Background: Periodontitis is a chronic inflammatory condition causing destruction of periodontal tissues, including alveolar bone. Fucoidan, a sulphated polysaccharide from brown algae, shows promising osteogenic and anti-inflammatory potential. This systematic review aimed to evaluate the osteoinductive potential of fucoidan on periodontal ligament stem cells (PDLSCs) for periodontal bone regeneration applications. Methods: Systematic review and meta-analysis were conducted following PRISMA guidelines across PubMed, Scopus, Cochrane, WorldCat, Google Scholar, Lens, Taylor & Francis Online, ScienceDirect, and ClinicalTrials.gov for studies published between January 2015 and April 2025. Inclusion criteria comprised: research on PDLSCs, experimental studies evaluating fucoidan-based treatments, and parameters of alkaline phosphatase activity, matrix mineralization, intracellular calcium levels, and expression of osteogenic markers. Study quality was assessed using a QUIN Tool. Results: From 207 identified articles, four studies met the inclusion criteria. All studies demonstrated that fucoidan and its derivatives enhanced alkaline phosphatase activity, extracellular matrix mineralization, and expression of osteogenic markers such as RUNX2, OCN, and OSX in PDLSCs. Two studies analyzed the activation of PI3K/Akt and Wnt pathways involved in osteogenic differentiation. Other studies confirmed fucoidan's effectiveness in inflammatory conditions resembling periodontitis by reducing pro-inflammatory cytokines TNF-α and IL-1β. One study involving in vivo validation showed that fucoidan-containing extract prevented alveolar bone loss in a rat model. Conclusion: Fucoidan demonstrates significant osteoinductive potential in PDLSCs, as evidenced by enhanced alkaline phosphatase activity, matrix mineralization, and osteogenic marker expression. Osteoinduction effects make fucoidan a promising natural biomaterial candidate for regenerative applications in periodontal bone defects.

Keywords: Fucoidan, periodontal ligament stem cells, osteogenesis, bone regeneration, periodontitis.