Remodeling of Engineered Tissue Anisotropy in Response to Altered Loading Conditions

Abstract

Structural and mechanical anisotropy are critical to the function of many engineered tissues. This study examined the ability of anisotropic tissue constructs to overcome contact guidance cues and remodel in response to altered mechanical loading conditions. Square tissues engineered from dermal fibroblasts and type-I collagen were uniaxially loaded to induce cell and matrix alignment. After an initial time, t*, of 5 to 72 hrs, loading was switched from the x-axis to the y-axis. Cell alignment was examined throughout the experiment until a steady state was reached. Before t*, cells spontaneously aligned in the x-direction. After t*, the strength of alignment transiently decreased then increased, and mean cell orientation transitioned from the x-to the y-direction following an exponential time course with a time constant that increased with t*. Collagen fiber orientation exhibited similar trends that could not be explained by passive kinematics alone. Structural realignment resulted in concomitant changes in biaxial tissue mechanical properties. The findings suggest that even highly aligned engineered tissue constructs retain the capacity to remodel in response to altered mechanical stimuli. This may have important functional consequences when an anisotropic engineered tissue designed in vitro is surgically implanted into a mechanically complex graft site.

A Novel Flow Bioreactor forIn VitroMicrovascularization

“…Collagen compaction also causes disorganization of the tissue structure and limits our ability to monitor structural changes in the gel that are caused exclusively by cells. 39,40 By constraining the gel to a constant horizontal dimension, we maintain a constant cross-sectional area for application of flow, and provide a high degree of reproducibility in the system. The flow system is designed such that flow rate can be easily changed, ranging from a fraction of a milliliter per minute to 10 mL per minute or higher.…”

A tissue adaptation model based on strain-dependent collagen degradation and contact-guided cell traction

“…Collagen adaptation over 72 h in uniaxially constrained fibroblast-populated collagen gels (Lee et al, 2008) was simulated by fully constraining top and bottom nodes and coupling the horizontal displacement of nodes along the left and right edges, separately, to simulate polyethylene sidebars. Mean angle and vector length of the fibril distribution are calculated for each integration point using a Matlab (Mathworks Inc) toolbox for circular statistics (Berens, 2009), taking into account that fibril angles are only unique within 1801.…”

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

“…Collagen remodeling in fibrin-or collagen-based tissue engineered (TE) constructs has been studied for example by Sander et al, 29 Hu et al 13 and Lee et al 19 These studies used cell-seeded collagen gels in a cruciform or square shape that could be stretched in two opposite directions, resulting in biaxial loading conditions. Static biaxial loading resulted in collagen orientation parallel to the direction of the highest stretch.…”