# Constructing 3D voxelated tissues with molecular architecture encoded modular biomaterials to understand and control stem cell function

> **NIH NIH R35** · UNIVERSITY OF VIRGINIA · 2024 · $387,104

## Abstract

PROJECT SUMMARY
Most biological tissues are not simply static materials but active living composites. They are composed of living
cells dispersed in nonliving polymers known as extracellular matrix. Decades of research in biomaterials have
demonstrated a multitude of ways in which polymeric materials can influence cells, and cells can modify
polymeric materials. Thus, recent advances in biomaterials design have shifted from pure elastic to viscoelastic
polymeric biomaterials featuring time-dependent mechanical properties. However, existing biomaterial design
largely relies on flexible linear polymers; such a simple molecular architecture intrinsically limits using linear
polymers to create biomaterials with nonlinear elasticity and relaxation dynamics matching the complexity and
variations in tissue-specific mechanics for dissecting intricate cell-matrix interactions. Moreover, there remains
a grand challenge in assembling cells and soft, viscoelastic biomaterials to create tightly organized structures
matching that of three-dimensional (3D) tissues for probing and exploiting cell-cell interactions. Trained as a
theoretical polymer physicist but later switched to experimental soft (bio)materials and bioengineering, I have
identified compelling opportunities for me to uniquely help address these challenges. Leveraging our expertise
in polymer physics, polymer chemistry, and bioengineering, I will develop platform technologies for constructing
voxelated 3D tissues with molecular architecture encoded modular biomaterials to understand and control stem
cell function. This is based on two research areas that I have been pioneering: (1) bottlebrush polymers and
networks and (2) voxelated bioprinting. In Thrust 1, I will develop modular bottlebrush gels to understand and
control cell-matrix interactions. This thrust is built on my lab's recent breakthrough in discovering a new way to
control the relaxation time without altering the shape of viscoelastic spectra of polymer networks. Leveraging my
expertise in theoretical polymer physics and soft matter, and based on how cells interact with matrix, I will
introduce two new sets of parameters to provide a more complete description of matrix strain-stiffening and
viscoelasticity. Further, I will develop general strategies for independently encoding stiffness, strain-stiffening,
relaxation time, and the shape of relaxation profile into the molecular architecture of bottlebrush gels. Using
these modular bottlebrush gels, I will dissect the impact of each parameter on the behavior of stem cells. Recently,
my lab proposed and showed the concept of voxelated bioprinting, a technology that enables precise
manipulation and assembly of highly viscoelastic spheric bio-ink droplets in 3D space. In Thrust 2, I will advance
our voxelated bioprinting technology to print multiple material voxels in which are encapsulated different types
of cells. I hypothesize that pre-defining the specific location and cell-cell interac...

## Key facts

- **NIH application ID:** 10939530
- **Project number:** 1R35GM154912-01
- **Recipient organization:** UNIVERSITY OF VIRGINIA
- **Principal Investigator:** Liheng Cai
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $387,104
- **Award type:** 1
- **Project period:** 2024-08-01 → 2029-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10939530

## Citation

> US National Institutes of Health, RePORTER application 10939530, Constructing 3D voxelated tissues with molecular architecture encoded modular biomaterials to understand and control stem cell function (1R35GM154912-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10939530. Licensed CC0.

---

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