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      Bone Regeneration Based on Tissue Engineering Conceptions — A 21st Century Perspective

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          Abstract

          The role of Bone Tissue Engineering in the field of Regenerative Medicine has been the topic of substantial research over the past two decades. Technological advances have improved orthopaedic implants and surgical techniques for bone reconstruction. However, improvements in surgical techniques to reconstruct bone have been limited by the paucity of autologous materials available and donor site morbidity. Recent advances in the development of biomaterials have provided attractive alternatives to bone grafting expanding the surgical options for restoring the form and function of injured bone. Specifically, novel bioactive (second generation) biomaterials have been developed that are characterised by controlled action and reaction to the host tissue environment, whilst exhibiting controlled chemical breakdown and resorption with an ultimate replacement by regenerating tissue. Future generations of biomaterials (third generation) are designed to be not only osteoconductive but also osteoinductive, i.e. to stimulate regeneration of host tissues by combining tissue engineering and in situ tissue regeneration methods with a focus on novel applications. These techniques will lead to novel possibilities for tissue regeneration and repair. At present, tissue engineered constructs that may find future use as bone grafts for complex skeletal defects, whether from post-traumatic, degenerative, neoplastic or congenital/developmental “origin” require osseous reconstruction to ensure structural and functional integrity. Engineering functional bone using combinations of cells, scaffolds and bioactive factors is a promising strategy and a particular feature for future development in the area of hybrid materials which are able to exhibit suitable biomimetic and mechanical properties. This review will discuss the state of the art in this field and what we can expect from future generations of bone regeneration concepts.

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          Most cited references200

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          Epidemiology of adult fractures: A review.

          The epidemiology of adult fractures is changing quickly. An analysis of 5953 fractures reviewed in a single orthopaedic trauma unit in 2000 showed that there are eight different fracture distribution curves into which all fractures can be placed. Only two fracture curves involve predominantly young patients; the other six show an increased incidence of fractures in older patients. It is popularly assumed that osteoporotic fractures are mainly seen in the thoracolumbar spine, proximal femur, proximal humerus and distal radius, but analysis of the data indicates that 14 different fractures should now be considered to be potentially osteoporotic. About 30% of fractures in men, 66% of fractures in women and 70% of inpatient fractures are potentially osteoporotic.
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            Recent advances in bone tissue engineering scaffolds.

            Bone disorders are of significant concern due to increase in the median age of our population. Traditionally, bone grafts have been used to restore damaged bone. Synthetic biomaterials are now being used as bone graft substitutes. These biomaterials were initially selected for structural restoration based on their biomechanical properties. Later scaffolds were engineered to be bioactive or bioresorbable to enhance tissue growth. Now scaffolds are designed to induce bone formation and vascularization. These scaffolds are often porous, made of biodegradable materials that harbor different growth factors, drugs, genes, or stem cells. In this review, we highlight recent advances in bone scaffolds and discuss aspects that still need to be improved. Copyright © 2012 Elsevier Ltd. All rights reserved.
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              The biology of fracture healing.

              The biology of fracture healing is a complex biological process that follows specific regenerative patterns and involves changes in the expression of several thousand genes. Although there is still much to be learned to fully comprehend the pathways of bone regeneration, the over-all pathways of both the anatomical and biochemical events have been thoroughly investigated. These efforts have provided a general understanding of how fracture healing occurs. Following the initial trauma, bone heals by either direct intramembranous or indirect fracture healing, which consists of both intramembranous and endochondral bone formation. The most common pathway is indirect healing, since direct bone healing requires an anatomical reduction and rigidly stable conditions, commonly only obtained by open reduction and internal fixation. However, when such conditions are achieved, the direct healing cascade allows the bone structure to immediately regenerate anatomical lamellar bone and the Haversian systems without any remodelling steps necessary. In all other non-stable conditions, bone healing follows a specific biological pathway. It involves an acute inflammatory response including the production and release of several important molecules, and the recruitment of mesenchymal stem cells in order to generate a primary cartilaginous callus. This primary callus later undergoes revascularisation and calcification, and is finally remodelled to fully restore a normal bone structure. In this article we summarise the basic biology of fracture healing. Copyright © 2011 Elsevier Ltd. All rights reserved.
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                Author and article information

                Journal
                Bone Res
                Bone Res
                Bone Research
                Nature Publishing Group
                2095-4700
                2095-6231
                September 2013
                25 September 2013
                : 1
                : 3
                : 216-248
                Affiliations
                [1 ]Institute of Health & Biomedical Innovation, Queensland University of Technology , Brisbane, Queensland, Australia
                [2 ]Orthopaedic Oncology Service, Princess Alexandra Hospital , Brisbane, Australia
                [3 ]Department of Surgery, University of Melbourne, St. Vincent's Hospital , Melbourne, Australia
                [4 ]Department of Orthopaedics, St. Vincent's Hospital , Melbourne, Australia
                [5 ]Bone and Soft Tissue Sarcoma Service, Peter MacCallum Cancer Centre , Melbourne, Australia
                [6 ]Orthopaedic and Trauma Services, Princess Alexandra Hospital , Brisbane, Australia
                [7 ]George W Woodruff School of Mechanical Engineering, Georgia Institute of Technology , Atlanta, GA, USA
                Author notes
                Article
                boneres201317
                10.4248/BR201303002
                4472104
                26273505
                add8b389-c86f-433d-91f5-3dd204d15ac5
                Copyright © 2013 Sichuan University
                Categories
                Review

                bone tissue engineering,regenerative medicine,additve manufacturing,clinical translation,scaffolds

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