Joseph Rich, PhD, Bringham Young University

Abstract: Innovations that deliver precise and tunable physical forces on hydrogels are of great interest for generating and manipulating biomimetic cellular constructs, including mechanosensitive cell models (e.g., endothelial cells, immune cells, and stem cells). This scalable innovation is necessary, from the cellular to tissue level, for advancing research into the fundamental biology of immune cell activation for immunotherapies or for guiding stem cell fate for tissue engineering-derived therapies. Various physical-force-based methods are currently under investigation for enabling these active biomaterials. These methods employ fluidic, tensile, viscoelastic, electromagnetic, optical, thermal, and acoustic forces. However, previous in vitro physical material deformation models have been limited by the lack of precise control of the resulting 3D distribution of forces or the absence of a biologically relevant scaffolding for scaling to relevant biomimetic tissue engineered models.

In this study, we present the development of an acoustic traveling wave induced shear torsion (A-TWIST) platform to precisely control the 3D deformation distribution of a biomimetic hydrogel. We quantified and characterized, for the first time, the macromaterial shear stress response of a hydrogel to the applied surface acoustic waves (SAWs) of the A-TWIST platform via rheometry. We then investigated how different hydrogel properties, including density and crosslinking, affected the SAW shear response. Next, we numerically simulated and experimentally verified the 2D and 3D deformation distribution induced by A-TWIST. Finally, we employed A-TWIST to strain a biomimetic hydrogel loaded with endothelial colony forming cells (ECFC) to demonstrate the biocompatible nature of A-TWIST to activate mechanosensitive cell models.

We found that with A-TWIST we could simulate and demonstrate controlled 3D deformation of biomimetic hydrogels. We also found that the different material properties of the hydrogel, density and crosslinking density, can also tune the desired shear stress response of the biomimetic matrix. Finally, we demonstrated that a 30% enhancement of volume of vascularization of ECFCs is achieved with tuned strain from A-TWIST. Overall, these results demonstrate a rigorous characterization and a novel application of acoustic forces for the precise and biocompatible 3D deformation of a biomaterial loaded with mechanosensitive cells and the resulting enhancement in tissue-level vascularization via A-TWIST. We anticipate future applications of this work to investigate custom deformation distributions and the impact of these extracellular strains on cellular pathways effecting their growth and organization. This will enable precisely engineered biological functions with other mechanosensitive cell models for unique applications in the field of biomedical engineering, tissue engineering, mechanobiology, and immunology.

This work was presented at BMES 2025, will be presented at MicroTAS 2026, and is currently under review in Nature Communications1.