Guided Bone Regeneration in Periodontics and Implantology: A Review
Abstract:The main goal of periodontal therapy is Infection management. All treatment modalities are highly influenced by a deep and advanced understanding of the diverse pathogenic microflora and the host immune response. They are aimed at controlling the periodontal infection thereby arresting further progression of disease but the anatomic changes that have already occurred like bone loss and angular defects needs correction. Guided bone regeneration (GBR) was introduced as a therapeutic modality aiming to achieve bone regeneration. As a main hindrance for successful bone healing and creation of new bone is the rapid formation of soft connective tissue and Ingrowths of soft tissue which disturbs or totally prevent osteogenesis in a defect or wound area, it is not surprising that newer methods are constantly being reviewed by the dental profession to improve upon and make bone regeneration safer and more predictably successful. Guided bone regeneration (GBR) is a technique of bone regeneration that basically evolved from guided tissue regeneration (GTR), a procedure performed for the regeneration of lost periodontium. GBR is for the regeneration of supporting bone. In GTR, the membrane is exposed and a closed wound is hard to achieve because GTR is applied to the teeth but in GBR, the wound can be completely covered. Because of less membrane exposure, the chance of infection is decreased making bone regeneration highly predictable. The possible indications for guided bone regeneration technique include bony defects, implants placed in extraction sockets, dehiscence, ridge augmentation & sinus lift procedures.
Key words: Guided Bone Regeneration, Implants, Bone grafts, Membranes.
Guided bone regeneration (GBR) was introduced as a treatment modality targeting to achieve bone regeneration through the practice of barrier membranes (Dahlin et al. 1988). The concept of crafting a isolated anatomic site with the aim to promote healing was first introduced 50 years ago.1 Guided bone regeneration (GBR) is a technique of bone regeneration that evolved from guided tissue regeneration (GTR) which is a procedure performed for the regeneration of lost periodontium. In GBR, the wound can be entirely enclosed. Because of reduced membrane exposure, the chance of infection is decreased resulting in decidedly predictable bone regeneration.
Dehiscence, fenestrations, or other peri-implant defects could be considered common problems when optimal restorative results are sought under less than ideal anatomical situations. The main concern of periodontists in treating these lesions is complete bone healing.2 A main deterrent for effective bone healing and formation of new bone is the swift creation of soft connective tissue. The osteogenesis in a defect or a wound area may be interrupted or entirely inhibited by the Ingrowths of soft tissue.3 Hence it is not surprising that newer methods are constantly being reviewed by the dental profession to improve upon and make bone regeneration safer and more predictably successful. Several techniques to regenerate bone through surgical intervention have been proposed which include grafts, barrier membranes, or even the combination of both. The possible indications for guided bone regeneration technique include periodontal bony defects, augmentation around implants placed in immediate & delayed extraction sockets, dehiscence defects around implants, ridge augmentation & sinus lift procedures.
It is an important concept that has enhanced understanding the basis of periodontal regeneration. It is a form of hypothesis that says the cell type which repopulates the root surface will determine the mode of repair or attachment that takes place. If it is mesenchymal cells from the PDL, regeneration occurs. If epithelial cells flourish along the root surface, a long junctional epithelium will result. If gingival connective tissue inhabits the root surface, a connective tissue attachment will result and root resorption may occur. If bone cells drift and adhere to the root surface, root resorption and ankylosis ensues. 1 (fig 1)
The ‘Osteopromotion principle’1 describes the technique of physically placing a barrier over sites of osseous deformities where insufficient vertical, buccal and/or lingual bone volume is present. This isolates the site from the neighbouring soft tissues, which are known to hamper with osteogenesis or the formation of new bone. The use of this term is appropriate to the jargon that describes bone forming mechanisms, such as osteoinduction, osteoconduction, osteogenesis, and osseointegration.
The comprehensive osteogenesis is augmented by the usage of the barrier membrane which precludes the rapid ingrowth of fibroblasts into a bony defect and stimulating the movement of osteogenic cells from the adjacent bony edges or bone marrow into the deficiency in an unhindered way. Continual osteogenesis can be brought about by keeping the barrier membrane in place and sealing off the bony defect which allows maturation of the newly formed bone.
