# Programmable Construction of 3D in vitro Disease Models Capturing Microenvironment Heterogeneity

> **NIH NIH P20** · UNIVERSITY OF NEBRASKA LINCOLN · 2022 · $181,591

## Abstract

PROJECT SUMMARY/ABSTRACT 
More than 90% of drug candidates that could pass preclinical validations eventually fail to be approved for 
clinical applications. A main cause of these failures is that conventional models—monolayer cultured cells 
and lab animals—are limited in the capability to recapitulate the native microenvironments. It is well 
demonstrated that 3D cultured cells, typically spheroids and scaffolds, can more closely mimic their natural 
behaviors. The emerging technologies of organoid and 3D bioprinting have been developed to significantly 
improve the complexity of these 3D platforms. However, lacking the guidance from surrounding biological 
cues, the intrinsic capability of cells may not be sufficient to drive self-organization for target tissue 
functions during the maturation and development. To dynamically model physiological microenvironments 
with spatiotemporal accuracy and re-establish directed cell-cell and cell-ECM interactions in vitro, in 
specific aim 1, 3D supporting matrices will be weaved with embedded biochemical and biomechanical 
cues. This will be enabled by programmably 3D printing cell-laden ECM-derived materials with the on-thefly ink formulation and following guided ECM remodeling by encapsulated fibroblasts. Specific aim 2 will 
explore if generated chemical and mechanical dual-gradients can direct multiscale vascularization of 
printed tissue constructs, a major challenge in tissue engineering. The perfusability of the vasculature will 
be evaluated. 3D tumor models will be assembled as a drug testbed to study how stromal barriers shape 
the resistance on therapeutic agents. Three innovations are featured by the proposed biofabrication 
strategy, including 1) 3D Print ECM-derived matrices with on-the-fly programmable formulation of bioinks 
and in situ crosslinking; 2) Direct cell migration, ECM remodeling, and angiogenesis with immobilized 
biochemical and biomechanical dual-gradients; 3) Construct tissue architectures by combining direct 3D 
bioprinting and postprint guided remodeling, toward 4D bioprinting. If successful, tumor parenchymal cells, 
multiscale vasculature and ECM barriers will be integrated within a single 3D model via a programmable 
process, providing three potential therapeutic targets for multi-specific, high-throughput drug screening

## Key facts

- **NIH application ID:** 10488677
- **Project number:** 5P20GM113126-07
- **Recipient organization:** UNIVERSITY OF NEBRASKA LINCOLN
- **Principal Investigator:** Fanben Meng
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $181,591
- **Award type:** 5
- **Project period:** 2016-08-15 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10488677

## Citation

> US National Institutes of Health, RePORTER application 10488677, Programmable Construction of 3D in vitro Disease Models Capturing Microenvironment Heterogeneity (5P20GM113126-07). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10488677. Licensed CC0.

---

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