"Periodontal Ligament-on-chip" As a Novel Tool for Studies on the Physiology and Pathology of Periodontal Tissues

Teeth exert fundamental physiological functions, such as mastication and speech, and are a key feature of oral health that affects life quality. Teeth are anchored to the alveolar bone via the periodontal ligament, which provides stability to the teeth and absorbs mechanical stresses during mastication. Periodontal infection leads to periodontitis, a severe inflammation of the supporting soft tissues that ultimately cause tooth loss. Despite the pressing need of periodontal regeneration for improved oral care, efficient in vitro models of the periodontal tissues are still missing, thus hampering the development of novel, faster, and more effective therapy modalities. Herein, a novel "periodontal ligament (PDL)-on-chip" model that integrates patient-derived periodontal ligament cells (PDLCs) and endothelial cells is introduced. This microfluidic platform provides optimal conditions for the formation of extensive and perfusable vascular networks. Furthermore, PDLCs elicit blood vessels' development and maturation while establishing close contacts with the endothelial cells. Potential applications for inflammatory periodontal diseases are also successfully displayed in the "PDL-on-chip" by stimulating inflammation and detecting inflammatory cytokines. This work offers a cornerstone for more complex and specialized microfluidic dental models, which are necessary to unravel complex oral diseases that affect individuals' general health that go beyond the field of dentistry.