Summary: Bone grafts are the second most common tissue transplanted in the United States, and they are an essential treatment tool in the field of acute and reconstructive traumatic orthopaedic surgery. Available in cancellous, cortical, or bone marrow aspirate form, autogenous bone graft is regarded as the gold standard in the treatment of posttraumatic conditions such as fracture, delayed union, and nonunion. However, drawbacks including donor-site morbidity and limited quantity of graft available for harvest make autograft a less-than-ideal option for certain patient populations. Advancements in allograft and bone graft substitutes in the past decade have created viable alternatives that circumvent some of the weak points of autografts. Allograft is a favorable alternative for its convenience, abundance, and lack of procurement-related patient morbidity. Options include structural, particulate, and demineralized bone matrix form. Commonly used bone graft substitutes include calcium phosphate and calcium sulfate synthetics—these grafts provide their own benefits in structural support and availability. In addition, different growth factors including bone morphogenic proteins can augment the healing process of bony defects treated with grafts. Autograft, allograft, and bone graft substitutes all possess their own varying degrees of osteogenic, osteoconductive, and osteoinductive properties that make them better suited for different procedures. It is the purpose of this review to characterize these properties and present clinical evidence supporting their indications for use in the hopes of better elucidating treatment options for patients requiring bone grafting in an orthopaedic trauma setting.
Bone fractures and segmental bone defects are a significant source of patient morbidity and place a staggering economic burden on the healthcare system. The annual cost of treating bone defects in the US has been estimated to be $5 billion, while enormous costs are spent on bone grafts for bone injuries, tumors, and other pathologies associated with defective fracture healing. Autologous bone grafts represent the gold standard for the treatment of bone defects. However, they are associated with variable clinical outcomes, postsurgical morbidity, especially at the donor site, and increased surgical costs. In an effort to circumvent these limitations, tissue engineering and cell-based therapies have been proposed as alternatives to induce and promote bone repair. This review focuses on the recent advances in bone tissue engineering (BTE), specifically looking at its role in treating delayed fracture healing (non-unions) and the resulting segmental bone defects. Herein we discuss: (1) the processes of endochondral and intramembranous bone formation; (2) the role of stem cells, looking specifically at mesenchymal (MSC), embryonic (ESC), and induced pluripotent (iPSC) stem cells as viable building blocks to engineer bone implants; (3) the biomaterials used to direct tissue growth, with a focus on ceramic, biodegradable polymers, and composite materials; (4) the growth factors and molecular signals used to induce differentiation of stem cells into the osteoblastic lineage, which ultimately leads to active bone formation; and (5) the mechanical stimulation protocols used to maintain the integrity of the bone repair and their role in successful cell engraftment. Finally, a couple clinical scenarios are presented (non-unions and avascular necrosis—AVN), to illustrate how novel cell-based therapy approaches can be used. A thorough understanding of tissue engineering and cell-based therapies may allow for better incorporation of these potential therapeutic approaches in bone defects allowing for proper bone repair and regeneration.
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