# A novel biomaterial approach for local delivery of hepatocyte growth factor to promote stem cell graft-host integration and spinal cord repair.

> **NIH NIH R21** · DREXEL UNIVERSITY · 2020 · $397,575

## Abstract

Traumatic spinal cord injury (SCI) causes partial or complete loss of sensory, motor, and autonomic functions
below the injury site. The lost neurons need to be replaced and axons of the remaining neurons need to
regenerate across or around the lesion site and re-establish functional neural connections. However, neurons
usually cannot renew themselves, and axon regeneration is restricted by the lack of intrinsic regeneration
capacity and extrinsic inhibitory environment in the injured spinal cord. Neural stem/progenior cell (NSPCs)
transplantation is a promising therapeutic strategy to replace the lost neurons and establish neuronal relays for
reconnecting neurons rostral and caudal to the injury site, to rebuild the damaged neural circuitry. However,
astroglial-fibrotic scar formation inhibits axon growth and grafted NSPC-host integration. Following SCI, reactive
astrocytes produce excessive chondroitin sulfate proteoglycans (CSPGs), a repulsive factor for neural growth,
to form glial scars. In addition, infiltrating fibroblasts secrete a large amount of collagen, which is the major
component of fibrotic scars. Collagen and CSPGs create a network of tough matrix in astroglial-fibrotic scars,
exhibiting a chemical and physical barrier hampering axon growth and graft-host tissue fusion, which led to
insufficient signal transmission across the lesion for functional recovery. The overall goal of this study is to
develop an effective and clinically applicable approach to promote grafted NSPCs-host integration and
reconstruction of neural circuit after SCI. Toward this goal, we will develop and test a novel biomaterial-based
approaches to (1) inhibit astroglial-fibrotic scar formation and (2) promote both host and graft axonal growth
across the scar, via local delivery of hepatocyte growth factor (HGF). HGF has been shown to promote a normal
wound healing process by promoting tissue regeneration and inhibiting fibrosis/collagen deposition in various
peripheral tissues outside of the central nervous system (CNS). Moreover, it has been shown to inhibit astrocytic
scar formation and CSPG deposition after SCI. We have developed polysaccharide-based complexes (particles)
self-assembled through electrostatic interactions for sustained delivery of HGF. The particles can be
encapsulated into agarose hydrogel and implanted into the intrathecal space of spinal cord for sustained local
delivery of HGF. Using a clinically relevant cervical contusion injury model, we found that local HGF treatment
significantly reduced collagen and fibrosis after SCI. Moreover, local HGF treatment also significantly reduced
astroglial scar and CSPGs. In this study, we aim to (1) determine the timing of NSPC transplantation following
cervical contusion SCI; and (2) determine if local delivery of HGF will promote graft-host integration and
functional recovery after SCI. Successful completion of these Aims will facilitate future clinical application of stem
therapy in spinal cord inj...

## Key facts

- **NIH application ID:** 10111144
- **Project number:** 1R21NS120161-01
- **Recipient organization:** DREXEL UNIVERSITY
- **Principal Investigator:** Yinghui Zhong
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $397,575
- **Award type:** 1
- **Project period:** 2020-09-30 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10111144

## Citation

> US National Institutes of Health, RePORTER application 10111144, A novel biomaterial approach for local delivery of hepatocyte growth factor to promote stem cell graft-host integration and spinal cord repair. (1R21NS120161-01). Retrieved via AI Analytics 2026-06-08 from https://api.ai-analytics.org/grant/nih/10111144. Licensed CC0.

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