Tissue Reorganization in Response to Mechanical Load Increases Functionality

Abstract

In the rapidly growing field of tissue engineering, the functional properties of tissue substitutes are recognized as being of the utmost importance. The present study was designed to evaluate the effects of static mechanical forces on the functionality of the produced tissue constructs. Living tissue sheets reconstructed by the self-assembly approach from human cells, without the addition of synthetic material or extracellular matrix (ECM), were subjected to mechanical load to induce cell and ECM alignment. In addition, the effects of alignment on the function of substitutes reconstructed from these living tissue sheets were evaluated. Our results show that tissue constructs made from living tissue sheets, in which fibroblasts and ECM were aligned, presented higher mechanical resistance. This was assessed by the modulus of elasticity and ultimate strength as compared with tissue constructs in which components were randomly oriented. Moreover, tissue-engineered vascular media made from a prealigned living tissue sheet, produced with smooth muscle cells, possessed greater contractile capacity compared with those produced from living tissue sheets that were not prealigned. These results show that the mechanical force generated by cells during tissue organization is an asset for tissue component alignment. Therefore, this work demonstrates a means to improve the functionality (mechanical and vasocontractile properties) of tissues reconstructed by tissue engineering by taking advantage of the biomechanical forces generated by cells under static strain.

Decellularization of Fibroblast Cell Sheets for Natural Extracellular Matrix Scaffold Preparation

“…Furthermore, the microarchitecture of the cell-derived ECM scaffolds can be modulated to achieve different space organization in order to enhance biomimicry. 8,9 Several studies have shown that there is superiority for the application of cell-derived ECM as a scaffold. 4,5,10 The cell-derived ECM can significantly enhance cell adhesion, migration, proliferation, and acquisition of in vivo-like morphology compared with reconstituted ECM.…”

A thermoresponsive, microtextured substrate for cell sheet engineering with defined structural organization

“…On the other hand, tissue engineered grafts made solely from cell-secreted ECM, using a "self-assembly" or cell sheet-based approach, could support high burst pressures and have shown success in vivo, yet lacked the desired organization [14]. However, further refinement of this approach using static mechanical load to align matured cell sheets has resulted in tissues with the desired cell/matrix organization and mechanical anisotropy [15]. These results are extremely encouraging, however, this method requires increasing the already lengthy incubation time in order generate such organization.…”

Passive Strain-Induced Matrix Synthesis and Organization in Shape-Specific, Cartilaginous Neotissues

“…[46][47][48] Further, treatment of cell-seeded collagen gels with sodium azide, an ATP inhibitor, or cytochalasin D, a cytoskeletal inhibitor, has been found to inhibit such matrix reorganization following mechanical stimulation. 49,50 Previous work has also correlated increased biomechanical properties in engineered neotissues with increased crosslinks, 38,51 suggesting that the greater functional properties in the middle zone of 10-g-loaded constructs are likely related to the increased crosslink content in this region. Such work indicates that cells, in response to a mechanical input, generate intrinsic traction forces to align compact, and crosslink collagen fibers such that they counter the newly loaded environment.…”