# Embedded Printing of Human Respiratory Model with Air-Liquid Interface for COVID-19 Research

> **NIH NIH R21** · UNIVERSITY OF FLORIDA · 2022 · $176,608

## Abstract

Project Summary
The overarching goal of this research is to fabricate an in vitro three-dimensional (3D) human respiratory
model with an air-liquid interface (ALI), which can serve as a platform for COVID-19 related biomedical
investigations. A recent COVID-19 outbreak, which is due to the infection of a severe acute respiratory
syndrome coronavirus 2 (SARS-CoV-2), results in more than 100 million confirmed cases and about 2.3 million
deaths with numbers increasing everyday globally. For COVID-19 related research, there remains an urgent
need for a 3D fully heterogeneous, cellular respiratory model, which can enhance our understanding of how
SARS-CoV-2 induces lung injury and facilitate the development of new treatments as complementary to animal
models and clinical patients. We therefore propose to develop such a human respiratory model, which 1)
expresses angiotensin-converting enzyme 2 (ACE2) protein and transmembrane protease serine type 2
(TMPRSS2) that allow viral entry to study the SARS-CoV-2 infection process, and 2) has the diffusional
permeability between the airway and primary fluid channel to enable the mass transport across ALI, permitting
the screening of clinically proven drugs for COVID-19 use. We hypothesize that an in vitro human respiratory
model can be realized by embedded printing and further developing a perfusable construct in a yield-stress
matrix bath containing primary human stromal, endothelial, and fibroblast cells.
Accordingly, two specific aims are proposed as follows:
Aim 1: Embedded printing and perfusion of a 3D in vitro human respiratory model in a stromal cell-based
 cross-linkable yield-stress matrix bath.
Aim 2: Characterization of the human respiratory model via detection of ACE2 receptor and TMPRSS2
 protease in the airway epithelium and determination of the diffusional permeability of ALI.
For the first time, a gelatin microgels and gelatin solution-based cross-linkable yield-stress cellular
composite matrix bath will be innovated for embedded printing of perfusable tissue constructs in it, enabling
human respiratory model fabrication. This model development study will result in an in vitro 3D human
respiratory model with ALI and cellular stroma by utilizing the novel cross-linkable yield-stress cellular matrix
bath for embedded printing, and no other models with this physiological complexity exist. Such a human
respiratory model will provide a versatile in vitro platform for studying the COVID-19 pandemic-related infection
process and screening related drugs.

## Key facts

- **NIH application ID:** 10353655
- **Project number:** 1R21HL162405-01
- **Recipient organization:** UNIVERSITY OF FLORIDA
- **Principal Investigator:** Yong Huang
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $176,608
- **Award type:** 1
- **Project period:** 2022-08-01 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10353655

## Citation

> US National Institutes of Health, RePORTER application 10353655, Embedded Printing of Human Respiratory Model with Air-Liquid Interface for COVID-19 Research (1R21HL162405-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10353655. Licensed CC0.

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