# Matrix-reinforcing and cell-instructive smart hydrogel for cartilage preservation

> **NIH VA IK2** · VETERANS HEALTH ADMINISTRATION · 2024 · —

## Abstract

Cartilage damage is extremely common in the active-duty and Veteran populations, both by trauma and wear-
and-tear. These initial injuries compromise the biophysical and biochemical environment around cells,
characterized by softening of the surrounding microenvironment and production of pro-inflammatory cytokines.
The softer cellular microenvironment leads to volumetric and morphological changes of the cartilage cells, or
chondrocytes, and the pro-inflammatory signaling leads to the continued degradation of the surrounding matrix.
Combined, these early degenerative changes lead to aberrant cell behavior and a vicious deteriorative process,
leading to progressive cartilage wear with time and culminating in osteoarthritis (OA). OA is a significant burden
on the Veteran population, causing pain, discomfort, and reduced quality of life. Halting the degenerative process
early in its progression, by specifically rehabilitating the cell and its surrounding environment, represents an
impactful and innovative approach to preventing or delaying the onset of OA. Thus, the overarching goal of this
proposal is to utilize a novel hyaluronic acid (HA) hydrogel system to both fortify damaged cartilage tissue and
provide persistent presentation of inflammation-inhibiting peptides, all with the goal of preventing the progression
of OA. This goal will be tested with the following specific aims:
Aim 1: Determine the restorative effect of PCM fortification on chondrocyte cytoskeletal organization and
mechano-transduction. First, a library of HA formulations and applications will be developed and tested on
damaged cartilage tissue to achieve 3-4 levels of PCM fortification. Then, in a cartilage explant culture model,
the impact of fortification on chondrocyte volume regulation, morphology, cytoskeletal composition and
organization, and mechano-transductive properties will be determined and compared to healthy cells.
Aim 2: Establish whether the combination of PCM fortification and persistent inflammatory inhibition prevents
catabolism and restores chondrocyte homeostasis. HA will be conjugated with cell-instructive peptides that mimic
an active sequence of IL-1 receptor antagonist (inhibits inflammation). In cartilage explants, the relative effects
of fortification and inflammatory-inhibiting peptide, and their combination, will be tested on inflammatory cytokine
release, matrix breakdown and loss, and matrix synthesis. Specifically, focus will be maintained on restoring the
balance of matrix synthesis and deposition (anabolism) with degradation (catabolism).
Aim 3: Evaluate the in vivo therapeutic effect of combined reinforcement and anti-inflammatory peptide
presentation on cartilage deterioration. In a Yucatan minipig model, partial-thickness defects will be treated with
fortification or a combination of fortification and anti-inflammatory peptide. Functional multi-scale biomechanical
testing and matrix retention and quality will be assessed at 1- and 3-months pos...

## Key facts

- **NIH application ID:** 10745912
- **Project number:** 5IK2RX003928-03
- **Recipient organization:** VETERANS HEALTH ADMINISTRATION
- **Principal Investigator:** Jay M Patel
- **Activity code:** IK2 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2024
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2022-01-01 → 2026-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10745912

## Citation

> US National Institutes of Health, RePORTER application 10745912, Matrix-reinforcing and cell-instructive smart hydrogel for cartilage preservation (5IK2RX003928-03). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10745912. Licensed CC0.

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