References

Ribeiro FV, Casarin RC, Palma MA Clinical and patient-centered outcomes after minimally invasive non-surgical or surgical approaches for the treatment of intrabony defects: a randomized clinical trial. J Periodontol. 2011; 82:1256-1266 https://doi.org/10.1902/jop.2011.100680
Nibali L, Yeh YC, Pometti D, Tu YK Long-term stability of intrabony defects treated with minimally invasive non-surgical therapy. J Clin Periodontol. 2018; 45:1458-1464 https://doi.org/10.1111/jcpe.13021
Nibali L, Pometti D, Tu YK, Donos N Clinical and radiographic outcomes following nonsurgical therapy of periodontal infrabony defects: a retrospective study. J Clin Periodontol. 2011; 38:50-57 https://doi.org/10.1111/j.1600-051X.2010.01648.x
Nibali L, Pometti D, Chen TT, Tu YK Minimally invasive non-surgical approach for the treatment of periodontal intrabony defects: a retrospective analysis. J Clin Periodontol. 2015; 42:853-859 https://doi.org/10.1111/jcpe.12443
Avila-Ortiz G, Ambruster J, Barootchi S American Academy of Periodontology best evidence consensus statement on the use of biologics in clinical practice. J Periodontol. 2022; 93:1763-1770 https://doi.org/10.1002/JPER.22-0361
Miron RJ, Sculean A, Cochran DL Twenty years of enamel matrix derivative: the past, the present and the future. J Clin Periodontol. 2016; 43:668-683 https://doi.org/10.1111/jcpe.12546
Koop R, Merheb J, Quirynen M Periodontal regeneration with enamel matrix derivative in reconstructive periodontal therapy: a systematic review. J Periodontol. 2012; 83:707-720 https://doi.org/10.1902/jop.2011.110266
Esposito M, Grusovin MG, Papanikolaou N Enamel matrix derivative (Emdogain) for periodontal tissue regeneration in intrabony defects. Cochrane Database Syst Rev. 2009; 2009:(4) https://doi.org/10.1002/14651858.CD003875.pub3
West N, Chapple I, Claydon N BSP implementation of European S3-level evidence-based treatment guidelines for stage I–III periodontitis in UK clinical practice. J Dent. 2021; 106 https://doi.org/10.1016/j.jdent.2020.103562
Rams TE, Listgarten MA, Slots J Utility of radiographic crestal lamina dura for predicting periodontitis disease-activity. J Clin Periodontol. 1994; 21:571-576 https://doi.org/10.1111/j.1600-051x.1994.tb00745.x
Nyman S, Lindhe J, Karring T, Rylander H New attachment following surgical treatment of human periodontal disease. J Clin Periodontol. 1982; 9:290-296 https://doi.org/10.1111/j.1600-051x.1982.tb02095.x
Gutierrez MA, Mellonig JT, Cochran DL Evaluation of enamel matrix derivative as an adjunct to non-surgical periodontal therapy. J Clin Periodontol. 2003; 30:739-745 https://doi.org/10.1034/j.1600-051x.2003.00374.x
Roccuzzo A, Imber JC, Stähli A Enamel matrix derivative as adjunctive to non-surgical periodontal therapy: a systematic review and meta-analysis of randomized controlled trials. Clin Oral Investig. 2022; 26:4263-4280 https://doi.org/10.1007/s00784-022-04474-1
Jentsch HFR, Roccuzzo M, Pilloni A Flapless application of enamel matrix derivative in periodontal retreatment: a multicentre randomized feasibility trial. J Clin Periodontol. 2021; 48:659-667 https://doi.org/10.1111/jcpe.13438
Trombelli L, Farina R, Vecchiatini R A simplified composite outcome measure to assess the effect of periodontal regenerative treatment in intraosseous defects. J Periodontol. 2020; 91:723-731 https://doi.org/10.1002/JPER.19-0127
Aimetti M, Stasikelyte M, Mariani GM The flapless approach with and without enamel matrix derivatives for the treatment of intrabony defects: a randomized controlled clinical trial. J Clin Periodontol. 2024; 51:1112-1121 https://doi.org/10.1111/jcpe.14028
Aimetti M, Ferrarotti F, Mariani GM, Romano F A novel flapless approach versus minimally invasive surgery in periodontal regeneration with enamel matrix derivative proteins: a 24-month randomized controlled clinical trial. Clin Oral Investig. 2017; 21:327-337 https://doi.org/10.1007/s00784-016-1795-2

