The aim of the present randomized controlled clinical study is to compare the clinical, radiographic, and patient-centered efficacy of adjunctive application of either enamel matrix derivative (EMD) or hyaluronic acid (HA) gel in conjunction with non-surgical therapy compared to non-surgical therapy alone following a 12-month healing period.

Therefore, the following question related to the study is raised:

• Does the adjunctive local application of EMD or HA to non-surgical submucosal mechanical treatment of peri-implantitis result in better clinical, radiographic, and patient-centered outcomes compared to non-surgical therapy alone?

A total of 60 patients referred to the Gazi University Department of Periodontology, will be randomly assigned to receive the local application of EMD or HA in combination with non-surgical submucosal mechanical treatment of peri-implantitis or non-surgical therapy alone. Clinical measurements will be recorded at baseline, 3, 6, and 12 months after surgeries. Patient oral health related to the treatment procedures using a written questionnaire [Oral Health Impact Profile (OHIP-14)] and post-treatment pain and overall patient satisfaction about treatment modalities responses will be evaluated prior to treatment and 3, 6, and 12 months following therapy.

Peri-implantitis is considered a growing public health problem in implant dentistry due to its higher prevalence and non-linear accelerating progression pattern. Hence, it is imperative to apply effective treatment strategies to manage this pathological condition. The existing evidence has shown unpredictable therapeutic strategies for peri-implantitis. Conventional non-surgical treatment procedures based on the removal of biofilm accumulation and debridement/instrumentation of the implant surface have exhibited limited disease resolution and persistent inflammation following therapy. Therefore, the application of adjunctive chemotherapeutic bioagents may provide greater disease resolution and reduce the need for surgical treatment.

The application of EMD as an adjunctive measure in peri-implantitis treatment has been suggested to provide favorable outcomes by accelerating wound healing, reducing inflammation, having antimicrobial and antiseptic effects, and osteopromotive features. Although some studies exhibited clinical and radiographic efficacy of EMD in augmentative and non-augmentative surgical management of peri-implantitis, there is no study in the available literature analyzing the effects of flapless application of EMD in non-surgical therapy of peri-implantitis. Cross-linked HA, which has recently been recognized as a featured adjuvant chemotherapeutic bioagent, has also been shown to have beneficial effects in periodontal wound healing and soft and hard tissue regeneration. The use of high-molecular-weight HA has been demonstrated to alter bacterial colonization in the advanced stage of peri-implantitis. However, there is limited evidence about the therapeutic effect of cross-linked HA in peri-implantitis management.

The hypothesis of the study is that the application of EMD and cross-linked HA adjunct to non-surgical therapy could lead to superior outcomes compared to non-surgical therapy alone in peri-implantitis treatment. The null-hypothesis (H0) is that no statistically significant difference in terms of the mean change of probing depth (PD) values after 12 months would be detected among all the study groups.

The aim of the present randomized controlled clinical study is to compare the clinical, radiographic, and patient-centered efficacy of adjunctive application of either enamel matrix derivative (EMD) or hyaluronic acid (HA) gel in conjunction with non-surgical therapy compared to non-surgical therapy alone following a 12-month healing period.

Inclusion Criteria:

• Systemically healthy and ≥18 years of age,
• Implants with an SLA® or SLActive® surface (Straumann Dental Implant System, Institute Straumann AG) have been in function for more than 1 year,
• Implant-supported prostheses accessible for self-performed plaque control and submarginal instrumentation,
• Absence of implant mobility.

Exclusion Criteria:

• Full-mouth plaque score (FMPS) > 20%
• Full-mouth bleeding score (FMBS) > 20%
• Cigarette smoking > 10 cig./day,
• Diagnosed with active periodontal disease,
• Having acute or chronic medical conditions or undergoing medications, such as intravenous amino-bisphosphonates, immunosuppressive drugs, and chemotherapy, that could interfere with the treatment outcome,
• Receiving antibiotic treatment in the previous 3 months.

It is preferred to share all IPD collected throughout the study after the study will be completed and at the publication stage.