Cyclic Stretching Triggers Cell Orientation and Extracellular Matrix Remodeling in a Periodontal Ligament 3d in Vitro Model.

During orthodontic tooth movement (OTM), the periodontal ligament (PDL) plays a crucial role in regulating the tissue remodeling process. To decipher the cellular and molecular mechanisms underlying this process in vitro, we need suitable 3D models that more closely approximate the situation in vivo. Here, we developed a customized bioreactor that allows dynamic loading of PDL-derived fibroblasts (PDLF). A Collagen-based hydrogel mixture was optimized to maintain structural integrity and constant cell growth during stretching. Numerical simulations showed a uniform stress distribution in the hydrogel construct under stretching. Compared to static conditions, controlled cyclic stretching resulted in directional alignment of collagen fibers and enhanced proliferation and spreading ability of the embedded PDLF cells. Effective force transmission to the embedded cells was demonstrated by a more than threefold increase in Periostin protein expression. The cyclic stretch conditions also promoted extensive remodeling of the extracellular matrix, as confirmed by increased glycosaminoglycan production. Our results highlight the importance of dynamic loading over an extended period of time to determine the behavior of PDLF and to identify in vitro mechanobiological cues triggered during OTM-like stimulus. The introduced dynamic bioreactor is therefore a useful in vitro tool to study these mechanisms. This article is protected by copyright. All rights reserved.