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Tendon Tissue Engineering: Effects of Mechanical and Biochemical Stimulation on Stem Cell Alignment on Cell‐Laden Hydrogel Yarns
Author(s) -
Rinoldi Chiara,
Costantini Marco,
KijeńskaGawrońska Ewa,
Testa Stefano,
Fornetti Ersilia,
Heljak Marcin,
Ćwiklińska Monika,
Buda Robert,
Baldi Jacopo,
Cannata Stefano,
Guzowski Jan,
Gargioli Cesare,
Khademhosseini Ali,
Swieszkowski Wojciech
Publication year - 2019
Publication title -
advanced healthcare materials
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.288
H-Index - 90
eISSN - 2192-2659
pISSN - 2192-2640
DOI - 10.1002/adhm.201801218
Subject(s) - mesenchymal stem cell , tissue engineering , tendon , materials science , gelatin , biomedical engineering , regeneration (biology) , stem cell , cell , regenerative medicine , biophysics , microbiology and biotechnology , anatomy , chemistry , biology , medicine , biochemistry
Fiber‐based approaches hold great promise for tendon tissue engineering enabling the possibility of manufacturing aligned hydrogel filaments that can guide collagen fiber orientation, thereby providing a biomimetic micro‐environment for cell attachment, orientation, migration, and proliferation. In this study, a 3D system composed of cell‐laden, highly aligned hydrogel yarns is designed and obtained via wet spinning in order to reproduce the morphology and structure of tendon fascicles. A bioink composed of alginate and gelatin methacryloyl (GelMA) is optimized for spinning and loaded with human bone morrow mesenchymal stem cells (hBM‐MSCs). The produced scaffolds are subjected to mechanical stretching to recapitulate the strains occurring in native tendon tissue. Stem cell differentiation is promoted by addition of bone morphogenetic protein 12 (BMP‐12) in the culture medium. The aligned orientation of the fibers combined with mechanical stimulation results in highly preferential longitudinal cell orientation and demonstrates enhanced collagen type I and III expression. Additionally, the combination of biochemical and mechanical stimulations promotes the expression of specific tenogenic markers, signatures of efficient cell differentiation towards tendon. The obtained results suggest that the proposed 3D cell‐laden aligned system can be used for engineering of scaffolds for tendon regeneration.

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