Diagnostic potential of Active-Matrix Metalloproteinase-8 for Peri-Implantitis: A Systematic Review

Background: Peri-implantitis is a progressive inflammatory disease leading to peri-implant bone loss and potential implant failure. Conventional diagnostic methods detect established tissue destruction but fail to identify early inflammatory activity. Active matrix metalloproteinase-8 (aMMP-8), a collagenase released during active inflammation, has been proposed as a potential biomarker for the early detection of peri-implant disease. This systematic review aimed to assess the diagnostic accuracy and clinical usefulness of aMMP-8 for the diagnosis of peri-implantitis in patients with dental implants. Methods: The review protocol was registered in PROSPERO (CRD420251267773). A comprehensive search was conducted in PubMed, Embase, and Scopus up to 31st October 2025, supplemented by manual and grey literature searches. Studies assessing aMMP-8 in peri-implant sulcular fluid (PISF) for the diagnosis of peri-implantitis were included. Data on biomarker detection methods, diagnostic performance in terms of sensitivity, specificity, accuracy and Area Under the Receiver Operating Characteristic Curve (ROC-AUC), and correlations with clinical indices were extracted. Study quality was assessed using the Newcastle-Ottawa Scale (NOS). A qualitative analysis was conducted by compiling a summary of findings table for all included studies. Results: Eight studies published between 2016 and 2025, with a total of 506 patients (293 with health peri-implant tissues or mucositis, and 213 diagnosed with peri-implantitis) met inclusion criteria. Study quality was generally high (mean NOS score: 7.1±0.6 (standard deviation)). Seven studies assessed aMMP-8 using point-of-care lateral flow immunoassay, and one used immunoassay after PISF freezing and thawing. aMMP-8 levels were consistently elevated in peri-implantitis compared to mucositis and healthy sites. Reported diagnostic sensitivity for peri-implantitis ranged 70-100%, specificity 74.1-100.0%, and ROC-AUC 0.80-0.88. Due to heterogeneity across included studies, no meta-analysis was performed. Conclusions: aMMP-8 in PISF represents a non-invasive biomarker with high diagnostic accuracy for early detection of peri-implantitis. Standardization of cutoff thresholds and longitudinal validation are required before routine clinical integration.