Tendon Tissue Engineering: Effects of Mechanical and Biochemical Stimulation on Stem Cell Alignment on Cell‐Laden Hydrogel Yarns

Abstract

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.

Role of Biomaterials and Controlled Architecture on Tendon/Ligament Repair and Regeneration

“…On a recent fabrication shift, researchers have tried to engineered T/L by directly printing of cell‐laden yarns . Rinoldi et al combined a co‐axial extrusion system with a microfluid device to 3D bioprint gelatin‐based hydrogel fibers loaded with human bone marrow–derived mesenchymal stem cells (hBM‐MSCs) . After biochemical and mechanical stimulation, cell orientation and tenogenic differentiation were observed.…”

Designer Self‐Assembling Peptide Hydrogels to Engineer 3D Cell Microenvironments for Cell Constructs Formation and Precise Oncology Remodeling in Ovarian Cancer

“…Luckily, synthetic chemistry has produced some inspired derivatives of native proteins. [ 48,49 ] Recently, a kind of semisynthetic hydrogel, GelMA hydrogel, is prepared to be applied in a broad range of biomedical researches, [ 50 ] including 3D bioprinting, [ 51 ] cardiac patch for heart repair, [ 52 ] specific tumor cell captures, [ 53 ] stem cell alignment for tendon tissue engineering, [ 54 ] the treatment of peripheral nerve damage, [ 55 ] and identification of tumor cell phenotype. [ 56 ] Due to the similarities in well‐defined morphological, compositional, and mechanical properties and, when properly designed, the similarities in biological features to the ECM, this kind of semisynthetic hydrogel is relatively a realistic kind of natural biomaterials to potentially use as a substitute of the ECM for reconstructive 3D cell models in tissue engineering, regenerative medicine, basic cancer researches, and some other items.…”

Advanced Bottom‐Up Engineering of Living Architectures

“…Moreover, know‐how from the textile industry, namely, knitting, weaving, and reeling has been transposed for the bottom‐up tissue engineering of fibrous structures due to its potential for generating biofunctional micro/macroscale constructs with improved bioactivity and mechanical properties . Interesting advances in this field include, but are not limited to, the fabrication of cell‐laden hydrogel yarns for tendon bioengineering through mechanical stimulation or the fabrication of vessel‐like networks with cell‐laden collagen fibers …”