Guided bone-regeneration techniques use either resorbable or nonresorbable membrane. Ideal membrane material should be biocompatible with tissue integration, be able to create and maintain space, be occlusive with selective permeability, and have good handling properties. Commercially available nonresorbable membranes are Gor-tex (e-PTFE), Cytoplast (d-PTFE), and titanium mesh. Resorbable membranes are available as natural and synthetic. Clinical trials, a systematic review and meta-analysis have shown no statistically significant difference in most clinical indications between both types of membrane. The choice of membrane varies according to the choice of grafting materials and nature of defect.
Guided tissue engineering has been proved successful for alveolar ridge augmentation, maxillary sinus implant site development, periodontal furcation defects, and treatment of intrabony pockets and socket preservation.
Numerous factors play a role in the success of guided bone regeneration, such as the choice of resorbable or nonresorbable membranes and the timing of membrane removal.
The type of membrane chosen depends on the requirements needed for space creation.
Nonresorbable membranes are required at load-bearing regions, such as in vertical ridge augmentation.
Resorbable membranes are recommended to be used in non–load-bearing regions, such as in maxillary sinus augmentation.
It is difficult to study resorbable versus nonresorbable membranes because the use of these 2 types of membrane are intimately tied to the site of augmentation and the material used. Aghaloo and Moy, in their 2007 meta-analysis of literature on hard-tissue augmentation techniques, noted that implant survival rate was the highest for guided bone regenerations (95.5%) versus the other techniques used.
The use of guided membranes in an attempt to improve the quality of bone grafting is not a new concept. In 1957, Murray and colleagues demonstrated new bone growth in dog femur, ileum, and spinal column using a plastic fenestrated cage as a barrier to soft-tissue invasion. Recognizing potential benefits of guided bone regeneration (GBR) in dentistry, in 1960 Linghorne presented the sequence of osteogenesis events, which he described as “pathologic and physiologic phases,” after bridging a 15-mm ostectomy site in dog fibula. In 1969, Richter and Boyne published a paper on new concepts in facial bone healing and grafting procedures, in which they presented the use of hematopoietic bone marrow placed in a vitallium meshwork lined with a Millipore filter to stabilize and discourage the ingrowth of fibrous tissue.
In the intervening period, the evolution of these bone-volume growth techniques has improved. According to Jimenez Garcia and colleagues, the use of a membrane technique prevents the migration of fibroblasts and soft connective tissue cells into the intended regeneration site. In 1996, Hermann and Buser discussed the critical surgical factors for adequate and predictable regeneration: use of an appropriate membrane, attaining primary soft-tissue healing, creation and maintenance of a membrane-protected space, close adaptation and stabilization of the membrane to the surrounding bone, and sufficient length of healing period. In 2006 Wang and Boyapati published the PASS principles: primary wound closure without tension to enable proper healing by means of first intention and reduction of the risk of membrane exposure, angiogenesis to promote blood supply, space maintenance to create a bed for the undifferentiated mesenchymal cells, and clot stability to allow for the proper development of these cells.
Concepts of guided tissue membranes and ideal properties
Current concepts to increase the outcome of successful bone regeneration are built on those already discussed and are broken down into ideal properties anticipated from the barrier membranes.
Biocompatibility : the membrane should not trigger host immune response, sensitization, or chronic inflammatory reaction and not adversely affect healing.
Space creation and maintenance : the membrane should have adequate toughness to create and maintain space to allow the ingrowth of nearby osteoblasts to regenerate bone, and have adequate strength to withstand the pressures from nearby muscles of mastication and the tongue.
Occlusivity and selective permeability : the membrane should prevent unwanted cells such as epithelial cells, fibrous tissue, or granulation tissue from entering into the intended bone-healing space, while permitting nearby osteoprogenitors, osteoblasts, and cells responsible for neovascularization as well as facilitating diffusion of the growth factors, signaling molecules, nutrients, and bioactive substances.
Tissue integration : membrane should fully integrate with the host tissue to provide structural integrity and provide mucosal support and stability. It should also have a sufficient adaptability between the bone-membrane border by sealing off the cavity, preventing fibrous tissue infiltration and encapsulation of the membrane.
Clinical manageability : the membrane should be easy to handle and should maintain its shape and position for easy placement.
Types of membranes: advantages and disadvantages
Various materials have been used to fabricate GBR membranes over the last decades. The types of membrane can vary widely from titanium mesh that is very rigid to membranes that are very flexible, and which may be bioresorbable or might require a second surgery to remove it at a later stage.
