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Barrier Membrane Materials for Guided Bone Regeneration (GBR)
Guided Bone Regeneration (GBR) is a technique that has been implemented in clinic for almost 30 years. The technique promotes growth of the hard tissue using a space-making barrier membrane which prevents the ingrowth of surrounding soft tissue. Sufficient augmentation of bone on oral sites, namely the alveolar ridge is crucial for implant attachment (figure 1) . Successful GBR is defined by four criteria: epithelium exclusion, space maintenance, fibrin clot stability and the primary wound closure .
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Current membrane materials available for commercial use are shown in Table 1 . The barriers may be used with a bone grafting material and can be subdivided into two main categories based on their ability to resorb. Their application is evaluated based on five main design criteria: Biocompatibility, Cell Occlusion, Tissue Integration, space-maintaining ability and ease of handling in a clinical setting . This essay will discuss the success of current materials used for GBR, and their limitations.
Figure 1: (a) sufficient bone width/height, (b) placement of a membrane for GBR (c) subsequent implant 
Expanded polytetrafluoroethylene (e-PTFE) was the first commercially available membrane, composed of a collar portion with pores allowing connective tissue augmentation and to prevent epithelial intrusions, and an occlusive part to prevent the flap tissues contacting the root surface . The exposure of e-PTFE is problematic as its rough surface induces bacterial colonisation and infection, compromising bone augmentation . High density PTFE (d-PTFE) has subsequently been adopted as a preferred alternative . The smaller pores prevent bacteria invasion and primary soft tissue closure is not required. Additionally, the relatively smooth surface improves the ease of removal .
Titanium mesh was introduced as a more stable and better space-making barrier, with small pores to allow interstitial fluid transfer. The metal offers excellent biocompatibility and mechanical properties- combining rigidity, elasticity and plasticity . Titanium-reinforced PTFE membranes show enhanced rigidity and malleability while maintaining sufficient protection for blood clot
Table 1: List of Commercial GBR Membranes 
formation  However, its stiff structure can lead to exposure of the membranes which can introduce morbidity and provoke premature removal .
Resorbable membranes remove the need for a second surgery, offer a better cost-benefit ratio and decrease the risk of patient morbidity, as well as potential tissue damage. There are two main types of resorbable materials utilised for GBR; synthetic polymers, namely polyglycolide (PGA) and polylactide (PLA), and natural collagen-based membranes .
Aliphatic polymer-based membranes can be produced on demand, adapted to give required properties due to the wide scope of polymers available and will breakdown to carbon dioxide and water via the Krebs cycle .
Collagen is the main component in connective tissues and its inherent biocompatible properties make it a very attractive material option . Collagen- based membranes encourage blood clot formation, enhance cell migration, are well received by patients and can integrate with surrounding connective tissues during degradation, creating an environment which promotes bone formation. Collagen membranes exhibit various structures and degradation rates, depending on their source, extraction and manufacturing method. Cross-linking of the collagen fibres can improve its relatively low rigidity and prolong the barrier function and has been linked with impeded vascularisation and tissue integration . Thicker collagenous membranes inhibit tissue penetration and promote bone formation; thus, layering is usually advantageous.
The main drawback of bioresorbable membranes is the inflammatory reactions associated with them, which can inhibit bone regeneration . Furthermore, the resorption rate of a polymer and collagen membrane is harder to predict and can vary greatly depending on polymer used or collagen source. When exposed, resorbable membranes break down very quickly due to enzyme action. This can induce healing, but if degradation incomplete bone regeneration is likely .
Collagen and synthetic polymeric membranes are much less robust than non-resorbable barriers and require use with a grafting material to prevent collapse . Bone graft materials (table 2) promote bone formation by varying mechanisms. Membrane-graft combinations generally exhibit improved bone regeneration .
Table 2: Summary of Bone Graft Materials 
Autogenous bone is considered the best grafting material due to its osteogenic (bone generating) abilities . Its high success rate can be attributed to its protein, bone-enhancing substrates, minerals and vital bone cell content. However, its use is limited by the volume of graft available and the morbidity risk during removal . Furthermore, resorption of the graft can occur if it is placed near the roots .
Allografts are derived from another individual of the same species, (either frozen, freeze-dried or demineralised freeze-dried bone) and remove the need for a second donor site which is beneficial to the patient . The grafts carry out bone growth by osteo-conductive and inclusive means, due to the presences of bone morphogenic proteins (BMP) thus bone formation is slower, and the volume is less than autografts .
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Xenografts originate from the tissue of another species and are widely used in GBR . They are usually stripped of their organic components to eliminate immune-reaction, giving a brittle calcium rich matrix structure material. Common xenograft materials include natural hydroxyapatite (HA) from animal bones and de-organified bovine bone (anorganic bone matrix, ABM); both possess properties that mimic bone minerals in humans and thus promote bone augmentation .
Alloplasts consist of either natural or synthetic materials, usually bioactive glass polymers, calcium sulphates or ceramics such as synthetic HA or tricalcium phosphate (TCP) . Their use removes the threat of disease transmission and their design and production can be controlled to a molecular level, allowing optimisation of the size and connections of macropores for vascular growth, the phase distribution and the morphology of the blocks and granules. However, a lack of knowledge of optimal surface characteristics to promote tissue interaction with the material limits this advantage .
Selection of a suitable graft material will depend on the recipient and the nature of defect, but a combination of graft materials usually creates an optimal environment by combining favourable mechanical and biological properties . When utilized with a barrier membrane, these graft composites are associated with superior GBR results.
The materials available for GBR span a wide range of properties and the ideal choice will depend on the bone defect. Non-resorbable membranes have been shown to promote bone augmentation. Resorbable membranes offer a more comfortable treatment option for the patient but must be used in conjunction with a supporting graft material to achieve comparable results.
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