# Hydrogel Delivery of Extracellular Vesicles to Treat Osteoarthritis

> **NIH VA I21** · PHILADELPHIA VA MEDICAL CENTER · 2021 · —

## Abstract

Articular cartilage has limited intrinsic healing capacity, and as a result, any injury, as well as
the natural aging process, may lead to osteoarthritis (OA). Various reconstructive techniques
are being employed for treatment of focal defects; however, there are few approaches
being developed to address damage across cartilage surfaces with OA and to alter the
progression of the disease. Although there are therapeutic molecules that may be of interest to
treat OA, their systemic application is limited due to off-target concerns and local injection has
limited efficacy due to short half-lives. To address these concerns, injectable hydrogels may be
used to locally delivery and sustain the release of therapeutics to the joint. The objective of
this study is to develop an injectable hydrogel for the delivery of therapeutic extracellular
vesicles (EVs) and to evaluate the EV/hydrogel therapy in a minipig model of OA. Two Aims
will be pursued towards this goal. In Aim 1 we will use our experience in biomaterial
development to engineer a shear-thinning and self-healing hydrogel based on hyaluronic acid
(HA). We will use dynamic covalent crosslinks to obtain these desired properties and will
encapsulate and release EVs isolated from pig mesenchymal stromal cells (MSCs). The MSC
EVs will be characterized for size, surface properties, and content before and after release
and the release kinetics will be monitored with fluorescent labeling from hydrogels with a range
of crosslink densities. This Aim will identify one hydrogel formulation that releases EVs over
several weeks that can be used for in vivo assessment in Aim 2. In Aim 2 we will test the
efficacy of our engineered hydrogel therapies in an in vivo setting. Using our Yucatan minipig
model of OA, we will evaluate functional outcomes (histology, MRI) after injection of our
hydrogels containing EVs. This evaluation will include activity measures (steps/day) and
joint range of motion using custom motion tracking systems that we previously developed.
Upon completion, we will have developed an injectable hydrogel therapeutic that is applied
through a simple process similar to viscosupplements to deliver therapeutics to alter the
progression of disease with OA. This therapy could be translated to the clinic for treatment of
the large number of OA patients in the Veteran population who have few treatment options
and could limit the number of total knee replacements performed.

## Key facts

- **NIH application ID:** 10176189
- **Project number:** 5I21RX003293-02
- **Recipient organization:** PHILADELPHIA VA MEDICAL CENTER
- **Principal Investigator:** Robert L Mauck
- **Activity code:** I21 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2021
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2020-06-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10176189

## Citation

> US National Institutes of Health, RePORTER application 10176189, Hydrogel Delivery of Extracellular Vesicles to Treat Osteoarthritis (5I21RX003293-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10176189. Licensed CC0.

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