When a tooth is extracted, the alveolar bone that supports the tooth resorbs over time. This resorption results in a reduction in alveolar bone volume, as shown in this clinical example of a missing upper right central incisor. The bone has diminished significantly in orofacial width, and this is in conflict with the fundamental requirement in implant dentistry that implants are placed in the correct prosthodontically determined position. When the alveolar bone resorbs, it is often necessary to augment the bone to ensure that implants can be placed correctly and be completely embedded in bone. This module will describe a specific technique for bone augmentation known as guided bone regeneration or GBR.

Guided bone regeneration is a bone augmentation technique that uses the principle of space maintenance within a bony defect with the use of a barrier membrane. The barrier membrane excludes rapidly proliferating epithelial cells and connective tissue fibroblasts, thus allowing the ingrowth of slower-growing bone cells and blood vessels into the blood clot within the defect. In this diagram, a defect in the bone is present. When the site is allowed to heal, there is partial bone regeneration at the edge of the defect, but the bone infill is incomplete because the epithelium and connective tissue proliferate quickly, occupying the space before the slower-growing bone cells can do so.

The experimental evidence that underpins the concept of guided bone regeneration was based on the research for periodontal regeneration in the early 1980s by Nyman and co-workers. This research used filtration filters to act as barrier membranes to promote regeneration of the periodontal tissues within an infrabony periodontal defect. This technique was given the term guided tissue regeneration, or GTR. In this technique, following reflection of a surgical flap, a barrier membrane is adapted over the defect and surrounding residual bone and tied to the neck of the tooth. The mucoperiosteal flap is then replaced over the membrane. The membrane prevents epithelial and connective tissue cells from migrating into the protected defect. The slow-growing bone cells and periodontal ligament cells gradually repopulate the protected space and regenerate the periodontal attachment and bone.

In the late 1980s, Dahlin and co-workers applied this barrier membrane principle to demonstrate the regeneration of bone tissue in experimental defects in preclinical studies. In this 'proof of principle' study, standardized "through-and-through" bone defects were created at the angles of the mandible in rats. On one side of the jaw, the defect was covered with a polytetrafluoroethylene, or PTFE, membrane, whereas the defect on the other side was left to heal without intervention and served as the control. The side treated with the PTFE barrier membrane showed complete regeneration of bone tissue within the defect at 3 and 6 weeks. In contrast, the untreated control defects did not heal with regeneration of bone but rather were filled with a combination of connective tissue and muscular tissue. This study established the proof that a bone defect protected by a barrier membrane could heal with complete regeneration of bone. The authors subsequently published a follow-up study in a monkey model that confirmed the proof of principle.

A study was performed to determine if bone could be regenerated over an exposed implant surface using the principles of guided bone regeneration. Implants were placed into the tibiae of rabbits. Dehiscence defects were created on the buccal aspect of the implant. Test implants were covered with a membrane made of expanded PTFE, or ePTFE, to maintain a protected space, whereas control implants were allowed to heal without a membrane. The soft tissues were closed over the implants, and histologic specimens were obtained after 6, 9, and 15 weeks of healing. The test implants covered with barrier membranes regenerated significantly more bone than the control implants. Furthermore, histologic examination showed that the newly regenerated bone had successfully integrated with the previously exposed implant surfaces.

A deeper understanding of the biological principles of guided bone was established in a study by Schenk and co-workers in 1994. In this study, the mandibular premolars in four foxhound dogs were extracted and the alveolar bone allowed to heal for 3 months. Standardized defects in the alveolar crest were created on each side of the jaws. Following randomization, half of the defects were covered with a barrier membrane made of ePTFE. The barrier membranes were stabilized with bone screws. The remaining defects served as untreated controls. No membranes were applied to these defects, and they were allowed to heal without intervention. Histologic specimens were obtained following 2 and 4 months of healing. In control defects, bone regeneration was restricted to the margins of the bone defect. The original space delineated by the bone defect had collapsed, and only partial regeneration of bone from the edge of the bone walls had occurred. The difference seen in defects protected by barrier membranes was dramatic. In the majority of sites, the original bone defect was filled with new bone and marrow spaces. By 4 months, completion of cortical and cancellous bone regeneration had occurred with the onset of bone remodeling. Bone repair in the membrane-protected defects followed the pattern of bone development and bone growth. An important observation was that in some membrane-protected sites, the defect had not completely healed at 4 months because of partial collapse of the barrier membrane. This issue will be addressed later in this module.

