Periodontal materials - Wiley Online Library

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Australian Dental Journal

The official journal of the Australian Dental Association

Australian Dental Journal 2011; 56:(1 Suppl): 107–118 doi: 10.1111/j.1834-7819.2010.01301.x

Periodontal materials I Darby* *Periodontics Unit, Melbourne Dental School, The University of Melbourne, Victoria.

ABSTRACT Periodontics is more associated with debridement of periodontal pockets and not generally thought of as using dental materials in the treatment of patients. However, the last 30 years have seen the development of materials used in regeneration of the periodontal tissues following periodontal disease, guided tissue regeneration, and the use of these materials in bone regeneration more recently, guided bone regeneration. The materials used include bone grafts and membranes, but also growth factors and cells-based therapies. This review provides an overview of the materials currently used and looks at contemporary research with a view to what may be used in the future. It also looks at the clinical effectiveness of these regenerative therapies with an emphasis on what is available in Australia. Keywords: Guided tissue regeneration, guided bone regeneration, bone grafts, membranes, tissue engineering. Abbreviations and acronyms: ADMG = acellular dermal matrix graft; BMP = bone morphogenic proteins; b-TCP = tricalcium phosphate; DBBM = deproteinized bovine bone minerals; DFDBA = demineralized freeze-dried bone allograft; EMD = Emdogain; ePTFE = expanded polytetrafluoroethylene membranes; FDBA = freeze-dried bone allograft; FFB = fresh frozen bone; FGF = fibroblast growth factor; GBR = guided bone regeneration; GTR = guided tissue regeneration; HA = hydroxyapatite; IGF = insulin-like growth factor; LJE = long junctional epithelial; PDGF = platelet-derived growth factor; PEG = polyethylene glycol; PTH = parathyroid hormone; SBC = Straumann Bone Ceramic; TGA = Therapeutic Goods Administration; TGF-b = transforming growth factor-b.

INTRODUCTION For many years the management of periodontal disease was to control the biofilm invariably resulting in repair and a long junctional epithelial attachment (LJE). However, the long-term goal of periodontal therapy is to regenerate the lost attachment. Melcher1 reported that the infill of periodontal defects was due to four tissues: epithelium, connective tissue, bone and periodontal ligament. As the epithelium had the highest rate of formation, it filled the defect first. This resulted in a series of seminal studies in Scandinavia in the late 1970s and early 1980s looking at the effect of each of the four tissues on periodontal healing.2–6 The authors showed epithelial attachment resulted in a LJE, connective attachment could result in root resorption, bone in ankylosis and the periodontal ligament in some replacement of the lost periodontium. From this the concept of periodontal guided tissue regeneration (GTR) was born, where a membrane is placed between the epithelium and connective tissues and the tooth surface to prevent them from forming an attachment and allowing reformation of a periodontal ligament. Over a decade of subsequent study showed how effective this concept was and led to further development and improvements in both materials and surgical ª 2011 Australian Dental Association

technique. With the introduction of implant dentistry and the need to regenerate bone, many of the periodontal GTR materials and techniques were applied resulting in the development of a procedure known as guided bone regeneration (GBR). This paper reviews the current status of the materials used in GTR and GBR, and whether or not they work. Particular attention is given to materials that are available in Australia. The field has moved into tissue engineering, which applies the principles of biology and engineering to the development of functional substitutes for damaged tissue.7 It involves three key elements: signalling molecules, supporting matrix and cells. This article will describe the current state of these and have a look to the future at the periodontal materials we may be using in a few years time. Bone graft materials Mechanisms of bone regeneration Bone regeneration through bone grafts is divided into osteogenesis, osteoinduction and osteoconduction. An osteogenic material contains tissues or cells from which the bone formation originates, whereas an osteoinductive material contains proteins or growth factors that 107

