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Scaffolds for Growth Factor Delivery As Applied to Bone Tissue Engineering

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Scaffolds for Growth Factor Delivery As Applied to Bone Tissue Engineering Hindawi Publishing Corporation International Journal of Polymer Science Volume 2012, Article ID 174942, 25 pages doi:10.1155/2012/174942 Review Article Scaffolds for Growth Factor Delivery as Applied to Bone Tissue Engineering Keith A. Blackwood,1 Nathalie Bock,1, 2, 3 Tim R. Dargaville,2 and Maria Ann Woodruff1 1 Biomaterials and Tissue Morphology Group, Institute of Health and Biomedical Innovation, Queensland University of Technology, 60 Musk Avenue, Kelvin Grove, QLD 4059, Australia 2 Tissue Repair and Regeneration Program, Institute of Health and Biomedical Innovation, Queensland University of Technology, 60 Musk Avenue, Kelvin Grove, QLD 4059, Australia 3 Regenerative Medicine Group, Institute of Health and Biomedical Innovation, Queensland University of Technology, 60 Musk Avenue, Kelvin Grove, QLD 4059, Australia Correspondence should be addressed to Maria Ann Woodruff, mia.woodruff@qut.edu.au Received 21 April 2012; Revised 3 September 2012; Accepted 25 September 2012 Academic Editor: Christopher Batich Copyright © 2012 Keith A. Blackwood et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. There remains a substantial shortfall in the treatment of severe skeletal injuries. The current gold standard of autologous bone grafting from the same patient has many undesirable side effects associated such as donor site morbidity. Tissue engineering seeks to offer a solution to this problem. The primary requirements for tissue-engineered scaffolds have already been well established, and many materials, such as polyesters, present themselves as potential candidates for bone defects; they have comparable structural features, but they often lack the required osteoconductivity to promote adequate bone regeneration. By combining these materials with biological growth factors, which promote the infiltration of cells into the scaffold as well as the differentiation into the specific cell and tissue type, it is possible to increase the formation of new bone. However due to the cost and potential complications associated with growth factors, controlling the rate of release is an important design consideration when developing new bone tissue engineering strategies. This paper will cover recent research in the area of encapsulation and release of growth factors within a variety of different polymeric scaffolds. 1. Introduction promotion of bone growth and to assist in regenerating wounds that would otherwise not heal. Advancements have Skeletal injuries are some of the most debilitating types led to the development of composite scaffolds, consisting of of injury known and can lead to severe long-term effects materials that have good structural characteristics combined without surgical intervention. These injuries may occur via with materials which promote bone growth, and one group trauma, disease (degenerative diseases and tumour exci- of molecules for this enhancement is growth factors (GFs). sions), or growth defects (such as cleft palette). Cost of treat- “Growth factor” is a term for several families of intra- ment in the US exceeded $17 billion in 2005 and is predicted cellular signalling proteins which have a number of different to rise to $25 billion per year by 2025 [1]. Importantly, demo- defined roles, such as recruitment of cells, as well as the graphic data reveals that, due to the ageing population, com- promotion of migration [3]anddifferentiation [4, 5] of these plications associated with the musculoskeletal system will cells. Specific GFs are responsible for the formation, matura- increase over the coming years [2]. It is therefore vital to have tion, and maintenance of tissues throughout the body. the best technologies available to orthopaedic surgeons to Several GF families play a role in the generation and assist bone repair. repair of bone: some stimulate pathways specific for the for- Over the last 30 years extensive work has been carried mation of bone, such as promoting osteoinduction [6], and out on the development of biomaterial scaffolds for the others such as vascular endothelial growth factor (VEGF) [3] 2 International Journal of Polymer Science and platelet-derived growth factor (PDGF) promote angio- a much more dense (10% porosity) making up the remaining genesis, the sprouting of new blood vessels from existing 80% of bone found in the human body. Cortical bone itself ones. is surrounded by the periosteum, a thin fibrous membrane. While many GFs play an extensive role in the de novo Bone has a remarkable ability to regenerate damaged formation of bone, in the field of tissue engineering there regions back to full functionality