In summary, the sequence of biological events is as follows: A bone defect is covered by a barrier membrane, creating a secluded space between the bone and the membrane. Bleeding from blood vessels in the surrounding bone marrow leads to the formation of a blood clot, or hematoma. The membrane serves as a physical barrier to exclude nonosteogenic cells, that is, epithelial cells and connective tissue fibroblasts, while allowing the ingrowth of slower-growing bone cells and blood vessels into the blood clot within the defect. The growth of new blood vessels, or angiogenesis, is accompanied by the recruitment of bone-forming osteoblasts and the onset of bone matrix deposition. Bone regeneration then progresses in a series of steps that resemble the regular pattern of bone growth, that is, bone remodeling and organization into normal bone structure.

The predictability of the GBR procedure depends not only on the creation of a protected space by the membrane but also on the morphology of the bone defect being treated. Bone walls provide an exposed surface of bone and marrow spaces. Osteogenic cells from the bone marrow are able to migrate along newly forming blood vessels into the blood clot in the defect. When two to three bone walls are present, the blood clot is protected and less likely to move or to be disturbed during the healing period.

Biological Principles of Guided Bone Regeneration, Key Learning Points: GBR is based on the principle of excluding faster-growing soft tissue cells from a bone defect, allowing the ingrowth of slower-growing bone cells and blood vessels. Barrier membranes are used to protect the bone defect and the blood clot within it. Studies showed that GBR resulted in cortical and cancellous bone regeneration, with bone remodeling and organization into normal bone structure. Two or three bone walls are needed for predictable bone regeneration.

When implants are placed in an ideal three-dimensional prosthodontic position, peri-implant defects in the surrounding bone may be created. Treatment is necessary to reconstruct the bone so that the endosseous part of the implant is completely covered in osseous tissue. This avoids exposing the rough part of the implant surface to the oral environment, which could risk formation of a bacterial biofilm and infection of the peri-implant tissues. The goal of treatment is also to ensure that the buccal and lingual bone walls are at least 1.5 mm in thickness. In esthetic areas, it is recommended that the facial bone wall be at least 2 mm thick to ensure proper support and stability of the overlying soft tissues. GBR allows clinicians to successfully place implants into resorbed alveolar bone that may not meet these specifications. The following slides will outline development of the GBR technique and materials.

With the biological principles of guided bone regeneration well-established in experimental studies, clinical studies soon followed in the early 1990s. These studies confirmed that the principles of guided bone regeneration could be successfully applied in patients requiring dental implant therapy. In this clinical case from 1991, the patient was missing the molar and premolar teeth on one side of the maxilla. Two one-piece implants were placed in the positions of the first and second premolars. The implant in the first premolar site was not fully covered by bone on the buccal aspect, where a dehiscence defect was present. Drill holes were created through the cortical bone into the marrow space around the defect. This was done to increase the potential for growth of new blood vessels and bone regenerating cells from the bone marrow. Autogenous bone chips, harvested from the retromolar area on the same side, were grafted over the defect and the drill holes. A nonresorbable ePTFE membrane was trimmed and adapted over the defect and graft. Two holes cut through the membrane allowed it to be secured around the necks of the implants.

After 6 months, the implants remained fully submerged beneath the mucosa. Surgical reopening confirmed regeneration of bone in the area of the previous defect on the buccal aspect of the implant in the first premolar site. These implants were subsequently restored with a splinted fixed dental prosthesis. In 2006,15 years later, the peri-implant tissues were healthy, and a radiograph confirmed the stable bone conditions.

For guided bone regeneration to be clinically successful, the barrier membranes are a key component, and ideally they should fulfill certain criteria. The materials should be biocompatible and well-tolerated by the body's tissues. They should be free of risks or safety concerns for the patient. In this context, there are two types of membranes - those that are inert and do not break down in the body's tissues, and those that are resorbable. Resorbable materials have a greater potential to cause tissue reactions due to the release of breakdown products into the body's tissues. The material should be cell occlusive, that is, able to exclude connective tissue cells from migrating into the defect into which bone regeneration is intended. A certain amount of permeability, however, is thought to be beneficial, as this may facilitate nutrient transfer across the barrier membrane and thus be important for bone regeneration. The membrane should allow some ingrowth and bonding of the connective tissue to its surface during healing. This provides greater stability and mechanical support of the wound during the healing period. The material should be able to create and maintain space in the region of the bone defect into which the initial blood clot will form. If the membrane collapses into the defect, the loss of space will decrease the volume of bone regenerated. The stiffness of the material is therefore an important factor. Lastly, the material should be easy to handle clinically. It should be readily trimmed to the correct shape and easily adapted to the surgical site.