I Darby cause proliferation and differentiation of progenitor cells found in the clot or granulation tissue to become bone forming cells. Osteoconductive materials act as a scaffold for the new bone to grow into and eventually replace. All three methods require a good blood supply, some form of mechanical support or a stable base and osteogenic cells. With osteoconductive materials, the cells primarily come from the blood vessels in the surrounding walls of the defect. Defects are usually classified as three-wall, twowall or one-wall, both around teeth and implants. The more walls, the better the stability of the graft and the bigger the area providing the blood vessels and cells resulting in greater bone formation. Properties of an ideal bone graft A graft material should be biocompatible, safe, nonallergenic, non-toxic, and have no risk of disease transmission. They should also be space maintaining, have a resorption rate similar to human bone, and a similar composition and particle size to human bone. In addition, space between particles should allow for ingrowth of blood vessels, be extensively researched and tested, and have easy handling properties.

particle size and space for vascular ingrowth. Depending on where it is harvested, it may contain bone progenitor cells and growth factors that stimulate growth. Autogenous grafts may be the slurry collected in a bone trap during surgery, particularly osteotomy and can be particles collected by scraping or chiselling the cortical plate or cancellous interior. Bone can be crushed to form cortical chips or removed as a block containing both cortical and cancellous parts. Common intraoral donor sites include the area neighbouring the surgical site, anterior nasal spine, canine fossa, zygoma and the tuberosity. The chin ⁄ symphysis or ramus ⁄ retromolar areas of the mandible are used for the harvesting of blocks. Extraoral sites are calvaria, iliac crest and tibia. Most methods result in an additional surgical procedure with concomitant morbidity of the donor site such as pain or dysthaesia. The volume of bone may be limited and the grafts may show an unpredictable resorption rate.8 The smaller the bone particle, the more quickly it is resorbed, diminishing the final amount of bone regenerated, such as that collected in a bone trap. Bone collected in a trap will probably also be contaminated by the bacteria in the oral cavity.9 Allogenic

Types of bone grafts Table 1 provides an overview of the main categories of graft materials and lists a number of commercial products. Autogenous Autogenous bone comes from the same individual and is thought of as the ‘gold standard’, fulfilling many of the ideal properties. It has an ideal composition,

Allogenic grafts come from another member of the same species, in our case another human. They may be fresh frozen bone (FFB), freeze-dried bone allograft (FDBA) or demineralized freeze-dried bone allograft (DFDBA) (Table 1). The preparation of FDBA and DFDBA reduces the immunogenicity of the grafts, but FFB carries a high risk of rejection and disease transmission. Risk aside, all materials are biocompatible. The material comes both as particulate or a block graft. Although all cellular material is removed, they

Table 1. Types of bone graft materials with commercial names or manufacturer. The commercial brands in bold are grafts the author knows are or were available in Australia within the last 10 years Autogenous

Allografts • Fresh frozen bone (FFB) • Freeze-dried bone allograft (FDBA) • Demineralized freeze-dried bone allograft (DFBDA) • Biohorizons

Xenografts • Bovine – Bio-Oss – OsteoGraf – Navigraft – Bio-Oss with Collagen – PepGen P-15 – Endobon • Equine – BioGen • Coral hydroxyapatite – Pro Osteon – Interpore 500 (HA + CC) – Biocoral • Algae hydroxyapatite – Frios – Algipore – C-Graft

Alloplasts or synthetic grafts • b-TricalciumPhosphate: • Cerasorb • KSI-Tricalciumphosphate • BioResorb • Ossaplast • Ceros

• • •



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• Rootreplica • Calc-i-Oss • Osteon Hydroxyapatite • Nanobone b-TCP & HA • Straumann Bone Ceramic Bioactive Glasses • PerioGlas • Biogran • Filler Bone Polymers • Bioplant HTR

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Periodontal materials still contain proteins that stimulate bone formation, such as bone morphogenic proteins (BMPs), showing both osteoconductive and osteoinductive properties.10 Widely used in America, they have only recently become available in Australia through BioHorizons. However, the material is still awaiting Therapeutic Goods Administration (TGA) registration at the time of writing.

disease and in sinus augmentation. It can be used in conjunction with autogenous particulate or block grafts and resorbable membranes.13,14 The Bio-Oss collagen block contains 10% porcine collagen and 90% DBBM and is designed for use in periodontal regeneration and extraction sockets (Fig 2). Alloplastic or synthetic grafts

