In Vitro 3D Culture of Human Pathological Tendon Stem/Progenitor Cells Enables the Evaluation of Inflammatory Marker...

Background/Objectives: Human tendon stem/progenitor cells (hTSPCs) isolated from tendinopathic tendon tissue were used to identify key inflammatory biomarkers, including reactive oxygen species (ROS), pro-inflammatory cytokine release, and type III collagen expression. This cellular model was employed as an in vitro platform to investigate the effects of a semiconductor-nanoparticles embedded fabric (hereafter named fabric) on inflammatory marker regulation. Methods: hTSPCs were cultured in both conventional monolayer conditions and within a three-dimensional (3D) bioplotted methacrylated collagen (ColMA) scaffold under perfusion. The cells were exposed to a microenvironment enriched with negative ions and far-infrared radiation generated by fabric to assess its modulatory effects on native inflammatory and fibrotic pathways. Results: Fabric exposure significantly reduced ROS levels and modulated cytokine signaling pathways. These changes were associated with observed enhanced cell viability and proper extracellular matrix composition profile, characterized by reduced type III collagen and increased type I collagen deposition. Consistent findings were observed at both the protein and gene expression levels. Notably, these effects were more evident in the 3D culture system, likely due to its greater biomimetic relevance and ability to more accurately reproduce the native cellular microenvironment. Conclusions: Overall, these preliminary findings suggest that fabric promotes a transition from a fibrotic toward a more regenerative tendon-like phenotype, likely mediated by redox balance which probably improved ECM remodeling. Further studies should evaluate the potential of semiconductor-based fabrics to support tendon regeneration in vivo.