Clinical Outcome of Treating Peri-Mucositis and Peri-implantitis with Adjunctive Enamel Matrix Derivative Application: A Systematic Review

Purpose: Enamel matrix derivative (EMD), the active component of Emdogain®, has been demonstrated to affect cytokines related to fibroplasia, angiogenesis, inflammation, and chemotaxis both in vitro and in vivo. However, whether the adjunctive application of EMD has clinical benefits on treating peri-mucositis and peri-implantitis has not been investigated thoroughly. The aim of this systematic review is to investigate the clinical outcomes of treating peri-implant diseases with adjunctive EMD application. Materials and Methods: A systematic search of multiple electronic databases including PubMed, Cochrane library, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Embase, and Scopus was carried out based on the PICOs structure for articles published up to September 2020. The primary outcomes were bleeding on probing (BoP), probing depth (PD), and radiographic bone level (RBL). Data and risk of bias were explored qualitatively. Results: The search identified 942 studies with 7 studies included for qualitative analysis. These studies reported 200 participants with 270 implants diagnosed with peri-mucositis (n=41) and peri-implantitis (n=229). For implants with peri-mucositis, BoP reduced significantly (83 to 25%) at the 3-month follow-up period for those treated with non-surgical mechanical debridement combined with adjunctive EMD (EMD group), while there was limited improvement for those treated by mechanical debridement alone (control group). PD also decreased (4.5 to 3.12 mm) in EMD group whereas an increase to 5.17 mm was demonstrated in the control group. For cases diagnosed with peri-implantitis, the high prevalence rate (83% - 100%) of BoP at baseline was significantly reduced in 2 prospective studies at the 2-10-years follow-up after surgical debridement, surface decontamination with bone graft, and EMD application. However, there was no statistical difference between surgical treatment with or without adjunctive EMD application in the other randomized controlled trials (RCTs) and half of the implants still demonstrated persistent BoP. Moreover, the PD can also be reduced significantly from 8.12 to 3.17 mm for those treated with adjunctive EMD while the RBL reduced from 4.41 to 2.31 mm at 2-10 year follow-up. The overall survival rate was 85-100% at 2-10 years follow-up. Conclusion: This review investigated the efficacy of adjunctive EMD for treating peri-implant diseases and was able to demonstrate its effect in reducing PD, reducing BoP, and increasing survival rate of treated implants from 2 to 10 years. The beneficial impacts of traditional surgical therapy on implants diagnosed with peri-implantitis were investigated; however, in terms of treating peri-implantitis, the definite efficacy of adjunctive usage of EMD should be determined based on more quantitative analysis and research in future.