Xenografts are derived from species other than that in which they are placed such as cows, horses or coral (Table 1). They generally act as a scaffold for new bone growth from the surrounding bony walls. Bio-coral is derived from calcifying corals containing calcium carbonate. Buser et al.11 compared a number of materials showing that although bone is formed at sites using a coral-derived graft, it was less than autogenous bone or a synthetic graft material. Deproteinized bovine bone minerals (DBBMs) are currently the most commonly used bone grafts and the market leader by far is Bio-Oss (Geistlich, Wolhusen, Switzerland) (Fig 1). Bio-Oss is currently derived from an Australian bovine herd around Melbourne. The bones are transported to Switzerland for treatment either by heat, chemicals or both to remove the organic components and prepared into two sizes of particles, cortical and cancellous, or a block. In use for over 10 years, there have been no reports of disease transmission. Bovine bone is very similar to human bone and fulfills many of the ideal properties. Extensively researched, it is well tolerated by the body with a slow substitution rate, allowing good long-term space maintenance. Histological sections show good integration of BioOss particles with newly formed bone filling the interparticle space and in direct contact with the BioOss.12 TGA approved, it is widely used in implant dentistry in ridge preservation, site augmentation, periimplant defects at the time of placement or following

Artificial bone graft materials generally contain different formulations of calcium and phosphate, such as tricalcium phosphate (b-TCP) and hydroxyapatite (HA) (Table 1). They may also be silica-based glasses, such as Perioglass or Biogran, or polymers such as Bioplant. In addition, they can act as carriers for growth factors or bone promoting cells. As they are completely synthetic there is no donor site, no limitation in amount and no risk of disease transmission. The manufacturing process also controls the particle size, interparticle spaces and consistency in an attempt to make them resemble natural bone as closely as possible. In their comparative study, Buser et al.11 showed b-TCP and HA were osteoconductive, but had differing patterns of resorption. They considered HA to be non-resorbable and b-TCP rapidly resorbable. Consequently, b-TCP showed faster bone healing with the explanation that the calcium and phosphate released by resorption were used in the formation of the new bone. However, a recent study suggested that because b-TCP resorbs so quickly it loses its space-making capacity.15 A biphasic calcium phosphate has been released, Straumann Bone Ceramic (SBC) (Institut Straumann AG, Basel, Switzerland), and is available in Australia (Fig 3). It is a homogenous 60 ⁄ 40 mixture of HA and b-TCP. The rapid dissolution of the b-TCP provides calcium and phosphate as well as space for bone formation, while the slower resorbing HA maintains the scaffold. Jensen et al.16 compared the percentage of new bone formation by SBC with autogenous bone, b-TCP alone and HA alone over a 24-week period. They showed that SBC

Fig 1. Bio-Oss, a deproteinized bovine bone mineral. (Image courtesy of Geistlich.)

Fig 2. Bio-Oss Collagen block. It is 90% DBBM and 10% collagen to promote better bone formation. (Image courtesy of Geistlich.)

Xenografts

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I Darby was better than HA alone, but was less than b-TCP and autogenous bone. A more recent study by this group varied the proportion of HA and b-TCP showing alteration of the substitution rate and bone formation, making the material in a 20 ⁄ 80 formulation comparable to an autograft.17 Membranes As mentioned above, membranes keep the soft tissue out of the periodontal or bony defect. They can also stabilize the clot, protect the newly forming bone and may allow concentration of growth factors and osteoprogenitor cells. Membranes should be biocompatible, cell occlusive, integrate with the tissue, allow for space maintenance or making, maintain the barrier function for as long as required and handle easily during surgery. Non-resorbable membranes should be easily retrievable and resorbable membranes should break down without damaging the graft or causing a foreign body reaction. Table 2 lists the types of membranes available with some commercial brands. Non-resorbable membranes were the first to be developed with Millipore (cellulose) used in the early GTR experiments followed by the development of expanded polytetrafluoroethylene membranes (ePTFE) (WL Gore, Flagstaff, AR, USA).18 More recently, titanium strips were used to reinforce the membrane and allow for space making. Widely used in the late 1980s and 1990s, they were extensively researched and found to predictably provide more attachment gain than open flap periodontal surgery.19 However, they are generally difficult to manipulate and required sutures around the necks of teeth to hold them in place. A second surgical procedure was required to remove them and many

