# 3D Encapsulation, Bioprinting and Controlled Delivery of Functionally Engineered EVs (FEEs)

> **NIH NIH R01** · UNIVERSITY OF ILLINOIS AT CHICAGO · 2023 · $474,057

## Abstract

Summary:
Tissue repair is a complex process that involves a delicate temporal balance between inflammatory and
regenerative mechanisms. In health, initial inflammatory events are replaced by regenerative processes in a
coordinated manner. This sequence is disrupted in diseased states and complex injuries. The goal of
regenerative medicine is to reestablish this balance by preventing chronic/aberrant inflammation and promoting
repair and regeneration in a tissue-specific manner. While stem cell and growth factor therapies have been
explored for this purpose traditionally, recent studies highlight the immunomodulatory and protective functions
of mesenchymal stem cell derived extracellular vesicles (MSC EVs). Although MSC EVs possess versatile
properties, to engage tissue-specific pathways and fit the goals of precision medicine with translational
relevance, MSC EVs have to be engineered for enhanced pathway-specific functionality and delivered on site
in a spatially and temporally controlled manner. In this proposal, leveraging our preliminary results and our
expertise in EV biology, immunology and bone biology, we hypothesize that: Spatiotemporal control of
immunomodulatory and regenerative pathways can be achieved by selective incorporation of Functionally
Engineered EVs (FEEs)in 3D printed scaffolds. Using bone regeneration as a model system, we will test this
hypothesis in three specific aims. In aim 1, we will generate functionally engineered EVs (FEEs) that target
specific osteoinductive and immunomodulatory pathways. In aim 2, we will develop a photocrosslinkable
alginate-based delivery system with EV carrier and release motifs for spatial localization and temporally
controlled delivery of the FEEs developed in aim 1. In aim 3, we will utilize 3D printing technology to print
defined structures encapsulating the FEEs for spatially and temporally controlled biphasic delivery in vivo. This
system will be tested in a rat calvarial defect model. From the proposed studies, we will develop a platform
technology that can impact the field of regenerative medicine beyond the craniofacial and musculoskeletal
systems.

## Key facts

- **NIH application ID:** 10633258
- **Project number:** 5R01DE030495-03
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT CHICAGO
- **Principal Investigator:** LYNDON F COOPER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $474,057
- **Award type:** 5
- **Project period:** 2021-06-18 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10633258

## Citation

> US National Institutes of Health, RePORTER application 10633258, 3D Encapsulation, Bioprinting and Controlled Delivery of Functionally Engineered EVs (FEEs) (5R01DE030495-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10633258. Licensed CC0.

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