# Enhanced Mitochondrial Viability via Engineered Hyrdogels for Intrathecal Spinal Cord Delivery

> **NIH NIH R01** · UNIVERSITY OF KENTUCKY · 2022 · $449,945

## Abstract

Project Summary/Abstract
Mitochondrial dysfunction is pivotal to the neuropathological sequelae following traumatic spinal cord
injury (SCI). During this initial time window, there is a significant loss of mitochondria with an
inflammatory/oxidative environment that perpetuates the pathophysiology. It is hypothesized that to
rescue the cellular damage occurring following SCI, one must replace damaged mitochondria, while also
changing the damaging microenvironment. We have documented that maintaining endogenous
mitochondrial bioenergetics with acetyl-l-carnitine (ALC), an alternative mitochondrial biofuel, or reducing
oxidative stress by replenishing endogenous antioxidant, glutathione (GSH) with N-acetylcysteine amide
(NACA) after SCI results in increased, but limited long-term functional neuroprotection. We have also
reported that acute mitochondrial transplantation (MitoTxp) using intraspinal injections of mitochondria
isolated from rat soleus muscle significantly preserved bioenergetic function 48hr post-SCI. However,
this was sporadically successful due to the challenges of both accumulating mitochondria at the site of
injury and maintaining their viability prior to cellular uptake. In the current proposal, we will develop a
thermo-gelling, erodible hydrogel system for the localized delivery of viable mitochondria to test the
neuroprotective efficacy of combined MitoTxp and pharmaceutical interventions (ALC and/or NACA) after
contusion SCI. The use of an injectable hydrogel will permit the development of a local environment which
can aide in maintaining mitochondrial health through optimization of the hydrogel niche. We will determine
1) optimum constituents for isolated mitochondria to remain viable for extended periods in polymeric
hydrogels, 2) whether exogenous mitochondria transplanted via less invasive intrathecal route equally
preserve integrity of bioenergetics compared to intraspinal route and 3) consequences of acute or
delayed MitoTxp in combination with ALC and/or NACA on bioenergetics, oxidative stress, and functional
neuroprotection after SCI.

## Key facts

- **NIH application ID:** 10447178
- **Project number:** 5R01NS119337-03
- **Recipient organization:** UNIVERSITY OF KENTUCKY
- **Principal Investigator:** Samirkumar Patel
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $449,945
- **Award type:** 5
- **Project period:** 2020-09-30 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10447178

## Citation

> US National Institutes of Health, RePORTER application 10447178, Enhanced Mitochondrial Viability via Engineered Hyrdogels for Intrathecal Spinal Cord Delivery (5R01NS119337-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10447178. Licensed CC0.

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