complications were reported, especially premature exposure, which were related to poorer defect fill.20 These issues led to the development of resorbable membranes. They can be divided into collagen and synthetic membranes, primarily using combinations of polyglycolide and ⁄ or polylactide (Table 2). Resolut (WL Gore, Flagstaff, AR, USA) was one of the first resorbable membranes developed, a combination of polylactide ⁄ polyglycolide ⁄ trimethylcarbonate. Recently, collagen membranes have been much used and the market leader is Bio-Gide (Geistlich, Wolhusen, Switzerland) (Fig 4). It is derived from porcine collagen Types I and III and is very biocompatible. It handles well before it gets wet. Once wet it collapses and adheres to what it covers. As a result, it often requires a graft material to support it. It degrades in about six to eight weeks, which may be prolonged by using a double layer. Extensively researched, it generally provides good regenerative outcomes. Exposure is not as catastrophic as that of ePTFE, with the membrane being degraded on contact with the oral cavity followed by soft tissue coverage. Collagen membranes have been cross-linked using glutaraldehyde, such as Ossix (Biomet 3i, Palm Beach, FL, USA) or BioMend (Zimmer, Carlsbad, CA, USA). This makes the membrane stiffer and less likely to collapse into the defect. It also prolongs the breakdown time, which may be beneficial when used in conjunction with grafts that have a low substitution rate. Rothamel et al.21 compared five commercially available membranes in a rat model reporting decreased tissue integration and fewer blood vessels with crosslinked collagen membranes. Released lately in Australia is an acellular dermal matrix graft (ADMG), Alloderm from Biohorizons (Biohorizons, Birmingham, AL, USA) (Fig 5). Obtained from tissue banks, it is human skin processed to remove the epidermis and cellular com-

Table 2. Overview of the types of membranes available with some commercial brands. The brands in bold are those the author knows were or are available in Australia • Non-resorbable • Resorbable – PTFE – Collagen • TefGen-FD, BioBarrier NP • Bio-Gide – ePTFE • Ossix • GoreTex • BioMend – Titanium-reinforced ePFTE – Polylactic • GoreTex • Guidor – Cellulose – Polylactic ⁄ polyglycolic • Millipore • Ethisorb – Rubberdam • Vicryl • Inion – PL, PG & Trimethylcarbonate • Gore Resolut – PG & TMC • Gore Resolut Adapt – Acellular Dermal Allograft • Alloderm – Polyethylene glycol • Membragel 110

Fig 3. An example of a synthetic graft material. Straumann Bone Ceramic, a homogenous biphasic calcium phosphate. It is a 60 ⁄ 40 mixture of HA and b-TCP. (Image courtesy of Straumann.) ª 2011 Australian Dental Association

Periodontal materials Growth factors

Fig 4. Bio-Gide, a porcine-derived resorbable membrane. (Image courtesy of Geistlich.)

Fig 5. An example of an acellular dermal matrix graft, Alloderm from Biohorizons.

ponent, leaving no risk of disease transmission or rejection and a material that is very similar to collagen in structure. It is too new to comment adequately on its effectiveness. Again, TGA permission is required per patient. Recently, a polylactide ⁄ polyglycolide membrane has been developed that is soft when applied but becomes rigid once in position (Inion GTR Biodegradable Membrane System; Inion Oy, Tampere, Finland).22 In 2010 a polyethylene glycol (PEG) gel was released on the market (Membragel, Institut Straumann AG, Basel, Switzerland) (Fig 6). Instead of placing a membrane, the gel is injected over the graft and sets to provide a solid barrier. Jung et al.,23 in 37 patients with an osseous defect, compared a collagen membrane against the PEG gel showing similar amounts a well-vascularized bone formed in both groups. However, more soft tissue complications were observed with the PEG gel, but these sites recovered uneventfully. Currently under further development at the time of writing, it looks promising and could be used as a carrier for growth factors. ª 2011 Australian Dental Association

