Introduction to cell-hydrogel mechanosensing

Abstract

The development of hydrogel-based biomaterials represents a promising approach to generating new strategies for tissue engineering and regenerative medicine. In order to develop more sophisticated cell-seeded hydrogel constructs, it is important to understand how cells mechanically interact with hydrogels. In this paper, we review the mechanisms by which cells remodel hydrogels, the influence that the hydrogel mechanical and structural properties have on cell behaviour and the role of mechanical stimulation in cell-seeded hydrogels. Cell-mediated remodelling of hydrogels is directed by several cellular processes, including adhesion, migration, contraction, degradation and extracellular matrix deposition. Variations in hydrogel stiffness, density, composition, orientation and viscoelastic characteristics all affect cell activity and phenotype. The application of mechanical force on cells encapsulated in hydrogels can also instigate changes in cell behaviour. By improving our understanding of cell-material mechano-interactions in hydrogels, this should enable a new generation of regenerative medical therapies to be developed.

Keywords: adhesion; bioreactor; contraction; hydrogel; mechanobiology; tissue engineering.

Figure 1.

Examples of cell-seeded hydrogels that have been under investigation to engineer tissues and organs. (Online version in colour.)

Figure 2.

Chemical structure of (a) the natural polymers agarose, alginate (showing one β-d-mannuronic acid and one α-l-guluronic acid unit), chitosan and hyaluronic acid and (b) the synthetic polymer poly(ethylene glycol) and two of its derivatives (poly(ethylene glycol) diacrylate and poly(ethylene glycol) dimethacrylate).

Figure 3.

Images of fibroblasts in (a) collagen and (b) agarose hydrogels stained using phalloidin-TRITC and recorded using a fluorescent microscope. (Online version in colour.)

Figure 4.

Schematic of the contraction process in a cell-seeded hydrogel: (a) cells are embedded in a hydrogel matrix, (b) cells elongate and adhere to fibres, (c) cells pull fibres causing them to buckle, (d) cells release and reattach to new fibres resulting in contraction of the hydrogel. (Online version in colour.)

Figure 5.

Schematic of different methods of applying force to cells in hydrogels: (a) no force, (b) tensile, (c) compression, (d) hydrostatic pressure and (e) fluid flow. (Online version in colour.)