Temporal Modulation of Stem Cell Activity Using Magnetoactive Hydrogels

Abstract

Cell activity is coordinated by dynamic interactions with the extracellular matrix, often through stimuli-mediated spatiotemporal stiffening and softening. Dynamic changes in mechanics occur in vivo through enzymatic or chemical means, processes which are challenging to reconstruct in cell culture materials. Here we present a magnetoactive hydrogel material formed by embedding magnetic particles in a hydrogel matrix whereby elasticity can be modulated reversibly by attenuation of a magnetic field. We show orders of magnitude change in elasticity using low magnetic fields and demonstrate reversibility of stiffening with simple permanent magnets. The broad applicability of this technique is demonstrated with two therapeutically relevant bioactivities in mesenchymal stem cells: secretion of proangiogenic molecules, and dynamic control of osteogenesis. The ability to reversibly stiffen cell culture materials across the full spectrum of soft tissue mechanics, using simple materials and commercially available permanent magnets, will make this approach viable for a broad range of laboratory environments.

Hydrogels with Reversible Mechanics to Probe Dynamic Cell Microenvironments

“…External triggers such as pH [4] and temperature [5] may not be biocompatible for certain cell types, whereas stimuli such as calcium ion concentration, [6] competitive binding partners, [7] or magnetic particle incorporation [8] contain components that may alter cell signaling or require a sustained stimulus. Another challenge is capturing a tunable and relevant range of elastic moduli over which to study cell behavior.…”

Spatially and temporally controlled hydrogels for tissue engineering

“…For example, genetically engineered protein-based hydrogels showed the potential to transfer the change in protein conformation to differences of the macroscopic properties of hydrogels [307–309]. Very recently, dynamic hydrogels that were responsible for external magnetic field were demonstrated with stiffness change of several orders of magnitude, which could be applied to modulate stem cell behavior including osteogenesis and secretion of proangiogenic molecules [310]. These novel approaches might find important biomedical applications due to the versatility and tunability of these systems.…”

Dynamic bioengineered hydrogels as scaffolds for advanced stem cell and organoid culture

“…Kilian and co-workers designed a polyacrylamide-based hydrogel with embedded magnetic carbonyl iron particles. [31] Application of a magnetic field caused the alignment of the embedded particles, which led to hydrogel stiffening from 0.1 to ∼90 kPa [ Fig. 2(a)].…”