Step 3 for the treatment of periodontal diseases: surgical regeneration of the periodontium

The ultimate goal of periodontal therapy is to restore periodontal tissue architecture, namely alveolar bone, cementum, periodontal ligament and gingival tissue to its original form and level of attachment. Despite significant advances in regenerative biology and surgical techniques over recent decades, case selection remains the most important criterion when considering whether a surgical regenerative approach is appropriate for a specific site in an individual patient. This article provides an overview of regenerative biology, surgical factors and the current S3-level guidelines when considering surgical regenerative techniques in the treatment of periodontitis.

Biological concepts in regeneration

Regenerative periodontology requires an understanding of the biological principles of wound healing to enable the clinician to guide or manipulate the process clinically to attain optimal outcomes. Before considering regenerative biology, it is important to understand the different healing scenarios for the periodontium following surgical intervention, namely:

• Repair: a biological process by which periodontal tissues lost due to periodontitis are replaced by new tissues that do not replicate the structure and function of the lost tissues. This is the process that occurs following traditional surgical procedures and includes the formation of a long junctional epithelial attachment to the root surface.
• Regeneration: a biological process by which the architecture and function of tissues lost due to periodontitis are replaced by tissues identical in structure and function to the original healthy tissues.¹

The first concept in regenerative wound healing was known as ‘domain theory’, leading to a focus on guiding the correct cells to the root surface by exclusion of the epithelial and gingival connective tissue cells, allowing development of new alveolar bone and periodontal ligament rather than a long junctional epithelium or gingival connective tissue attachment.² Based on this theory, the first successful regenerative procedure was completed in 1982 on a lower lateral incisor using a non-resorbable membrane, which aimed to prevent occupation of the wound with epithelial and gingival connective tissue cells – a concept termed guided-tissue regeneration (GTR).³

As knowledge and research on periodontal wound healing have evolved, complex processes have been unravelled that are more important than simple exclusion of cells and which were the most likely reason for successful regeneration in these early studies. These include:

• Space provision;
• Wound stability (and biomodification);
• Primary intention healing.⁴

While cellular activity is important during the wound healing process, it is the molecular signalling activity by cells that dictates how the tissue heals. This has led to a surge in research on biological agents, such as enamel matrix proteins and growth factors, with a range of products now available on the market to the surgeon (Table 1).

Based on these newer principles, both surgical techniques and regenerative biomaterials have evolved allowing for greater predictability of results and ability to optimise outcomes in a greater variety of clinical situations. These are discussed in the next section.

Surgical considerations for regenerative approaches

General medical considerations

As for any surgical intervention the patient's medical status may provide absolute contraindications to surgery in general practice. These include, but are not limited to:

• Uncontrolled diabetes and other uncontrolled systemic diseases (e.g. unstable angina);
• Severe uncontrolled immunocompromise;
• Severe uncontrolled bleeding conditions (e.g. haemophilia);
• Intravenous bisphosphonate therapy;
• Cigarette smokers demonstrate reduced treatment responses in all forms of periodontal therapy and this includes regenerative periodontal surgery.⁵

It is the authors' opinion that advanced regenerative procedures should not be undertaken in smokers, without careful consideration and clear justification.

Strategic importance of the tooth

In many cases the strategic value of the tooth to be treated must be considered as part of a wider restorative plan when deciding whether regenerative procedures are appropriate. Teeth that act as abutments for a fixed/removable prosthesis may shift the decision towards regenerative surgery. In other situations, the presence of multiple teeth with hopeless prognoses and which require removal, may tip the decision to a pragmatic one that includes removal of the target tooth to accommodate a wider prosthetic rehabilitation. However, the guiding principal of treatment planning should remain retention of teeth wherever possible, as recommended in the most recent S3-level clinical guideline for stage IV periodontitis.⁶

Microsurgical equipment

Atraumatic soft tissue management is a fundamental requirement for regenerative procedures because it is the soft tissue protecting the underlying blood clot that facilitates optimal healing. To ensure minimal trauma to the flap, as well as to allow for primary intention healing, microsurgical equipment has developed from microsurgical blades/handles through to tweezers, elevators and suture forceps.

Flap design

Flap design has progressed from conventional intrasulcular incisions to minimally invasive papilla-preservation techniques allowing for predictable primary intention healing and wound stability (Figure 1). Surgical approaches can generally be classified into those involving two flaps (one buccal and one palatal/lingual flap is raised (Figure 2) or one flap where the defect is accessed from the buccal (or palatal/lingual) aspect alone (Figure 3) with the advantage of the latter providing greater overlying soft-tissue stability for wound healing. The technique of choice will be dictated by the defect morphology and access to the root surface ensuring adequate root surface decontamination.

