Resective Bone Surgery and Guided Tissue Regeneration PDF

NEAR EAST UNİVERSİTY FACULTY OF DEPARTMENT OF PERIODONTOLOGY RESECTİVE OSSEOUS SURGERY- PERİODONTAL REGENERATİON AND RECONSTRUCTİVE SURGERY Learning Outcomes: 1-Will be able to define resective bone surgery. 2- Will be able to list the indications and principles of resective bone surgery. 3- Will be able to list types of resective bone surgery. 4- Will be able to describe the treatment of furcation defects. 5- Will be able to list factors affecting success in the treatment of bone defects. 6-Will be able to list types of wound healing after periodontal treatment. 7- Will be able to list factors influencing the success of regenerative techniques. 8- Will be able to list methods used in regenerative treatment. 9- Will be able to classify bone graft materials. 10- Will be able to define guided tissue regeneration (GTR) technique. 11-Will be able to list materials used in GTR. The damage resulting from periodontal disease manifests in variable destruction of the tooth- supporting bone. Generally, bony deformities are not uniform; they are not indicative of the alveolar housing of the tooth before the disease process and do not relect the overlying gingival architecture. Bone loss has been classiied as either “horizontal” or “vertical,” but in fact, bone loss is most often a combination of horizontal and vertical loss. Horizontal bone loss generally results in a relative thickening of the marginal alveolar bone because bone tapers as it approaches its most coronal margin. The effects of this thickening and the development of vertical defects leave the alveolar bone with countless combinations of bony shapes. If these various topographic changes are to be altered to provide a more physiologic bone pattern, a method for osseous recontouring must be followed. Osseous surgery may be deined as the procedure by which changes in the alveolar bone can be accomplished to rid it of deformities induced by the periodontal disease process or other related factors such as exostosis and tooth supraeruption. Osseous surgery can be either additive or subtractive. Additiveosseous surgery includes procedures directed at restoring the alveolar bone to its original level, whereas subtractive osseous surgery is designed to restore the form of preexisting alveolar bone to the level present at the time of surgery or slightly more apical to this level. Additive osseous surgery brings about the ideal result of periodontal therapy; it implies regeneration of lost bone and reestablishment of the periodontal ligament, gingival ibers, and junctional epithelium at a more coronal level. Subtractive osseous surgery procedures provide an alternative to additive methods and should be used when additive procedures are not feasible. These subtractive procedures are discussed in this chapter. Selection of Treatment Technique The morphology of the osseous defect largely determines the treatment technique to be used. One-wall angular defects usually need to be recontoured surgically. Three-wall defects, particularly if they are narrow and deep, can be successfully treated with techniques that strive for new attachment and bone reconstruction. Two-wall angular defects can be treated with either method, depending on their depth, width, and general coniguration. Therefore, except for one-wall defects and wide, shallow two-wall defects, and interdental craters, osseous defects are treated with the objective of obtaining optimal repair by natural healing processes. Rationale Osseous resective surgery necessitates following a series of strict guidelines for proper contouring of alveolar bone and subsequent management of the overlying gingival soft tissues. The speciics of these techniques are discussed later in this chapter. The techniques discussed here for osseous resective surgery have limited applicability in deep intrabony or hemiseptal defects, which could be treated with a different surgical approach. Osseous surgery provides the purest and surest method for reducing pockets with bony discrepancies that are not overly vertical and also remains one of the principal periodontal modalities because of its long-term success and predictability. Osseous resective surgery is the most predictable pocket reduction technique. However, more than any other surgical technique, osseous resective surgery is performed at the expense of bony tissue and attachment level. Thus its value as a surgical approach is limited by the presence, quantity, and shape of the bony tissues and by the amount of attachment loss that is acceptable. The major rationale for osseous resective surgery is based on the tenet that discrepancies in level and shapes of the bone and gingiva predispose patients to the recurrence of pocket depth postsurgically. Although this concept is not universally accepted, and the procedure induces loss of radicular bone in the healing phase, recontouring of bone is the only logical treatment choice in some cases. The goal of osseous resective therapy is to reshape the marginal bone to resemble that of the alveolar process undamaged by periodontal disease. The technique is performed in combination with apically positioned laps, and the procedure eliminates periodontal pocket depth and improves tissue contour to provide a more easily maintainable environment. The relative merits of pocket reduction procedures are discussed in; this chapter discusses the osseous resective technique and how and where it may be accomplished. Bone dictates the form of the gingiva and determines much of the residual pocket depth. It is proposed that the conversion of the periodontal pocket to a shallow gingival sulcus enhances the patient’s ability to remove plaque and oral debris from the dentition. Similarly, the ability of dental professionals to maintain the periodontium in a state free of gingivitis and periodontitis is more predictable in the presence of shallow sulci. The more effective the periodontal maintenance therapy, the greater is the longitudinal stability of the surgical result. The eficacy of osseous surgery therefore depends on its ability to affect pocket depth and to promote periodontal maintenance. Normal Alveolar Bone Morphology Knowledge of the morphology of the bony periodontium in a state of health is required to perform resective osseous surgery correctly. The characteristics of a normal bony form are as follows: 1. The interproximal bone is more coronal in position than the labial or lingual-palatal bone and pyramidal in form. 2. The form of the interdental bone is a function of the tooth form and the embrasure width. The more tapered the tooth, the more pyramidal is the bony form. The wider the embrasure, the more lattened is the interdental bone mesiodistally and buccolingually. 3. The position of the bony margin mimics the contours of the cementoenamel junction. The distance from the facial bony margin of the tooth to the interproximal bony crest is latter in the posterior than the anterior areas. This “scalloping” of the bone on the facial surfaces and lingual-palatal surfaces is related to tooth and root form, as well as tooth position within the alveolus. Teeth with prominent roots or those displaced to the facial or lingual side may also have fenestrations or dehiscences. The molar teeth have less scalloping and a latter proile than bicuspids and incisors. Although these general observations apply to all patients, the bony architecture may vary from patient to patient in the extent ofcontour, coniguration, and thickness. These variations may be both normal and healthy. Terminology Numerous terms have been developed to describe the topography of the alveolar housing, the procedure for its removal, and the resulting correction. These terms should be clearly deined. Procedures used to correct osseous defects have been classiied in two groups: osteoplasty and ostectomy. Osteoplasty refers to reshaping the bone without removing tooth-supporting bone. Ostectomy, or osteoectomy, includes the removal of tooth-supporting bone. One or both of these procedures may be necessary to produce the desired result. Terms that describe the bone form after reshaping can refer to morphologic features or to the thoroughness of the reshaping performed. Examples of morphologically descriptive terms include negative, positive, lat, and ideal. These terms all relate to a preconceived standard of ideal osseous form. Positive architecture and negative architecture refer to the relative position of interdental bone to radicular bone. The architecture is “positive” if the radicular bone is apical to the interdental bone. The bone has “negative” architecture if the interdental bone is more apical than the radicular bone. Flat architecture is the reduction of the interdental bone to the same height as the radicular bone. Osseous form is considered to be “ideal” when the bone is consistently more coronal on the interproximal surfaces than on the facial and lingual surfaces. The ideal form of the marginal bone has similar interdental height, with gradual, curved slopes between interdental peaks. Terms that relate to the thoroughness of the osseous reshaping techniques include “deinitive” and “compromise.” Deinitive osseous reshaping implies that further osseous reshaping would not improve the overall result. Compromise osseous reshaping indicates a bone pattern that cannot be improved without signiicant osseous removal that would be detrimental to the overall result. References to compromise and deinitive osseous architecture can be useful to the clinician, not as description of a morphologic feature, but as terms that express the expected therapeutic result. Factors in Selection of Resective Osseous Surgery The relationship between the depth and coniguration of the bony lesion or lesions with root morphology and the adjacent teeth determines the extent that bone and attachment are removed during resection. Bony lesions have been classiied according to their coniguration and number of bony walls. The technique of ostectomy is best applied to patients with early to moderate bone loss (2 to 3 mm) with moderate-length root trunks18 that have bony defects with one or two walls. These shallow to moderate bony defects can be effectively managed by osteoplasty and ostectomy. Patients with advanced attachment loss and deep intrabony defects are not candidates for resection to produce a positive contour. To simulate a normal architectural form, so much bone would have to be removed that the survival of the teeth could be compromised. Two-walled defects, or craters, occur at the expense of the interseptal bone. As a result, they have buccal and lingual or palatal walls that extend from one tooth to the adjacent tooth. The interdental loss of bone exposes the proximal aspects of both adjacent teeth The buccal-lingual interproximal contour that results is opposite to the contour of the cementoenamel junction of the teeth. Two-walled defects (craters) are the most common bony defects found in patients with periodontitis. If the facial and lingual plates of this bone are resected, the resultant interproximal contour would become more lattened or ovate. However, conining resection only to ledges and the interproximal lesion results in a facial and lingual bone form in which the interproximal bone is located more apically than the bone on the facial or lingual aspects of the tooth. This resulting anatomic form is reversed, or negative, architecture. Although the production of a reversed architecture