which bone regeneration is required in large quantity, such as for skeletal reconstruction of large bone defects created by trauma, infection, tumour resection and skeletal abnormalities, or cases in which the regenerative process is compromised, including avascular necrosis, atrophic non-unions and osteoporosis. Currently, there is a plethora of different strategies to augment the impaired or 'insufficient' bone-regeneration process, including the 'gold standard' autologous bone graft, free fibula vascularised graft, allograft implantation, and use of growth factors, osteoconductive scaffolds, osteoprogenitor cells and distraction osteogenesis. Improved 'local' strategies in terms of tissue engineering and gene therapy, or even 'systemic' enhancement of bone repair, are under intense investigation, in an effort to overcome the limitations of the current methods, to produce bone-graft substitutes with biomechanical properties that are as identical to normal bone as possible, to accelerate the overall regeneration process, or even to address systemic conditions, such as skeletal disorders and osteoporosis.
Highlights
Bone possesses the intrinsic capacity for regeneration as part of the repair process in response to injury, as well as during skeletal development or continuous remodelling throughout adult life [1,2]
Standard approaches widely used in clinical practice to stimulate or augment bone regeneration include distraction osteogenesis and bone transport [6,7], and the use of a number of different bone-grafting methods, such as autologous bone grafts, allografts, and bone-graft substitutes or growth factors [8,9]
There are even non-invasive methods of biophysical stimulation, such as low-intensity pulsed ultrasound (LIPUS) and pulsed electromagnetic fields (PEMF) [11,12,13], which are used as adjuncts to enhance bone regeneration
Summary
Bone possesses the intrinsic capacity for regeneration as part of the repair process in response to injury, as well as during skeletal development or continuous remodelling throughout adult life [1,2]. Tissue engineering The tissue-engineering approach is a promising strategy added in the field of bone regenerative medicine, which aims to generate new, cell-driven, functional tissues, rather than just to implant non-living scaffolds [58] This alternative treatment of conditions requiring bone regeneration could overcome the limitations of current therapies, by combining the principles of orthopaedic surgery with knowledge from biology, physics, materials science and engineering, and its clinical application offers great potential [58,59]. Bone-tissue engineering combines progenitor cells, such as MSCs (native or expanded) or mature cells (for osteogenesis) seeded in biocompatible scaffolds and ideally in threedimensional tissue-like structures (for osteoconduction and vascular ingrowth), with appropriate growth factors (for osteoinduction), in order to generate and maintain bone [60] The need for such improved composite grafts is obvious, especially for the management of large bone defects, for which the requirements for grafting material are substantial [8]. Fibrodysplasia ossificans progressiva, a rare genetic disorder, is an example of how an abnormal metabolic condition can be viewed as evidence for systemic regeneration of large amounts of bone secondary to alterations within the BMP signalling pathway [88], and may indicate unique treatment potentials
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