# Engineering of biomaterials with controlled biomolecule delivery for cardiovascular applications

> **NIH NIH R01** · OREGON HEALTH & SCIENCE UNIVERSITY · 2024 · $647,359

## Abstract

Project Summary
Currently, cardiovascular disease ranks as the leading cause of death in the United States. It is projected that
by 2035, over 130 million adults in the U.S. will have some form of cardiovascular disease. Vascular graft
technologies with patency rates equivalent to the clinical success of autologous grafting are lacking. Our goal is
to utilize novel biomaterial surface modifications and develop nucleic acid delivery technology to improve host-
biomaterial interactions with particular focus on the failure mechanism of neointimal hyperplasia resulting from
smooth muscle cell proliferation and migration. Previous work by our team has optimized surface characteristics
(physical topographies and biochemical modifications) to promote endothelialization without increasing
thrombosis. However, the addition of controlled therapeutic nucleic acid delivery with this proposal will address
intimal hyperplasia by directly altering smooth muscle cell phenotype. This work will develop the material surface
delivery techniques to alter host-biomaterial responses, which occur after graft implantation. Our use of poly(vinyl
alcohol) (PVA) biomaterials is integral to these studies because it is a highly modifiable material; however, these
results can be readily translated to other modifiable off-the-shelf materials. Our aims are to: (1) develop nonviral
delivery of miR145 with surface- and sustained-release via nanoparticles complexed to our novel PVA-CDI
immobilized aminated fucoidan (PCAF) biomaterials, (2) characterize the effects of PCAF delivered miR145 on
vascular cell responses, including endothelial cells, neutrophils, macrophages, and fibroblasts and (3)
characterize the in vivo effects of PCAF-delivered miR145 on neointimal formation under healthy and diseased
states. Using PCAF with previously established topographies and surface chemistries known to support
endothelialization while maintaining hemocompatibility, we will utilize innovative gene delivery technologies in
conjunction with our clinically relevant animal models. These strict models have the potential to improve
translation by testing the material modifications in a whole, non-anticoagulated, flowing blood model of
thrombosis and a clinically relevant end-to-side model of vascular grafting implantation. The deliverables for this
project will include (1) efficient and sustainable delivery of miRNA-145 from our previously optimized PCAF to
smooth muscle cells (SMCs), (2) induction of the SMC contractile phenotype without causing endothelial
dysfunction, inflammation, or thrombosis, and (3) confirming a reduction of neointima formation in vivo without
harmful “off-target” effects or harmful accumulation in organs. The potential significance of this translational
project is the improved design of novel, functional biomaterial surfaces for cardiovascular applications. While we
are focused on vascular graft applications in this proposal, the principles of surface controlled responses c...

## Key facts

- **NIH application ID:** 10890394
- **Project number:** 1R01HL168868-01A1
- **Recipient organization:** OREGON HEALTH & SCIENCE UNIVERSITY
- **Principal Investigator:** Monica T Hinds
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $647,359
- **Award type:** 1
- **Project period:** 2024-07-19 → 2028-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10890394

## Citation

> US National Institutes of Health, RePORTER application 10890394, Engineering of biomaterials with controlled biomolecule delivery for cardiovascular applications (1R01HL168868-01A1). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/10890394. Licensed CC0.

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