minimizes the amount of ostectomy that is performed, it is not without consequences. Peaks of bone typically remain at the facial and lingualpalatal line angles of the teeth (widow’s peaks). During healing, the soft tissue tends to bridge the embrasure from the most coronal height of the bone on one tooth to the most coronal heights on the adjacent teeth. The result is therefore the tendency to replicate the attachment contour on the tooth. The interproximal soft tissues invest these peaks of bone, which may subsequently resorb with a tendency to rebound without gain in attachment over time. Interproximal pocket depth can recur. Ostectomy to a positive architecture requires the removal of the line–angle inconsistencies (widow’s peaks), as well as some of the facial, lingual, and palatal and interproximal bone. The result is a loss of some attachment on the facial and lingual root surfaces but a topography that more closely resembles normal bone form before disease. Proponents of osseous resection to create a positive contour believe that this architecture, devoid of angles and spines, is conducive to the formation of a more uniform and reduced soft tissue dimension postoperatively. The therapeutic results are less pocket depth the use of ostectomy variet depth and coniguration of the treated osseous defects. Osseous resection applied to two-wall intrabony defects (craters), the most common osseous defects, results in attachment loss at the proximal line angles and the facial and lingual aspects of the affected teeth without affecting the base of the pocket. The extent of attachment loss during resection to a positive architecture has been measured. When the technique is properly applied to appropriate patients, the mean reduction in attachment circumferentially around the tooth has been determined to be 0.6 mm at six probing sites. In practical terms, this means that the technique is best applied to interproximal lesions 1 to 3 mm deep in patients with moderate to long root trunks. Patients with deep, multiwalled defects are not candidates for resective osseous surgery. They are better treated with regenerative therapies or by combining osteoplasty to reduce bony ledges and to facilitate lap closure with new attachment and regeneration procedures. Osseous resective surgery should never compromise the prognosis of the tooth. Examination and Treatment Planning The potential for the use of resective osseous surgery is usually identiied during a comprehensive periodontal examination. Suitable patients display the signs and symptoms of periodontitis.The gingiva may be inlamed, and deposits of plaque, calculus, and oral debris may be present. An increased low of crevicular luid may be detected, and bleeding on probing and exudation are often observed. Periodontal probing and exploration are key aspects of the examination. Careful probing reveals the presence of (1) pocket depth greater than that of a normal gingival sulcus, (2) the location of the base of the pocket relative to the mucogingival junction and attachment level on adjacent teeth, (3) the number of bony walls, and (4) the presence of furcation defects. Transgingival probing, or sounding, using local anesthesia conirms the extent and coniguration of the intrabony component of the pocket and of furcation defects Routine dental radiographs do not identify the presence of periodontitis and do not accurately document the extent of bony defects. Radiographs cannot accurately document the number of bony walls and the presence or extent of bony lesions on the facialbuccal or lingual-palatal walls. Well-made radiographs provide useful information about the extent of interproximal bone loss, the presence of angular bone loss, caries, root trunk length, and root morphology. Films also facilitate the identiication of other dental pathoses that require treatment. In addition, a radiographic survey serves as a means of evaluating the success of therapy and documenting the patient’s longitudinal stability.Treatment planning should provide solutions for active periodontal diseases and correction of deformities that result from periodontitis. Methods of Resective Osseous Surgery The reshaping process is fundamentally an attempt to gradualize the bone suficiently to allow soft tissue structures to follow the contour of the bone. The soft tissue predictably attaches to the bone within certain speciic dimensions. The length and quality of connective tissue and junctional epithelium that reform in the surgical site depend on numerous factors, including the health of the tissue, condition and topography of the root surface, and proximity of the bone surrounding the tooth. Each of these factors must be controlled to the best of the clinician’s ability to obtain the optimal result, making osseous resective surgery an extremely precise technique. Reshaping of the bone may necessitate selective changes in gingival height. These changes must be calculated and accounted for in the initial lap design. For this reason, it is important for the clinician to know about the underlying bone tissue before flap relection. The clinician must gain as much indirect knowledge as possible from soft tissue palpation, radiographic assessment, and transgingival probing (sounding). Radiographic examination can reveal the existence of angular bone loss in the interdental spaces; these areas usually coincide with intrabony pockets. The radiograph does not show the number of bony walls of the defect or document with any accuracy the presence of angular cone defects on facial or lingual surfaces. Clinical examination and probing are used to determine the presence and depth of periodontal pockets on any surface of any tooth and can also provide a general sense of the bony topography, although intrabony pockets can go undetected by probing. Both clinical and radiographic examinations can indicate the presence of intrabony pockets when the clinicianinds (1) angular bone loss, (2) irregular bone loss, or (3) pockets of irregular depth in adjacent areas of the same tooth or adjacent teeth. The experienced clinician can use transgingival probing to predict many features of the underlying bony topography. The information thus obtained can change thetreatment plan. For example, an area that had been selected for osseous resective surgery may be found to have a narrow defect that was unnoticed in the initial probing and radiographic assessment and is ideal for augmentation procedures. Such indings can and do change the lap design, osseous procedure, and results expected from the surgical intervention. Transgingival probing is extremely useful just before lap relection. It is necessary to anesthetize the tissue locally before inserting the probe. The probe should be “walked” along the tissue–tooth interface so that the operator can feel the bony topography. The probe may also be passed horizontally through the tissue to provide three-dimensional information regarding bony contours (i.e., thickness, height, and shape of the underlying base). However, this information is still “blind,” and although it is undoubtedly better than probing alone, it has signiicant limitations. Nevertheless, this step is recommended immediately before the surgical intervention. The situations that can be encountered after periodontal lap relection vary greatly. When all soft tissue is removed around the teeth, there may be larger exostoses, ledges, troughs, craters, vertical defects, or combinations of these defects. Therefore, each osseous situation presents uniquely challenging problems, especially if reshaping to the optimal level is contemplated. Conclusion Although osseous surgical techniques cannot be applied to every bony abnormality or topographic modiication, it has been clearly demonstrated that properly used osseous surgery can eliminate and modify defects, as well as gradualize excessive bony ledges, irregular alveolar bone, early furcation involvement, excessive bony exostosis, and circumferential defects. When properly performed, resective osseous surgery achieves a physiologic architecture of marginal alveolar bone conducive to gingival lap adaptation with minimal probing depth. The advantages of this surgical modality include a predictable amount of pocket reduction that can enhance oral hygiene and periodic maintenance. It also preserves the width of the attached tissue while removing granulomatous tissue and providing accessfor debridement of the radicular surfaces. In addition, the osseous resection technique permits recontouring of bony abnormalities, including hemiseptal defects, tori, and ledges. Its substantial beneits include proper assessment for restorative procedures (e.g., crown lengthening) and assessment of restorative overhangs and tooth abnormalities (e.g., enamel projections, enamel pearls, perforations, fractures). Consequently, resective osseous surgery can be an important technique in the armamentarium necessary to provide a maintainable periodontium for periodontal patients. Osseous Resection Technique Instrumentation Numerous hand and rotary instruments have been used for osseous resective surgery. Some excellent clinicians use only hand instruments and rongeurs, whereas others prefer a combination of hand and rotary instruments. Rotary instruments are useful for the osteoplastic steps outlined previously, whereas hand instruments provide the most precise and safest results with ostectomy procedures. Piezoelectric surgical techniques,, have also been used with success for osseous surgical resective techniquesRegardless of instrumentation used, care and precision are required for each step of the procedure to prevent excessive bone removal or root damage, both of which are irreversible illustrates some of the instruments commonly used for osseous resection techniques. To address the many clinical situations, the following sequential steps are suggested for resective osseous surgery : 1. Vertical grooving 2. Radicular blending 3. Flattening interproximal bone 4. Gradualizing marginal bone Not all steps are necessary in every case, but the sequencing of the steps in the order given is necessary to expedite the reshaping procedure, as well as to minimize the unnecessary removal of bone. illustrates bone reshaping in lap surgery for speciic anatomic defects. Vertical Grooving Vertical grooving is designed to reduce the thickness of the alveolar housing and to provide relative prominence to the radicular aspects of the teeth. It also provides continuity from the interproximal surface onto the radicular surface. It is the first step of the resective process because it can deine the general thickness- and subsequent form of the alveolar housing. This step is usually performed with rotary instruments, such as round carbide burs or diamonds. The advantages of vertical grooving are most apparent with thick bony margins, shallow crater formations, or other areas that require maximal osteoplasty and minimal ostectomy. Vertical grooving is contraindicated in areas with close roots or thin alveolar housing. Radicular Blending Radicular blending, the second step of the osseous reshaping technique, is an extension of vertical grooving. Conceptually, it is an attempt to gradualize the bone over the entire radicular surface to provide the best results from vertical grooving. This provides a smooth, blended surface for good lap adaptation. The indications are the same as for vertical grooving (i.e., thick ledges of bone on the radicular surface, where selective surgical resection