Tenets of GBR:
To accomplish superior clinical results, the GBR membrane must have these properties:1
Cell exclusion: To inhibit epithelial cells and/or gingival fibroblasts from getting access to the wound site.
Tenting: The membrane is snugly fitted and fixed such that it prolongs 2 to 3 mm further than the borders of the defect in all directions. To prevent inadvertent flap perforation, the corners are rounded off.
Scaffolding: A fibrin clot occupies the tented space in the beginning, which functions as a framework for the in-growth of progenitor cells. The neighbouring bone or bone marrow contributes the cells in GBR
Stabilization: During healing, the membrane should shield the clot from being troubled by flap movement which lies above. It is often secured into its place with sutures, mini bone screws, bone tacks or simply pushed underneath the margins of the flaps at the phase of closure.
Framework: The membrane must be sustained to avert breakdown in case of non-space preserving defects like dehiscences or fenestrations. Bone-replacement grafts assists as an inner structure to offer a degree of support to the graft. Firmer membranes like titanium-reinforced membranes can be used for this.
Aspects influencing effective regeneration:
For successful outcomes with guided bone regeneration, following factors should be considered:1
1. Patient factors: Factors such as behavioral and psychological problems, systemic complications, plaque-control effectiveness, smoking, stress, and noncompliance with instructions may have negative impact on treatment outcomes. These factors should be controlled as the probability of the treatment success gets reduced.
2. Defect anatomy: Defects that are not space making will most likely require the use of bone grafting materials. The chances of infection & complications will increase in such cases.
3. Presurgical factors: Factors include effective plaque control and patients, compliance to treatment, proper chemotherapeutic agents, surgical and prosthetic treatment planning and infection control with antibiotics.
4. Surgical factors: Infection control to maintain a sterile environment, adequate membrane adaptation and fixation to ensure wound stability, proper implant placement, and space maintenance are all important considerations for a successful regenerative outcome.
5. Post surgical factors: Careful post-operative patient care and monitoring is critical for success with GBR. Infection or plaque control may necessitate the use of chemotherapeutic rinses.
Bone grafts & substitutes
Determining the grafting material to be used is based on the objective of the surgical procedures. If the objective is to have filler for the osseous defect, any graft material may be used. However, if the objective is to restore the grafted site to obtain a living bone as the result, the type of grafting material must be considered4. The osteoinductive materials are the only grafting materials of choice for regenerating bone at the deficient site. The replacement of the graft material at the grafted site by the host is either cell mediated or solution mediated. In either case, real living bone is to be result in the defect.
From purely a bone growth perspective, autogenous bone remains the best material because of its osteogenic properties. However, it has its disadvantages and it is not indicated in every situation. Xenografts, allografts, and potentially alloplasts also have their appropriate place in dental applications.5 The mode of action is one of three phenomena:
Osteoconduction is defined as an implantable matrix that provides channels for bone growth at the interface. There is no osteogenic capability of these grafting materials. Therefore, those materials which provide simply a framework or scaffold effect for the host bone-forming cells to infiltrate, proliferate and form new bone, are known as osteoconductive. Examples include calcium phosphate, polymers, silica, calcium sulfate, and others.
Osteoinduction is defined as an implantable matrix that provides natural stimulation of bone formation throughout the implantable material, not just at the interface. The objective of this material is to be replaced by new bone from the host. Examples include autogenous bone graft from the host, freeze-dried bone and various bone morphogenic proteins (BMP) that are either synthetic or nonsynthetic.
Osteotrophic is defined as an implantable matrix that provides improvement of bone formation by its chemical or structural characteristics in the presence of osteogenic precursor cells. An example of osteotrophic material is a natural bovine-derived hydroxyapatite (HA).
Bone grafting material is generally classified as autografts, allografts, xenografts or alloplasts.5
1. Autografts: Autografts transplants are those taken from one region and placed in another region in the same individual. Autografts are known as the “gold standard” because of the absence of antigenicity of the graft .
2. Allografts: Transplants from one individual to a genetically nonidentical individual of the same species are known as allografts. The success of these grafts is well documented.
