# Building biophysical and biochemical complexity in 3D cell and tissue constructs

> **NIH NIH R35** · UNIVERSITY OF VIRGINIA · 2024 · $373,474

## Abstract

Abstract
Within healthy adult tissues, a developing organism, and disease environments alike, cells exist in environments
where they receive and integrate external signals according to a phenotypic state, yielding responses in
cellular activities and behaviors or modifications to phenotypic state. Fundamental understanding of cellular
functioning and disease progression depends in part on our ability to systematically build and perturb model
cellular systems in vitro, and pressing biomedical challenges in translational medicine might be addressed
through the technology that enables breakthroughs in tissue engineering, including in meeting the critical
needs of patients awaiting organ transplants. Over the past decades, a range of biofabrication technologies
have been used to precisely arrange cells and materials within two- and three-dimensional structures. These
technologies have broadened our understanding biology and increased the complexity of tissue constructs that
might be used therapeutically. While biofabrication approaches developed over this time have greatly
benefitted our abilities to probe and understand biological questions—especially with respect to cells and their
environments—and to engineer cell-material constructs that recapitulate features of native tissues, significant
challenges persist in building multiscale biomimetic tissue constructs. Our lab’s research is focused on
addressing these challenges through the development and application of new biofabrication technologies that
are based on innovation in the design and use of hydrogel biomaterials. Within the next five years, the lab aims
to develop and apply unique hydrogel-based technology to bioprinting to address the critical need for
capabilities to create vascularized tissue constructs in which cell and material complexity can be specified in
extravascular regions and that can support dense cell populations. The lab will also develop new biofabrication
technologies that will allow unique capabilities for high resolution control over cellular and material structures
within macroscale constructs, with the goal of being able to simultaneously control a broad range of
microenvironmental features—including cell-cell interactions, biochemical cues, and biomechanical cues—that
a given cell experiences. We aim to develop technological capabilities and ultimately apply these capabilities to
building complex tissue constructs that might be used as platforms for studying tissue and vascular responses
to perturbations by physical and biological stimuli and to address key challenges in tissue engineering to
develop therapeutic tissue constructs. The work in this proposal thus aims to advance capabilities in the fields
of biofabrication and tissue engineering, with broad potential impacts in applied and translational research.

## Key facts

- **NIH application ID:** 10927246
- **Project number:** 5R35GM147410-03
- **Recipient organization:** UNIVERSITY OF VIRGINIA
- **Principal Investigator:** Christopher B Highley
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $373,474
- **Award type:** 5
- **Project period:** 2022-09-15 → 2027-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10927246

## Citation

> US National Institutes of Health, RePORTER application 10927246, Building biophysical and biochemical complexity in 3D cell and tissue constructs (5R35GM147410-03). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10927246. Licensed CC0.

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