The first membrane to be developed for clinical use was made from expanded polytetrafluoroethylene, or ePTFE. It became evident that there were three main problems with ePTFE. First, these membranes lacked rigidity and tended to collapse into bone defects, particularly if these defects were large. The second problem was that the material was difficult to handle clinically. Due to its hydrophobic nature, ePTFE does not easily adapt to the bone around a defect. The edges lift easily, requiring bone screws or tacks to fixate it. Care must also be taken to keep these membranes at a distance of at least 1.5 millimeters from the adjacent teeth involved in the surgical flap. This prevents bacterial plaque from colonizing the membrane through the gingival crevice during the wound healing stage. ePTFE membranes were also associated with a high incidence of wound dehiscence and premature membrane exposure. This was a significant complication, as premature membrane exposure often resulted in an accumulation of plaque and infection of the surrounding soft tissues. The consequence was that premature membrane exposure was almost always associated with a reduced amount of bone regeneration around the implants, which resulted in a compromised outcome. These membranes were also nonresorbable, and a second surgical procedure was required for their removal. The need for a second surgery was a disadvantage to patients, and it prolonged the total treatment time due to the additional phase of soft tissue healing.

Over time, other nonresorbable membranes have been developed, including high-density PTFE membranes and titanium-reinforced PTFE membranes. However, these membranes presented the same problems of premature membrane exposure, difficulty in clinical handling, and need for a second procedure to remove them. Membranes made of PTFE are commercially available but are not as widely used as in the past.

The clinical difficulties associated with nonresorbable ePTFE membranes led to the research and development of resorbable membranes. There are two main types of materials in current use - polymeric membranes and collagen membranes. Polymeric membranes are made of the synthetic polyesters polyglycolide or polylactide, or copolymers of these two materials. They can be produced in strictly controlled conditions and in large quantities. Within the tissues of the body, they completely biodegrade via the Krebs cycle to produce carbon dioxide and water. The main disadvantage of these membranes is that their biodegradation is associated with the presence of multinucleated giant cells and an inflammatory reaction in the soft tissues.

Today, most of the collagen membranes for use with guided bone regeneration are made of type I collagen or from a combination of type I and type III collagen. The collagen is derived from animal sources, mainly bovine or porcine material. Collagen membranes biodegrade rapidly through the enzymatic actions of macrophages and polymorphonuclear leukocytes. To reduce the rate of biodegradation and to prolong their barrier function, some manufacturers cross-link the collagen. Cross-linking with glutaraldehyde is the most widely used method, but there is a risk of residual cytotoxic residue in the membrane after the manufacturing process.

The main advantage of the resorbable membranes is that they are less susceptible to complications. If premature membrane exposure occurs, secondary soft tissue healing takes place within 4 weeks, and the bone regenerative outcome remains favorable. Collagen membranes are also simpler to handle clinically and adapt well to the surgical site once they are wetted with blood or saline. Significantly, the membranes do not need to be removed via a second surgical procedure because they biodegrade. The main disadvantage is that non-cross-linked collagen membranes collapse easily because they do not have space-maintaining properties.

The next clinical issue was the problem of collapse of the barrier membrane. In larger defects, barrier membranes made from either resorbable or nonresorbable materials tend to collapse into the defect because they are not rigid. Several methods have been introduced to reduce this tendency and to prevent membrane collapse. The most common method is to incorporate a bone graft or bone substitute under the barrier membrane. The graft occupies the space within the defect, supports the membrane, and prevents it from collapsing. Autologous bone grafts have a high osteogenic potential, but they tend to resorb and lose volume over time. Bone substitutes or bone fillers with lower substitution rates are better at maintaining volume but have less osteogenic potential.

At this time, there is no ideal bone grafting material. Composite grafts of autogenous bone and bone fillers such as deproteinized bovine bone mineral are now commonly used. These composite grafts retain the osteogenic potential of autogenous bone in combination with the lower substitution rate of bone fillers for volume maintenance.