is desired). Naturally, this step is not necessary if vertical grooving is very minor or if the radicular bone is thin or fenestrated. Both vertical grooving and radicular blending are purely osteoplastic techniques that do not remove supporting bone. Flattening Interproximal Bone Flattening of the interdental bone requires the removal of very small amounts of supporting bone. It is indicated when interproximal bone levels vary horizontally. By deinition, most of the indications for this step are one-walled interproximal defects or hemiseptal defects. The omission of lattening in such cases results in increased pocket depth on the most apical side of the bone loss. Gradualizing Marginal Bone The inal step in the osseous resection technique is also an ostectomy process. Bone removal is minimal but necessary to provide a sound, regular base for the gingival tissue to follow. Failure to remove small bony discrepancies on the gingival line angles (widow’s peaks) allows the tissue to rise to a higher level than the base of the bone loss in the interdental area.. This may make the process of selective recession and subsequent pocket reduction incomplete. This step of the procedure also requires gradualization and blending on the radicular surface. Flap Placement and Closure After performing resection, the clinician positions and sutures the laps. Flaps may be replaced to their original position, to cover the new bony margin, or they may be apically positioned. Replacing the lap in areas that previously had deep pockets may result initially in greater postoperative pocket depth, although a selective recession may diminish the depth over time. Positioning the lap apically to expose marginal bone is one method of altering the width of the gingiva (denudation). However, such lap placement results in more postsurgical resorption of bone and patient discomfort than if the newly created bony margin were covered by the lap. Positioning the lap to cover the new margin minimizes postoperative complications and results in optimal postsurgical pocket depths. Suturing may be accomplished using a variety of different suture materials and suture knots4. The sutures should be placed with minimal tension to coapt the laps, prevent their separation, and maintain the position of the laps. Sutures placed with excessive tension rapidly pull through the tissues. Postoperative Maintenance Sutures may be removed at various times after placement. Nonresorbable sutures such as silk are usually removed after 1 week of healing, although some of the newer synthetic materials may be left for up to 3 weeks or longer without adverse consequences. Resorbable sutures maintain wound approximation for varying periods of 1 to 3 weeks or more, depending on the type of suture material. A second postoperative visit is often performed at the second or third week, and the surgical site is lightly debrided for optimal results. Professional prophylaxis for complete plaque removal should be done every 2 weeks until healing is complete or the patient is maintaining appropriate levels of plaque control. Healing should proceed uneventfully, with the attachment of the flap to the underlying bone completed in 14 to 21 days. Maturation and remodeling can continue for up to 6 months. It is usually advisable to wait at least 6 weeks after completion of healing of the last surgical area before beginning dental restorations. For those patients with a major cosmetic concern, it is wise to wait as long as possible to achieve a postoperative soft tissue position and a stable sulcus. Specific Osseous Reshaping Situations The osseous corrective procedure previously described is classically applied to shallow craters with heavy faciolingual ledges. The correction of other osseous defects is also possible; however, careful case selection for deinitive osseous surgery is extremely important. Correction of one-walled hemiseptal defects requires that the bone be reduced to the level of the most apical portion of the defect. Therefore, great care should be taken to select the appropriate case. If one-walled defects occur next to an edentulous space, the edentulous ridge is reduced to the level of the osseous defect. Other situations that complicate osseous correction are exostoses, malpositioned teeth, and supraerupted teeth. Following the four steps previously outlined best controls each of these situations. In most situations, the unique feature of the bony proile is well managed by prudently applying the same principles. However, some situations require deviation from the deinitive osseous reshaping technique; examples include dilacerated roots, root proximity, and furcations that would be compromised by osseous surgery. In the absence of ledges or exostoses, elimination of the bony lesion begins with reduction of the interdental walls of craters, the one-walled component of angular defects, and wells (moats) and grooving into sites of early involvement. The walls of the crater may be reduced at the expense of the buccal, lingual, or both walls. The reduction should be made to remove the least amount of alveolar bone required to (1) produce a satisfactory form, (2) prevent the therapeutic invasion of furcations, and (3) blend the contours with the adjacent teeth. The selective reduction of bony defects by “ramping” the bone to the palatal or lingual to avoid involvement of the furcations has been advocated by. In the presence of heavy ledges of bone, it is usually wise to do osteoplasty irst to eliminate any exostoses or reduce the buccal or lingual bulk of the bone (eFig. 62.11). It is common practice to incorporate a degree of vertical grooving during the reduction of bony ledges because this facilitates the process of blending the radicular bone into the interproximal areas at the next step. One-walled or hemiseptal defects usually require the removal of some bone from the tooth with the greatest coronal bony height. This removal of bone may result in a signiicant reduction in attachment on relatively unaffected adjacent teeth to eliminate the defect. However, if a tooth in the surgical ield has one-walled defects on both its mesial and its distal surface and this is recognized during examination, the severely affected tooth may be extruded by orthodontic therapy during disease control treatment to minimize or eliminate the need for resection of bone from the adjacent teeth. PERİODONTAL REGENERATİON AND RECONSTRUCTİVE SURGERY Intrabony and furcation defects are sequelae of periodontal disease. Ideally, these defects are managed in a timely fashion through periodontal regeneration. In the past, the results of regenerative therapy were inconsistent and unpredictable. The current status of regenerative therapy has dramatically changed and improved due to research and a better understanding of the biology of the tissues that comprise the periodontal attachment. The various surgical approaches including bone replacement grafts, guided tissue regeneration (GTR), and a better understanding of biologic mediators and tissue engineering have improved the predictability of regeneration as another choice for therapy. This chapter reviews the current strategies and clinical decision making for optimizing regenerative success. When the periodontium is damaged by inlammation or as a result of surgical treatment, the defect heals either through periodontal regeneration or repair. In periodontal regeneration, healing occurs through the reconstitution of a new periodontium, which involves the formation of alveolar bone, functionally aligned periodontal ligament, and new cementum. Alternatively, repaidue to healing by replacement with epithelial and/or connective tissue that matures into various nonfunctional types of scar tissue is termed new attachment. Histologically, patterns of repair include long junctional epithelium, ankylosis, and/or new attachment.Although the stability of periodontal repair is not clear, the ideal goal of periodontal surgical therapy is periodontal regeneration. Today, several highly reproducible regenerative approaches are used, as evidenced by clinical attachment gain, decreased pocket probing depth, radiographic evidence consistent with bone ill, and overall improvements in periodontal health. These clinical improvements can be maintained over long periods (>10 years). Assessment of Periodontal Wound Healing It is sometimes dificult in clinical and experimental situations to determine whether regeneration or new attachment has occurred and the extent to which it has occurred. Although various types of evidence of reconstruction exist, the proof of principle for the type of healing is determined by histologic studies. Once deined, the evidence found subsequently by clinical, radiographic, and surgical reentry indings is implied. All these methods have advantages and shortcomingsthat should be well understood and considered in individual cases and when critically evaluating the literature. Reconstructive Surgical Techniques Reconstructive techniques can be subdivided into three major therapeutic approaches: non– bone graft–associated, graft-associated, and biologic mediator–associated new attachment and regeneration. In clinical practice, it is common for clinicians to combine these various approaches. Histologic Methods Only through histologic analysis can one deine the nature of the reparative tissue. In periodontal reconstructive surgery, the goal is to achieve periodontal regeneration. Classically, experimental animal model systems are used whereby reference notches are placed at the base of bony defects or at the apical extent of calculus deposits. Periodontal regeneration is considered to have occurred when the newly formed functionally aligned periodontium is coronal to the apical extent of the notches. Reparative tissue response may include long junctional epithelium, connective tissue adhesion, and root resorption associated with ankylosis. The healing may be dominated by periodontal regeneration; localized areas of repair may be present.Unfortunately, this approach cannot be used in human studies because it would be unethical to extract the treated tooth, especially when it responded positively to therapy. In rare circumstances, human histologic evidence is available if the tooth is to be extracted in conjunction with orthodontic or restorative therapy. Clinical Methods Clinical methods to evaluate periodontal reconstruction consist of comparisons between pretreatment and posttreatment pocket probings and determinations of clinical gingival indings. The probe can be used to determine pocket depth, attachment level, and bone level. Clinical determinations of attachment level are more useful than probing pocket depths because the latter may change as a result of displacement of the gingival margin. Several studies have determined that the depth of penetration of a probe in a periodontal pocket varies according to the degree of inlammatory involvement of the tissues immediately beneath the pocket. Therefore, even though the forces used may be standardized with pressure-sensitive probes, an inherent margin of error in this method is dificult to overcome. Fowler and colleagues calculated this error to be 1.2 mm, but it is even greater when furcations are probed Bone probing performed with the patient under anesthesia is not subject to this error and has been found to be as accurate as bone height measurements made on surgical reentry. Measurements of the defect should be made before and after treatment from the same