Microrheology for biomaterial design

Abstract

Microrheology analyzes the microscopic behavior of complex materials by measuring the diffusion and transport of embedded particle probes. This experimental method can provide valuable insight into the design of biomaterials with the ability to connect material properties and biological responses to polymer-scale dynamics and interactions. In this review, we discuss how microrheology can be harnessed as a characterization method complementary to standard techniques in biomaterial design. We begin by introducing the core principles and instruments used to perform microrheology. We then review previous studies that incorporate microrheology in their design process and highlight biomedical applications that have been supported by this approach. Overall, this review provides rationale and practical guidance for the utilization of microrheological analysis to engineer novel biomaterials.

FIG. 1.

Dynamic light scattering (DLS) microrheology. (Left panel) Frequency-dependent mechanics of intestinal mucus from healthy and dextran sulfate sodium (DSS)-induced colitis mice as determined using DLS microrheology. (Right panel) Confocal imaging of mucus (green) in the colon of DSS-treated and healthy mice. Reproduced with permission from Krajina et al., ACS Cent. Sci. 3, 1294 (2017). Copyright 2017 American Chemical Society. Further permissions related to the material excerpted should be directed to the ACS.

FIG. 2.

Optical tweezers for active microrheology. Optically trapped probes used to exert oscillatory (as pictured) or constant strain on material of interest. Measured force and particle displacement are used to determine the frequency-dependent mechanical response. Reproduced with permission from R. M. Robertson-Anderson, ACS Macro Lett. 7, 968 (2018). Copyright 2018 American Chemical Society. Further permissions related to the material excerpted should be directed to the ACS.

FIG. 3.

Visualization and direct measurement of biomaterial network geometry. (a) Porosity of agarose gels was characterized based on individual trajectories determined using particle tracking microrheology. (b) Based on this analysis, pore size distribution were determined as a function of agarose concentration. Reprinted with permission from L. Jiang and S. Granick, ACS Nano 11, 204 (2017). Copyright 2017 American Chemical Society. Further permissions related to the material excerpted should be directed to the ACS.

FIG. 4.

Microrheological analysis of sol–gel transitions. A microfluidic device coupled with particle tracking microrheology used to monitor reversible, osmotic pressure-induced gelation and degradation of fibrous colloidal gels composed of hydrogenated castor oil. MSD of embedded probes was periodically measured during solvent exchange with the gelling agent (glycerin) and water where the color bar indicates the current time of experiment. Republished with permission from Wehrman et al., Lab Chip 17, 2085 (2017). Copyright 2017 Royal Society of Chemistry, Clearance Center, Inc.

FIG. 5.

Designing injectable peptide biomaterials for regenerative medicine using microrheology. (a) and (b) Shear-thinning and self-healing properties of two peptide hydrogel formulations after syringe injection determined based on measured MSD. (Lower panel) Each gel supported differentiation of adult neural stem cells. Reproduced with permission from Wong Po Foo et al., Proc. Natl. Acad. Sci. U. S. A. 106, 22067 (2009). Copyright 2009 National Academy of Sciences of the United States of America.