# Self-assembling Peptide Nanofiber Hydrogels for Nerve Regeneration

> **NIH NIH R01** · RICE UNIVERSITY · 2020 · $361,351

## Abstract

Project Summary / Abstract
This renewal proposal builds on our successes in developing a nanostructured material we call “MultiDomain
Peptides” or MDPs. Amongst the many discoveries during our first funding period, we found that these
hydrogels have remarkable properties in vivo, in particular: 1) The MDP amino acid sequence can be tailored
for rapid or slow degradation. 2) The hydrogel is entirely infiltrated by host cells within 7 days where the large
number of cells interacting with the MDP matrix provides for powerful and rapid response to the matrix. 3) No
fibrous encapsulation is observed up to 42 days in vivo allowing for good communication between our
nanostructured matrix and the biological system. 4) Biomimetic amino acid sequences can be added to the
base MDP structure allowing it to provoke desired biological responses such as angiogenesis and
neurogenesis. Published data from our previous funding period and unpublished preliminary data presented
here demonstrate the extremely powerful angiogenic and neurogenic properties of carefully designed MDPs
which is unprecedented elsewhere in the literature and is the basis for the current proposal. A key feature of
our approach is that the MDP hydrogel is composed of just a single designed, synthetic peptide. There is no
need for additional growth factors or cells, either of which increases the challenge of clinical translation due to
unforeseen and undesirable biological responses such as immune reaction, host rejection or tumor formation.
The current proposal has four aims which can be summarized as follows. In aim 1 we prepare a new series of
nanofibrous MDP hydrogels each containing a unique mimic of a growth factor or extracellular matrix protein.
The chemistry, nanostructure and materials properties are characterized in this aim. In aim 2 we test the the
MDP’s ability to activate expected cellular receptors. We also assess their performance in subcutaneous
injections in healthy mice. We assess inflammatory response, cellular infiltration, cytokine expression,
angiogenesis and neurogenesis. Based on these results antibody depletion studies will allow us to dissect the
mechanism of action. Aim 3 moves our study of tissue regeneration in the specific context of neural
regeneration. Two major sets of experiments are proposed. The first utilizes a cell culture model of neurite
sprouting to allow rapid screening of candidate MDPs. The second is a sciatic nerve injury model in rats. This
in vivo test of neuroregeneration allows more rapid and economical assessment of regeneration before moving
the more clinically relevant rabbit model. In aim 4 we examine nerve regeneration of the inferior alveolar nerve
of the rabbit. MDP hydrogels with demonstrated angiogenic and neurogenic properties will be used to
accelerate regeneration.
Our interdisciplinary team combines expertise in chemistry, materials science, nanotechnology, neuroscience
and clinical medicine. We will generate data that will provid...

## Key facts

- **NIH application ID:** 9983650
- **Project number:** 5R01DE021798-09
- **Recipient organization:** RICE UNIVERSITY
- **Principal Investigator:** Jeffrey Dale Hartgerink
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $361,351
- **Award type:** 5
- **Project period:** 2011-12-01 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9983650

## Citation

> US National Institutes of Health, RePORTER application 9983650, Self-assembling Peptide Nanofiber Hydrogels for Nerve Regeneration (5R01DE021798-09). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9983650. Licensed CC0.

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