Particle diffusion in extracellular hydrogels

TL;DR

This study investigates how the composition and crosslinking of hyaluronan-based hydrogels affect microscopic particle diffusion, providing insights into tissue transport mechanisms and guiding biomimetic hydrogel design for medical applications.

Contribution

It systematically analyzes the effects of gel composition and crosslinking on particle diffusion using combined microscopy techniques, revealing the role of network structure and stress relaxation.

Findings

Particle diffusivity depends on particle size and network pore size.

Addition of collagen induces caged particle dynamics.

Network stress relaxation influences particle mobility.

Abstract

Hyaluronic acid is an abundant polyelectrolyte in the human body that forms extracellular hydrogels in connective tissues. It is essential for regulating tissue biomechanics and cell-cell communication, yet hyaluronan overexpression is associated with pathological situations such as cancer and multiple sclerosis. Due to its enormous molecular weight (in the range of millions of Daltons), accumulation of hyaluronan hinders transport of macromolecules including nutrients and growth factors through tissues and also hampers drug delivery. However, the exact contribution of hyaluronan to tissue penetrability is poorly understood due to the complex structure and molecular composition of tissues. Here we reconstitute biomimetic hyaluronan gels and systematically investigate the effects of gel composition and crosslinking on the diffusion of microscopic tracer particles. We combine ensemble-averaged measurements via differential dynamic microscopy with single-particle tracking. We show that the particle diffusivity depends on the particle size relative to the network pore size and also on the stress relaxation dynamics of the network. We furthermore show that addition of collagen, the other major biopolymer in tissues, causes the emergence of caged particle dynamics, which is not present in the one-component systems. Our findings are useful for understanding macromolecular transport in tissues and for designing biomimetic extracellular matrix hydrogels for drug delivery and tissue regeneration.