Cellulose acetate (Millipore) was the first material used to keep gingival connective tissue away from the root surface and allow periodontal regeneration. Commercially available nonresorbable guided tissue regeneration (GTR) membranes for periodontal regeneration and GBR membranes for alveolar bone regeneration are expanded polytetrafluoroethylene (e-PTFE) and high-density PTFE (d-PTFE), both of which are available with or without titanium reinforcement.
Numerous studies have shown positive results with the use of e-PTFE membranes, widely known as Gore-tex (W.L. Gore & Associates, Flagstaff, AZ, USA). However, premature exposure of e-PTFE membranes is relatively common and is reported to be around 30% to 40%. Membrane exposure may lead to infection and lack of new bone formation as a result of fibrous tissue ingrowth. Primary closure is necessary over e-PTFE membranes, which can be challenging in larger defects. Another disadvantage of nonresorbable membranes is the need for additional surgery to remove the membrane, increasing the risk of exposing newly regenerated bone to bacteria. Timing of membrane removal is also important because early removal can lead to resorption of regenerated bone, whereas late removal can increase the risks of bacterial contamination and infection.
The e-PTFE membrane has been replaced with d-PTFE, marketed as Cytoplast barrier membranes (Osteogenic Biomedical, Lubbock, TX, USA). This membrane has high density and smaller pore size (0.2 μm), preventing bacterial infiltration and leading to lower risks of infection when exposed. In addition, primary closure over the membrane is not necessary. In a randomized controlled trial, no difference was detected in the mean vertical bone defect fill after 6 months with either e-PTFE and d-PTFE membrane; however, d-PTFE membrane was easier to remove than e-PTFE.
Titanium mesh (eg, Ti-Micromesh; ACE, Brockton, MA, USA) is also commercially available as nonresorbable GBR membrane. Various studies have demonstrated that titanium mesh membranes have sufficient strength and toughness to provide space maintenance and prevent contour collapse from mucosal compression because of its elasticity. In addition, they are less susceptible to bacterial contamination secondary to its smooth surface. However, stiffness of the material and sharp edges caused by trimming and contouring can cause mucosal irritation and are associated with higher risk of membrane exposure. In addition, the removal of titanium mesh can be challenging. In a randomized clinical treatment trial of atrophic alveolar bone in the posterior mandible, similar vertical bone gain and implant stability was achieved by using either titanium mesh or d-PTFE membrane.
Requirement for a second surgical procedure to remove a barrier membrane is the major disadvantage of nonresorbable membranes. Since the early 1990s, bioresorbable membranes have been successfully used clinically. Resorbable membranes are available as natural and synthetic membranes. Natural membranes are manufactured using bovine or porcine collagen or chitosan. Commercially available synthetic membranes are made up of organic aliphatic polymers such as polyglycolic acid or polylactic acid, and their modifications. These include poly- dl -lactic acid, polylactic-glycolic acid, polyglycolic acid-trimethylene carbonate, poly- ld -lactic-glycolic acid-trimethylene carbonate, and poly- dl -caprolactone.
Collagen has the ability to attract and activate gingival fibroblast cells and stimulate fibroblast DNA synthesis. Biocompatible type 1 and type 3 collagen membranes are commercially available with varying rates of resorption ranging from 0.5 month (CollaPlug; Zimmer Biomet, Warsaw, IN, USA) up to 10 months (Mem-Lok RCM; BioHorizons, Birmingham, AL, USA). Chitosan is biodegradable and biocompatible, and possesses antimicrobial and osteoinductive properties. Synthetic membranes have advantages of biocompatibility and complete hydrolysis as well as removal by proteolytic enzymes from the body. These membranes are resorbed by the body with variable resorption time from 1.5 to 24 months depending on the type and properties of the materials.
More recently, resorbable allograft membranes derived from natural biological materials such as human placental amnion chorion tissue (BioXclude; Snoasis Medical, Golden, CO, USA), human pericardium (Mem-Lok Pericardium; BioHorizons), human fascia lata (Fascia Lata Tissuenet; TissueNet, Orlando, FL, USA), and human fascia temporalis (Tutoplast Fascia Temporalis; Biodynamics International, Milwaukee, WI, USA) has become commercially available. As processed biological materials, they carry minimal risk of inflammatory or foreign body reactions. In a study comparing different types of membranes on New Zealand white rabbits, fascia lata, pericardium, and e-PTFE membranes showed significantly better bone regeneration than fascia temporalis.
