Collagen‐I/silk‐fibroin biocomposite exhibits microscalar confinement of cells and induces anisotropic morphology and migration of embedded fibroblasts

Abstract

Microstructural anisotropy of tumor-associated matrix correlates with invasion of cancer cells into the surrounding matrix during metastasis. Here, we report the fabrication and characterization of a three-dimensional (3D) silk-fibroin/collagen-I biocomposite based cell-culture model that exhibits microstructural and biochemical anisotropy. Using RGD-deficient silk-fibroin fibers to confine collagen-I gelation, we develop a silk-fibroin/collagen-I (SFC) bio-composite in a one-step process allowing control over the microstructural and biochemical anisotropy and the pore-size. Two forms of the SFC bio-composite are reported: a sandwich (S fc ) configuration amenable to live-cell microscopy and an unsupported membrane (M fc ) for use as a scaffold.Both microscalar and macroscalar mechanical properties of the SFC bio-composite are characterized using atomic force microscope (AFM)-based indentation and tensile-testing. We find that the modulus of stiffness of both S fc and M fc can be controlled and falls in the physiological range of 5-20 kPa. Furthermore, the modulus of stiffness of M fc exhibits a~200% increase in axial direction of microstructure, as compared to lateral direction. This implies a highly anisotropic mechanical stiffness of the microenvironment. Live-cell morphology and migration studies show that both the morphology and the migration of NIH-3 T3 fibroblasts is anisotropic and correlates with microstructural anisotropy. Our results show that SFC bio-composite permits proliferation of cells in both S fc and M fc configuration, promotes cell-migration along the major axis of anisotropy and together with morphological and migration data, suggest a potential application of both the composite configurations as a biomimetic scaffold for tissue engineering applications. K E Y W O R D S aligned scaffold, anisotropy, cell-migration, silk-fibroin SUPPORTING INFORMATION Additional supporting information may be found online in the Supporting Information section at the end of this article. How to cite this article: Konar S, Edwina P, Ramanujam V, Arunachalakasi A, Bajpai SK. Collagen-I/silk-fibroin biocomposite exhibits microscalar confinement of cells and induces anisotropic morphology and migration of embedded fibroblasts.

Psidium guajava L. phenolic compound-reinforced lamellar scaffold for tracheal tissue engineering

“…The degree is measured between 0 and 1, where 0 corresponds to a fully isotropic structure, while 1 corresponds to a completely anisotropic structure [ 62 ]. The organization presented by ECM fibers within fabrics can vary from anisotropic (fiber alignment, directional amplification of binder density) to isotropic (randomly aligned, uniform binder availability) [ 63 ].…”

Engineering Anisotropic Cell Models: Development of Collagen Hydrogel Scaffolds with Magneto‐Responsive PEG Microgels for Tissue Engineering Applications

“…Fibroblasts have been previously reported to align in anisotropic conditions. [43,44] Efficient cell adhesion and proliferation has been reported in a collagen/PEG hydrogel using human fibroblasts. [45] Similarly, our results demonstrated that NHDF cells efficiently grew within collagen-Anisogels, exhibiting alignment with the unidirectional orientation of the PEG microgels established during the initial gelation process and up to 7 days in culture.…”

Nanoparticulates reduce tumor cell migration through affinity interactions with extracellular migrasomes and retraction fibers

“…Compared to the round shape, a spindle-like morphology endows cells with greater migration capability. 26,27 Thus, the alteration in cellular morphology induced by NPs was closely related to the attenuated cell migration.…”