Tenogenic Induction of Human MSCs by Anisotropically Aligned Collagen Biotextiles

Abstract

A novel biofabrication modality, electrophoretic compaction with macromolecular alignment, was utilized to make collagen threads that mimic the native tendon’s structure and mechanical properties. A device with kinematic electrodes was designed to fabricate collagen threads in continuous length. For the first time, a 3D-biotextile was woven purely from collagen. Mechanical properties and load-displacement behavior of the biotextile mimicked those of the native tendon while presenting a porosity of 80%. The open pore network facilitated cell seeding across the continuum of the bioscaffold. Mesenchymal stem cells (MSCs) seeded in the woven scaffold underwent tenogenic differentiation in the absence of growth factors and synthesized a matrix that was positive for tenomodulin, COMP and type I collagen. Up-regulation of tenomodulin, a tendon specific marker, was 11.6 ± 3.5 fold, COMP was up-regulated 16.7 ± 5.5 fold, and Col I was up-regulated 6.9 ± 2.7 fold greater on ELAC threads when compared to randomly oriented collagen gels. These results demonstrate that a bioscaffold woven by using collagen threads with densely compacted and anisotropically aligned substrate texture stimulates tenogenesis topographically, rendering the electrochemically aligned collagen as a promising candidate for functional repair of tendons and ligaments.

A Self‐Powered Piezo‐Bioelectric Device Regulates Tendon Repair‐Associated Signaling Pathways through Modulation of Mechanosensitive Ion Channels

“…The expression of Tnmd has been shown to become upregulated in tendon cells when cultured on the aligned scaffold and mechanically stimulated. [51] Our results were consistent with these findings, where hTDCs cultured on aligned fibrous scaffold demonstrated a typical tenocyte-like morphology together with high levels of Tnmd. Conversely, hTDCs cultured on planar control surfaces showed low Tnmd mRNA levels and phenotypic drift (transdifferentiation).…”

Woven collagen biotextiles enable mechanically functional rotator cuff tendon regeneration during repair of segmental tendon defects in vivo

“…), they also express a tendon‐specific marker. These data are in agreement with previous experiments in vitro which demonstrated there is upregulation of scleraxis and increased tenomodulin production in MSCs seeded onto ELAC threads . A notable finding from these experiments in vivo is that the ELAC fibers within the group containing the scaffold alone (no MSCs) appear to be sufficient to induce tenogenic differentiation of the cells that infiltrate and encapsulate the scaffold, as no significant differences in presence of tenomodulin were noted between scaffold‐alone and cell‐seeded groups (Figure and Table ).…”

Heparinized collagen sutures for sustained delivery of PDGF-BB: Delivery profile and effects on tendon-derived cells In-Vitro

“…However, in day 14 and 21 time points col I and tenomodulin gene expression were moderately lower for PDGF-BB including threads than threads absent with the PDGF-BB. In previous publications we showed electrochemically aligned collagen threads to guide MSCs toward tenogenic lineage via topographical cues and without administration of growth factors [25, 29]. Similar to the current study, previous work [29] from our group demonstrated that addition of BMP-12 (GDF-5) reduces the expression of scleraxis and tenomodulin moderately by day 14.…”