point within the defect and with the same angulation of the probe. This reproducibility of probe placement is dificult and may be facilitated in part by using a grooved stent to guide the introduction of the probe. Preoperative andpostoperative comparability of probing measurements that do not use this standardized method may be open to question Radiographic Methods Radiographic evaluation of periodontal regeneration allows assessment of the bone tissue adjacent to the tooth. This technique also requires carefully standardized techniques for reproducible positioning of the ilm and the tube. Even with standardized techniques, the radiograph does not show the entire topography of the area before or after treatment. Furthermore, thin bone trabeculae may exist before treatment and may go undetected radiographically because a certain minimal amount of mineralized tissue must be present to register on the radiograph. Several studies have demonstrated that radiographs, even those taken with standardized methods, are less reliable than clinical probing techniques. A comparative study of pretreatment bone levels and posttherapy bone ill with 12-month reentry bone measurements showed that linear radiographic analysis signiicantly underestimates pretreatment bone loss and posttreatment bone ill. Studies with subtraction radiography have enhanced the usefulness of radiographic evaluation. A comparative study of linear measurement, computer-assisted densitometric image analysis (CADIA), and a method combining the two reported that the combination method offers the highest level of accuracy. Surgical Reentry The surgical reentry of a treated defect after a period of healing can provide a good view of the state of the bone crest that can be compared with the view taken during the initial surgical intervention and can also be subject to measurements. Models from impressions of the bone taken at the initial surgery and later at reentry can be used to assess the results of therapy. This method is very useful but has two shortcomings: It requires a frequently unnecessary second procedure, and it does not show the type of attachment that exists All recommended techniques include careful case selection and complete removal of all irritants on the root surface. Although thiscan be done in some cases as a closed procedure, in most cases it should be done after exposure of the area with a lap. Flap design and incisions should follow the for laps used in reconstructive surgery. Trauma from occlusion, as well as other factors, may impair posttreatment healing of the supporting periodontal tissues, thus reducing the likelihood of new attachment. Occlusal adjustment or splinting, if needed, is therefore indicated. Systemic antibiotics are generally used after reconstructive periodontal therapy, although deinitive information on the advisability of this measure is still lacking. Case reports have shown extensive reconstruction of periodontal lesions after scaling, root planing, and curettage, with systemic and local treatment using penicillin or tetracycline, in combination with other forms of therapy Non–Graft-Associated Reconstructive Procedures The following sections discuss the rationale and techniques that must be considered for a successful outcome in achieving new attachment or periodontal bone regeneration in response to non–graftassociated reconstructive surgical therapy. This approach is used in Europe and Asia where human bone graft is not available due to regulatory restraints. Of these procedures, GTR is the main procedure used in clinical practice. More recent evidence suggests that the laser-assisted new attachment procedure (LANAP) may also result in new attachment and regeneration, but further clinical trials are needed to test its eficacy and parameters for success. Additionally, several procedures are of historical interest: (1) the removal of the junctional and pocket epithelium; (2) the prevention of their migration into the healing area after therapy; (3) clot stabilization, wound protection, and space creation; and (4) biomodiication of the root surfaces. Although these procedures are not used individually as reconstructive approaches, some of these strategies are currently incorporated into reconstructive surgery as adjuncts. Guided Tissue Regeneration GTR is used for the prevention of epithelial migration along the cemental wall of the pocket and for maintaining space for clot stabilization. Derived from the classic studies of Nyman, Lindhe, Karring, and Gottlow, this method is based on the assumption that periodontal ligament and perivascular cells have the potential for regeneration of the attachment apparatus of the tooth.‡ GTR consists of placing barriers of different types (membranes) to cover the bone and periodontal ligament, thus temporarily separating them from the gingival epithelium and connective tissue. Excluding the epithelium and the gingival connective tissue from the root surface during the postsurgical healing phase not only prevents epithelial migration into the wound but also favors repopulation of the area by cells from the periodontal ligament and the bone). In the United States, GTR is often performed with some type of bone graft as a scaffolding agent, so it is a combined therapy. As indicated earlier, in Europe and in other parts of the world, because of regulatory and religious constraints, human graft materials are not available, so it is performed as a traditional GTR procedure and may be occasionally used in conjunction with other graft materials as combined therapy. Initial animal experiments using Millipore ilters (Millipore Sigma, Burlington, MA) and Telon membranes resulted in regeneration of cementum and alveolar bone and a functional periodontal ligament. Clinical case reports indicate that GTR results in a gain in attachment level.15,16 Histologic studies in humans provided evidence of periodontal reconstruction in most cases, even with horizontal bone loss. The use of polytetraluoroethylene (PTFE) membranes has been tested in controlled clinical studies in mandibular molar furcations and has shown statistically signiicant decreases in pocket depths and improvement in attachment levels after 6 months, but bone level measurements have been inconclusive. A study of maxillary molar furcations did not result in signiicant gain in attachment or bone levels.With the regenerative success associated with the use of nonresorbable membrane, the advantages and disadvantages of this approach became apparent. Notably, problems such as membrane exposure, which resulted in no or limited regeneration and the need for a secondary procedure for surgical removal, resulted in the development of biodegradable membranes. Today in clinical practice, most GTR procedures use biodegradable membranes, whereas the nonresorbable membranes, especially those with titanium reinforcement struts, are used for regeneration of large intrabony defects and implant site development. Nevertheless, the historical research using nonresorbable membranes and the development of various types of biodegradable membranes are valuable. Laser-Assisted New Attachment Procedure The role of laser in periodontal therapy remains controversial. Nevertheless, the use of neodymium:yttrium-aluminumgarnet (Nd:YAG) to perform surgical LANAPs has been reported for the management of chronic periodontitis, and it can potentially result in new attachment and periodontal regenerationMany questions remain about LANAP. The irst refers to the exact mechanism and parameter by which healing by new attachment versus regeneration occurs with LANAP therapy. The frequency, consistency, and extent of regeneration have not been deined, nor has this approach been compared with other established regenerative therapies. This comparison, along with other randomized controlled trials, will be needed for meta-analysis to determine whether LANAP is equivalent or superior to other conventional therapy. As with all periodontal therapy, the long-term stability of the regeneration also needs to be explored. Graft Materials and Procedures Numerous therapeutic grafting modalities for restoring periodontal osseous defects have been investigated. Periodontal reconstruction can be attained without the use of bone grafts in meticulously treated three-wall defects (intrabony defects) and in periodontal and endodontic abscesses. New attachment is more likely to occur when the destructive process has occurred rapidly, such as after treatment of pockets complicated by acute periodontal abscesses and after treatment of acute necrotizing ulcerative lesions. The use of graft materials at one time was to provide regenerative inductive effect, but it should be viewed primarily as providing a scaffold for healing. The following classiications of bone graft material are important. Grafts are categorized either by their origins or function during healing. Categorizations by origin include the following: (1) autografts are bone obtained from the same individual; (2) allografts are bone obtained from a different individual of the same species; and (3) xenografts are bone from a different species. Bone graft materials are also evaluated based on their osteogenic, osteoinductive, or osteoconductive potential. Osteogenesis refers to the formation or development of new bone by cells contained in the graft. Osteoinduction is a chemical process by which molecules contained in the graft (e.g., bone morphogenetic proteins) convert the neighboring cells into osteoblasts, which in turn form bone. Osteoconduction is a physical effect by which the matrix of the graft forms a scaffold that favors outside cells to penetrate the graft and form new bone. Periodontal defects as sites for transplantation differ from osseous cavities surrounded by bony walls. Saliva and bacteria may easily penetrate along the root surface, and epithelial cells may proliferate into the defect, thus resulting in contamination and possible exfoliation of the grafts. Therefore the principles established to govern transplantation of bone or other materials into closed Graft materials have been developed and tried in many forms. To familiarize the reader with various types of graft material, as deined by either the technique or the material used, a brief discussion of each is provided. All grafting techniques require presurgical scaling, occlusal adjustment as needed, and exposure of the defect with a full-thickness flap. The flap technique best suited for grafting purposes is the papillapreservation flap because it provides complete coverage of the interdental area after suturing. The use of antibioticsafter the procedure is generally recommended. Autogenous Bone Grafts Historically, extraoral sites for bone harvesting have been from the iliac crest, but this approach is seldom performed due to medical and legal concerns. Intraoral sites can be effective, especially when Nonresorbable Membranes In classic animal and human studies demonstrating the eficacy of GTR, cellulose acetate ilters were used. As this technique became more prevalent, the irst commercial membrane was produced from expanded PTFE (ePTFE). This membrane has all the properties necessary for GTR barriers in that it (1) is a cellular barrier, (2) is biocompatible, (3) provides space for the healing tissue, (4) permits tissue integration, and (5) is clinically manageable. Much of our current understanding of GTR is based on studies using ePTFE membranes. Although these membranes are used less frequently now, they are still popular for guided bone regeneration and ridge preservation, so it is important to understand the clinical procedures for managing these membranes. The clinical effectiveness of ePTFE membranes is dependent on technique. Preservation of the keratinized gingiva and a relatively thick overlying surgical lap are critical to avoid perforation of the flap by the membrane during healing. After the surgical area has been flapped, the defect is degranulated and the root surface scaled and root planed. The ePTFE membrane is trimmed to adapt to tooth coniguration, secured by ePTFE sutures, and the lap is repositioned. Although much of the emphasis in the literature is on adapting the membrane to the defect, no membrane can ever be perfectly adapted. Despite gaps, these membranes appear to be successful. After membrane placement, healing is allowed to proceed for 4 to 6 weeks. Barring any membrane exposure, a second surgery is performed to remove the membrane. During this removal, the healing tissue appears reddish and granulomatous. Aftermembrane removal, the area should not be probed for 3 months. Radiographic evidence of bone ill is usually present after 6 months and should continue over the course of 1 year. Clinical studies have shown that ePTFE membranes used in GTR procedures are more effective than surgical debridement in correcting intrabony defects.