3. Xenografts: Transplants from one species to another are known as xenografts. Animal bone, most commonly bovine, is specially processed to make it biocompatible and sterile. The graft material acts as filler, which, in time, the body replaces with host bone.
Alloplasts: Transplants are a synthetic, chemically derived bone substitute, composed of calcium phosphate. This may be absorbable or nonabsorbable.
Membranes for guided bone regeneration
The ideal requirements of the membrane for guided bone regeneration can be stated as: 3 Biocompatible.
Various membrane materials have been used by many clinicians for effective bone regeneration with varying results. The membranes may be also classified by its origin as, 5 Autograft – Subepithelial or connective tissue graft
Many studies on bone regeneration using membranes have been reported. Studies by Dahlin et al6, Becker et al7 and Lazzara et al8, Zitzmann et al, Micheal McGinnis et al and Lillian Carpio et al showed better bone regeneration with e-PTFE barrier membrane.
As far as various other materials are concerned, Ou & Bao concluded that PHB membrane can enhance bone formation and can be used for GBR.9 In another study by Michael Peleg et al, lyophilized human dura matter was used as a resorbable barrier to promote bone formation.10Novaes and Souza have reported that acellular dermal matrix graft can be used as resorbable membrane for promoting bone formation.11
Guided bone regeneration in implant therapy:
GBR in implant treatment is particularly suitable for fixture positioning in patients having dehiscence or fenestration defects. The place and path of fixture positioning is limited in knife-edge alveolar crests or in alveolar ridges with discernible facial/buccal depressions. Enhancement of alveolar ridge can be done with GBR. Fixture placement in extraction sockets was once thought to be unpredictable because it is hard to attain consistent primary stabilization and to locate the fixture neck correctly beside the bone. GBR conserves the altitude of the alveolar bone reduced during the healing of an extraction socket, thereby escalating the certainty of bone regeneration.12 Alveolar ridge augmentation using GBR enables the fixture to be appropriately positioned in depth and direction, widening the scope of implant indications and making functional and esthetic results possible.
There are two methods to use GBR in implant treatment: 12
Simultaneous approach – Fixture placement and GBR are executed simultaneously to generate more bone adjoining the fixture.
Indications of the simultaneous approach:
Dehiscence or fenestration defects resulting because of collapse in the facial or buccal surface in the anterior teeth extraction sockets.
If greater than 5mm of fixture surface is uncovered through fenestration or dehiscence defects and if greater than one wall is lost around the fixture. 12
When the alveolar process shows marked resorption.
If the bone is thin around the fixture.
Staged approach – Here, GBR is employed to improve the alveolar ridge or restore ridge morphology before fixture placement. The fixture is positioned subsequent to healing.
Indications for staged approach: 13
Insufficient vertical and buccolingual bone for fixture placement and stabilization.
Bone resorption extending to one third of the root apex of the extracted tooth due to a severe osseous defect.
a large and flat osseous defect with insufficient bone width (less than 5.0mm) such that fixture placement cannot be achieved in the proper prosthetic position and angle.
Maxillary anterior ridge morphology leading to an unpredictable esthetic result after fixture placement.
Gingival recession along with severe loss of facial bone plate.
Severe circumferential osseous defect and vertical osseous defect.
When simultaneous fixture placement with barrier membrane is difficult due to a large osseous defect around the fixture.
Guided bone regeneration in immediate extraction socket
With the recent concepts of GBR, it has been proved that bone promotion can be done around implants placed in immediate extraction sockets also. Lazzara first discussed the concept of placing implants into immediate extraction sockets and augmenting these sites with e-PTFE barrier membranes.8 The principal reason for using this procedure is to preserve the alveolar ridge width and height, thereby preserving the maximum amount of bone for implant placement. Secondary reasons are the potential decreased restorative interval between tooth removal and implant restoration. (Fig 2)
Dental conditions such as root fractures, failed endodontic therapy, and advanced periodontal disease.
Teeth with unrestorable carious lesions or poor crown-to-root ratios.
Considering esthetic limitations and attaining primary stability, the premolar region is the best position for the immediate implant. Adequate bone surrounding the extraction socket makes primary stability probable, facilitating fixture placement straightaway after extraction.8
Areas of insufficient depth due to proximity of the maxillary sinus or inferior alveolar canal.
