Spatiotemporal Control over Cell Proliferation and Differentiation for Tissue Engineering and Regenerative Medicine Applications Using Silk Fibroin Scaffolds

Abstract

Research on tissue engineering has been actuated for want of improved treatments and has now come out as a likely alternative to organ transplantation. The two indispensable components for regeneration of tissues are cells and scaffolds. Stem cells are undifferentiated cells that have proliferative capacity and the ability to differentiate into specific mature lineages, which is called plasticity. The physical and chemical signals from the surrounding microenvironment can influence the proliferation as well as the differentiation of stem cells into more specialized cell types and thus play an important role regulating the fate of the stem cells. Over decades, scientists have revealed that the stem cells' growth and differentiation can be stimulated and regulated by scaffold properties. Silk fibroin has been used in both in vitro and in vivo tissue engineering applications and has shown promising results, particularly for bone tissue engineering applications. For successful application of stem cells in tissue engineering, directed differentiation of stem cells will have to include approaches that not only regulate cell-fate specification but also cell maturation to access a complete range of cell types and stages. One of the ways of achieving this is by modifying the surface properties of the scaffold to have control over the stem cell behavior and final product. In this spotlight on application, we recapitulate the current developments of silk-based materials and their surface modifications for patterning of cells and stem cell differentiation with a focus on bone tissue engineering.

The Materiobiology of Silk: Exploring the Biophysical Influence of Silk Biomaterials on Directing Cellular Behaviors

“…Silk films with carboxylic groups induced chondrogenic differentiation of human mesenchymal stem cell (hMSC), whereas those with phosphate groups induced osteogenic differentiation. Furthermore, grafting of these functional groups on silk simultaneously can provide spatiotemporal control over differentiation on the same surface (Patil et al, 2020). Surface functionalization can also be used to mimic ECM specific signaling.…”

“…In a separate study, soft lithography was used to surface pattern SF to evaluate the effect of surface morphology on cell proliferation, orientation, and ECM alignment on corneal fibroblasts ( Gil et al, 2010 ). Interestingly, the depth of the grooves was found to have greater impact on the cell orientation compared to the width ( Patil et al, 2020 ). Patterning silk has also been harnessed to design “co-culture” systems that provide spatial control over homo- and hetero-typic cellular interactions at the micron level ( Battiston et al, 2014 ).…”

“…SF can be amalgamated or cross-linked with proteins, polysaccharide, polymers, and other functional materials to make composites with the advantages of both materials ( Patil et al, 2020 ). Cell adherence on silk is often hampered as a consequence of its hydrophobicity.…”

Antibacterial and wound healing activities of silver nanoparticles embedded in cellulose compared to other polysaccharides and protein polymers

“…Various species of silk worm such as Bombyx mori can be used to extract SF (70-80%) with cytocompatibility, high adhesiveness and suitable mechanical properties emanating from brillar structure with the β-sheet crystal of (Gly-Ser-Gly-Ala-Gly-Ala) n , which can promote the adhesion of platelets and proliferation of stem cells (Patil et al 2020;Anuduang et al 2020). Anti-adhesion, antiplanktonic, and inhibition of bio lm was indicated for AgNPs/gentamycin-loaded SF-based lm of titanium.…”

Biomolecular Electron Controller Composed of Nanobiohybrid with Electrically Released Complex for Spatiotemporal Control of Neuronal Differentiation

“…Moreover, cell differentiation begins as soon as the cells are seeded onto the array, and therefore physicochemical cues are not well suited to achieve temporal control of cell differentiation. [ 26–28 ] Recent studies have reported that myogenic differentiation and angiogenesis can be achieved through engineered optogenetics, thus allowing for spatiotemporal control of cell differentiation. [ 29 ] Although spatiotemporal control was achieved to some extent using light‐responsive recombinant cells via the implementation of gene recombination techniques, this approach exhibited several disadvantages that hindered its practical application.…”