# Multiscale Stereolithogrphic Bioprinting of Stage-Matching Vascularized Tumor Models

> **NIH NIH R21** · BRIGHAM AND WOMEN'S HOSPITAL · 2020 · $266,454

## Abstract

Project Summary
 Cancer is one of the major causes of morbidity and mortality. The cancer microenvironment is highly
complex, and is highly dynamic with distinctive key features present at each of the different stage of the
disease. In particular, the large-scale growth of a tumor ultimately requires a blood supply. In comparison to
healthy tissues, the tumor vessels are structurally and functionally abnormal. Moreover, the tumor
vascularization is stage-dependent and significantly contributes to the phenotype determination as well as
behaviors of the tumors such as their oxygenation levels. To fully grasp the complexity of the tumor
microenvironment, as well as screening of various anti-cancer drugs, it has been increasingly realized that in
vitro engineered human cancer models are strongly desired, as the conventional animal-based xenograft
cancer models do not necessarily recapitulate the human physiology and drug responses. However, major
challenges associated with current 3D in vitro tumor models include their oversimplified structures and limited
vascularization potential. To overcome these limitations, recent advances in rapid prototyping methods in
bioprinting together with novel bioinks now potentially enable us with precise architectural control to fabricate
biomimetic tumor microenvironment that may potentially better reproduce their phenotypes and functions,
which have been rarely demonstrated so far. We propose that, by optimizing a stereolithographic bioprinter
that allows for high-definition manipulation over microarchitectures, it would be possible to, for the first time,
precisely reproduce the structure of a tumor and its associated microenvironmental cues. By combining image
analysis to allow for bioprinting of tumor models with stage-matching vascularization patterns (thus local
oxygenation levels), we hypothesize that their phenotypes can be more accurately preserved in vitro. In Aim 1,
we will optimize our custom-designed multi-material stereolithographic bioprinting system and tumor matrix
materials for the bioprinting of breast cancer microenvironment including its associated vasculature. In Aim 2,
we will integrate image analysis with the bioprinting system to generate breast cancer models with stage-
matched vascularization patterns, analyze their oxygenation, and conduct preliminary validation on the
phenotypic maintenance of these in vitro models with their in vivo counterparts in mice.

## Key facts

- **NIH application ID:** 9961583
- **Project number:** 5R21EB025270-03
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** Y. Shrike Zhang
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $266,454
- **Award type:** 5
- **Project period:** 2018-09-15 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9961583

## Citation

> US National Institutes of Health, RePORTER application 9961583, Multiscale Stereolithogrphic Bioprinting of Stage-Matching Vascularized Tumor Models (5R21EB025270-03). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9961583. Licensed CC0.

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