A Tympanic Piezo-Bioreactor Modulates Ion Channel-Associated Mechanosignaling to Stabilize Phenotype and Promote Tenogenesis in Human Tendon-Derived Cells.

Preserving the function of human tendon-derived cells (hTDCs) during cell expansion is a significant challenge in regenerative medicine. In this study, a non-genetic approach is introduced to control the differentiation of hTDCs using a newly developed tympanic bioreactor. The system mimics the functionality of the human tympanic membrane, employing a piezoelectrically tuned acoustic diaphragm made of polyvinylidene fluoride-co-trifluoroethylene and boron nitride nanotubes.

FAK, vinculin, and talin control mechanosensitive YAP nuclear localization.

Focal adhesions (FAs) are nanoscale complexes containing clustered integrin receptors and intracellular structural and signaling proteins that function as principal sites of mechanotransduction in part via promoting the nuclear translocation and activation of the transcriptional coactivator yes-associated protein (YAP). Knockdown of FA proteins such as focal adhesion kinase (FAK), talin, and vinculin can prevent YAP nuclear localization. However, the mechanism(s) of action remain poorly understood.

Adhesive peptide and polymer density modulate 3D cell traction forces within synthetic hydrogels.

Cell-extracellular matrix forces provide pivotal signals regulating diverse physiological and pathological processes. Although mechanobiology has been widely studied in two-dimensional configurations, limited research has been conducted in three-dimensional (3D) systems due to the complex nature of mechanics and cellular behaviors. In this study, we established a platform integrating a well-defined synthetic hydrogel system (PEG-4MAL) with 3D traction force microscopy (TFM) methodologies to evaluate deformation and force responses within synthetic microenvironments, providing insights that are not tractable using biological matrices because of the interdependence of biochemical and biophysical properties and complex mechanics.

Analyzing immune response to engineered hydrogels by hierarchical clustering of inflammatory cell subsets.

Understanding the immune response to hydrogel implantation is critical for the design of immunomodulatory biomaterials. To study the progression of inflammation around poly(ethylene glycol) hydrogels presenting Arg-Gly-Asp (RGD) peptides and vascular endothelial growth factor, we used temporal analysis of high-dimensional flow cytometry data paired with intravital imaging, immunohistochemistry, and multiplexed proteomic profiling. RGD-presenting hydrogels created a reparative microenvironment promoting CD206 cellular infiltration and revascularization in wounded dorsal skin tissue.