Tendon injuries and tendinopathies represent major clinical challenges due to the tissue’s intrinsic hypovascularity and low cellularity, which constrain its reparative capacity. Typically induced by mechanical overuse or senescence, these disorders follow a pathological continuum, from reactive to degenerative tendinopathy, characterized by progressive alterations in cell phenotype, ECM architecture, and biomechanical properties. Although numerous signalling pathways are implicated in tendon repair, the molecular mechanisms regulating tenogenesis and functional regeneration remain incompletely elucidated, necessitating the development of targeted regenerative approaches such as tendon tissue engineering. This study aimed to enhance tenogenic differentiation of MSCs and TPSCs by modulating biological signalling within a controlled in vitro niche. Central to this approach was the design of anisotropic electrospun polycaprolactone (PCL) scaffolds that recapitulate the native tendon’s hierarchical architecture, providing topographical, biochemical and mechanical cues for lineage commitment. The tenoinductive potential of GDF-5, GDF-6, and GDF-7 was systematically evaluated to delineate their individual and comparative roles in directing tenocyte differentiation in both air (21%) and physiological (2%) oxygen concentration. Following the identification of GDF-7 as the most potent tenoinductive factor, scaffold biofunctionalization was achieved through incorporation of mesoporous silica nanoparticles (MSNs) for sustained and localized delivery of GDF-7, thereby enhancing cellular responsiveness and promoting tenogenic differentiation. Moreover, cyclic mechanical loading under physoxic oxygen conditions significantly enhanced tenogenic commitment, upregulating tendon-specific gene expression and promoting extracellular matrix maturation. These results highlight the efficacy of bio-hybrid constructs integrating structural, biochemical, and mechanical cues to emulate the native tendon microenvironment and support the development of advanced regenerative therapies for tendon repair.
Vera Citro (Thu,) studied this question.