Strain Gradient Programming in 3D Fibrous Hydrogels to Direct Graded Cell Alignment

Abstract

Biological tissues experience various stretch gradients which act as mechanical signaling from the extracellular environment to cells. These mechanical stimuli are sensed by cells, triggering essential signaling cascades regulating cell migration, differentiation, and tissue remodeling. In most previous studies, a simple, uniform stretch to 2D elastic substrates has been applied to analyze the response of living cells. However, induction of nonuniform strains in controlled gradients, particularly in biomimetic 3D hydrogels, has proven challenging. In this study, 3D fibrin hydrogels of manipulated geometry are stretched by a silicone carrier to impose programmable strain gradients along different chosen axes. The resulting strain gradients are analyzed and compared to finite element simulations. Experimentally, the programmed strain gradients result in similar gradient patterns in fiber alignment within the gels. Additionally, temporal changes in the orientation of fibroblast cells embedded in the stretched fibrin gels correlate to the strain and fiber alignment gradients. The experimental and simulation data demonstrate the ability to custom‐design mechanical gradients in 3D biological hydrogels and to control cell alignment patterns. It provides a new technology for mechanobiology and tissue engineering studies.

Micropatterning the organization of multicellular structures in 3D biological hydrogels; insights into collective cellular mechanical interactions

“…The silicone carrier can also aid with in-vivo implantation of the gel in desired tissue region, for regenerative medicine applications. The silicone carrier can also be exploited in biomechanical stretching experiments, in which the gel can be strained externally through stretch of the silicone carrier, as we demonstrated in our previous studies [59][60][61]. The silicone carrier also facilitates the stacking of several layers of patterned gels to create a 3D layered assembly of gel-patterned cells, as we have demonstrated.…”

Parametric optimization of culture chamber for cell mechanobiology research

“…1,2 The mechanical signals continuously stimulate cells and trigger different behaviors regulating cell activities, such as growth, proliferation, and migration. [3][4][5] Studies have demonstrated that mechanical stimulation affects organ morphogenesis, 6 skeletal muscle differentiation, 7 and central nervous system development. 8 However, it is difficult to directly observe the mechanisms of cell mechanobiological responses due to the complexity of the in vivo environment, and the challenges also occur in studying cell responses in isolated animal tissues.…”