§ In intrabony and furcation defects, gains are made in clinical attachment level (3 to 6 mm), improved bone levels (2.4 to 4.8 mm), and probing depth reductions (3.5 to 6 mm). Studies have demonstrated that these regenerative results can be maintained over the course of several years. The advent of titanium- reinforced ePTFE allowed for the formation of larger spaces, thus permitting correction of larger defects This resulted in signiicant clinical improvements using titanium-reinforced ePTFE compared with ePTFE. To determine how regeneration can be enhanced with GTR technique, the prolonged retention of ePTFE membranes was evaluated. After allowing the membrane to be retained for 4 months, surgical reentry after 1 year determined that the mean bone ill of intrabony defects was 95%. This suggests that prolonged retention of a barrier membrane is desirable if no tissue perforation is present. This inding is consistent with many clinical reports of the improved bone quality associated with guided bone regeneration in implant site development. The major problem with using nonresorbable membranes is that the membrane is exposed to the oral environment during healing. On exposure, the membrane is contaminated and colonized by oral microlora. Several studies have shown that contamination of the surgical ield can result in decreased formation of new attachment. If the membrane is exposed, the infection can be temporarily managed with topical application of chlorhexidine. This may minimize the infection and extend the time the membrane can be retained in place subsequently by gelatinases and peptidase. A resurgence has occurred in the use of calcium sulfate as a regeneration material because it can be used as a pavable resorbable barrier in combination with bone or bone substitutes. The calcium sulfate is bioresorbed through a giant cell reaction. Several features make these bioresorbable membranes easier to manage clinically: (1) they are more tissue compatible than nonresorbable membranes, (2) the timing for resorption can be regulated by the amount of cross-linkage in the synthetic polymer and collagen membrane or the amount of heat-processed calcium sulfate chips in calcium sulfate barrier, and (3) a second surgical procedure is not required to retrieve the nonresorbable membrane. Biodegradable Membranes Bioresorbable membranes have replaced the routine use of ePTFE membranes in GTR. There are basically three types of bioresorbable membranes: (1) polyglycoside synthetic polymers (i.e., polylactic acid, polylactate-polygalactate copolymers), (2) collagen, and (3) calcium sulfate. Polyglycoside membranes degrade as the result of random nonenzymatic cleavage of the polymer, to produce polylactide and polyglycolide, which are converted to lactic acid and pyruvate, respectively, and metabolized by the enzymes of the Krebs cycle. Porcine collagen membranes are degraded by collagenases and One GTR study compared the use of bioresorbable membranes (polylactate- polygalactate copolymer) versus ePTFE membranes, with surgical debridement as a control.47 After 1 year, signiicant gains in clinical attachment level (CAL) were observed in all three groups. There was no difference in CAL gain between the two membrane groups, with both of them gaining 2 mm or more. In both membrane groups, 83% of the sites improved 4 mm or more, which was signiicantly better than the surgical debridement control group. These indings indicate that GTR procedures are equally effective when using resorbable and nonresorbable membranes. This inding has been conirmed by other investigators.A large, multicenter clinical study reported the use of bioresorbable membranes in consecutively treated intrabony defects. After 1 year, investigators found that CAL improved by 79%, and 78% of the sites improved by 4 mm or more. An average of 3 mm of bone ill was measured radiographically. Compromised clinical results occurred when membranes were exposed or patients had poor plaque control. The search for resorbable membranes has included trials and tests with numerous materials and collagens from different species such as bovine, porcine, Cargile membrane derived from the cecum of an ox, polylactic acid, polyglactin 910 (Vicryl, Johnson & Johnson Dental Care Division, New Brunswick, NJ), synthetic skin (Biobrane, Smith & Nephew, London, United Kingdom), and freeze- dried dura mater. Clinical studies with a mixture of copolymers derived from polylactic acid and acetyl tributyl citrate resorbable membranes (Guidor membrane, no longer on the market) and a poly-d,l-lactideco-glycolide (Resolut membrane, also no longer on the market) showed signiicant gains in clinical attachment and bone ill.The potential of using autogenous periosteum as a membrane and also to stimulate periodontal regeneration was explored in two controlled clinical studies, one of grade II furcation involvements in mandibular molars and another of interdental defects. The periosteum was obtained from the patient’s palate by means of a window lap. Both studies reported that autogenous periosteal grafts can be used in GTR and result in signiicant gains in clinical attachment and osseous defect ill. Non–Graft-Associated Procedures of Historical Interest Removal of Junctional and Pocket Epithelium Since the earliest attempts at periodontal new attachment, the presenceof junctional and pocket epithelium has been perceived as a barrier to successful therapy because its presence interferes with the direct apposition of connective tissue and cementum, thus limiting the height to which periodontal fibers can insert to the cementum. Several methods have been recommended to remove the junctionaland pocket epithelium. These include curettage, chemical agents, ultrasonics, lasers, and surgical techniques. Curettage Results of removal of the epithelium by means of curettage vary from complete removal to persistence of as much as 50%.288 Although curettage is not a reliable procedure, occasional bone regeneration does occur.. Ultrasonic methods, lasers, and rotary abrasive stones have also been used, but their effects cannot be controlled because of the clinician’s lack of vision and tactile sense when using these methods. Chemical Agents Chemical agents have also been used to remove pocket epithelium, usually in conjunction with curettage. The drugs used most often have been sodium sulide, phenol camphor, antiformin, and sodium hypochlorite. However, the effect of these agents is not limited to the epithelium, and their depth of penetration cannot be controlled. These drugs are mentioned here for their historical interest. Biomodification of Root Surface Changes in the tooth surface wall of periodontal pockets (e.g., degenerated remnants of Sharpey ibers, accumulation of bacteria and their products, disintegration of cementum and dentin) interfere with new attachment. Although these obstacles to new attachment can be eliminated by thorough root planing, the root surface of the pocket can be treated to improve its chances of accepting the new attachment of gingival tissues. Several substances have been proposed for this purpose, including citric acid, ibronectin, and tetracycline. Citric Acid. One in a series of studies applied citric acid to the roots to demineralize the surface, thereby attempting to induce cementogenesis and attachment of collagen ibers. The following actions of citric acid have been reported: 1. Accelerated healing and new cementum formation occur after surgical detachment of the gingival tissues and demineralization of the root surface by means of citric acid.238 2. Topically applied citric acid on periodontally diseased root surfaces has no effect on nonplaned roots, but after root planing, the acid produces a 4-µm-deep demineralized zone with exposed collagen fibers 3. Root-planed, non–citric acid–treated roots are left with a surface smear layer of microcrystalline debris. Citric acid application not only removes the smear layer, exposing the dentinal tubules, but also makes the tubules appear wider and with funnel-shaped oriices. 4. Citric acid has also been shown in vitro to eliminate endotoxins and bacteria from the diseased tooth surface. 5. An early ibrin linkage to collagen ibers exposed by the citric acid treatment prevents the epithelium from migrating over treated roots. This technique using citric acid has been extensively investigated in animals and humans. Studies in dogs have shown encouraging. results, especially for the treatment of furcation lesions, but the results in humans have been contradictory.∥ The recommended citric acid technique is as follows: 1. Raise a mucoperiosteal lap and thoroughly instrument the root surface, thus removing calculus and underlying cementum. 2. Apply cotton pledgets soaked in a saturated solution of citric acid (pH of 1.0) for 2 to 5 minutes. 3. Remove pledgets, and irrigate root surface profusely with water. 