Light-Induced Cell Alignment and Harvest for Anisotropic Cell Sheet Technology

Abstract

Well-organized orientation of cells and anisotropic extracellular matrix (ECM) are crucial in engineering biomimetic tissues, such as muscles, arteries, and nervous system, and so on. This strategy, however, is only beginning to be explored. Here, we demonstrated a light-induced cell alignment and harvest for anisotropic cell sheets (ACS) technology using light-responsive TiO nanodots film (TNF) and photo-cross-linkable gelatin methacrylate (GelMA). Cell initial behaviors on TNF might be controlled by micropatterns of light-induced distinct surface hydroxyl features, owing to a sensing mechanism of myosin II-driven retraction of lamellipodia. Further light treatment allowed ACS detachment from TNF surface while simultaneously solidified the GelMA, realizing the automatic transference of ACS. Moreover, two detached ACS were successfully stacked into a 3D bilayer construct with controllable orientation of individual layer and maintained cell alignment for more than 7 days. Interestingly, the anisotropic HFF-1 cell sheets could further induce the HUVECs to form anisotropic capillary-like networks via upregulating VEGFA and ANGPT1 and producing anisotropic ECM. This developed integrated-functional ACS technology therefore provides a novel route to produce complex tissue constructs with well-defined orientations and may have a profound impact on regenerative medicine.

A Physiology-Inspired Multifactorial Toolbox in Soft-to-Hard Musculoskeletal Interface Tissue Engineering

“…Tissue engineering strategies have been addressing the effects of cell conditioning under Although not yet applied to soft-to-hard interface tissue engineering, these strategies hold promising features to be manipulated envisioning the creation of a gradient of cells, cellular alignment, and cellular environments. (B-D) Reproduced, with permission, from [27]. Progresses in magnetic force-based tissue engineering are also supporting the development of magnetic cell sheets (magCS).…”

“…Next-generation cell sheet engineering is taking this technology to a higher level of organization in recreating complex tissues. The development of anisotropic cell sheets using stripe-like micropatterned thermoresponsive surfaces [26] ( Figure 2A) and, recently, light-induced cell alignment and cell sheet harvest [27] ( Figure 2B-D) hold promising results to be explored for interfacial tissue engineering. More recent trends have been exploring magnetic force-based tissue engineering.…”

Potential‐Responsive Surfaces for Manipulation of Cell Adhesion, Release, and Differentiation

“…[1,2] Apoptosis, [3] adhesion, [4][5][6][7] proliferation, [6] migration, [8] and differentiation [9][10][11] phenotypes of cells are closely associated with molecular-level biophysical cues created within the extracellular matrix (ECM). Cell adhesion can be modulated dynamically by applying negative and positive potentials to surfaces functionalized with tailored monolayers.…”

“…[1,2] Apoptosis, [3] adhesion, [4][5][6][7] proliferation, [6] migration, [8] and differentiation [9][10][11] phenotypes of cells are closely associated with molecular-level biophysical cues created within the extracellular matrix (ECM). [1,2] Apoptosis, [3] adhesion, [4][5][6][7] proliferation, [6] migration, [8] and differentiation [9][10][11] phenotypes of cells are closely associated with molecular-level biophysical cues created within the extracellular matrix (ECM).…”

“…The higher accessibility of the peptide under ap ositive applied potential causes phenotypic changes in the cells that are hallmarks of osteogenesis,w hereas lower accessibility of the peptide promoted by negative potentials leads to adipogenesis.Biophysical cues play essential roles in regulating cellular behavior in vivo and in vitro. [1,2] Apoptosis, [3] adhesion, [4][5][6][7] proliferation, [6] migration, [8] and differentiation [9][10][11] phenotypes of cells are closely associated with molecular-level biophysical cues created within the extracellular matrix (ECM). Hence,g aining control over the biophysical cues that can influence cellular behavior would facilitate the design of an optimal ECM for controlling cellular processes and defining cell fate.Promoting specific interactions between molecular interfaces and cells has emerged as apromising means to modulate cellular processes.A rg-Gly-Asp (RGD) peptides were the first synthetic molecular structures found to promote cell adhesion.…”