Mechanical Stretching for Tissue Engineering: Two-Dimensional and Three-Dimensional Constructs

Abstract

Mechanical cell stretching may be an attractive strategy for the tissue engineering of mechanically functional tissues. It has been demonstrated that cell growth and differentiation can be guided by cell stretch with minimal help from soluble factors and engineered tissues that are mechanically stretched in bioreactors may have superior organization, functionality, and strength compared with unstretched counterparts. This review explores recent studies on cell stretching in both two-dimensional (2D) and three-dimensional (3D) setups focusing on the applications of stretch stimulation as a tool for controlling cell orientation, growth, gene expression, lineage commitment, and differentiation and for achieving successful tissue engineering of mechanically functional tissues, including cardiac, muscle, vasculature, ligament, tendon, bone, and so on. Custom stretching devices and lab-specific mechanical bioreactors are described with a discussion on capabilities and limitations. While stretch mechanotransduction pathways have been examined using 2D stretch, studying such pathways in physiologically relevant 3D environments may be required to understand how cells direct tissue development under stretch. Cell stretch study using 3D milieus may also help to develop tissue-specific stretch regimens optimized with biochemical feedback, which once developed will provide optimal tissue engineering protocols.

Strain-induced Collagen Organization at the Micro-level in Fibrin-based Engineered Tissue Constructs

“…Applied strains and strains sensed at the tissue level may change with time, since the mechanical properties of the tissue also changes with time. It is also suggested by Rhiel et al 26 that the ECM might be disintegrated by stretch, altering the strain the cells will sense. Hence, applied strains, development of the ECM and changing tissue properties with time result in unknown applied strains to the cells.…”

“…Due to the intermittent cyclic protocol, resting periods prevent cells from possible adaptation to mechanical conditioning, and thus preventing possible unwanted long-term decline in strain effects. 26 It was shown that with increasing strain magnitude between 2 and 16%, collagen density increases exponentially. 3 So with a higher strain magnitude than used in Protocol B, it is possible that due to more collagen formation, collagen remodeling occurs at an even faster rate.…”

Overcoming physical constraints in bone engineering: ‘the importance of being vascularized’

“…doi:10.1016/S0091-679X(10)98007-2.]. The strain rate of specific waveforms may be adjusted to achieve desired results (Riehl, Park, Kwon, & Lim, 2012). Stretch frequency has been shown to orchestrate cell orientation through the remodeling of focal adhesions and stress fibers in endothelial cells (Hsu, Lee, & Kaunas, 2009).…”

Fibrin Gels Exhibit Improved Biological, Structural, and Mechanical Properties Compared with Collagen Gels in Cell-Based Tendon Tissue-Engineered Constructs

“…12,13 Tendon and ligament progenitor (TLP) cells respond to these mechanical stimuli by enhancing SCX expression and other ECM proteins. 7,[14][15][16] These cell-ECM interactions during development are important in defining the composition and organization of these tissues. Similarly, understanding how cell-material interactions affect TEC formation will lead to more effective strategies for soft tissue repair.…”