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Journal of biomedical materials research. Part A2024; 112(12); 2149-2159; doi: 10.1002/jbm.a.37766

Heterogeneous distribution of viscosupplements in vivo is correlated to ex vivo frictional properties of equine cartilage.

Abstract: Intra-articular injections of hyaluronic acid (HA) are the cornerstone of osteoarthritis (OA) treatments. However, the mechanism of action and efficacy of HA viscosupplementation are debated. As such, there has been recent interest in developing synthetic viscosupplements. Recently, a synthetic 4 wt% polyacrylamide (pAAm) hydrogel was shown to effectively lubricate and bind to the surface of cartilage in vitro. However, its ability to localize to cartilage and alter the tribological properties of the tissue in a live articulating large animal joint is not known. The goal of this study was to quantify the distribution and extent of localization of pAAm in the equine metacarpophalangeal or metatarsophalangeal joint (fetlock joint), and determine whether preferential localization of pAAm influences the tribological properties of the tissue. An established planar fluorescence imaging technique was used to visualize and quantify the distribution of fluorescently labeled pAAm within the joint. While the pAAm hydrogel was present on all surfaces, it was not uniformly distributed, with more material present near the site of the injection. The lubricating ability of the cartilage in the joint was then assessed using a custom tribometer across two orders of magnitude of sliding speed in healthy synovial fluid. Cartilage regions with a greater coverage of pAAm, that is, higher fluorescent intensities, exhibited friction coefficients nearly 2-fold lower than regions with lesser pAAm (R = -0.59, p < 0.001). Collectively, the findings from this study indicate that intra-articular viscosupplement injections are not evenly distributed inside a joint, and the tribological outcomes of these materials is strongly determined by the ability of the material to localize to the articulating surfaces in the joint.
© 2024 Wiley Periodicals LLC.
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Publication Date: 2024-06-23 PubMed ID: 38923105DOI: 10.1002/jbm.a.37766Google Scholar: Lookup
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  • Journal Article
  • Research Support
  • N.I.H.
  • Extramural
  • Research Support
  • U.S. Gov't
  • Non-P.H.S.

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

Overview

  • This study investigates how a synthetic hydrogel used for joint lubrication distributes inside live horse joints and how its distribution affects the frictional properties of equine cartilage.
  • The researchers found that the synthetic lubricant accumulates unevenly in the joint, and areas with more lubricant have significantly lower friction, suggesting that lubricant localization influences joint lubrication effectiveness.

Background

  • Osteoarthritis (OA) is a common joint disease often treated with intra-articular injections of hyaluronic acid (HA), which act as viscosupplements to improve joint lubrication.
  • Despite their widespread use, the exact mechanism and effectiveness of HA injections are not fully understood, leading to interest in developing synthetic alternatives.
  • A synthetic polyacrylamide (pAAm) hydrogel, at 4% weight content, has shown promising lubrication and cartilage binding properties in laboratory (in vitro) tests.
  • There was a gap in knowledge regarding how this synthetic hydrogel distributes and functions inside a living large animal joint, specifically in horses, an important model for human joint conditions.

Study Objectives

  • To measure the distribution and localization of fluorescently labeled pAAm hydrogel within the equine metacarpophalangeal or metatarsophalangeal joint (fetlock joint) after injection.
  • To assess whether variations in pAAm localization correlate with changes in the frictional (tribological) properties of the articular cartilage.

Methods

  • Fluorescent labeling of the synthetic pAAm hydrogel allowed visualization using planar fluorescence imaging techniques, enabling quantification of hydrogel distribution across joint surfaces in vivo.
  • Injections were performed into the fetlock joints of horses to simulate clinical intra-articular viscosupplementation.
  • The frictional properties of cartilage tissue were measured ex vivo using a custom-built tribometer that tested cartilage samples at two orders of magnitude different sliding speeds to mimic physiological conditions.
  • Friction coefficients from cartilage regions with varying levels of pAAm coverage were recorded and statistically analyzed.

Key Findings

  • The pAAm hydrogel was detected throughout the joint surfaces but was distributed heterogeneously, with the highest concentration near the injection site.
  • Cartilage regions with greater quantities of pAAm (indicated by higher fluorescence intensities) displayed friction coefficients approximately half of those in regions with less pAAm.
  • There was a significant negative correlation (R = -0.59, p < 0.001) between the amount of hydrogel present and the coefficient of friction measured, confirming that higher hydrogel localization improves lubrication.

Conclusions and Implications

  • This study demonstrates that intra-articular injections of viscosupplements, such as synthetic pAAm hydrogels, do not distribute evenly within a joint.
  • The effectiveness of viscosupplementation in reducing friction in articular cartilage strongly depends on how well the material localizes to the contacting joint surfaces.
  • These findings underscore the importance of optimizing delivery methods to ensure even distribution or targeted localization of lubricants within joints to maximize therapeutic benefits.
  • The use of synthetic hydrogels like pAAm shows promise as a viscosupplement that can bind and lubricate cartilage, potentially offering an alternative to natural HA with controllable properties.

Broader Context

  • Successful joint lubrication is crucial for managing OA and related joint disorders by minimizing cartilage wear and reducing pain.
  • Better understanding of lubricant distribution after injection can guide the design of new viscosupplements and injection protocols in veterinary and human medicine.
  • Further research might explore how to improve uniformity of lubricant spread within joints or develop materials that target specific cartilage areas more effectively.

Cite This Article

APA
Vishwanath K, McClure SR, Bonassar LJ. (2024). Heterogeneous distribution of viscosupplements in vivo is correlated to ex vivo frictional properties of equine cartilage. J Biomed Mater Res A, 112(12), 2149-2159. https://doi.org/10.1002/jbm.a.37766

Publication

Journal of biomedical materials research. Part A
ISSN: 1552-4965
NlmUniqueID: 101234237
Country: United States
Language: English
Volume: 112
Issue: 12
Pages: 2149-2159

Researcher Affiliations

Vishwanath, Karan
  • Department of Materials Science and Engineering, Cornell University, Ithaca, New York, USA.
McClure, Scott R
  • Midwest Equine Surgery and Sport Medicine, Boone, Iowa, USA.
Bonassar, Lawrence J
  • Meinig School of Biomedical Engineering, Cornell University, Ithaca, New York, USA.
  • Sibley School of Mechanical and Aerospace Engineering, Cornell University, Ithaca, New York, USA.

MeSH Terms

  • Animals
  • Horses
  • Friction
  • Cartilage, Articular / metabolism
  • Viscosupplements / administration & dosage
  • Acrylic Resins / chemistry
  • Hydrogels / chemistry
  • Hyaluronic Acid / chemistry

Grant Funding

  • DMR1719875 / Cornell Center for Materials Research
  • S10OD025049 / National Institute of Health
  • 2245367 / National Science Foundation LEAP-HI CMMI

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