# Using Modified Synthetic MicroRNAs to Control Foreign Body Reactions In Vivo

> **NIH NIH R21** · UNIVERSITY OF CONNECTICUT SCH OF MED/DNT · 2021 · $206,261

## Abstract

The goal of the present grant is to develop and validate the effectiveness of artificial microRNA-mimic/inhibitor (a-
miR-m/i)-based coatings to suppress foreign body reactions to S.Q. injected micro-beads in vivo. If these pre-
translational studies of a-miR-m/i coatings in mice are successful, in the future we will evaluate their effectiveness in
vivo using porcine models of implantable medical devices.
 The explosion of implantable medical devices has been “god sent” by dramatically improving the quality and length
of life for a wide variety of patients worldwide. These devices range from simple metal screws, to the artificial pancreas
(glucose sensor & insulin pump infusion sets) that help control blood glucose levels in patients with diabetes.
Unfortunately, the functional lifespan of these medical implants are frequently shortened by implant-induced chronic
inflammation referred to as foreign body reactions (FBR). Although there have been decades of research and development
to discover a “rosette stone” to defeat FBR, no true breakthroughs or disruptive technology has been developed to
overcome FBR. There is a clear need for the development of a truly disruptive technology, we believe that a-miR-m/i
coatings are that disruptive technology. The original discovery of powerful micro-RNAs, which regulate a wide range of
cells and network functions, led to the creation of micro-RNA-m/i, which in turn led to the development of modified
synthetic microRNA we have designated as artificial microRNA-mimic (a-miR-m) and inhibitor (a-miR-i) based
therapeutics. We propose to use these a-miR-m/i as micro-bead coatings to control FBR in vivo by 1) suppressing
inflammation and pathologic fibrosis, as well as 2) induce neovascularization (blood and lymphatic vessels) to enhance
successful integration of medical devices into healthy surrounding tissue. To our knowledge, there are currently no
publications related to the use of a-miR-m/i to enhance implantable device biocompatibility in the literature. The
goal of the present application is to develop foundational data on the ability of a-miR-m and a-miR-i (with and
without basement membrane (BM) adjunct coatings), to enhance the biocompatibility in a simple FBR model, i.e.
subcutaneous micro-bead injections (murine MB model). For the present studies, BM adjuvants represent a prototype
coating, but in the future studies, we will consider various other natural and synthetic coatings for depoting a-miR-m/i.
Initially, we will use cell culture models to determine the ability of specific a-miR-m and a-miR-i in suppressing pro-
inflammatory activity by targeting 1) M1/M2 macrophages, 2) fibrosis by targeting fibroblasts, and 3) neovascularization
by targeting M2 macrophages and vascular endothelial cells (VEC) in vitro. The a-miR-m/i optimized in vitro will then
be evaluated in vivo. Using the mouse model, we will evaluate a-miR-m/i only coated micro-beads (i.e. non-BM-coated
(Wo) and a-miR-m/i BM-coated (W) micro...

## Key facts

- **NIH application ID:** 10114211
- **Project number:** 5R21AI151840-02
- **Recipient organization:** UNIVERSITY OF CONNECTICUT SCH OF MED/DNT
- **Principal Investigator:** DON KREUTZER
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $206,261
- **Award type:** 5
- **Project period:** 2020-03-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10114211

## Citation

> US National Institutes of Health, RePORTER application 10114211, Using Modified Synthetic MicroRNAs to Control Foreign Body Reactions In Vivo (5R21AI151840-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10114211. Licensed CC0.

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