# Mechanisms of Prosthetic Arterial Bypass Graft Failure

> **NIH NIH R01** · BETH ISRAEL DEACONESS MEDICAL CENTER · 2020 · $756,151

## Abstract

This is a proposal to create a biologically active prosthetic arterial graft (PG) incorporating gene silencing and
gene overexpression in an antithrombotic and pro-angiogenic surface. The research team is unique in its
cohesiveness and breadth of expertise including nanotechnology, polymers, gene therapy, vascular biology,
and surgery, all with an established focus on vascular grafts.
This project builds on our long-standing work where we have 1) characterized the lesion of anastomotic
neointimal hyperplasia (AIH) downstream of the prosthetic graft, 2) established the role of blood flow-surface
interaction in AIH pathogenesis, 3) determined the unique gene signature associated with AIH development,
including identification of high profile pathogenic and protective targets, 4) documented delivery of siRNA from
a prosthetic surface to knockdown pathogenic genes in vascular smooth muscle cells, 5 ) documented adeno
associated virus (AAV) mediated delivery of atheroprotective genes to the vascular wall and through the
prosthetic surface to endothelial cells and, 6) demonstrated the advantages of a cryogel coating as a delivery
system for antithrombotic and pro-angiogenic molecules and gene therapy.
Based on this knowledge and achievements, we propose an optimized approach to create a highly functional
and adaptable flow surface. We will build a composite PG comprising three components: A) A `backbone' graft
composed of standard polyethyleneterephthalate (PET), B) An anti-thrombotic (heparin) gel with improved cell
attachment properties (RGD) to be applied to the graft prior to cryogelation, and C) Biologic therapeutic agents
to be incorporated in the cryogel-PG prior to surgery, which would create a high capacity multifunctional
bioactive flow surface. Using gene therapy technologies, biologics with anti-inflammatory and atheroprotective
properties that have been fully validated by our group will be incorporated to synthesize the composite PG.
Our goal is to optimize the composite PG for delivery of drugs and biologics from the flow surface into the PG
microenvironment. This would target the circulating cells invading the pseudo intima, decreasing contact
activation and platelet aggregation. Additionally, this will modulate endothelial and smooth muscle cells of the
native artery at the anastomosis site as to prevent their phenotypic switch that fuels AIH. In a rabbit model we
will implant the composite PG with the bioactive gel applied intraluminally and/or extraluminally. We will then
gauge efficacy of drug delivery, and determine its effect on PG molecular signature and AIH.
This is a stepwise study bringing to bear the necessary and broad range of expertise on the effective
application of a multifunctional bioactive prosthetic arterial graft to improve outcome. This work will also serve
as proof of concept to instill bioactivity and adapt biomaterials for therapeutic purposes such as endografts,
hernia repair, and wound coverage.

## Key facts

- **NIH application ID:** 9876954
- **Project number:** 5R01HL021796-33
- **Recipient organization:** BETH ISRAEL DEACONESS MEDICAL CENTER
- **Principal Investigator:** CHRISTIANE FERRAN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $756,151
- **Award type:** 5
- **Project period:** 1987-07-01 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9876954

## Citation

> US National Institutes of Health, RePORTER application 9876954, Mechanisms of Prosthetic Arterial Bypass Graft Failure (5R01HL021796-33). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9876954. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*