# The mechanics of host cell repopulation of engineered tissues

> **NIH NIH R15** · WORCESTER POLYTECHNIC INSTITUTE · 2024 · $126,579

## 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. This diversity
supplement will enable additional studies within the scope of the parent grant in addition to
mentoring activities to support a student from a marginalized community.

## Key facts

- **NIH application ID:** 11044577
- **Project number:** 3R15HL167235-01S1
- **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:** $126,579
- **Award type:** 3
- **Project period:** 2023-03-01 → 2026-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11044577

## Citation

> US National Institutes of Health, RePORTER application 11044577, The mechanics of host cell repopulation of engineered tissues (3R15HL167235-01S1). Retrieved via AI Analytics 2026-06-12 from https://api.ai-analytics.org/grant/nih/11044577. Licensed CC0.

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