with no scarring. However has been particular interest in using bone morphogenetic if the trauma is too large, defect healing cannot occur without proteins (BMPs) for the treatment of bone defects [4, 7, 8]. surgical intervention, with the sheer size of the defect exceed- BMPs are a family of GFs closely associated with the growth, ing the bones’ natural healing ability. This is often the case maturation, and regulation of bone, and they are considered during complex fractures and large tumour excision [16]. the most potent stimulator of new bone formation. Defects occurring in different regions of the body can lead to Currently, the most commonly used clinical technique anumberofdifferent complications. For example, cranial using BMPs is the relatively straightforward method of defectsdonotnaturallyhealwellandoftenrequiresurgical combining reconstituted BMP with collagen scaffolds just intervention for satisfactory healing [17]. When dealing with prior to implantation [9, 10]. The scaffold and BMP are a cranial defect, issues arise due to contour irregularities, but supplied separately, and the scaffold is soaked in the GF when dealing with spinal fractures another set of fundamen- solution before implantation. This technique, while clinically tal problems arise revolving around the need to provide more accepted, exhibits poor GF release characteristics, eluting robust mechanical support, whilst maintaining movement BMP rapidly and presenting the wound site with a BMP [18]. concentration far above those found in normal physiological Autologous bone grafting (transplant from the same conditions. Due to the short half-life of GFs in situ, the patient) is the “gold standard” treatment for bone defects. high concentrations are needed to maintain a therapeutical Cancellous bone sourced from the iliac crest is usually used release profile. This technical shortfall not only increases the and has the potential for facilitating de novo bone formation cost of the therapy, but also generates serious concerns over due to the natural presence of GFs which promote angiogen- long-term complications associated with the high dosage of esis and osteogenesis [19]. While effective, the use of auto- GFs [11].Itwouldbemorefavourabletohaveasmaller logous bone has severe limitations, mainly revolving around therapeutic dose delivered, at appropriate physiological levels the need for a donor site from the same patient which causes over the time period of the wound-healing process. a secondary wound site, in addition to limited available Several techniques have been employed to control the supply, and risk of infection [20]. In a recent review, release profiles of GFs from scaffolds. Many of these tech- Dimitriou et al. revealed that 19.4% of iliac crest donor sites niques involve encapsulating the GFs within degradable have complications ranging from infection, fracture, nerve polymer networks, such that they are slowly released from injuries, chronic donor site pain, hernias, and haematoma the degrading scaffold into the wound site. By understanding [21]. It should be noted that techniques are being developed the release kinetics, this process has the potential to maintain to reduce the rate of complications with a reamer/irrig- a therapeutic dose for longer than the currently available ator/aspirator system developed by Synthes Inc. (West rapidly releasing scaffolds. Microspheres and hydrogels are Chester, PA, USA) which has shown reduction in compli- the most commonly studied matrices for this type of encap- cations of the donor site down to >6%. However the total sulation. numberofcompletedstudieswiththissystemisstillsmall Delivery systems for GFs [12, 13] as well as other thera- [21]. peutics [14] have already been reviewed several times over Allografting (transplant from a different patient) has the last decade. Thus this paper will focus on providing an been successfully used, predominantly in hip surgery where in-depth discussion on the most recent strategies and tech- major femoral bone loss has occurred [22], but this tech- niques being utilised for the production of GF-eluting nique has similar limitations to autografting, with difficulty scaffolds providing sustained release of GFs, thus moving in sourcing the grafting materials, as well as the potential for towards providing a more physiologically relevant environ- infection from donor to host. ment for the promotion of bone regeneration. Due to the shortcomings of the current clinical approaches, there remains an important niche to fill, such as, the field of tissue engineering has emerged to develop meth- 2. Basic Structure of Bone ods to bridge the existing gap in clinical treatments for severe bone loss. The skeletal structure of mammals plays many important roles throughout the body, ranging from structural
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