Development of the GBR Technique, Key Learning Points: PTFE membranes have lost their dominance because of problematic handling, soft tissue dehiscences, and the need for membrane removal. Resorbable membranes are most prevalent in clinical practice, particularly those made of collagen. Membrane support is predominantly provided by grafting materials, either autogenous bone, bone substitutes, or a combination of the two. The use of biodegradable collagen membranes, bone grafts and substitutes has simplified the GBR technique. There is no longer a need for fixation of the membrane. Support for the membrane is provided by bone grafts and bone substitutes. The use of resorbable membranes reduces the risk of premature membrane exposure, and if it does occur, spontaneous healing of the soft tissue is predictable. As the membrane does not need to be removed, a second surgical procedure is no longer required.

This Learning Objective will examine various clinical situations in which the GBR technique can be used to ensure that implants will be completely embedded in bone. First, the GBR procedure is a reliable means for augmenting bone when an apical fenestration occurs. This defect is often encountered when an implant is placed in a prosthodontically determined position in which the thickness of bone is insufficient in the apical region. A part of the implant is exposed, but the coronal part of the bone is intact, with the neck area of the implant covered by bone. These defects can usually be treated simultaneously with the placement of the implant with good predictability. This case illustrates the management of a fenestration defect at an implant replacing the upper right canine. Following flap reflection and preparation of the osteotomy, the implant was inserted with good stability, but a fenestration defect occurred along the body of the implant. After creating drill holes through the cortical bone to promote new blood vessel formation and bone cell migration, autogenous bone chips were placed over the exposed surfaces of the implant, followed by a layer of particulate bovine bone mineral. A resorbable collagen membrane was then adapted over the graft. A clinical image and radiograph show the 10-year outcome with an esthetic emergence profile and stable crestal bone height.

Guided bone regeneration is also used to address crestal bone defects that are commonly seen when implants are placed into healing extraction sites. If the morphology of the crestal defect is favorable, GBR can be performed simultaneously with implant placement. The deciding factor as to whether peri-implant defects are favorable or unfavorable for simultaneous bone augmentation is the number of bone walls present at the defect. If the peri-implant defect has two or three intact bone walls, the conditions are favorable for simultaneous bone augmentation. In these diagrams, the bone walls are identified by the arrows. Two- and three-wall defects are usually found in fresh or healing extraction sockets. Some clinicians refer to these defects as being contained or lying within the envelope of the alveolar bone. Two- and three-wall bone defects can be grafted with particulate bone and/or bone substitutes with the greatest predictability for success.

On the other hand, if the defect has only one or no bone walls, the defect is considered to be unfavorable for simultaneous bone augmentation. These types of defects are commonly encountered in long-standing healed extraction sites. A staged approach should be adopted in this situation, which usually involves augmentation of the bone with autogenous block bone grafts supplemented by particulate grafting material.

This clinical case demonstrates simultaneous GBR and implant placement in the presence of a three-wall defect at the upper left central incisor site. After the implant was placed in the correct three-dimensional position, part of the facial surface of the implant was exposed, but the implant had primary stability and was surrounded by three bone walls. The exposed implant surface was covered by autogenous bone chips harvested from the vicinity of the surgical site. Slow-resorbing bone substitute particles were placed on top of the autogenous bone. The graft was then covered by a resorbable barrier membrane, followed by primary closure of the soft tissue with tension-free suturing. Six years after this procedure, the mucosal level and contours mimic the contralateral tooth, and a sagittal view of 3D follow-up imaging shows adequate bone thickness and height on the grafted facial aspect of the implant.

Early implant placement following 4 to 8 weeks of soft tissue healing is commonly performed as an alternative to immediate implant placement. However, this often results in a crater-like bone defect on the the facial aspect of the implant in anterior sites due to resorption of the bundle bone that comprises most of the thin facial bony ridge. A GBR procedure termed "contour augmentation" can be used to compensate for this ridge alteration at the time of implant placement. In contour augmentation, the facial bone wall is deliberately over-augmented using the GBR technique to create the preconditions for a stable, esthetic result. Over-augmentation also mimics the root eminence of a natural tooth. A clinical study has shown that contour augmentation is an effective technique to establish and maintain a facial bone wall in the long term.