Defect anatomy

The shape of the bony defect is the principle local factor dictating the feasibility for a regenerative approach. Bone defects can be classified as either suprabony (where the base of the pocket remains coronal to the alveolar bone crest) or infrabony/vertical (where the apical extent of pocket lies below the alveolar crest). Figure 4 demonstrates the radiographic appearance of supra- and infrabony defects. Infrabony defects can be further subclassified based on their depth, width and number of bony walls. As the number of bony walls increases, radiographic infill and CAL gain improve with treatment, primarily because the defect can contain a more stable clot.⁷ Novel techniques, such as the ‘soft tissue wall technique’ combine regenerative surgical approaches with mucogingival techniques with the aim of coronally advancing tissue and using connective tissue grafts to convert one-walled non-contained defects to three-walled contained defects.⁸ The angle of the defect also plays a role with wider angled defects (≥36 degrees) demonstrating less radiographic infill following regenerative surgery compared to narrower defects.⁹

Furcation involvement

As the horizontal and vertical grade of furcation increases, the risk of tooth loss increases.^10,11 The primary aim of regenerative therapies around furcation-involved teeth, therefore, aims to convert furcation-involved teeth to grade 0 (known as furcation closure) or grade 1, where they can then be successfully maintained long term by both patient and professional. Owing to the nature of furcation anatomy, a contained defect suitable for regeneration is only present in the grade 2 situation (Figure 5). Through and through defects (i.e. grade 3) are non-contained and unsuitable/unpredictable for regenerative therapy, although can potentially still be managed via other approaches (e.g. furcation tunnelling, root resection/hemisection).¹²

Endodontic–periodontal lesions

Owing to the infrabony/vertical nature of defects treated with regenerative procedures, it is not uncommon for bone loss to approach the apex of a tooth. In cases where there is suspected endodontic involvement, sensibility testing should ascertain the pulp status and if necessary, endodontic therapy should be completed prior to surgery. If peri-operative instrumentation beyond the apex is also expected, endodontic therapy should be considered prior to surgery. Where there is evidence of suboptimal primary root canal therapy, root canal re-treatment should be completed before surgery. Based on these criteria, the evidence suggests that root-treated teeth demonstrate comparable outcomes to vital teeth when treated with regenerative surgery.¹³

Mobility

Baseline mobility has been demonstrated to impact on clinical outcomes associated with regenerative procedures, with reduction in CAL gain observed as mobility increases.¹⁴ This is most likely to be due to micromovements within the blood clot that impair the healing process. It is therefore necessary to identify and manage mobility prior to regenerative procedures, which may include carefully prescribed occlusal adjustments and the use of localized cleansable splints (e.g. wire and composite).

Biomaterial selection

To stimulate regenerative activity, wound biomodification can be considered at the time of surgical intervention. This can take the form of bone graft materials, membranes, or the application of biologics promoting molecular and cellular activity during healing, which favour regenerative outcomes.

As discussed, early regenerative approaches used non-resorbable membranes made of PTFE. Membranes have now evolved and include resorbable options, which are the primary choice for regenerative procedures around teeth, if a membrane approach is to be employed.

Bone graft materials can be subclassified based on either their origin or their mode of action (Table 2). In terms of their mode of action, bone graft materials may demonstrate one or more different modes of action, with the ideal bone graft material exhibiting osteogeneic, osteo-inductive and osteoconductive behaviours. These graft materials can be used alone or alongside membranes/biologics in what are termed ‘combination approaches.’

There is no ‘one size fits all approach’ when it comes to the application of biomaterials: defect location (furcation vs interproximal vs combined) and anatomy (two-walled/three-walled/wide/narrow) should be considered for each individual case. Patient preference must also be taken into account, particularly as many commonly used biomaterials are derived from animal products. Owing to the significant increase in biomaterials available on the market and commercialization of regenerative periodontal care, it remains the responsibility of the surgeon to ensure that the biomaterials selected for regenerative procedures have the appropriate safety, clinical efficacy, and histological data when demonstrating regenerative healing.

Suture techniques

Closure of the surgical site by primary intention is an essential part of wound healing. A variety of suture techniques are available to the surgeon to manage the wound margins and provide primary intention healing. One commonly used technique is the Laurell–Gottlow (modified internal mattress) suture, and its variants, which combines the eversion of the wound margin achieved with the internal mattress suture with the inversion achieved with a single interrupted suture.¹⁵

Sutures for regenerative procedures should be monofilament in nature to reduce bacterial contamination and wicking along the biomaterials used/wound margin. This will generally lead to the use of non-resorbable sutures, which are generally removed at 2–4 weeks. Smaller sutures sizes (e.g. 5-0, 6-0, 7-0) are favoured in modern periodontal surgery to reduce soft tissue trauma and tension on the soft tissue during closure.

