# Clickable Extracellular Vesicles to Silk-Based Biomaterials for Regenerative Medicine

> **NIH NIH U01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2024 · $703,775

## Abstract

PROJECT SUMMARY
 Successful regenerative medicine approaches require harnessing the appropriate cell signals at the
right time to direct host tissue functions. These signals are often informed by the natural regenerative
processes controlled during development and homeostasis by mesenchymal stem cells (MSCs) and
their secreted extracellular vesicles (EVs), which allow a cell-based yet cell-free approach for
downstream regenerative technologies. This multidisciplinary, MPI proposal brings together a team of
two senior investigators leading regenerative medicine-focused group with complementary strengths,
co-investigators with critical roles, and industrial partner RoosterBio, Inc. Together, we will create and
test an innovative enabling technology to stably incorporate EVs to a biomaterial intended for tissue
engineering and regenerative medicine applications. Specifically, we will use a novel azide-based click
chemistry technique to controllably immobilize EVs to silk fibroin as a demonstrative application, but
immobilization can also be done on other biomaterials, substrates, or surfaces, or even tissues. We
chose silk as our biomaterial in this application given its FDA-approved status and wide use.
 We hypothesize that “azide-clickable" MSC-derived EVs (which we will refer to simply as “Az-EVs”)
will have more stable immobilization to silk fibroin biomaterials than unmodified EVs, and this will result
in higher regenerative potency. To test this hypothesis and provide proof-of-concept applications, we
will pursue four specific aims:
Aim 1 - Demonstrate and validate Az-EV immobilization to silk fibroin-based materials;
Aim 2 - Demonstrate the MSC-mimicking effects of Az-EVs immobilized to silk in vitro;
Aim 3 - Demonstrate the regenerative effects of Az-EVs in a mouse chronic wound healing model;
Aim 4 - Demonstrate the regenerative effects of Az-EVs in a rat tissue engineered vascular graft model.
 Partner RoosterBio, Inc. will “industrialize” (scale-up) the production of MSC-derived Az-EVs for
commercialization to make available to other researchers and clinicians.
 This research will provide insight to the efficacy of this novel selective EV immobilization
technology to efficiently direct EV delivery within a biological system of interest. Our proof-of-concept
studies will demonstrate how utilization of this regenerative technology can aid in treating chronic
wounds and enabling TEVGs with improved patency rates.

## Key facts

- **NIH application ID:** 10916248
- **Project number:** 5U01EB034450-02
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** PHIL GORDON CAMPBELL
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $703,775
- **Award type:** 5
- **Project period:** 2023-09-01 → 2028-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10916248

## Citation

> US National Institutes of Health, RePORTER application 10916248, Clickable Extracellular Vesicles to Silk-Based Biomaterials for Regenerative Medicine (5U01EB034450-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10916248. Licensed CC0.

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