Case report: non-surgical regeneration with adjunctive enamel matrix derivative

From Volume 51, Issue 10, November 2024 | Pages 713-718

Authors

Devan S Raindi

BDS Hons (Birm) MJDF RCS (Eng) MClinDent Hons (KCL) MPerio RCS (Edin) AFHEA, BDS Hons (Birm), MJDF RCS (Eng), MClinDent Hons (KCL), MPerio RCS (Edin), AFHEA

Periodontal Research Group, Institute of Clinical Sciences, University of Birmingham

Articles by Devan S Raindi

Email Devan S Raindi

Paul Weston

Periodontal Research Group, Institute of Clinical Sciences, University of Birmingham

Articles by Paul Weston

Iain Chapple

PhD, BDS, FDS RCPS, FDS RCS, CCST(Rest Dent), PhD, BDS, FDSRCPS, FDSRCS, CCST (Rest Dent)

Periodontal Research Group, Institute of Clinical Sciences, University of Birmingham

Articles by Iain Chapple

Abstract

A 48-year-old female patient referred to the Birmingham Dental Hospital for generalized periodontitis presented with a residual 8-mm pocket and infrabony defect around her LL2 after Step 1 and 2 of therapy. Following discussion of treatment options, a minimally invasive non-surgical technique was completed alongside the addition of a biologic, a therapeutic agent applied to enhance regenerative or reparative effects during wound healing and in this case, enamel matrix derivative. At 6 months, pocket closure was evident, as well as radiographic evidence of bony infill. The patient remains in ongoing supportive periodontal therapy at 3-monthly intervals.

CPD/Clinical Relevance: Addition of biologics traditionally used during surgical therapy may provide improvements when used alongside minimally invasive non-surgical treatment.

Article

The ultimate goal of treating periodontitis is not only to resolve the inflammatory lesion and thus prevent progressive attachment loss, but also to regenerate all lost periodontal tissues, i.e. alveolar bone with periodontal ligament inserting into cementum. Traditionally, procedures aimed at regenerating lost periodontal tissues require a surgical approach to access the specific bony defect in question.

Surgical techniques have evolved over the past 50 years as our understanding of the biological principles of wound healing has developed. Surgical approaches necessitate microsurgical instruments and aim to provide minimally invasive approaches to access and manage the defect, allowing for a stable blood clot that can co-ordinate a healing response favouring a regenerative outcome rather than repair.

While novel surgical approaches continue to be described in the literature, with the common theme being papilla preservation, it must be recognized that no incision/flap elevation (i.e. non-surgical therapy) provides the ideal soft tissue compartment to support the regenerative processes to take place.

This has led to a recent surge in research describing minimally invasive non-surgical therapy (MINST) as a method to manage infrabony defects without automatically assuming that surgical intervention is required. Although there is no current standard definition for MINST, the authors propose a definition of the concept being ‘a non-surgical approach to periodontal therapy focused on biofilm removal, without intentional loss of tooth structure, alongside minimal soft tissue trauma to allow optimal clot stabilization for wound healing.’

