Zinc-integrated strategies in active periodontal therapy: Mapping the evidence to the EFP stepwise framework - A...

Periodontitis is a significant global health burden, requiring effective management strategies to prevent tooth loss. The European Federation of Periodontology (EFP) S3-level clinical practice guidelines (2020) advocate a comprehensive, stepwise therapeutic approach to periodontal therapy, emphasizing the need for effective adjunctive regenerative modalities to limit the disease progression. Zinc, a trace element with well-established anti-inflammatory, antimicrobial and regenerative properties, has drawn significant attention in this domain. However, its diverse applications across the modern therapeutic protocols remain unmapped.

The primary objective of this review was to map the available evidence regarding zinc-integrated therapeutic strategies within active periodontal therapy and evaluate their alignment with the first three steps of EFP framework over the last five years.

The review considered human clinical trials and in vivo animal studies including the biological validation phases of hybrid biomaterial research, published between January 2020 and December 2025 that evaluated zinc-integrated interventions for periodontal or alveolar bone defects.

This scoping review followed the methodology of the Joanna Briggs Institute. A systematic search was executed across PubMed, Scopus, and Web of Science using a consolidated keyword strategy. Study selection, data extraction and evidence grading, using Oxford Centre for Evidence-Based Medicine 2009 levels of Evidence were performed to map study characteristics, zinc formulations, and clinical outcomes against the EFP framework.

A total of 1239 records were identified, with 68 studies included in the final synthesis. Evidence for Step 1 and conventional Step 2 was primarily derived from clinical trials (Level 1b) evaluating zinc containing oral hygiene products and local delivery agents, demonstrating significant potential in biofilm and gingival inflammation reduction. Conversely, most Step 2 smart nanomaterials and Step 3 surgical regeneration evidence remained confined to preclinical animal models (Level 5).

Zinc interventions offer potential, stage-specific benefits across EFP framework. Although early-phase biofilm control is effectively managed by zinc-driven ecological modulation, more invasive subgingival and surgical applications currently lack longitudinal human validation. While preclinical scaffolds exhibit profound osteoimmunomodulatory capabilities, clinical translation is fundamentally bottlenecked by element's dose-dependent cytotoxicity. Simultaneously, preclinical development should consider transitioning from conventional zinc-containing additives toward true zinc-based structural alloys. Ultimately, advancing these innovations into long-term clinical trials alongside rigorous multi-omic safety monitoring is necessary to fully realise zinc's potential as a key component in periodontal therapy.