Transforming Growth Factor Beta 3-Loaded Decellularized Equine Tendon Matrix for Orthopedic Tissue Engineering.

ABSTRACT

Transforming growth factor beta 3 (TGFß3) promotes tenogenic differentiation and may enhance tendon regeneration in vivo. This study aimed to apply TGFß3 absorbed in decellularized equine superficial digital flexor tendon scaffolds, and to investigate the bioactivity of scaffold-associated TGFß3 in an in vitro model. TGFß3 could effectively be loaded onto tendon scaffolds so that at least 88% of the applied TGFß3 were not detected in the rinsing fluid of the TGFß3-loaded scaffolds. Equine adipose tissue-derived multipotent mesenchymal stromal cells (MSC) were then seeded on scaffolds loaded with 300 ng TGFß3 to assess its bioactivity. Both scaffold-associated TGFß3 and TGFß3 dissolved in the cell culture medium, the latter serving as control group, promoted elongation of cell shapes and scaffold contraction (p < 0.05). Furthermore, scaffold-associated and dissolved TGFß3 affected MSC musculoskeletal gene expression in a similar manner, with an upregulation of tenascin c and downregulation of other matrix molecules, most markedly decorin (p < 0.05). These results demonstrate that the bioactivity of scaffold-associated TGFß3 is preserved, thus TGFß3 application via absorption in decellularized tendon scaffolds is a feasible approach.