Biomimetic fibrillar hydrogels: effect of confinement and anisotropy on the mechanical response to strain

Man-made nanofibrillar hydrogels have emerged as a class of biomimetic materials reproducing the filamentous structure and properties of the extracellular matrix, acting as scaffolds for three-dimensional cell culture and tissue engineering and offering applications in sensing and soft robotics. The mechanical response of fibrous gels to strain is largely governed by the strong asymmetry in the deformation energy of the constituent filaments that are soft upon compression and stiff upon extension. This presentation highlights biologically relevant implications of such mechanical asymmetry.

In the first example, confinement of fibrin hydrogels to narrow capillaries recapitulated occlusion of blood vessels with blood clots. We show experimentally and theoretically that filamentous gels respond to such confinement in a qualitatively different manner than gels formed by single-molecule flexible strands. Under strong confinement, fibrous gels exhibit a very weak elongation and an asymptotic decrease to zero of their biaxial Poisson’s ratio. Such response results in strong gel densification and a weak flux of liquid through the gel. This behavior sheds light on the resistance of strained occlusive blood clots to lysis with therapeutic agents and stimulates the development of effective endovascular plugs for stopping vascular bleeding or suppressing blood supply to tumors.

The second example highlights the importance of structural anisotropy of fibrous hydrogels. For the synthetic filamentous hydrogel with a structure reproducing the organization of fibers in the collagen network surrounding cancer tumors, we integrated the cavitation rheology method with polarized optical microscopy, as well as hydrogel imaging, to show that hydrogel’s response to radial compression (replicating invasive tumor growth) is governed by the type and degree of structural anisotropy of the gel network. The effective Young’s modulus increased with a higher degree of lateral fiber orientation and decreased with stronger radial fiber alignment. These findings underline the importance of the design of ‘precision biomaterials’ that faithfully recapitulate key microenvironmental characteristics of cancer tumors.