When teeth are planned for extraction, it is important to assess the socket morphology and particularly the facial bone wall status. When the facial wall is missing due to trauma or infection, or in the presence of a large bone defect, as shown on the radiographic image of an upper left central incisor, bone augmentation is imperative. In this situation, tooth extraction combined with ridge preservation using the GBR technique is recommended. Ridge preservation can be done at the time of extraction, or in case of infection, it can be done several weeks after extraction once the infection has resolved. It is important to note that implants should not be placed when it is anticipated that the residual ridge morphology or a large bone defect will prevent attainment of primary stability for an implant placed in the prosthodontically determined position.

GBR is also indicated for augmentation of long-standing healed extraction sites where a staged approach is appropriate. These bone defects are typically one-wall or no-wall defects that do not provide the protection and stability of the graft needed for simultaneous grafting and implant placement. In this clinical case, a corticocancellous block of bone was fixated at the site of the defect, and then a particulate bone graft was layered superficially over and around the bone block to achieve the desired ridge contour. Stabilization of the graft with a screw, placement of a barrier membrane, and tension-free primary closure of the surgical flaps are fundamental to the success of staged bone augmentation. After 4 to 6 months of healing the block bone and particulate grafts should be sufficiently incorporated, at which time the fixation screw can be removed and the implants placed.

When bone height and width is insufficient for implant placement in the posterior maxilla, GBR in conjunction with sinus floor elevation is indicated. Sinus floor elevation, or SFE, is an augmentation procedure for the placement of implants in the posterior maxilla where pneumatization of the maxillary sinus and/or vertical loss of alveolar bone has occurred. This combined GBR/SFE procedure can be performed either simultaneously with implant placement, or as a staged procedure. In this clinical case, the patient presented for replacement of the maxillary right second premolar and first molar. Radiographic and clinical examination revealed vertical bone loss as well as buccal flattening of the alveolar crest at the first molar site. Cone beam computed tomography confirmed the vertical and horizontal alveolar deficiency; however, there was sufficient bone for simultaneous augmentation and implant placement.

The agreed-upon treatment plan was implant placement with simultaneous GBR and augmentation of the maxillary sinus using a lateral window technique. After complete removal of bone in the lateral wall of the sinus, the sinus membrane was elevated. The next step was preparation of the implant osteotomies. Then, a composite graft of autologous bone chips and bone substitute was introduced into the prepared sinus cavity, followed by insertion of the implants. The implant at the second premolar site exhibited a fenestration defect. The apical fenestration was covered with autologous bone chips, and then the surgical site was covered with a second layer of particulate bone substitute for contour augmentation. A periapical radiograph confirmed adequate elevation of the sinus floor.

A final indication for the GBR procedure is preservation of the alveolar ridge following removal of an implant. Reasons for implant removal vary but can include malpositioning, implant fracture, and recurrent peri-implantitis leading to progressive bone loss. Preservation and/or augmentation of the residual bone surrounding a failed or fractured implant will facilitate replacement of the implant as well as making it a more predictable procedure. The GBR technique can be used in a simultaneous procedure in which the failed implant is removed, a new implant is inserted in the correct three-dimensional position, and GBR is used for contour augmentation.

Indications for GBR, Key Learning Points: Defects that can be treated simultaneously with implant placement using guided bone regeneration include apical fenestrations, two- or three-wall crestal defects, and contour augmentation. Clinical situations that are not favorable for simultaneous bone augmentation and which should be treated with a staged GBR approach include one- or no-wall crestal defects, long-standing healed extraction sites, and post-extraction sites in need of ridge preservation. The GBR technique can be applied in either a simultaneous or staged manner depending on clinical circumstances in conjunction with sinus floor elevation and implant removal.

Principles of Guided Bone Regeneration, Module Summary: GBR is based on the principle of promoting bone regeneration within a defect by excluding nonosteogenic cells with a barrier membrane. GBR is most predictable in 2- and 3-wall defects, which provide clot protection and serve as a source of osteogenic and angiogenic cells. In the most common technique, a resorbable collagen membrane is supported by autogenous bone and/or bone substitutes. Advantages of this technique include a low risk of premature membrane exposure, predictable soft tissue healing, and fewer surgical interventions. The use of a simultaneous vs. staged technique depends on the clinical circumstances and bone defect morphology.