The first study demonstrating that minimally invasive non-surgical approaches are equivalent to surgical intervention was a randomized control trial where infrabony defects were randomized to non-surgical or surgical approaches. The non-surgical approach involved the use of fine tipped ultrasonics/mini-curettes with minimal trauma to the soft tissue while the surgical approach involved a minimally invasive surgical technique without the use of biomaterials. At 6 months, no differences in clinical parameters were noted, but the non-surgical group experienced less chairtime.1 A further retrospective cohort, over a 5-year period within a private practice setting, showed the effectiveness of employing a minimally invasive non-surgical approach to infrabony defects with radiographic evidence of bony infill and positive outcomes across a range of clinical parameters.2,3,4

As MINST becomes more mainstream, it seems only sensible that clinicians should try to optimise the outcomes with the addition of biologics (in a similar fashion to those employed surgically). Biologics are defined as therapeutic agents with biological activity that are administered to achieve an enhanced regenerative or reparative effect.5 Recent research has therefore investigated the addition of biologic adjuncts as a way of wound biomodification, rather than simply the addition of local antimicrobial therapies, which are focused on biofilm control.

Enamel matrix derivatives (EMD) seem a sensible candidate as their benefit for surgical regenerative procedures is well documented within the periodontal literature.6,7,8 They have an array of actions that promote regenerative healing, such as effects on mesenchymal cell attachment, spreading and chemotaxis, as well as upregulation of growth factors. They have also been shown to have positive effects on the proliferation of PDL fibroblasts and osteoblasts.9 They are conventionally used as part of Step 3 in the treatment of periodontitis, and have a recommendation for use as part of regenerative surgery of both infrabony defects and specific Class II furcations.10

This case report describes a minimally invasive non-surgical approach to residual probing pocket depths after Steps 1 and 2 of periodontal treatment, alongside the use of an enamel matrix derivative (EMD) to promote periodontal regeneration.

Case report

A 48-year-old female was referred by her general dental practitioner to the Birmingham Dental Hospital regarding concerns over progressive bone loss. Following clinical and radiographic assessment, she was diagnosed with generalized periodontitis Stage IV Grade C – unstable – risk factors: nil.

Following an initial course of non-surgical therapy, which included tailored oral hygiene instruction, supragingival professional mechanical plaque removal (PMPR) and subgingival PMPR of sites 4 mm and bleeding on probing ≥5 mm, a re-evaluation was undertaken at 3 months. Sites with residual probing depths were re-instrumented non-surgically and a further re-evaluation completed at 3 months. At this point a localized 8-mm pocket remained interproximally on the mesial aspect of the LL2 with associated suppuration on probing (Figure 1a). There was no pocketing >3 mm associated with the mid-buccal and mid-lingual aspect of the tooth. A peri-apical radiograph confirmed 80% bone loss and an infrabony defect associated with the mesial aspect of the LL2 (Figure 1b).

Figure 1. (a) Pre-treatment pocketing of 8 mm following two rounds of conventional non-surgical therapy. (b) Baseline long cone peri-apical radiograph demonstrating an infrabony defect with 80% bone loss affecting LL2.

Following discussion with the patient various options were proposed to treat the defect namely:

  • Further round of subgingival PMPR + local delivery of antimicrobials;
  • Subgingival PMPR with the use of adjunctive enamel matrix derivative (Emdogain, Institut Straumann AG, Basel, Switzerland);
  • Regenerative periodontal surgery with adjunctive use of biomaterials.
  • The patient opted for non-surgical therapy with the use of enamel matrix derivative. The non-surgical therapy was completed in line with the principles of minimally invasive non-surgical techniques (by the first author), namely the use of slimline ultrasonics (Cavitron, Dentsply Sirona, Weybridge, Surrey), mini-gracey curettes (LM Dental, Parainen, Finland) and a focus on atraumatic management of the soft tissue (Figure 2). Local anaesthetic was applied in the form of buccal infiltrations using articaine 4% with 1:100,000 adrenaline. The use of magnification was employed through (x3.5 Omnioptics, Orascoptic, Stockley Park, Uxbridge)

    Figure 2. Peri-operative photographs demonstrating (a) ultrasonic debridement, (b) use of micro-curettes, and (c) immediately post-operative minimal soft tissue trauma.