Surgical aftercare

Appropriate patient and professional post-operative care ensures that healing of the tissue is monitored carefully both in the short and long term. Patients should be provided with:

• Appropriate analgesic advice with consideration of their medical history;
• Chemical disinfection (e.g. chlorhexidine 0.2% mouthwash) for at least the first 2 weeks while the patient abstains from mechanical plaque removal in the surgical area;
• Advice on appropriate diet;
• Gauze to apply pressure in case of post-operative bleeding;
• Contact information for follow up questions/concerns;
• A review appointment.

Reassessment of the regenerative site should be completed at 6 months to allow sufficient time for healing of soft and hard tissue. During this period, interim supportive periodontal therapy appointments should be provided to ensure maintenance of the remaining dentition, as well as reinforcing tailored oral hygiene instruction at the site level. Plaque accumulation at the surgical site during the post-operative healing period can induce a chronic inflammatory response that delays/subverts healing. The frequency and number of maintenance appointments is not standardized, although some studies have employed professional supragingival plaque removal at weekly to fortnightly intervals for the initial healing period of 6–8 weeks followed by 3-monthly supportive therapy.^16,17

Outcomes for regenerative surgery

Successful periodontal regeneration can only truly be confirmed histologically via evidence of new alveolar bone and cementum with inserting periodontal ligament fibres. In clinical practice, this is clearly not an option, and therefore, surrogate clinical measures are used to inform success. Long-term success is primarily dictated by tooth retention, although surrogate clinical measures, such as probing pocket depth reduction, bleeding on probing, clinical attachment level and pocket closure provide important measures in the shorter term about the health of the tooth and its long-term prognosis.

Improvements in tooth prognosis and tooth survival are a fundamental aim of any form of periodontal therapy, and a common clinical decision is considering the ‘extraction threshold’ for a tooth and its subsequent prosthetic replacement. Fortunately, the periodontal literature is replete with evidence confirming the benefits of periodontal treatment, even in teeth with advanced clinical attachment loss, and thus suggest caution before assigning a tooth for removal and prosthodontic replacement.

A systematic review exploring the long-term survival rates of periodontally compromised teeth and implants demonstrated consistently that, irrespective of the type of periodontal therapy, the survival rates of dental implants do not exceed that of successfully treated and maintained teeth.¹⁸ This concept carries over to furcation-involved teeth, where a cost-effectiveness comparison study concluded that not only did implant-supported crowns have shorter survival times, but were the more costly therapy compared with tooth retention, despite the presence of any grade of furcation.¹⁹

Specific to regenerative therapy, one randomized control trial treated teeth assigned with a ‘hopeless’ prognosis to either removal and prosthetic replacement (implant or tooth-supported bridge), or to a test group where they received regenerative periodontal surgery (including management of mobility/loss of vitality/occlusion) followed by 3-monthly maintenance care. At the 5-year follow-up, only two out of the 25 treated teeth in the test group were lost, representing a 92% survival rate, with a subsequent 10-year survival rate of 88% (one further tooth lost) in a cohort of teeth previously considered of ‘hopeless’ prognosis. Further subanalyses revealed that as well as the biological savings in the test group, tooth retention provided economic savings over the 10-year period when including the costs of tooth replacement at baseline.^20,21Figures 6 and 7 demonstrate the radiographic outcomes achievable with regenerative surgery with appropriate case selection and a surgical approach.

Two systematic reviews relevant to regenerative surgery were produced as part of the development of the S3-level guideline for stage IV periodontitis by the EFP. They investigated the clinical outcomes of regenerative surgery compared with access flap surgery and the outcomes associated with regenerative surgical treatment of furcation defects.

When comparing regenerative surgery to access flap surgery (with any type of access flap design), meta-analysis demonstrated a statistically significant additional benefit to regenerative surgery for both CAL (1.34 mm) and probing pocket depth reduction (1.20 mm).²² When considering class II furcations, the evidence suggests that regenerative approaches lead to an almost 21 times increased likelihood of furcation closure/conversion to class I, as well as additional benefits in both vertical and horizontal CAL gain compared with open flap debridement alone. The use of bone graft materials tended to provide the best benefits in terms of biomaterial selection.²³

S3-level clinical guideline relevant to regenerative surgery

As part of the EFP S3-level guideline for the treatment of periodontitis, surgical therapy is considered a treatment option when entering step 3, that is the presence of residual sites following initial non-surgical therapy. It may be necessary to consider a second round of non-surgical therapy in many cases before the decision for surgery becomes appropriate.

Table 3 provides a summary of the relevant guideline recommendations in relation to surgical regenerative interventions produced by the EFP including the adolopment outcome by the British Society of Periodontology for UK clinical practice.^24,25

Conclusion

Regenerative periodontal surgery is an important treatment modality in securing the long-term prognosis of severely compromised periodontally involved teeth. With the correct case selection and surgical approach, regenerative procedures provide additional benefits to access flap surgery and can avoid the need for tooth removal and the subsequent technical/biological complications that may accompany prosthetic tooth replacement.