# Engineered 3D microfluidic tubular device as multimodal, functional tissue model

> **NIH VA I21** · U.S. DEPT/VETS AFFAIRS MEDICAL CENTER · 2024 · —

## Abstract

Abstract: Calcium phosphate (CaP) deposition is characteristic of several life-threatening kidney and cardio-
vascular diseases; thus, understanding CaP biomineralization is essential for developing new clinical
therapies. Previous studies either analyzed extracted stones from patients or reproduced CaP deposits in
quasi-2 dimensional (D) in vitro systems. However, such approaches fail to capture real-time kinetic
information of mineralization and the 3D cellular microenvironments found in vivo – both of which are essential
for understanding CaP biomineralization. Despite extensive research, mechanisms by which crystals nucleate,
grow, and aggregate into stones are still poorly understood due to a lack of suitable bioanalytical tools that
offer dynamic control over the microenvironments. Using our novel 3D microfluidic (MF)-based workbench that
we achieved previously with unattained precision in controlling dynamic, spatiotemporal biological conditions of
in vivo tubular systems, we will elucidate the origin and mechanisms of calcium mineralization and CaP stone
formation. To recreate in vivo-like conditions, we will use an improved functional 3D-renal tubular system
(RTS) using porous membranes to examine apical↔basal transport. This transformative strategy will allow us
to evaluate/validate the contribution of dynamic microenvironmental cues (e.g., cellular regulations, microscale
hydrodynamics) in CaP stone formation. Our overall hypothesis is that the combined interplay between
tubular epithelial cells and its luminal fluid within these vivo-like RT structures would recapitulate normal and
pathophysiological biomineralization by identifying precise microenvironmental dynamic factors influencing
CaP stone formation. We will systematically evaluate the role of molecular factors (e.g., ionic supersaturation,
stone forming activators/inhibitors) and dynamic microenvironmental cues that underlie CaP stone formation.
We propose to (i) reprogram/recreate a fluidic microenvironment in improved 3D MF devices using polarized
tubular epithelia, and (ii) mimic the in vivo stone-forming conditions by regulating cellular microenvironment
(oxidative stress, inflammation, and fibrosis) within these 3D in vitro microsystems. Our rationale is that the
sequential introduction of factor(s) of stone formation within the perfused constructs will allow us to identify
currently unknown molecular bases of pathophysiological biomineralization. In Aim 1, we will validate the
functional 3D-MFs by examining the endogenous (biomolecules), exogenous (environmental) factors, and the
effects of inner lumen topological defects to determine factors regulating nucleation, growth, and dissolution of
CaP crystals. In Aim 2, we will map and characterize real time step-by-step dynamic growth patterns/rates of
crystal towards stone formation. In Aim 3, we will invoke the processes of fibrosis, inflammation, calcification,
and apoptosis at controlled times to determine the impact on ...

## Key facts

- **NIH application ID:** 10920891
- **Project number:** 1I21BX006418-01A1
- **Recipient organization:** U.S. DEPT/VETS AFFAIRS MEDICAL CENTER
- **Principal Investigator:** Bidhan Chandra Bandyopadhyay
- **Activity code:** I21 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2024
- **Award amount:** —
- **Award type:** 1
- **Project period:** 2024-07-01 → 2027-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10920891

## Citation

> US National Institutes of Health, RePORTER application 10920891, Engineered 3D microfluidic tubular device as multimodal, functional tissue model (1I21BX006418-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10920891. Licensed CC0.

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