4. Replace the lap and suture. The use of citric acid has also been recommended in conjunction with coverage of denuded roots using free gingival grafts Fibronectin. Fibronectin is the glycoprotein that ibroblasts require to attach to root surfaces. The addition of ibronectin to the root surface may promote new attachment. However, increasing ibronectin above plasma levels produces no obvious advantages. Adding ibronectin and citric acid to lesions treated with GTR in dogs did not improve the results. Tetracycline. In vitro treatment of the dentin surfaces with tetracycline increases binding of fibronectin, which in turn stimulates fibroblast attachment and growth while suppressing epithelial cell attachment and migration. Tetracycline also removes an amorphoussurface layer and exposes the dentin tubules. In vivo studies, however, have not shown favorable results. A human study showed a trend for greater connective tissue attachment after tetracycline treatment of roots. Tetracycline gave better results when used alone than when combined with ibronectin.4 Tetracycline has been used as an adjunctive procedure in preparation of the root in regenerative procedures and is a recommended step for use with biologic mediators. Surgical Techniques Surgical techniques have been recommended to eliminate the pocket and junctional epithelium. The excisional new attachment procedure (ENAP) consists of an internal bevel incision performed with a surgical knife, followed by removal of the excised tissue.332 No attempt is made to elevate a lap. After careful scaling and root planing, interproximal sutures are used to close the wound. This approach has been modiied and is used in conjunction with the ND:YAG laser in the previously described LANAP procedure. Glickman89 and Prichard231 advocated performing a gingivectomy to the crest of the alveolar bone and debriding the defect. Excellent results have been obtained with this technique in uncontrolled human studies. The modiied Widman flap, as described by Ramfjord and colleagues,235 is similar to the excisional new attachment procedure but is followed by elevation of a lap for better exposure of the area.The internal bevel incision eliminates the pocket epithelium Preventing or Impeding the Epithelial Migration Elimination of the junctional and pocket epithelium may not be suficient because the epithelium from the excised margin may rapidly proliferate to become interposed between the healing connective tissue and the cementum. For experimental purposes, several investigators have analyzed, in animals and humans, the effect of excluding the epithelium by amputating the crown of the tooth and covering the root with the flap (“root submergence”). This experimental technique not only excludes the epithelium but also prevents microbial contamination of the wound during the reparative stages. Successful repair of osseous lesions in the submerged environment was reported, but obviously this method has little or no clinical application. Two other methods have been proposed to prevent or impede the migration of the epithelium. One consists of the total removal of the interdental papilla covering the defect and its replacement with a free autogenous graft obtained from the palate. During healing, the graft epithelium necroses and is slowly replaced by proliferating epithelium from the gingival surface. The graft simply delays the epithelium from proliferating into the healing area. This method has not been widely used. The second approach is the use of coronally displaced laps, which increase the distance between the epithelial wound edge and the healing area. This technique is particularly suitable for the treatment of mandibular molar furcations and has been used mostly in conjunction with citric acid treatment of the roots. Periodontal regeneration after the use of this technique has been demonstrated histologically in humans. Clot Stabilization, Wound Protection,and Space Creation Some investigators have attributed the successful results reported with graft materials, barrier membranes, and coronally displaced flaps to the indings that these techniques protect the wound and create a space for undisturbed and stable maturation of the clot. This hypothesis suggests that preservation of the root surface fibrin clot interface prevents apical migration of the gingival epithelium and allows for connective tissue attachment during the early wound healing period.The importance of space creation for bone repair has long been recognized in orthopedic and maxillofacial surgery. Transference of this concept to periodontal therapy has been explored for treatment of periodontal and peri-implant osseous defects and for root coverage. The space can be created by using a titanium-reinforced ePTFE membrane to prevent its collapse. For the study of reconstructive techniques, these membranes were placed over experimentally created supra-alveolar bone defects in dogs, and considerable bone reconstruction was reported. The following is a discussion of the GTR technique. donor sites adjacent to the defects are available. Despite the popularity of using allograft, this should always be a consideration, especially as one reviews the historical development of the use of autografts from intraoral sites. Bone Allografts Obtaining donor material for autograft purposes necessitates inlicting surgical trauma on another part of the patient’s body. Obviously, it would be to the patient’s and therapist’s advantage if a suitable substitute could be used for grafting purposes that would offer similar potential for repair and not require the additional surgical removal of donor material from the patient. However, both allografts and xenografts are foreign to the patient and therefore have the potential to provoke an immune response. Attempts have been made to suppress the antigenic potential of allografts and xenografts by radiation, freezing, and chemical treatment.Bone allografts are commercially available from tissue banks. They are obtained from cortical bone within 12 hours of the death of the donor, defatted, cut in pieces, washed in absolute alcohol, and deep-frozen. The material may then be demineralized, subsequently ground and sieved to a particle size of 250 to 750 µm, and freeze-dried. Finally, it is vacuum- sealed in glass vials. Numerous steps are also taken to eliminate viral infectivity. These include exclusion of donors from known high-risk groups and various tests on the cadaver tissues to exclude individuals with any type of infection or malignant disease. The material is then treated with chemical agents or strong acids to inactivate the virus, if still present. The risk of human immunodeiciency virus (HIV) infection has been calculated as 1 in 1 to 8 million and is therefore characterized as highly remote. Freeze-Dried Bone Allograft Several clinical studies by Mellonig, Bowers, and coworkers reported bone ill exceeding 50% in 67% of the defects grafted with freeze-dried bone allograft (FDBA) and in 78% of the defects grafted with FDBA in combination with autogenous bone. FDBA, however, is considered an osteoconductive material, whereas demineralized FDBA (DFDBA) is considered an osteoinductive graft. Laboratory studies have found that DFDBA has a higher osteogenic potential than FDBA and is therefore preferred. Demineralized Freeze-Dried Bone Allograft Experiments by Urist312–315 established the osteogenic potential of DFDBA. Demineralization in cold, diluted hydrochloric acid exposes the components of bone matrix, which are closely associated with collagen ibrils and have been termed bone morphogenetic proteins (BMPs). In 1975, Libin and colleagues163 reported three patients with 4 to 10 mm of bone regeneration in periodontal osseous defects. Subsequent clinical studies were made with cancellous DFDBA and cortical DFDBA. DFDBA resulted in more desirable results (2.4 mm vs. 1.38 mm of bone ill). Bowers and associates, in a histologic study in humans, showed new attachment and periodontal regeneration in defects grafted with DFDBA. Mellonig and colleagues tested DFDBA against autogenous materials in the calvaria of guinea pigs and showed it to have similar osteogenic potential. These studies provided strong evidence that DFDBA in periodontal defects results in signiicant probing depth reduction, attachment level gain, and osseous regeneration. The combination of DFDBA and GTR has also proved to be very successful264; however, limitations of the use of DFDBA include the possible, although remote, potential of disease transfer from the cadaver. A bone-inductive protein isolated from the extracellular matrix of human bones, termed osteogenin or BMP-3, has been tested in human periodontal defects and seems to enhance osseous regeneration.23 This bone-inductive protein is discussed later in this chapter. Xenografts Bone products from other species have a long history of use in periodontal therapy. A few of these xenograft products are mentioned here for historical purposes but are no longer used today. Bovinederived bone (Bio-Oss, Geistlich Pharma, Princeton, NJ) is used in combination with GTR for periodontal regeneration. This material is also used in combination with autologous bone for ridge augmentation. Calf bone (Boplant), treated by detergent extraction, sterilized, and freeze-dried, has been used for the treatment of osseous defects Kiel bone is calf or ox bone denatured with 20% hydrogen peroxide, dried with acetone, and sterilized with ethylene oxide. Anorganic bone is ox bone from which the organic material has been extracted by means of ethylenediamine; it is then sterilized by autoclaving.These materials have been tried and discarded for various reasons. Currently, an anorganic, bovine-derived bone marketed under the brand name Bio-Oss (Geistlick Pharma) has been successfully used both for periodontal defects and in implant surgery. It is an osteoconductive, porous bone mineral matrix from bovine cancellous or cortical bone. The organic components of the bone are removed, but the trabecular architecture and porosity are retained. The physical features permit clot stabilization and revascularization to allow for migration of osteoblasts, leading to osteogenesis. Bio-Oss is biocompatible with the adjacent tissues, and it elicits no systemic immune response. Osseous Coagulum. Robinson249 described a technique using a mixture of bone dust and blood that he termed osseous coagulum. The technique uses small particles ground from cortical bone. The advantage of the particle size is that it provides additional surface area for the interaction of cellular and vascular elements. Sources of the graft material include the lingual ridge on the mandible, exostoses, edentulous ridges, the bone distal to a terminal ooth, bone removed by osteoplasty or ostectomy, and the lingual surface of the mandible or maxilla at least 5 mm from the roots. Bone is removed with a carbide bur #6 or #8 at speeds between 5000 and 30,000 rpm, placed in a sterile dappen dish and used to ill the defect. The obvious advantage of this technique is the ease of obtaining bone from an area already exposed during surgery. The disadvantages are its relatively low predictability and the inability to procure adequate material for large defects.65 Although notable success has been reported by many individuals, studies documenting the eficacy of the technique are still inconclusive. Cancellous Bone Marrow Transplants Cancellous bone can be obtained from the maxillary tuberosity, edentulous areas, and healing sockets. The maxillary tuberosity frequently contains abundant cancellous bone, particularly if the third molars are not present. After a ridge incision is made distally from the last molar, bone is removed with a curved rongeur. Care- should be taken not to extend the incision too far distally to avoid entering the mucosal tissue of the pharyngeal area. In addition, the location of the maxillary sinus must be analyzed on the radiograph to avoid entering or disturbing it. Edentulous ridges can be approached with a lap, and cancellous bone and marrow are removed with curettes, back-action chisels, or trephine. Extraction sockets are allowed to heal for 8 to 12 weeks before reentering and removing the newly formed bone from the apical portion, which is used as the donor material. Bone From Extraoral Sites The use of fresh or preserved iliac cancellous marrow bone has been extensively investigated. This material has been used by orthopedic surgeons for years. Data from human and animal studies support its use, and the technique has proved successful in osseous defects with various numbers of walls. It has also been successful in furcations and even supracrestally to some extent. However, because of numerous problems associated with