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      Bone regenerative medicine: classic options, novel strategies, and future directions

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          Abstract

          This review analyzes the literature of bone grafts and introduces tissue engineering as a strategy in this field of orthopedic surgery. We evaluated articles concerning bone grafts; analyzed characteristics, advantages, and limitations of the grafts; and provided explanations about bone-tissue engineering technologies. Many bone grafting materials are available to enhance bone healing and regeneration, from bone autografts to graft substitutes; they can be used alone or in combination. Autografts are the gold standard for this purpose, since they provide osteogenic cells, osteoinductive growth factors, and an osteoconductive scaffold, all essential for new bone growth. Autografts carry the limitations of morbidity at the harvesting site and limited availability. Allografts and xenografts carry the risk of disease transmission and rejection. Tissue engineering is a new and developing option that had been introduced to reduce limitations of bone grafts and improve the healing processes of the bone fractures and defects. The combined use of scaffolds, healing promoting factors, together with gene therapy, and, more recently, three-dimensional printing of tissue-engineered constructs may open new insights in the near future.

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          Most cited references121

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          Bone regeneration: current concepts and future directions

          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.
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            Osteoinduction, osteoconduction and osseointegration.

            Osteoinduction is the process by which osteogenesis is induced. It is a phenomenon regularly seen in any type of bone healing process. Osteoinduction implies the recruitment of immature cells and the stimulation of these cells to develop into preosteoblasts. In a bone healing situation such as a fracture, the majority of bone healing is dependent on osteoinduction. Osteoconduction means that bone grows on a surface. This phenomenon is regularly seen in the case of bone implants. Implant materials of low biocompatibility such as copper, silver and bone cement shows little or no osteoconduction. Osseointegration is the stable anchorage of an implant achieved by direct bone-to-implant contact. In craniofacial implantology, this mode of anchorage is the only one for which high success rates have been reported. Osseointegration is possible in other parts of the body, but its importance for the anchorage of major arthroplasties is under debate. Ingrowth of bone in a porous-coated prosthesis may or may not represent osseointegration.
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              Biomedical applications of collagen.

              Collagen is regarded as one of the most useful biomaterials. The excellent biocompatibility and safety due to its biological characteristics, such as biodegradability and weak antigenecity, made collagen the primary resource in medical applications. The main applications of collagen as drug delivery systems are collagen shields in ophthalmology, sponges for burns/wounds, mini-pellets and tablets for protein delivery, gel formulation in combination with liposomes for sustained drug delivery, as controlling material for transdermal delivery, and nanoparticles for gene delivery and basic matrices for cell culture systems. It was also used for tissue engineering including skin replacement, bone substitutes, and artificial blood vessels and valves. This article reviews biomedical applications of collagen including the collagen film, which we have developed as a matrix system for evaluation of tissue calcification and for the embedding of a single cell suspension for tumorigenic study. The advantages and disadvantages of each system are also discussed.
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                Author and article information

                Contributors
                Journal
                J Orthop Surg Res
                J Orthop Surg Res
                Journal of Orthopaedic Surgery and Research
                BioMed Central
                1749-799X
                2014
                17 March 2014
                : 9
                : 18
                Affiliations
                [1 ]Department of Pathology, School of Veterinary Medicine, Shiraz University, Shiraz 71345, Iran
                [2 ]Division of Surgery and Radiology, Department of Clinical Sciences, School of Veterinary Medicine, Shiraz University, Shiraz 71345, Iran
                [3 ]Department of Tissue Engineering and Regenerative Medicine, Reproductive Biotechnology Research Center, Avicenna Research Institute, ACECR, Tehran 3197619751, Iran
                [4 ]Department of Musculoskeletal Disorders, School of Medicine and Surgery, University of Salerno, Salerno 84084, Italy
                [5 ]Centre for Sports and Exercise Medicine, Queen Mary University of London, Barts and the London School of Medicine and Dentistry, Mile End Hospital, 275 Bancroft Road, London E1 4DG, UK
                Article
                1749-799X-9-18
                10.1186/1749-799X-9-18
                3995444
                24628910
                118fdf90-2be6-43ba-a2be-bf3c7bcddcc1
                Copyright © 2014 Oryan et al.; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 10 September 2013
                : 20 February 2014
                Categories
                Review

                Surgery
                bone graft,tissue engineering,regenerative medicine,three-dimensional printing,orthopedic research

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