# Cell-free vascular grafts: immunological response and vascular regeneration

> **NIH NIH R01** · STATE UNIVERSITY OF NEW YORK AT BUFFALO · 2020 · $573,346

## Abstract

ABSTRACT
Cardiovascular disease is the leading cause of death in the United States. In particular, coronary artery disease
is the most common disorder, with over 350,000 bypass grafting procedures performed every year and an
estimated total cost of $26 billion annually, according to the AHA. Tissue engineering approaches using native
or synthetic scaffolds and even scaffold-free strategies have developed functional and implantable vascular
grafts that have been tested in small and large animal models, as well as in human clinical trials 1-12. In recent
years, the field has focused on engineering acellular (A)-TEVs as a potential alternative approach that may
provide off-the-shelf grafts for treatment of cardiovascular disease. Recently, we reported successful
development of A-TEV based on small intestinal submucosa (SIS) that was functionalized sequentially with
heparin and vascular endothelial growth factor (VEGF-165, denoted as VEGF) 13,14. This A-TEV was implanted
successfully into the arterial circulation of small (mice) 15 and large (sheep) animal models 13, demonstrating
patency, endothelialization and regeneration of contractile vascular wall. Interestingly, VEGF-decorated grafts
were populated by anti-inflammatory, M2 macrophages, while vascular grafts containing heparin alone contained
mostly M1 type macrophages 15. What is more, VEGF containing grafts had an architecture that was similar to
native arteries, in contract to grafts without VEGF (heparin alone), which appeared disorganized and lacked well-
defined endothelium and vascular wall. This prompted us to hypothesize that successful regeneration of A-TEV
in vivo may depend on generating an anti-inflammatory and pro-regenerative environment, which may be
modulated (at least in part) by the immobilized VEGF (iVEGF) decorating the surface of the grafts.
In this proposal, we seek to investigate this hypothesis in three specific aims. In Aim 1, we will explore the
mechanism through which VEGF modulates the inflammatory response. In Aim 2, we will employ novel
transgenic mouse models to monitor monocyte infiltration into the grafts and study the role of VEGF signaling
on inflammation and graft regeneration. Finally, in Aim 3 we will explore the long-term patency and remodeling
of A-TEV in a large, pre-clinical animal model (ovine) to assess the clinical potential of these grafts.
This is a highly innovative proposal that seeks to investigate how regulating the inflammatory response may
affect the patency and regeneration of vascular grafts. We also seek to determine the clinical potential of these
VEGF-based A-TEVs in a large, pre-clinical animal model. Given the importance of the inflammatory response
for tissue regeneration, our work may have broader implications for regenerative medicine. Our productivity
during the last funding cycle (35 publications), the promising discoveries including mechanistic and translational
studies that originated from our laboratory, and the excellent team...

## Key facts

- **NIH application ID:** 9912445
- **Project number:** 1R01HL151196-01
- **Recipient organization:** STATE UNIVERSITY OF NEW YORK AT BUFFALO
- **Principal Investigator:** Stelios T. Andreadis
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $573,346
- **Award type:** 1
- **Project period:** 2020-04-10 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9912445

## Citation

> US National Institutes of Health, RePORTER application 9912445, Cell-free vascular grafts: immunological response and vascular regeneration (1R01HL151196-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9912445. Licensed CC0.

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