Growth factors are the signalling molecules that regulate cell growth and development. They modulate cell proliferation, migration, extracellular matrix formation and other cellular functions. Some may also function as cell differentiation factors.24 Key growth factors are platelet-derived growth factor (PDGF), transforming growth factor-b (TGF-b), fibroblast growth factor (FGF), insulin-like growth factor (IGF), vascular endothelial growth factor, parathyroid hormone (PTH) and BMP. PDGF has good mitogenic and chemotactic properties for cells and is released from the clot at the start of the healing cascade. Fibroblast growth factors are involved in the induction of angiogenesis, regulation of the proliferation and differentiation of cells including fibroblasts, endothelial cells, osteoblasts and periodontal ligament cells.25 The first attempts used semi-purified natural materials such as platelet-rich plasma and enamel matrix proteins. More recent attempts have used recombinant human proteins. Platelet-rich plasma is derived from centrifuged autologous blood by drawing off the platelet-rich buffy zone. This is resuspended in a small volume of blood and placed in the periodontal or bony defect, or added to a graft material. Whilst it has been somewhat beneficial when used in periodontal or implant regeneration,26 it has fallen out of favour recently. Enamel matrix proteins stem from the study of tooth development and observation of a relationship between these proteins and the formation of the root surface, especially cementum.27 Developed originally by Biora in Sweden, enamel matrix proteins are extracted from the tooth buds of piglets, suspended in a polyglycol gel and marketed as Emdogain (EMD) (Institut Straumann AG, Basel, Switzerland) (Fig 7). EMD contains over 95% amelogenin with small amounts of enamelin and other proteins. Initial studies showed histological evidence of regeneration in experimentally created periodontal defects in monkeys.28 Subsequent clinical studies showed the material to be of benefit in infrabony and angular periodontal defects.29,30 Further studies have shown that EMD also contains a number of growth factors and stimulates production of further growth factors, such as BMPs and promotes angiogenesis.24 Recombinant proteins are synthetically produced by DNA technology and are replicas of natural proteins. Manufacturing growth factors removes the issues of varying concentration and amounts of growth factors in naturally derived materials and allows for the use of a single protein at any concentration desired. BMP are a family of glycoproteins involved in all aspects of bone formation, from initiation to the amount and cessation of bone formation. BMP-2 and BMP-7 have been developed as recombinant human proteins for use 111

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Fig 6. Straumann MembraGel in situ application. (a) The defect following implant placement, (b) augmentation of the defect, (c) application of the gel, and (d) hardening of the gel. (Images courtesy of Straumann).

primarily in orthopaedics, but also periodontics and implant dentistry. They have been mixed with bone grafts and placed in collagen plugs to improve the outcome of ridge preservation.31,32 However, their use is not yet approved in Australia and the cost of production is currently prohibitively high. In an attempt to improve outcomes, graft materials and growth factors have been combined. Emdogain Plus is a mixture of EMD and Straumann Bone Ceramic. Bio-Oss Collagen is the incorporation of 10% collagen into DBBM. Both are available in Australia. One product not available in Australia is GEM 21S. GEM 21S (Osteohealth, Shirley, NY, USA) contains b-TCP and PDGF, which has been approved for use in the treatment of infrabony and furcation

lesions in the USA.33 Its use does seem to improve clinical parameters more than just open flap surgery or the graft alone and these results were maintained for up to three years.33 Gene therapy or delivery Most growth factors used in tissue engineering have a very short half-life. In addition, they may not be present at the right time or in the correct amount when needed. The transduction of cells with genes for particular growth factors is a novel and exciting area. Using an adenovirus, Giannobile et al.34 has successfully transferred PDGF and BMP-7 genes into cementoblasts, fibroblasts and other periodontal cell types. When the cells containing the PDGF or BMP-7 gene were placed in periodontal defects in rats, they stimulated bone and cementum regeneration.35,36 Using this approach it may be possible to manipulate the periodontal healing response so it mimics regeneration. However, the safety and efficacy of this technique need to be evaluated.24 Cell-based materials Cell sheets

Fig 7. Emdogain. Enamel matrix proteins extracted from porcine tooth buds. (Image courtesy of Straumann.) 112

