Construction of tendon replacement tissue based on collagen sponge and mesenchymal stem cells by coupled mechano-chemical induction and evaluation of its tendon repair abilities.

Tissue engineering is an ideal therapeutic strategy for the development of functional tendon replacement tissue for tendon repair in the clinic. Currently, the synergistic roles of mechano-chemical factors and the mechanisms involved in tendon repair and regeneration are not fully understood. In this study, we developed a three-dimensional (3D) culture system based on a silicone chamber and collagen sponge scaffold that can deliver cyclic mechanical stretch and biochemical stimulation to bone marrow-derived mesenchymal stem cells (BMSCs) seeded on the scaffold. We found that the combined stimulation of cyclic stretch and transforming growth factor beta 1 (TGF-ß1) treatment not only increased cell viability but also synergistically promoted the differentiation of BMSCs into tenocytes in a 3D culture environment. Meanwhile, the combined stimulation increased the Young's modulus of the BMSC-collagen sponge constructs by reducing the porosity of the scaffold compared to the non-treated constructs. Furthermore, a rat Achilles tendon in situ repair experiment showed that enhanced tendon regeneration was achieved using the BMSC-collagen sponge construct combined with cyclic stretch and TGF-ß1, as confirmed by Achilles functional index (AFI) measurement, morphological observation, histological analysis, and mechanical testing. These results suggest that this approach could offer a practical benefit in tendon healing and future tendon tissue engineering. STATEMENT OF SIGNIFICANCE: This study aims to disclose the crucial roles of the coupled induction by mechano-chemical stimulation in tendon tissue engineering and clarifies their collaborative control mechanisms. We developed a three-dimensional (3D) culture system based on a silicone chamber and collagen sponge scaffold that could deliver cyclic mechanical stretch and biochemical stimulation to bone marrow-derived mesenchymal stem cells (BMSCs). We found that the combined stimulation of cyclic stretch and transforming growth factor beta 1 (TGF-ß1) could result in an improvement of tissue-engineered construct for enhancing tendon healing. These results suggest that this approach could offer a practical benefit in tendon healing and future tendon tissue engineering.