# The mechanics of host cell repopulation of engineered tissues

> **NIH NIH R15** · WORCESTER POLYTECHNIC INSTITUTE · 2024 · $143,886

## Abstract

Project Summary/Abstract
We propose to determine how the dynamic mechanical environment of the valve regulates the attachment,
invasion, and differentiation of host cells into “off-the-shelf” decellularized tissue engineered heart valves
(TEHVs). We hypothesize that dynamic mechanical stretch and fluid shear stress regulate repopulation of the
TEHV matrix by enhancing and aligning 3D matrix adhesions and activating latent TGF-beta from the matrix.
To test our hypothesis, biopolymer scaffolds seeded with fibroblasts will be cast in stretchable wells and
microfluidic chambers until remodeled into isotropic or aligned neo-tissues and then decellularized in situ. We
will then quantify the extent to which vascular and circulating cells adhere to and invade the matrix under cyclic
stretch or dynamic flow conditions relevant to in vivo implantation. Cell attachment, infiltration, proliferation,
apoptosis, phenotype, and endothelial-to-mesenchymal transition markers will be quantitatively monitored over
time. TGF-beta activation and 3D matrix adhesion protein content and alignment will be examined, and
associated signal transduction pathways will be interrogated to determine the mechanisms governing the cell
responses. The results from this systematic study will have a direct impact on TEHV development by
determining the signals that aid (or hinder) host cell repopulation of the valve matrix with the goal of optimizing
valve design for adaptive remodeling under complex in vivo conditions. The administrative supplement will
enable additional studies within the scope of the parent grant in addition to mentoring activities to support
students from marginalized communities.

## Key facts

- **NIH application ID:** 11039004
- **Project number:** 3R15HL167235-01S2
- **Recipient organization:** WORCESTER POLYTECHNIC INSTITUTE
- **Principal Investigator:** Kristen L Billiar
- **Activity code:** R15 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $143,886
- **Award type:** 3
- **Project period:** 2023-03-01 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11039004

## Citation

> US National Institutes of Health, RePORTER application 11039004, The mechanics of host cell repopulation of engineered tissues (3R15HL167235-01S2). Retrieved via AI Analytics 2026-06-12 from https://api.ai-analytics.org/grant/nih/11039004. Licensed CC0.

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