Because resorbable membranes do not require secondary surgery for their removal, there is a reduced risk of infection and less tissue damage. As such, there is decreased pain and discomfort, along with decreased costs associated with a second surgery. However, the timing and degree of resorption of the membrane can be unpredictable. Premature resorption can lead to gradual loss of strength, membrane collapse, and loss of the ability to maintain space. Loss of strength can decrease bone regeneration, allowing fibrous tissue ingrowth, and prolonged or incomplete resorption can be associated with membrane exposure, inflammation, and bacterial contamination. These disorders can jeopardize the healing of the newly formed bone. In general, as resorbable membranes are not as stiff as nonresorbable membranes they do not allow tenting of the tissues.
Studies comparing resorbable and nonresorbable membranes
There are multiple comparative studies of resorbable versus nonresorbable membranes, each with its strengths and weaknesses. To facilitate the understanding of the topic, this section focuses firstly on a systematic review and meta-analysis and secondly on clinical trials that address GBR in different sites.
Systematic Review and Meta-Analysis
Lim and colleagues retrospectively reviewed and performed a meta-analysis of 21 qualitative and 15 qualitative clinical trials to compare the wound-healing complications among resorbable and nonresorbable membranes, and found no statistically significant difference between the types of membrane used.
Class II furcation defects
A substantial number of comparative studies of resorbable and nonresorbable membranes exists regarding the treatment of class II furcation defects. Coffesse and colleagues (1997), Scott and colleagues (1997) , Eickholz and colleagues (1997), and Karapataki and colleagues (1999) found no significant difference in probing depth reduction, clinical attachment gain, and vertical and horizontal bone fill between groups. Both resorbable membrane groups and nonresorbable membrane groups showed significant clinical and radiographic improvements. In a randomized multicenter study of 38 patients conducted in 1995, Hugoson and colleagues found a statistically significant improvement in clinical attachment level in both horizontal and vertical direction in the resorbable membrane group. The nonresorbable membrane group showed improvement in clinical attachment in the vertical direction only. Gingival recession was significantly higher in the nonresorbable membrane group compared with resorbable membranes. In a long-term study in 2006, Eickholz and colleagues found that treatment of class II furcation defects demonstrated stable horizontal attachment gain after 10 years with no statistically significant difference among the types of membrane used.
Class III furcation defects
Class III through-and-through furcation defects respond poorly to GTR techniques. No significant gain in pocket depth or vertical probing attachment levels were observed in both type of barrier membranes when used in class III furcations.
Intrabony periodontal defects
Multiple clinical trials conducted to compare absorbable and nonresorbable barrier membranes in the treatment of intrabony periodontal defects failed to show statistically significant differences in probing depth reduction, clinical attachment level gain, and bone fill. In a 10-year follow-up study on treatment of intrabony defects conducted in 2008, Pretzl and colleagues found no statistically significant difference in the stability of vertical attachment gain between the 2 membranes groups after GTR therapy.
Ridge preservation procedures
In 2012, Arbab and colleagues found no statistically significant differences in horizontal and vertical ridge dimension changes between the use of resorbable and nonresorbable membrane for ridge preservation. In addition, the viable bone gain in the extraction sockets was histologically found to be the same for both membrane groups. The investigators concluded that the choice of barrier membrane has no effect on the outcome of the ridge preservation both clinically and histologically.
Implant site development
In a 2014 double-blind randomized clinical trial, Merli and colleagues compared the efficacy of resorbable and nonresorbable barriers for vertical ridge augmentation procedure with simultaneous implant placement, and found no significant differences in radiographic vertical bone gain at the 6-year follow-up visit.
Maxillary sinus augmentation
A study comparing the use of resorbable versus nonresorbable barrier membranes for maxillary sinus augmentation revealed uneventful healing and successful closure of the lateral sinus walls. At the microscopic level, higher amount of fibrous connective tissue ingrowth was observed in the bone samples obtained from the resorbable membrane group; however, the difference did not affect the clinical outcome.
Peri-implant bony defects
Randomized controlled trials comparing the efficacy of resorbable and nonresorbable membrane in the treatment of bony defects around endosseous dental implants revealed no statistically significant difference in clinical parameters between the 2 membrane types. Both membranes were proved to be successful when used in combination with particulate bone grafts.