Another approach is to culture cells, such as fibroblasts, in the laboratory to create cell sheets or scaffolds full of cells that could be used in regeneration.37 Hasegawa et al.38 created periodontal ligament cell sheets in vitro ª 2011 Australian Dental Association

Periodontal materials and transplanted them into a dehiscence defect model in immunodeficient rats. Four weeks post-surgery they were able to show regenerated ligament tissues anchored to the previously root-planed dentine surface. This approach has been used to seed cells onto a membrane or mesh in the treatment of gingival recession with similar results to standard soft-tissue grafting techniques.24 Stem cells Stem cells are the foundation cells for every organ and tissue in the body.39 They have two defining characteristics: the ability for indefinite self-renewal to give rise to more stem cells and the ability to differentiate into a number of specialized daughter cells. The two main types are embryonic and adult. Human embryonic are derived from spare blastocysts created by in vitro fertilization and have numerous ethical and religious issues. However, they can be maintained in an undifferentiated state in vitro for an indefinite period, while retaining their ability to differentiate into all types of specialized cells in the body.39 Adult stem cells have been identified in most foetal and adult tissues, especially those that ‘continually replenish themselves’, such as blood and dermis.39 They are thought to be involved in long-term tissue maintenance and are generally multipotent cells that form only a limited number of cell types corresponding with their origin.39 Most stem cell research in the periodontal tissues has focused on mesenchymal stem cells, which are of interest as they have the potential to treat musculoskeletal disease. Seo et al.40 were the first to report the presence of mesenchymal stem cells in the periodontal ligament. More recently, immortalized dental follicle cells were shown to be able to generate periodontal ligament-like tissue after implantation.41 It remains to be determined what is the best stem cell source for regeneration of the periodontal ligament, but represents a great step forward in a more predictable biologicallybased therapy.39

overview. In brief, conflicting evidence is available for the use of bone graft materials.33 A review of bone grafts used in the treatment of infrabony defects and furcation lesions improved clinical attachment level and decreased probing depths over and above that of open flap surgery.42 There were no apparent differences between materials used. However, issues of study design heterogeneity and differences in the materials prevented sufficient evidence to support the use of bone grafts from being found.43 Autogenous and allogenic grafts may or may not support the formation of new attachment, whereas alloplastic graft materials may only result in repair.33 Overall, the use of bone grafts alone in the regeneration of periodontal osseous defects is not supported.33 The outcomes of GTR are much clearer. The use of either resorbable or non-resorbable membranes does result in regeneration. However, non-resorbable membranes are prone to exposure and infection. The indications and outcomes are also fairly well defined. The use of GTR in intrabony44 and Class II mandibular furcations45 reproducibly provides a better outcome than open flap surgery alone. GTR is not recommended for maxillary Class III furcations and the equivocal outcomes in maxillary Class II furcations suggest its use for such defects is not worthwhile.46,47 The clinical and radiographic outcomes of GTR appear to be stable for at least 10 years.48–50 GTR is often combined with bone graft materials. For example, Bio-Gide is not a rigid membrane and will collapse into the defect if not supported by a graft, such as Bio-Oss. The outcomes of this combined approach are similar to GTR alone.51,52 Of the materials available in Australia, Bio-Oss and Bio-Gide have been shown to have a successful longterm benefit53,54 (Fig 8).

Do these materials work in our patients? The short and somewhat flippant answer is yes. However, one should be aware of the filling effect of the materials that may result in ‘improved’ attachment levels due to the defect being filled, but not resulting in regeneration. Histology is the only way to confirm that regeneration has taken place. Periodontal outcomes Ivanovski33 reviewed the outcomes of periodontal regeneration in the Australian Dental Journal supplement, An update in contemporary periodontics, and readers are referred to this for a more detailed ª 2011 Australian Dental Association

Fig 8. Use of DBBM in a two-wall periodontal defect. This would be covered with a resorbable membrane to help contain the graft and keep the soft tissue away. 113