    Following thorough debridement of the root surface, and ensuring minimal trauma to the soft tissue, Emdogain was applied to the root surface subgingivally. This involved initial application of a 24% EDTA root conditioning agent (PrefGel, Straumann) for 2 minutes into the periodontal pocket followed by irrigation with sterile saline. Superfloss (Oral-B, Proctor and Gamble) was used to ensure moisture control prior to application of Emdogain, ensuring initial contact to the root surface before any blood. Prior to patient discharge, haemostasis was achieved, ensuring a stable blood clot was present with no active bleeding from the treated site, via use of a wetted gauze to provide marginal tissue closure of the pocket (Figure 3). Systemic antibiotics were not provided following therapy.

    Figure 3. Application of enamel matrix derivative commencing with (a) 24% EDTA PrefGe, (b) use of Superfloss to obtain moisture control prior to (c) application of Emdogain with a thin cannula.

    The patient was provided with personalized oral hygiene to commence from the following day, which included the use of interdental brushes and a powered toothbrush. At 3 months, the patient received a supportive periodontal therapy appointment to include supragingival PMPR and reinforcement of oral hygiene instruction. No probing of the LL2 or subgingival PMPR was completed at this visit to allow continued healing. To allow for the regenerative processes anticipated during healing, including the maturation of alveolar bone, the patient was re-evaluated at 6 months by a specialist periodontist (PW) with six-point pocket charting and radiographic assessment to act as a baseline for future care.

    The re-assessment examination revealed a reduction in probing pocket depth from 8 mm to 3 mm with only 1 mm increase in recession establishing a clinical attachment gain of 4 mm. Radiographic examination demonstrated significant bony infill of the infrabony defect (Figure 4) and evidence of a lamina dura suggestive of stability.11

    Figure 4. (a) Pre- and (b) post-operative radiographs (6 months) demonstrating evidence of bony infill and an intact lamina dura.

    The patient was been enrolled on 3-monthly supportive periodontal care with annual re-assessment.

    Discussion

    From the first surgical regenerative case successfully completed on a human tooth in 1982,12 flap design has continued to evolve with a variety of surgical approaches described within the literature. The common theme with novel surgical approaches, however, is a focus on minimal trauma to the soft tissue, with as minimally invasive an access as possible. The reason for this primarily being that our understanding of regenerative wound healing has developed to appreciate that a stable wound with primary intention healing is fundamental to allow regenerative processes to take place.

    It should therefore be no surprise that MINST is being applied more and more in clinical practice. A universally accepted protocol for MINST is yet to be established, although research methodology reveals common concepts underpinning the technique. Table 1 highlights various protocols applied within the literature when investigating MINST, including the original protocol from the randomized control trial in 2011. The common themes associated with MINST described within the literature include:

  • Thorough debridement of the root surface to the base of the periodontal pocket (biofilm removal);
  • The use of a combination of mini-curettes and ultrasonics with thin and delicate tips;
  • The use of magnification/loupes;
  • Caution to preserve the stability of the soft tissue/minimal trauma to the soft tissue.

  • Study MINST protocol
    Ribeiro et al1 Careful scaling and root planing with mini-curettes and use of ultrasonic devices with specific thin and delicate tips. The instruments were carefully inserted through the periodontal pockets of defect-associated teeth to debride the root surface, with caution taken to preserve the stability of soft tissues
    Nibali et al2,4 Thorough debridement of the root surface to the base of the periodontal pocket with local anaesthesia. Minimal trauma to the soft tissue with the use of piezo-electric devices with thin and delicate tips, and the use of mini curettes Magnification (x3.4) was used, and stimulation of a stable blood clot by natural filling of the defect with blood following debridement was attempted
    Aimetti et al18 Careful debridement with the combined use of mini-curettes and ultrasonic instruments with thin and delicate tips. Use of a gingival retractor, x12.5 magnification and a microsurgical mirror to access the periodontal pocket with caution taken to avoid soft tissue trauma. The use of sterile wetting gauze was used to apply gentle compression to the gingival margin to preserve stability of the soft tissues and obtain pocket marginal closure
    Jentsch et al15 Following application of local anaesthetic with vasoconstrictor, sites were carefully debrided with a combination of mini-curettes and ultrasonics with thin and delicate tips. Sterile wetting gauze was used to apply gentle compression to the gingival margin to preserve stability of the soft tissues and obtain pocket marginal closure

