Periodontal Ligament-Mimetic Fibrous Scaffolds Regulate YAP-Associated Fibroblast Behaviors and Promote Regeneration of Periodontal Defect in Relation to the Scaffold Topography

Abstract

Although multiple regenerative strategies are being developed for periodontal reconstruction, guided periodontal ligament (PDL) regeneration is difficult because of its cellular and fibrous complexities. Here, we manufactured four different types of PDL-mimic fibrous scaffolds on a desired single mat. These scaffolds exhibited a structure of PDL matrix and human PDL fibroblasts (PDLFs) cultured on the scaffolds resembling morphological phenotypes present in native PDLF. The scaffold-seeded PDLF exerted proliferative, osteoblastic, and osteoclastogenic potentials depending on the fiber topographical cues. Fiber surface-regulated behaviors of PDLF were correlated with the expression patterns of yes-associated protein (YAP), CD105, periostin, osteopontin, and vinculin. Transfection with si-RNA confirmed that YAP acted as the master mechanosensing regulator. Of the as-spun scaffolds, aligned or grid-patterned microscale scaffold regulated the YAP-associated behavior of PDLF more effectively than nanomicroscale or random-oriented microscale scaffold. Implantation with hydrogel complex conjugated with microscale-patterned or grid-patterned scaffold, but not other types of scaffolds, recovered the defected PDL with native PDL-mimic cellularization and fiber structure in the reformed PDL. Our results demonstrate that PDL-biomimetic scaffolds regulate topography-related and YAP-mediated behaviors of PDLF in relation to their topographies. Overall, this study may support a clinical approach of the fiber−hydrogel complex in guided PDL regenerative engineering.

Advancing Dentistry through Bioprinting: Personalization of Oral Tissues

“…Innovative efforts have been directed at designing fibrous scaffolds that mimic the structure of the periodontal ligament (PDL) matrix, along with the integration of human PDL fibroblasts (PDLFs). These scaffolds, cultured with PDLFs, mirror the morphological traits observed in native PDLFs and evoke proliferative, osteoblastic, and osteoclastogenic potentials based on fiber topographical cues [133,134].…”

Effects of Improper Mechanical Force on the Production of Sonic Hedgehog, RANKL, and IL-6 in Human Periodontal Ligament Cells In Vitro

“…In periodontal tissue, PDLFs attach cement to neighboring alveolar bones, and fibrous connective tissue is involved in this process; 100s of collagen fibers, such as Sharpey's and oxytalan fibers, are included [36]. PDLFs react sensitively to mechanical stimulation through interaction with the fiber-formed matrix [37][38][39]. In this study, HGFs, which were used as a control, reacted to mechanical stimulation, but the reactivities to weights for the production of RANKL and IL-6 were weaker than those of PDLFs.…”

Distinct and overlapping functions of YAP and TAZ in tooth development and periodontal homeostasis

“…Those findings have been confirmed in studies on periodontal fibroblasts ( Table 1 ). For example, Kim et al found that YAP not only influenced the morphology and cytoskeleton of PDLFs but it also regulated their proliferation and mineralization through a PDL-mimic fibrous scaffold model ( Kim et al, 2023 ). Moreover, the application of static strain to human PDLFs (hPDLFs) results in significant nuclear translocation of YAP, which is mediated by the activation of extracellular signal regulated kinase (ERK)1/2 ( Hulter-Hassler et al, 2017 ).…”