# Modeling of human HSV infection: development of immune-competent 3D skin-on-chip with vascular perfusion

> **NIH NIH R01** · UNIVERSITY OF WASHINGTON · 2022 · $533,495

## Abstract

SUMMARY
Conventional mechanistic research and drug development relies heavily on in vivo animal models and in vitro
cell culture systems. Although conventional in vitro cultured 2D or 3D cells enable the analysis of signaling
pathways and the identification of signature genes associated with responses of infection or various conditions
and treatments, they can't reproduce complex cell-cell and cell-matrix interactions occurring in the tissue
microenvironment. Animal models provide understanding on in vivo integrated multi-organ responses but
serious concerns exist over their predictive value and biological relevance to humans. In fact, more and more
drug candidates have failed to advance from Phase I to Phase III clinical trials and to reach the market. Critical
challenges to reduce costly failures in clinical trials highlight the urgency to generate better model systems for
preclinical testing of drug efficacy and safety in humans, and for understanding molecular mechanisms
underlying thousands of human diseases. A three-dimensional (3D) human tissue model promises compelling
advantages to predict complex physiological functions, immune responses to infectious diseases, and
pharmacological responses to therapeutic agents. Such a synthetic tissue model has outstanding potential for
reliable drug efficacy testing and as a superior replacement for an animal model, especially for those infectious
diseases that do not have adequate animal models. Skin is the largest organ of the human body and forms a
barrier to protect the body against pathogens and penetration of potential harmful substances. In order to
mimic the organ-level skin pathophysiology in humans, we propose to harness bioengineering approaches to
develop an in vitro 3D `skin-on-chip' that incorporates circulating immune cells into the normal architecture of
skin epidermis and dermis for modeling of viral-host interactions in human herpes simplex virus (HSV)
infection. Our Specific Aims are: 1) Establish and validate a vascularized 3D `skin-on-chip' platform using
donor-derived primary cells for modeling of HSV infection and identifying key immune responses for protection.
2) Recapitulate a tissue resident memory T-cell compartment in 3D vascularized `skin-on-chip' for modeling of
antigenic specificity, cell density and TCR diversity in tissue resident memory T-cell mediated local immune
protection.

## Key facts

- **NIH application ID:** 10328978
- **Project number:** 5R01AI143773-03
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Jia Zhu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $533,495
- **Award type:** 5
- **Project period:** 2020-02-15 → 2025-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10328978

## Citation

> US National Institutes of Health, RePORTER application 10328978, Modeling of human HSV infection: development of immune-competent 3D skin-on-chip with vascular perfusion (5R01AI143773-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10328978. Licensed CC0.

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