iPSC‐derived tenocytes seeded on microgrooved 3D printed scaffolds for Achilles tendon regeneration

Abstract

Tendons and ligaments have a poor innate healing capacity, yet account for 50% of musculoskeletal injuries in the United States. Full structure and function restoration postinjury remains an unmet clinical need. This study aimed to assess the application of novel three dimensional (3D) printed scaffolds and induced pluripotent stem cell‐derived mesenchymal stem cells (iMSCs) overexpressing the transcription factor Scleraxis (SCX, iMSCSCX+) 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 iMSCSCX+ and outcomes were assessed in vitro via gene expression analysis and immunofluorescence. In vivo, rat Achilles tendon defects were repaired with iMSCSCX+‐seeded microgrooved scaffolds, microgrooved scaffolds only, or suture only and assessed via gait, gene expression, biomechanical testing, histology, and immunofluorescence. iMSCSCX+‐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 + iMSCSCX+‐treated group compared to the controls. Tensile testing of the tendons demonstrated improved biomechanical properties of the Scaffold + iMSCSCX+ group compared with the controls. Histology and immunofluorescence demonstrated more regular tissue formation in the Scaffold + iMSCSCX+ group. This study demonstrates the potential of 3D‐printed scaffolds with cell‐instructive surface topography seeded with iMSCSCX+ as an approach to tendon defect repair. Further studies of cell‐scaffold constructs can potentially revolutionize tendon reconstruction by advancing the application of 3D printing‐based technologies toward patient‐specific therapies that improve healing and functional outcomes at both the cellular and tissue level.

Facile and rapid fabrication of a novel 3D-printable, visible light-crosslinkable and bioactive polythiourethane for large-to-massive rotator cuff tendon repair

“…In recent years, numerous tissue engineering studies have made significant technical and conceptual advancements and contributions to tackle the development and fabrication of mechanically competent and pro-regenerative tendon biomaterial scaffolds for clinical repair. These include novel strategies based on cells [ [51] , [52] , [53] , [54] , [55] , [56] , [57] , [58] ], biological/biochemical cues [ 51 , [59] , [60] , [61] , [62] , [63] , [64] , [65] , [66] ], and biomaterial scaffolds [25,30,40,51,54,55, [67] , [68] , [69] , [70] , [71] , [72] , [73] ] as well as commercially available collagenous matrices such as GraftJacket™, Restore Orthobiologic Implant™ and Zimmer® Collagen Repair Patch [ 30 ] or commercially available synthetic polymers such as polyurethane-based SportsMesh Soft Tissue Reinforcement/Artelon® [ 30 ]. This body of work has made significant progress in the development of next-generation tendon therapeutics.…”