# Microscale Mechanobiology for Musculoskeletal Tissue Engineering using Advanced Ultrasound Techniques

> **NIH NIH R01** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2020 · $361,877

## Abstract

Project Summary
Mechanical forces are a key component of the cellular microenvironment, and are well established to have
potent effects on cells and tissues. The passive mechanical properties of two-dimensional cell substrates and
three-dimensional extracellular matrices have been shown to influence progenitor cell phenotype and can be
used to direct cell function. In addition, active stimulation of cells and tissues using externally applied forces
has been applied at both the cell and tissue level to induce a variety of responses. Mechanobiology is
particularly relevant to musculoskeletal tissues, but there is a gap in our understanding of the physical
properties of the tissue environment on length scales that cells sense. This project builds on preliminary work
by the project team in applying advanced ultrasound techniques to studying the microscale physical properties
of engineered musculoskeletal tissues composed of cell-seeded mineralizing hydrogels. It integrates spectral
ultrasound imaging (SUSI), dual-mode ultrasound elastography (DUE), and ultrasound-induced compressive
stimulation. SUSI is a technique that uses the backscattered radiofrequency spectrum to derive information
about the composition of a sample. DUE applies acoustic radiation force to deform hydrogels and measure
their mechanical properties. Focused ultrasound-induced compression also applies acoustic pressure to
mechanically stimulate tissues. A key feature of ultrasound techniques is that they are noninvasive and
therefore can be used to study developing tissues over time. In addition, imaging and deformation can be
applied at sub-millimeter resolution. This project will combine these advanced ultrasound techniques to create
a system that can comprehensively characterize and stimulate engineered musculoskeletal tissues at the
microscale. The target application is to potentiate bone formation using mesenchymal stem cells (MSC)
embedded in a 3D hydrogel matrix. The Specific Aims are 1) to integrate spectral ultrasound imaging (SUSI)
and dual-mode ultrasound elastography (DUE) to compositionally and mechanically characterize mineralizing
tissues, 2) to probe the effects of passive matrix mechanical properties on MSC phenotype using SUSI-DUE,
3) to actively stimulate osteogenic differentiation of MSC in hydrogel matrices using ultrasound-induced cyclic
compression, and 4) to apply SUSI-DUE to catalyze and monitor bone regeneration in vivo. This project will
investigate musculoskeletal mechanobiology using an innovative new tool that could have important impact on
regenerative medicine. The long term goal is a therapeutic intervention to potentiate bone formation in
indications where accelerated healing would lead to improved outcomes, such as treatment of non-unions and
recalcitrant spinal fusions.

## Key facts

- **NIH application ID:** 9974508
- **Project number:** 5R01DE026630-04
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** CHERI X DENG
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $361,877
- **Award type:** 5
- **Project period:** 2017-08-01 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9974508

## Citation

> US National Institutes of Health, RePORTER application 9974508, Microscale Mechanobiology for Musculoskeletal Tissue Engineering using Advanced Ultrasound Techniques (5R01DE026630-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9974508. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*