iPSC-derived tenocytes seeded on microgrooved 3D printed scaffolds for Achilles Tendon Regeneration.

Tendons and ligaments have a poor innate healing capacity, yet account for 50% of musculoskeletal injuries in the US. Full structure and function restoration post-injury remains an unmet clinical need. This study aimed to assess the application of novel 3D printed scaffolds and induced pluripotent stem cell-derived mesenchymal stem cells (iMSCs) overexpressing the transcription factor Scleraxis (SCX, iMSC SCX+ ) as a new strategy for tendon defect repair. The polycaprolactone (PCL) scaffolds were fabricated by extrusion through a patterned nozzle or conventional round nozzle. Scaffolds were seeded with iMSC SCX+ and outcomes were assessed in vitro via gene expression analysis and immunofluorescence. In vivo, rat Achilles tendon defects were repaired with iMSC SCX+ -seeded microgrooved scaffolds, microgrooved scaffolds only, or suture only and assessed via gait, gene expression, biomechanical testing, histology, and immunofluorescence. iMSC SCX+ -seeded on microgrooved scaffolds showed upregulation of tendon markers and increased organization and linearity of cells compared to non-patterned scaffolds in vitro. In vivo gait analysis showed improvement in the Scaffold+iMSC SCX+ -treated group compared to the controls. Tensile testing of the tendons demonstrated improved biomechanical properties of the Scaffold+iMSC SCX+ group compared to the controls. Histology and immunofluorescence demonstrated more regular tissue formation in the Scaffold+iMSC SCX+ group. This article is protected by copyright. All rights reserved.