    For this case, we elected to use local anaesthetic with the use of a vasoconstrictor. It should be noted that some MINST protocols avoid the use of a vasoconstrictor to promote filling of the defect with blood following the procedure and allow a stable blood clot, which would lead to optimal wound healing. There is, however, no evidence to date that suggests superior outcomes using local anaesthetics without vasoconstrictors for this procedure.

    The use of EMDs as an adjunct for non-surgical therapy is not new, with a randomized controlled trial investigating their use dating back to 2003. This initial study applied Emdogain as an adjunct to non-surgical therapy of an infrabony defect as part of initial subgingival PMPR, and demonstrated no significant benefit to its use based on PPD reduction and CAL gain.13 However, it must be noted that the non-surgical approach describes instrumentation of the root surface until ‘hard and smooth,’ and no mention of atraumatic soft tissue management, which does not follow the principles of MINST.

    More recently, a systematic review and meta-analysis found that when looking at the outcomes of PPD reduction and CAL gain, the addition of EMD failed to provide a benefit when compared with non-surgical therapy alone.14 These results must be interpreted with caution, and not as evidence for a lack of potential for these materials. This first meta-analysis on the topic included only four studies, which when appraised in detail, showed that the timing of the EMD application as an adjunct varied, with some studies using the biologic at Step 2 and others at Step 3. As this case report has demonstrated, adequate moisture/bleeding control is required for correct/effective application of Emdogain and therefore, it may be more pragmatic to consider its use at Step 3 of therapy once inflammation has reduced, and thus tissue quality has begun to improve, and if residual pocketing remains.

    The use of PPD reduction and CAL gain as the best outcome measures must also be considered because the factor that dictates clinical decision making and the need for further intervention (e.g. surgery) is whether pocket closure (PPD ≤4 mm with no BOP) has been achieved. A more recent multi-centre randomized control trial has investigated pocket closure following the application of EMD alongside non-surgical therapy at Step 3 (i.e. initial therapy had been completed and residual pocketing remained) compared with a control group receiving repeated non-surgical treatment alone. At 12 months, 80% of the test sites demonstrated pocket closure compared with 42% in the control group, suggesting that EMDs could play a role in the treatment of residual pockets prior to considering surgery.15 Most recently, where regenerative therapies are being applied, the use of composite outcome measures (pocket closure AND the need for CAL gain ≥3 mm), first described by Trombelli and colleagues16 for surgical intervention, are now being applied to MINST-based research. A recent randomized control trial demonstrated more sites treated with EMD achieving successful composite outcome measures compared with those receiving non-surgical therapy alone.17

    The limitations of a single case report must be considered and, in particular, the lack of a control group allowing comparison of this outcome with viable alternatives, such as minimally invasive non-surgical therapy alone, or a minimally invasive surgical approach with or without biomaterials, which may produce similar/superior regenerative outcomes.

    Conclusion

    Accepting the limitations of case reports, this case demonstrates the potential of EMDs as an adjunct to minimally invasive non-surgical therapy for the treatment of infrabony defects when residual pocketing remains after Step 2 of therapy. Future research in the form of randomized controlled trials should be encouraged in this area, alongside data on patient reported outcomes, because this approach could be used by a range of dental professionals and may avoid the need for surgical intervention.