its use, the technique is no longer in use. Some of the problems were postoperative infection, bone exfoliation, equestration, varying rates of healing, root resorption, and rapid recurrence of the defect. Other problems were increased patient expense and dificulty in procuring the donor material. include sclera, dura, cartilage, cementum, dentin, plaster of Paris, plastic materials, ceramics, and coral-derived materials. None offers a reliable substitute for bone graft materials; some of these materials are briely presented here to offer a complete picture of the many attempts that have been made to solve the critical problem of periodontal regeneration. Tissue Engineering With Biologic Mediators In wound healing, the natural healing process usually results in tissue scarring or repair. By using tissue engineering, the wound healing process is manipulated so that tissue regeneration occurs. This manipulation usually involves one or more of the three key elements: the signaling molecules, scaffold or supporting matrices, and cells The use of tissue engineering for periodontal regeneration and dental implant site preparation has been reviewed. Enamel Matrix Derivative for Periodontal Regeneration EMD has been effective in the treatment of infrabony defects The histologic evidence of EMD-induced periodontal regeneration has been conirmed in a clinical case report. A mandibular lateral incisor destined for orthodontic extraction was treated with acid etching and EMD. After 4 months, the tooth was extracted and examined histologically. Regenerated cementum covered 73% of the defect, and regenerated alveolar bone covered 65%. This histologic inding was later conirmed in other case reports,whereas new connective tissue attachment was reported in another case series where EMD was used in combination with a bone-derived xenograft. EMD has been shown to be safe for clinical use. Calcium Phosphate Biomaterials Several calcium phosphate biomaterials have been tested since the mid-1970s and are currently available for clinical use. Calcium phosphate biomaterials have excellent tissue compatibility and do not elicit any inlammation or foreign body response. These materials are osteoconductive; therefore, they act as a scaffold for blood clots to be retained to allow bone formation. Two types of calcium phosphate ceramics have been used, as follows: 1. Hydroxyapatite (HA) has a calcium-to-phosphate ratio of 1.67, similar to that found in bone material. HA is generally nonbioresorbable. 2. Tricalcium phosphate (TCP), with a calcium-to-phosphate ratio of 1.5, is mineralogically B-whitlockite. TCP is at least partially bioresorbable. Case reports and uncontrolled human studies have shown that calcium phosphate bioceramic materials are well tolerated and can result in clinical repair of periodontal lesions. Bioactive Glass Bioactive glass consists of sodium and calcium salts, phosphates, and silicon dioxide. For its dental applications, it is used in the form of irregular particles measuring 90 to 170 µm.When this material comes into contact with tissue fluids, the surface of the particles becomes coated with hydroxycarbonate apatite, incorporates organic ground proteins such as chondroitin sulfate and glycosaminoglycans, and attracts osteoblasts that rapidly form bone.206 Coral- Derived Materials Two different coralline materials have been used in clinical periodontics: natural coral and coral-derived porous HA. Both are biocompatible, but whereas natural coral is resorbed slowly (several months), porous HA is not resorbed or takes years for resorption. Clinical studies on these materials showed pocket reduction, attachment gain, and bone level gain. Coral-derived materials have also been studied in conjunction with membranes, with good results. Both materials have demonstrated microscopic cementum and bone formation, but their slow resorbability or lack of resorption has hindered clinical success in practice. clinical trial failed to show signiicant differences in clinical and radiographic measure between Recombinant Human Platelet-Derived Growth Factor for Periodontal Regeneration PDGF is one of the earliest growth factors studied for its effect on wound healing because it is a potent mitogenic and chemotacticfactor for mesenchymal cells in cell culture. Histologic evidence of periodontal regeneration was first reported in experimental defects in beagle dog. During the development of PDGF for clinical use, recombinant human PDGF (rhPDGF) was used in conjunction with allogenic bone to correct class II furcations and interproximal intrabony defects on hopeless teeth. Histologic evidence of successful periodontal regeneration in the furcation lesion with excellent ill has been noted. A human clinical trial was conducted using rhPDGF and recombinant human insulin-like growth factor 1 (rhIGF-1). Subsequently, the effectiveness of 0.3 mg/mL of rhPDGF in combination with β-TCP to improve attachment level gain, bone level, and bone volume signiicantly compared with β-TCP alone was demonstrated after 6 months in a multicenter clinical trial.A subset of these patients was followed for 24 months, and a representative case series was reported to be stable, with increases in radiographic bone ill compared with the end results after 6 months A review of these cases indicates that the results were stable after 3 and 5 years. Another case series suggested that rhPDGF with freeze- dried bone allograft can be combined to achieve excellent results in severe periodontal intrabony defects. These indings were conirmed by another randomized control trial.The combination of rhPDGF with a β-TCP carrier is now commercially available (GEM 21S, Osteohealth, Shirley, NY). These preliminary studies using rhPDGF-TCP suggest that it is easy to use, requires no barrier membranes, and has results comparable or superior to those of other regenerative graft materials. The potential for using rhPDGF for regeneration of furcation defects and implant site preparation still needs to be evaluated. Additionally, considerable clinical interest has been expressed in combining rhPDGF-BB with other bone replacement grafts, particularly bone allografts and xenografts. Combined Techniques Periodontal new attachment and bone reconstruction have been challenges for clinicians throughout the history of periodontal therapy. To take advantage of the different bone graft materials and biologic mediators, clinicians have combined these graft materials with the use of membranes in an attempt to ind a predictable technique to regenerate bone. Several clinicians have proposed a combination of the techniques previously described in an attempt to enhance their results. Clinical Guidelines to Guide Clinicians in Their Patient Management Clinical guidelines for the management of patients with periodontal disease ideal management of periodontal defects consists of the early diagnosis and appropriateaddressing of the defect When defects are detected early, before the formation of intrabony and furcation lesions, a predictable outcome can be obtained with scaling, root planing, and conventional osseous surgery Even early narrow intrabony (3 mm, periodontal regeneration should be considered Assessment of defect morphology and the patient’s clinical and systemic-behavioral determinants is critical for regenerative success. Consideration of these issues, in addition to the patient’s desires, will deine the selection of the regenerative approach to be used. Long-term stability is possible, but the individual outcome is inluenced by patient-related considerations such as smoking and compliance with periodontal maintenance and monitoring. Should patient-related or clinical determinants be unfavorable for periodontal regeneration, appropriate therapy must be selected Therapeutic Considerations The selection of an appropriate therapeutic approach is one that is based on accurate assessment of the periodontal defect, one’s past clinical experience, familiarity with the various regenerative and resective techniques, and the patient’s selection of the regenerative options. Successful regenerative surgery requires delicate and timely tissue management to minimize tissue shrinkage. Some of these important surgical considerations are good passive lap closure for encasement of the graft materials and a lap design to allow tension-free suture placement. These concepts of using conservative and minimally invasive lap approaches have been introduced as minimally invasive surgery (MIS). Patient-Related Considerations Classic studies of poor plaque control and poor postoperative recall compliance have indicated that much of the therapeutic gain from periodontal surgery will deteriorate. Similarly, the positive results from GTR regenerative procedure have been shown to deteriorate with poor complianceProgressive deterioration in these patients have been demonstrated to be associated with a higher incidence of infection with putative periodontal pathogens (Porphyromonas gingivalis, Prevotella intermedia, and Aggregatibacter actinomycetemcomitans) Areas such as furcation and root proximity situations have also been shown to be dificult to maintain, and as a result, the risk for deterioration is higher.As a clinician in practice, it is important to remember that the patient presented to the clinician with behavioral (plaque or bioilm) and anatomic problems, which resulted in periodontal disease. After therapy, the dificult challenge is to motivate patients to be skilled, enthusiastic, and passionate about their oral hygiene and compliant with periodontal maintenance. Smoking is a behavioral challenge that the therapist must always assess if the patient is a smoker. Smoking not only promotes disease progression, but also results in adverse therapeutic outcomes.It has been implicated as having a detrimental effect on periodontal wound healing following surgical procedures, as well as to inluence periodontal regeneration adversely. Tooth and Defect Related Considerations Therapeutic success is inluenced by the tooth’s importance in prosthetic rehabilitation, its endodontic status, and the osseous defect characteristics. The critical question to be addressed is whether the involved dentition is strategically important to treat and maintain by using regenerative periodontal theapy.305 If the tooth has little or no importance in the overall treatment plan, extraction may be indicated to avoid potential technical dificulties, postsurgical complications, and expenses. Strategic extraction may also improve access for better- plaque or bioilm removal by the patient and compliance.If a tooth is deemed essential, it is important to assess its endodontic status before the clinician proceeds with periodontal regenerative therapy. A positive endodontic status is necessary before one proceeds with regenerative therapy. The inancial consideration is also important for undertaking regenerative therapy. In a clinical scenario, if endodontic therapy, periodontal regenerative therapy, and restorative therapy are all necessary to retain a tooth, the inancial commitment may indicate the possible extraction and replacement with a dental implant or a prosthesis.Characteristics of the defect, such as the overall osseous pocket depth, width, and walls, can inluence clinical outcome in respons in place of regeneration that may consist of long-term maintenance or the removal of the tooth and replacement with a prosthesis such as a dental implant or another form of prosthesis. Before regenerative