I Darby The outcome of EMD has also been extensively researched and reviewed. The results show consistently better healing using EMD than open flap surgery55 (Fig 9). In comparison with GTR and bone grafts, similar results are produced,56,57 but the use of EMD and a bone graft, such as Bio-Oss, may be particularly advantageous.58 This combination could be useful in supporting the soft tissues and maintaining space in one- or two-wall defects. Recently, Sculean et al.59 reported a 10-year follow up of sites treated with EMD. They showed that their outcomes could be maintained satisfactorily over this period. Lastly, growth factors have been tested in periodontal defects, but not to the same extent. Ivanovski33 reported that PDGF had not been used on its own, but in combination with allogenic or b-TCP bone grafts. In conjunction with an allogenic bone graft, PDGF produced a clear clinical benefit, whereas combined with b-TCP the clinical outcomes were similar to b-TCP alone. The benefit of platelet-rich plasma combined with bone graft materials and ⁄ or GTR is not proven. There are too few studies and the method of preparation of the platelet-rich plasma seems to affect the outcome.33 Implant outcomes Staged or site augmentation prior to implant placement When there is insufficient bone to allow primary stability, proposed implants sites may be augmented by horizontal and ⁄ or vertical grafting.60 At the Fourth ITI Consensus Conference, Jensen and Terheyden60

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reported that techniques are available to effectively and predictably increase the horizontal width of the alveolar ridge. The outcome depended on the number of bony walls and the materials used. Augmentation utilizing autogenous bone blocks with or without membranes results in higher gains in ridge width and lower complication rates than use of particulate materials with or without a membrane. Techniques are also available to increase the vertical height of the alveolar ridge. However, the predictability is substantially lower than horizontal ridge augmentation procedures. Augmentation utilizing autogenous bone blocks with or without membranes results in higher gains in ridge height than use of particulate materials with or without a membrane. The complication rate related to vertical augmentation of the alveolar ridge is substantially higher than horizontal ridge augmentation procedures. Sinus augmentation may be used when there is insufficient bone height in the posterior maxilla. Three approaches are possible depending on initial bone height, amount of augmentation required and whether primary stability can be achieved. These are transalveolar, using an osteotome to raise the cortical plate underlying the sinus floor and pack a bone graft into the osteotomy site to raise the sinus floor, a lateral window approach and a lateral window with simultaneous implant placement. Chiapasco et al.,61 in a recent review of augmentation procedures, concluded that lateral window sinus floor elevation procedures are predictable for augmenting bone. Many bone graft materials have been used and all seem to increase the height and amount of bone available for implant placement.

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Fig 9. Clinical use of Emdogain. (a) The defect after access and debridement, (b) placement of the EMD gel after two minutes of root surface conditioning with EDTA, and (c) one week post-surgery. 114

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Periodontal materials Ridge preservation: is this ridge preservation or socket preservation?

Simultaneous augmentation at the time of implant placement

Darby et al.62 reviewed the outcomes of various ridge preservation procedures and reported that irrespective of materials and techniques used, ridge preservation resulted in a greater orofacial dimension of bone than when no ridge preservation procedures are performed. Both DBBM and DFDBA produced similar results in terms of the percentage of bone formed and residual graft particles in core samples removed at time of implant placement. Membranes, such as ePTFE, collagen and ADMG produced good results with and without the use of grafts, but needed to be covered by soft tissue. ePFTE membranes were noted to have a high rate of exposure which resulted in a poor outcome. Exposure of collagen membranes, whilst detrimental, could be managed and was not as catastrophic. Where a particulate graft was used, the best results were produced when the graft was covered (Fig 10). Two studies have reported the use of collagen sponges to act as a carrier for rhBMP-2 or impregnated with P-15, a synthetic polypeptide intended to mimic the a1 chain of Type 1 collagen, for management of extraction sockets and shown that the incorporation of the growth factor resulted in much greater bone formation in the socket.32,63

Implant placement into a healed ridge may result in a partial exposure of the buccal aspect of the implant requiring some form of grafting to cover and allow bone formation on the exposed surface (Fig 11). Augmentation of dehiscensce and fenestration type defects has been shown to be effective in reducing the amount of exposed implant surface irrespective of technique and materials used.60 However, complete resolution of dehiscensce and fenestration type defects cannot be predictably accomplished irrespective of the grafting protocol employed. The use of a membrane in conjunction with a bone graft increased the defect fill with resorbable membranes, providing the better result and the fewest incidences of membrane exposure when compared to non-resorbable. Donos et al.64 have noted that GBR by membrane alone, or in conjunction with DBBM were effective methods to manage such defects. Another method of simultaneous augmentation is to place autogenous bone chips on the exposed implant threads, then covered with DBBM followed by a double layer of collagen membrane.13 This method has been a successful approach for over 15 years.

