# Molecular engineering of HA-based lubricants for articular cartilage

> **NIH NIH R01** · DUKE UNIVERSITY · 2024 · $581,707

## Abstract

ABSTRACT
Altered lubrication of articular cartilage following joint injury increases friction between the sliding cartilage
surfaces, leads to deterioration of cartilage, and hastens the development of osteoarthritis (OA). OA due to joint
injury, termed as post-traumatic osteoarthritis (PTOA), is estimated to account for at least 12% of all OA cases
in the United States and approximately half of the individuals with an anterior cruciate ligament (ACL) injury
develop PTOA regardless of the ACL reconstruction. Replenishing the synovial fluid and thereby restoring the
articular cartilage lubrication has been demonstrated to benefit the joint. The overarching goal of the proposed
study is to investigate the potential of cartilage-adhering, self-healing hyaluronic acid molecules to prevent or
delay the degeneration of articular cartilage, and thereby osteoarthritis, following injury or trauma. The
molecularly engineered HA-based lubricants are designed to integrate the function of both hyaluronic acid and
lubricin, two key components of the synovial fluid, while exhibiting self-repairing ability. The self-healing
properties are incorporated to ensure both long-term retention and adaptability of the lubricant within the
mechanically active joint, while the cartilage adhering properties are expected to improve boundary lubrication.
We hypothesize that the dynamic cartilage-adhering molecules that integrate the molecular features of HA and
lubricin and simultaneously exhibit self-healing properties will protect the articular cartilage and prevent or slow
down the progression of PTOA. Towards this, we will: (i) develop cartilage-adhering, self-healing HA molecules
and determine the effect of molecular architecture-lubrication function relationship, (ii) determine the effect of the
molecular architecture of the proposed novel HA-based lubricants on chondroprotection by using a joint-on-chip
platform, and (iii) determine the effect of these lubricants on mitigating the development of post-traumatic
osteoarthrits. The proposed studies will enable a new paradigm in which intra-articular injection of self-healing
HA-bottle brush molecules could be an important treatment following acute injury to ameliorate or delay PTOA,
or they could be used as an adjunct after surgical repair to improve the outcome.

## Key facts

- **NIH application ID:** 10892179
- **Project number:** 5R01AR082809-02
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Shyni Varghese
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $581,707
- **Award type:** 5
- **Project period:** 2023-07-21 → 2028-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10892179

## Citation

> US National Institutes of Health, RePORTER application 10892179, Molecular engineering of HA-based lubricants for articular cartilage (5R01AR082809-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10892179. Licensed CC0.

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