# Functional Activation and Targeting of Exosomes for Regenerative Medicine

> **NIH NIH R01** · UNIVERSITY OF ILLINOIS AT CHICAGO · 2021 · $379,763

## Abstract

Summary:
 Stem Cell Lineage Determination (SCLD) is a necessary and important step required for successful
regeneration of tissues lost due to disease or injury. Existing tissue engineering approaches employ the use of
growth factors and morphogens along with relevant biomaterials to achieve SCLD. However, this approach to
SCLD is limited by several factors such as dosage, delivery, ectopic activity, adverse immunological
complications and aberrant differentiation. As a result of these limitations, the single morphogen system has
either caused significant clinical complications (from FDA approved growth factors such as BMP2) or has failed
to be translationally successful. The need of the hour is a replacement for this single morphogen/growth factor
system that is biomimetic in nature and does not pose the same threats to translation. In this regard, the use
of exosomes can be beneficial owing to their biomimetic nature, their ability to be endocytosed by recipient
cells and their positive immunological reactions. However, two fundamental questions need investigation to
aid the use of exosomes as nano biomimetic tools to achieve SCLD in regenerative medicine. They are: 1.
Can exosomes be targeted to biomaterials for localized delivery? 2. Can exosomal composition be modified to
induce tissue-specific SCLD? This application is an effort to bridge this knowledge gap. We propose to
engineer targetability and lineage-specific functionality into exosomes to generate Functionally Activated
Targeted Exosomes (FATE). In this application, we will use bone regeneration as a model system to study the
generation, evaluation and application of FATE for regenerative medicine. We propose three specific aims to
achieve this goal. In Aim 1, we will engineer exosomes with enhanced binding characteristics to ECM proteins
type I collagen and Fibronectin to enable biomaterial-mediated site-specific targeting. In Aim 2, we will
engineer osteoinductive functionality into the targeting exosomes using two distinct approaches and evaluate
the resulting FATE in vitro. In Aim 3, we will evaluate the targeting and functionality of FATE generated in aim
2 in vivo in a critical size rat calvarial defect model. The successful completion of these studies will serve as
proof-of-principle that cell-derived nano vesicles (exosomes) can be engineered to possess characteristics
required to enhance SCLD for tissue-specific regeneration.

## Key facts

- **NIH application ID:** 10165690
- **Project number:** 5R01DE027404-04
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT CHICAGO
- **Principal Investigator:** PRAVEEN GAJENDRAREDDY
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $379,763
- **Award type:** 5
- **Project period:** 2018-07-15 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10165690

## Citation

> US National Institutes of Health, RePORTER application 10165690, Functional Activation and Targeting of Exosomes for Regenerative Medicine (5R01DE027404-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10165690. Licensed CC0.

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