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Fig 10. Ridge preservation using Bio-Oss and Bio-Gide. (a) Extraction socket, (b) Bio-Oss in socket and filling buccal dehiscence, (c) Bio-Gide membrane covering graft, and (d) Re-exposure of the site for implant placement eight months later. (Images courtesy of Dr Fiona Little.) ª 2011 Australian Dental Association

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I Darby Peri-implant disease At the Sixth European workshop on Periodontology Consensus Conference, Claffey et al.65 reviewed the outcomes of regenerative therapy for peri-implantitis. They reported that the great variation in the amount of bone fill may be related to defect type and ⁄ or regenerative technique. However, the use of a bone graft alone or a membrane resulted in a better outcome compared to debridement alone. The use of both a bone graft and membrane appeared to provide the best results and resulted in more reintegration than surgery alone. However, many of these studies have been undertaken in animal models and there is a general paucity of literature in this field. The use of histology is the only way to confirm reintegration and this data is also lacking. This field will be an area of great research over the next few years. Growth factors The use of growth factors in implant dentistry is still in its infancy, lacking a sufficient body of evidence to provide meaningful outcomes and conclusions. Growth

factors such as BMP-2, BMP-7, GDF-5, PDGF and PTH have been used for all forms of bone augmentation discussed above and the results appear promising.66 Whilst there is no doubt these factors promote bone formation, the ideal concentrations still need to be determined and safety issues currently remain. CONCLUSIONS The area of periodontal materials has expanded greatly over the last 40 years and will continue to advance in line with increasing medical understanding of the human body. We have gone from a phase of testing to routine use of membranes and bone grafts with predictable and successful outcomes.67 The materials available in Australia, although limited, are still able to provide good clinical outcomes for our patients. The evidence for use of DBBM and a collagen membrane is plentiful, but as yet there is little information about biphasic calcium phosphate. The use of growth factors, genes and stem cells appears promising and will be the future. However, the next few years will be a process of trial and error until the best materials and ⁄ or combinations of materials are found. Coupled with this is the requirement to develop methods that release the right factor in the right concentration at the right time and in a safe manner. It is a really exciting time to be involved in periodontics and implant dentistry. CONFLICT OF INTEREST STATEMENT The author has been involved in presenting educational programmes relating to periodontal regenerative products for a number of different manufacturers, but has no direct financial interest in these products or the companies which manufacture them. Products shown in the photographs were given to the author by the manufacturers or permission for their use was provided by the manufacturer. REFERENCES 1. Melcher AH. On the repair potential of periodontal tissues. J Periodontol 1976;47:256–260. 2. Nyman S, Karring T. Regeneration of surgically removed buccal alveolar bone in dogs. J Periodontol Res 1979;14:86–92. 3. Nyman S, Karring T, Lindhe J, Plante´n S. Healing following implantation of periodontitis-affected roots into gingival connective tissue. J Clin Periodontol 1980;7:394–401. 4. Karring T, Nyman S, Lindhe J. Healing following implantation of periodontitis affected roots into bone tissue. J Clin Periodontol 1980;7:96–105. 5. Nyman S, Gottlow J, Karring T, Lindhe J. The regenerative potential of the periodontal ligament. An experimental study in the monkey. J Clin Periodontol 1982;9:257–265.

Fig 11. Use of DBBM and a collagen membrane for simultaneous augmentation at the time of implant placement. 116

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Address for correspondence: Associate Professor Ivan Darby Periodontics Melbourne Dental School 720 Swanston Street Parkville VIC 3010 Email: [email protected]

ª 2011 Australian Dental Association