Bone regeneration: current concepts and future directions

Rozalia Dimitriou, Elena Jones, Dennis McGonagle, Peter V Giannoudis, Rozalia Dimitriou, Elena Jones, Dennis McGonagle, Peter V Giannoudis

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.

Figures

Figure 1
Figure 1
Male patient 19 years of age with infected non-union after intramedullary nailing of an open tibial fracture. (A). Anteroposterior (AP) and lateral X-rays of the tibia illustrating osteolysis (white arrow) secondary to infection. The patient underwent removal of the nail, extensive debridement and a two-staged reconstruction of the bone defect, using the induced membrane technique for bone regeneration (the Masquelet technique). (B) Intraoperative pictures showing: (1) a 60 mm defect of the tibia (black arrow) at the second stage of the procedure; (2) adequate mechanical stability was provided with internal fixation (locking plate) bridging the defect, while the length was maintained (black arrow); (3) maximum biological stimulation was provided using autologous bone graft harvested from the femoral canal (black arrow, right), bone-marrow mesenchymal stem cells (broken arrow, left) and the osteoinductive factor bone morphogenetic protein-7 (centre); (4) the graft was placed to fill the bone defect (black arrow). (C) Intraoperative fluoroscopic images showing the bone defect after fixation. (D) Postoperative AP and lateral X-rays at 3 months, showing the evolution of the bone regeneration process with satisfactory incorporation and mineralisation of the graft (photographs courtesy of PVG).

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