Breaking Barriers: Evaluating Challenges in Advancing Periodontal Ligament Cell-Derived Organoids.

The objective of this review was to critically evaluate the available literature on the development of periodontal ligament organoids. Articles concerning periodontal ligament organoids were considered eligible. References were selected in a two-phased process. Electronic databases PubMed and Scopus were screened up to June 2024, yielding 1101 studies. After removing duplicates, titles, and abstracts were screened, resulting in 44 articles being included in this review. A detailed analysis of the included articles was organized into four categories: (1) the cell lineages used, including the simultaneous use of two or more cell types, (2) the extracellular matrix composition, (3) the organoid preparation methods, and (4) the characterization techniques employed. The main findings show that collagen combined with biodegradable polymers-such as poly(caprolactone), poly(glycolic acid), and poly(lactic acid)-is the most used material. Periodontal ligament cells and periodontal fibroblasts were the most used cell types, due to their role in extracellular matrix remodeling. The most frequent analyses performed included alkaline phosphatase, extracellular matrix mineralization, and gene expression, providing insights into differentiation and periodontal regeneration. Cementogenic differentiation was the most studied, followed by osteogenic, chondrogenic, adipogenic, and epithelial differentiation. However, challenges remain, including methodological inconsistencies and the need for scaffold optimization. Future research should focus on standardizing protocols, improving biomaterials, and integrating bioprinting techniques to improve clinical translation.