These properties are mainly attributed to the remarkable hierarchical architecture, which is constituted by the soft collagen protein and stiffer apatite mineral, as shown in Fig. 1. Īs a rigid organ in body, the bone is able to support and protect various organs but is also able to facilitate mobility. The applications of stem cell therapy and natural bioinorganic ions as well as the musculoskeletal tissue engineering approach have been extensively investigated, ,,. However, the clinical applications of BMPs as off-label drug have been concerned due to supraphysiological dosage, adverse clinical outcomes and cost issue. The former bone substitutes are generally only osteoconductive and mainly being applied in reconstruction of large bone defects, while the rhBMPs are basically osteoinductive with the capability of enhancing the fracture healing. rhBMP-2 and rhBMP-7) are most widely used, either alone or combined. hydroxyapatite (HAp), CaP cements and ceramics), and recombinant human bone morphological proteins (rhBMPs, e.g. Among those synthetic bone substitutes and biological factors, calcium phosphate (CaP)-based biomaterials (e.g. Bone grafting procedures are also being gradually shifted from natural grafts to synthetic bone substitutes and biological factors. To address these limitations, tremendous alternatives and options have been brought by the emergence of synthetic bone substitutes during the past decades, which made bone grafts and substitutes (BGS) among the most promising market in the orthopaedic industry and it is reported that the revenue from the global market is over two billions in 2013. More importantly, the amounts of available natural bone grafts traditionally used are still far from meeting the clinical demands, especially when facing the impending global pandemic of aging and obesity. Nevertheless, inferior healing was observed compared to the use of autologous grafts and potential for transmission of disease and other infective agents were also reported. They are primarily osteoconductive, while reduced osteoinductivity is retained only in demineralized bone matrix (DBM) preparations. Bone allografts dominantly share the second higher option for orthopaedic surgeons and nearly one third of all bone grafts used in North America are allografts since they are available in various forms and large quantities. However, the concerns of limited supply and donor site complications are still maintained. Among all clinical available grafts, autologous bone is still being considered as the gold standard since all necessary properties required in bone regeneration in term of osteoconduction, osteoinduction and osteogenesis are combined. Over two million bone grafting procedures were performed annually worldwide, which is the second most frequent tissue transplantation right after blood transfusion. Hence, this paper aims to review the currently available bone grafts and bone substitutes as well as the biological and bio-inorganic factors for the treatments of bone defect.īone grafting is one of the most commonly used surgical methods to augment bone regeneration in orthopaedic procedures. Alternatively, bioinorganic ions such as magnesium, strontium and zinc are considered as alternative of osteogenic biological factors. Although clinical applications of these factors have exhibited good bone formation, their further application was limited due to high cost and potential adverse side effects.
To address this problem, addition of various growth factors, such as bone morphogenetic proteins (BMPs), parathyroid hormone (PTH) and platelet rich plasma (PRP), into structural allografts and synthetic substitutes have been considered. Hence, the enhancement of osteointegration of these grafts and substitutes with host bone is considerably important. Nevertheless, the integration of allogeneic grafts and synthetic substitutes with host bone was found jeopardized in long-term follow-up studies. Bone grafts have been predominated used to treat bone defects, delayed union or non-union, and spinal fusion in orthopaedic clinically for a period of time, despite the emergency of synthetic bone graft substitutes.
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