therapy, it is important to perform an endodontic assessment. This is to eliminate the possibility that the defect is the result of an endodontic-periodontal lesion. Should this be case, endodontic treatment may resolve that portion of the defect due to the endodontic lesion. If a residual defect still persists, periodontal therapy should be initiated. A common misconception is that regenerative therapy ends with a postoperative assessment a few months after treatment. Most therapeutic approaches have maximal healing results after 12 months. As such, postoperative monitoring should occur at least 12 months later. Additionally, these regenerated areas should be monitored at every recall visit because poor hygiene, uncorrectable tooth anatomy, and undiagnosed endodontic problems will cause these areas to relapse. Should failures due to these causes be determined, it may be prudent to consider strategic extraction. The endpoint for active periodontal therapy should comprise a stable periodontal attachment level, absence of inlammation or bleeding, and a periodontal anatomic environment that is conducive for the patient and the clinician to maintain excellent oral hygiene. A successful long-term periodontal outcome is also dependent on a patient who will be compliant with the maintenance visits. Conclusion The surgical procedure can be technically demanding, and when success is achieved, maintenance of positive results is highly dependent on patients’ oral hygiene habits and compliance with periodontal maintenance. Despite all these dificulties, periodontal regeneration is a clinical possibility that can be offered to patients. The clinician must carefully evaluate the various regenerative and reparative approaches and decide which technique may result in the best clinical outcome. With the advent of new regenerative approaches, such as biologic modiiers such as EMD and growth factors, we must critically evaluate how they may improve our ability to regenerate periodontal defects. Treatment planning in periodontics also has changed dramatically because of the acceptance of dental implants as viable long-term options for replacing missing teeth. With the increased predictability Bone Morphogenetic Proteins for Periodontal andImplant Site Regeneration BMPs comprise a group of regulatory glycoproteins that are members of the transforming growth factor beta superfamily that function as differentiation factors. These proteins induce cellular differentiation of stem cells into chondroblastic and osteogenic cells. Much of the research interest has focused on BMP-2 (OP-2), BMP-3 (osteogenin), and BMP-7 (OP-1).40 BMPs have been demonstrated to be present in FDBA and DFDBA, but the levels are so low that BMP is not biologically active. In fact, the amount of BMP is so low that it takes approximately 10 kg of bovine bone to yield only 2 µg of BMP It is only through recombinant DNA technology that BMP has been made available for clinical use. Use of Recombinant Human Fibroblast Growth Factor 2 for Periodontal Regeneration The potential use of recombinant human FGF-2 (rhFGF-2) for periodontal regeneration has been reviewed. Preliminary beagle and nonhuman primate studies demonstrated that topical application of FGF-2 into intraosseous defects in alveolar bones induces signiicant periodontal tissue regeneration.299 Histologic observation revealed new cementum with Sharpey fibers, new functionally oriented periodontal ligament ibers, and new alveolar bone These indings suggest that topical application of FGF-2 may be eficacious in regeneration of human periodontal tissue that has been destroyed- by periodontitis. Cell Therapy Cell therapy has been used in periodontal surgery (Osteocel Plus, NuVasive, San Diego, CA). Stem cells have the potential to improve urrent bone regeneration. These cells can expedite cell recruitment, be target cells for growth factor delivery, and promote early extracellular matrix formation. All of these cellular activities increase the bioactivity of the graft. The concentration of multipotential stromal cells (MSCs) in a commercially available cellular bone allograft was compared with fresh age-matched iliac crest bone and bone marrowaspirate. Without cultivation or expansion, this allograft contains cells with cell surface markers called cluster differentiation (CD) markers that are found with immunotyping of osteoprogenitor cells and osteoblasts. These cells displayed an “osteoinductive” molecular signature and the presence of CD45-CD271+CD73+CD90+CD105+ Allogenic and Alloplastic Bone-Grafting Materials The classic approach to orofacial regeneration since the 1980s has been the use of bone grafts or substitutes to repair periodontal and maxillofacial defects. The literature contains several excellent reviews on the use of autografts, allografts, and alloplastic graft materials. Since 2000, mineralized and demineralized freeze-dried boneallografts (FDBA and DFDBA) have often been the regeneration material of choice. In addition to their availability and putative osteogenic potential, various clinical studies indicate that 2 to 3 mmof bone ill is possible with FDBA and DFDBA. However, other studies have questioned the osteogenic potential of bone allografts by suggesting that this may vary depending on the bone bank or batch processing procedures used, and donor characteristics. Due to varying osteoinductive properties, which are not areas the US Food and Drug Administration regulates, growth factors and morphogens with FDBA and DFDBA are not commercially available. However, off-label use of this combination is common both in orthopedic and oral-periodontal surgical procedures. Alternatively, a variety of xenograft and alloplastic grafting materials is available as scaffolding agents for tissue engineering. Alloplastic bone grafts consist of ceramics, such as HA, porous HA,β-TCP, and biocompatible composite polymers (e.g., hard tissue replacement). Of these allografts, β-TCP is used in combination with rhPDGF-BB. In the development of rhPDGF-BB for clinical use, the biosynthetic β-TCP was used because it possessed deined andreproducible properties as required by the Food and Drug Administration. Allografts were not desirable because of varying osteogenic potential and properties.Extensive animal and human studiesdemonstrated biocompatibility of β-TCP with no reports of adverse reactions. This material physically ills bone defects, provides a scaffold for new bone formation, and prevents soft tissue collapse into the wound site. Clinically, β- TCP is osteoconductive and supports early healing. β-TCP resorbs at varying rates depending on the chemical structure, porosity, and particle size. Absorption, release, and bioactivity studies indicate that either β-TCP or calcium sulfate can be an effective carrier for PDGF-BB. Approximately 45% of the adsorbed PDGF-BB was released after 10 days. In clinical studies with rhPDGF-BB, this material resorbs and is replaced with regenerated periodontium. Supericial granules at the soft tissue interface appear to resorb at a slower rate. More recently, the use of β-TCP coated with recombinant human growth and differentiation factor-5 was evaluated for its osteoinductive and osteoconductive properties in an experimental rat calvarial critical size defect.Histomorphometric results suggest that this proprietary coating of growth factor on β-TCP achieved superior bone regeneration compared with conventional materials. These latter two studies indicate that the absorption and release kinetics of signaling agents are areas that require further elucidation if we are to achieve optimal regenerative response. Collagen Carriers Collagen is the main structural protein for tissue support. It also plays an essential role in wound healing by providing a biologic scaffold for cellular activities such as cell attachment, migration, and proliferation. Collagen has been widely used in tissueengineering for seeding of mesenchymal stem cells, as well as incorporation of growth factors. Because most collagens arederived from bovine dermal or skeletal tissue, concerns related to he purity, quality, immunogenicity, and potential for prion transmission have been raised. Calcium Sulfate Calcium sulfate is one of the oldest bone graft materials. Early clinical and animal studies indicate that calcium sulfate is biocompatible, degrades over time, is subsequently replacedwith regeneratedbone, and may be used in an infected area with no complications. More recent studies indicate that it also has barrier properties,enhances angiogenesis, and may be effective as a delivery vehicle for antibiotics, as well as growth factors.Rosenblum and associates demonstrated that FGF was observed to be released ata rate directly proportional to the rate of calcium sulfate dissolution. A secondary beneit of calcium sulfate dissolution is a local decrease in pH. An interesting study in the orthopedic literature reported that when an experimental sheep distal femoral cancellous defect was illed with calcium sulfate, increased immunostaining for BMP-2, BMP-7, transforming growth factor beta, and PDGF-BB was observed.All of these growth factors have been demonstrated tostimulate bone formation and development. Calcium sulfate wasfound to be a suitable carrier for rhPDGF-BB with a longer release kinetic proile (~16 days) as compared to β-TCP.13 Because bothmaterials are resorbable, the current debate centers on whether a longer sustained release of rhPDGF-BB would be more advantageous to periodontal and bone regeneration. Other Carriers Bioresorbable polymers of poly lactic-co-glycolic acid and polyglycolicacid have been considered as scaffolding agents for tissue engineeringdue to their biodegradable and tissue compatibility properties. Although these agents were promising as carriers for osteogenic factors in animals,variable tissue responses have made clinical application of these materials problematic. These tissue responses include inlammation, foreign body reaction, and local acid accumulation during polymer degradation. of implants, questions arise regarding when to treat severe periodontal defects with regenerative procedures and when to perform strategic extraction in preparation for implant placement. Sometimes the best management of a periodontal defect may be extraction in lieu of periodontal regeneration or when regenerative efforts have been unsuccessful. Extraction would minimize further bone loss and provide the maximum volume of bone at the future implant healing site. This paradigm shift has complicated our views about regeneration. With dental implants as viable alternatives, we need to redeine periodontal prognosis and consider strategic extraction more often. Conversely, heroic regenerative procedures would be contraindicated.Periodontal regeneration continues to be one of the primarytherapeutic approaches toward the management of periodontal defects. Although evidence suggests that present regenerative techniques can lead to periodontal regeneration, the use of GTR and biologic modiiers can enhance these results. The crucial challenge for the clinician isto assess critically whether a periodontal defect can be correctedwith a regenerative approach, or whether it would be better managedwith osseousresection for a slight periodontal defect and with strategic extraction for an advanced diseased state. REFERENCE: 1-Newman M, Takei H, Klokkevold P, Carranza F (2019). Clinical Periodontology, 13th Ed., Elsevier.

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