Bottom of the extraction socket or width of the extraction socket is less than 4-5mm, or the site depth is not more than 10 mm.
Others include areas of periodontal disease with acute inflammation or where complete curettage of the extraction socket is not possible.12
Guided bone regeneration in dehiscence defects and delayed extraction sockets
Fenestrations and dehiscence defects can be treated with a barrier alone but rely on the stiffness of the material to maintain the space in naturally space making defects. Currently, indications for membrane placement to ensure a highly predictable outcome should therefore be restricted to moderate defects such as superficial dehiscence defects, fenestration defects, and extraction sockets. If a larger defect is present, the addition of a bone graft is recommended.14 Preoperative diagnosis is necessary to predict these compromised sites and to evaluate presurgically whether they are suitable for simultaneous placement of an implant and a barrier membrane. Appropriate diagnostic procedures include intraoral bone mapping and radiographic techniques, and cross-sectional views of the jaw bone by CT scan.
GBR in dehiscence defects:
If the implant is placed in an optimal position for an esthetic and functional restoration, a dehiscence or fenestration defect can be expected. This exposed implant surface can be treated by utilizing the guided bone regeneration (GBR) technique, either in conjunction with implant placement (simultaneous approach) or as a ridge augmentation procedure before implant placement (staged approach).
GBR in delayed extraction sockets:
Maxillary and mandibular premolars, canines, and incisors are ideal candidates for extraction and immediate implant placement when severe periodontal breakdown, root fractures, or endodontic failures are evident. There are four prerequisites: 3 After tooth extraction, the socket must present sufficient residual walls.
The extraction socket must be free of pathosis.
The available soft tissue should allow primary closure.
Apical to the apex of the socket, an adequate volume of healthy jawbone must be available to assure good initial stabilization of the implant.
In delayed extraction socket treatment, after all the diagnostic procedures are carefully evaluated, the tooth is planned for extraction. The tooth is extracted atraumatically, while preserving the surrounding bone walls. The socket is debrided of granulation tissue with curettes and excavators. The flaps are released and soft tissue closure is achieved with horizontal mattress and interrupted sutures.
In situations where extraction socket is unsuitable to place an implant, the original protocol of a 6- to12-month healing period is followed to allow complete ossification of the socket or a staged approach utilizing the GBR technique for localized ridge augmentation is recommended.
When complete coverage has occurred, the flap is raised as mentioned earlier and soft tissue that is present in the coronal half of the socket should be removed. The implant is then placed at least 3 to 4mm beyond the original apex of the socket to ensure stability. Bleeding from the bone preparation should allow the formation of a clot in the space between the exposed implant surface and the socket walls. The area is then covered with membrane and stabilized to prevent any ingrowth of gingival connective tissue. The flap management and suturing technique will allow primary flap closure and further procedures are the same as described for dehisced implant sites.
Localized ridge augmentation using guided bone regeneration:
Guided bone regeneration is used to facilitate vertical and horizontal bone regeneration in the damaged alveolar ridge in order to achieve adequate edentulous ridge morphology either for esthetic and functional purposes or for subsequent implant placement. This staged approach is predictable and appears to be better than extracting the tooth and concurrently inserting the implant or to extracting the tooth and not doing a ridge enhancement method.
Horizontal ridge augmentation:
Horizontal ridge augmentation is necessary when the presurgical evaluation reveals that the width of the alveolar ridge is insufficient for adequate implant placement.
Two different applications of GBR are possible: 15
a) Simultaneous approach, utilizing membranes to regenerate the bone defect (dehiscence or fenestrations) around an inserted implant.
b) Staged approach, utilizing membranes for localized ridge augmentation and subsequent implant placement into the newly regenerated alveolar ridge in a second surgical procedure.
Vertical ridge augmentation:
This is done when the bone height is inadequate for long term implant stability, or when prosthetic rehabilitation will cause disproportionately long crowns and an unfavorable implant/crown ratio.
