The Role of Biologically Active Materials in Peri-Implant Diseases

Background/Objectives: Peri-implant diseases, encompassing peri-implant mucositis and peri-implantitis, affect 43% and 18.8–23% of implant-bearing patients, respectively, representing significant clinical challenges in implant dentistry. While mechanical debridement remains foundational, biologically active materials offer promising adjunctive regenerative strategies. This narrative review synthesises current evidence regarding five biologically active materials: enamel matrix derivative (EMD), platelet-rich fibrin (PRF), fibroblast growth factor-2 (FGF-2), recombinant human platelet-derived growth factor-BB (rhPDGF-BB/GEM 21S®), and polynucleotide–hyaluronic acid combinations (Regenfast®). Methods: The relevant literature was identified using electronic databases, including MEDLINE, PubMed, Scopus, and Google Scholar. This review focused on clinical studies and randomised controlled trials with a minimum follow-up of six months investigating biologically active materials in peri-implant disease management. Material mechanisms, clinical efficacy, therapeutic limitations, and evidence quality were systematically evaluated. Attention was directed toward identifying genuine biological distinctions between peri-implant and periodontal disease contexts. Results: EMD demonstrates efficacy exclusively within multimodal surgical protocols, with isolated application yielding limited benefits. rhPDGF-BB shows superior periodontal regenerative capacity; however, dedicated peri-implantitis trials remain absent. FGF-2 exhibits paradoxical osteogenic suppression despite bone fill achievement, limiting peri-implant applicability. PRF and Regenfast® demonstrate a mechanistically sound rationale yet lack substantive peri-implant disease validation. The critical findings revealed that peri-implant regeneration fundamentally differs from periodontal regeneration: implants lack periodontal ligament anatomy, rendering ligamentogenic differentiation-promoting agents biologically inappropriate. Conclusions: Contemporary biologically active materials demonstrate compelling periodontal efficacy yet remain inadequately validated for peri-implantitis management. This disparity reflects authentic biological distinctions rather than insufficient investigation. Until multicentre randomised controlled trials stratify efficacy across distinct peri-implant disease presentations, practitioners must prioritise evidence-based surgical fundamentals—meticulous decontamination, strategic grafting, and optimised wound healing—integrating biologically active materials judiciously within comprehensive, anatomy-respecting treatment protocols.