Sinus floor elevation or sinus lifts procedure:
Sinus floor elevation or sinus lift procedure as it was called by the inventor; Dr. H. Tatum is a surgical procedure which is meant to increase the vertical bone dimensions in the lateral maxilla to make implant surgery possible. The principle of this operation is the internal augmentation of the maxillary sinus bottom.15
Insufficient bone height in edentulous lateral maxilla where dental implants are required for oral rehabilitation and alternative solutions are not possible. The suprastructures can be total fixed bridges and overdentures on implants, partial fixed bridges, and solitary crowns.15
Former sequelae sinus surgery (like Caldwell Luc operations).
Minimally invasive GBR
Conventional GBR procedures may still be associated with excessive tension on the suture lines, which often results in suture line opening and early membrane exposure and hence, infection. Complete tension-free primary closure is a key point to prevent such complications.16
A new technique called ‘Minimally Invasive GBR’ uses nonconventional incision lines, along with balloon-assisted elevation of the periosteum. It is a “tunneling” technique that allows performing GBR by creating a relatively small vertical incision, as opposed to traditional horizontal incisions. This technique is particularly suggested for partially or completely edentulous mouth with insufficient localized jaw bone volume so as to receive dental implants. Usually, no adverse events such as membrane exposure, tissue dehiscence, infection or implant failure occurs. Primary closure without tension on the suture line is easily accomplished. Suture line opening and early membrane exposure has not been observed with this technique and no apparent limitations or shortcomings of this method have been reported.
The role of growth factors in bone augmentation
Another adjunct to regenerative therapy is osteogenic stimulating substrates to enhance bone formation. One group is the bone morphogenetic proteins (BMPs), belonging to the transforming growth factor (TGF-) superfamily. Of this family, recombinant human bone morphogenetic protein (rhBMP-2) has shown significant signs of bone-enhancing potential. Recently, studies showed substantial preclinical data of rapid new bone formation using rhBMP-2 in critical size defects. The surgical placement of recombinant human bone morphogenetic protein –2 (rhBMP-2) in peri-implantitis defects and the subsequent bone formation and reosseointegration was evaluated by Hanish et al. The results showed that rhBMP-2 has the potential to encourage bone creation and osseointegration in advanced peri-implantitis defects.17 Similar results were also proved by Sykaras et al and David Cochran et al.
Becker et al evaluated bone promotion around implants inserted into fresh sockets with large buccal dehiscences treated with e-PFTE membranes alone or in combination with cortical DFDBA or with the combination of platelet-derived growth factor –BB and insulin-like growth factor-1 (PDGF/IGF-1). After 18 weeks, a significant gain in clinical bone levels was present in both the e-PTFE membrane alone group and PTFE and PDGF/IGF-1 group, but not in the PTFE and DFDBA group.18
Nociti et al also demonstrated a greater extension of bone-to-implant contact, a larger percentage of bone area and greater intensity of bone labeling for immediate implants partially in contact with bone and treated with PDGF and IGF-1 when compared to controls.19 New approaches to enhance the vitality of bone grafts has been introduced by using platelet-rich plasma (PRP).
A new approach to stimulate periodontal regeneration has employed enamel matrix proteins. A heterogenous mixture of proteins containing amelogenins as a major constituent has been shown to stimulate the creation of acellular cementum and collagenous fibers. Studies by Marcio Casati et al have shown positive outcomes in bone healing and regeneration with enamel matrix proteins.20
The dental profession has entered into a new era with respect to bone preservation and reconstruction. However, the technique and materials of the future are still on the “drawing board”. The future will be determined by a joint effort of all disciplines. The communication among clinicians and researchers must be maintained to provide the best possible care to patients.
With the present day techniques, it is possible to regenerate the osseous tissue predictably when the principles and concepts of guided bone regeneration are followed properly. Guided bone regeneration (GBR) has become an important tool in a periodontist’s armamentarium to deliver the desired result. The predictability of this procedure have been proved and established through various experimental and clinical studies. Diagnosis, treatment planning, careful execution of the surgical treatment, post-operative follow-up and appropriate surgical technique selection are all important factors in achieving success.
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Fig 1: Diagram showing the various cells of periodontium -1) gingival epithelium 2) alveolar bone 3) gingival connective tissue cells and 4) periodontal ligament cells which can influence the periodontal regeneration (Melcher, 1976)
Fig 2: Diagram showing the procedure of GBR in immediate extraction socket.