Intra-articular TSG-6 delivery from heparin-based microparticles reduces cartilage damage in a rat model of osteoarthritis

As a potential treatment for osteoarthritis (OA), we have developed injectable and hydrolytically degradable heparin-based biomaterials with tunable sulfation for the intra-articular delivery of tumor necrosis factor-alpha stimulated gene-6 (TSG-6), a protein known to inhibit plasmin which may degra...

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Bibliographic Details
Published in:Biomaterials science 2018-05, Vol.6 (5), p.1159-1167
Main Authors: Tellier, Liane E, Treviño, Elda A, Brimeyer, Alexandra L, Reece, David S, Willett, Nick J, Guldberg, Robert E, Temenoff, Johnna S
Format: Article
Language:English
Subjects:
Animals
Arthritis
Biocompatibility
Biological activity
Biomedical materials
Cartilage
Cartilage - drug effects
Cell Adhesion Molecules - administration & dosage
Cell Adhesion Molecules - pharmacology
Cell Adhesion Molecules - therapeutic use
Degradation
Drug Carriers - chemistry
Heparin - analogs & derivatives
Injections, Intra-Articular
Injury prevention
Knee
Male
Microparticles
Osteoarthritis, Knee - drug therapy
Rats
Rats, Sprague-Dawley
Sulfation
Surgical implants
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Summary:As a potential treatment for osteoarthritis (OA), we have developed injectable and hydrolytically degradable heparin-based biomaterials with tunable sulfation for the intra-articular delivery of tumor necrosis factor-alpha stimulated gene-6 (TSG-6), a protein known to inhibit plasmin which may degrade extracellular matrix within OA joints. We first assessed the effect of heparin sulfation on TSG-6 anti-plasmin activity and found that while fully sulfated (Hep) and heparin desulfated at only the N position (Hep-N) significantly enhanced TSG-6 bioactivity in vitro, fully desulfated heparin (Hep-) had no effect, indicating that heparin sulfation plays a significant role in modulating TSG-6 bioactivity. Next, TSG-6 loaded, degradable 10 wt% Hep-N microparticles (MPs) were delivered via intra-articular injection into the knee at 1, 7, and 15 days following medial meniscal transection (MMT) injury in a rat model. After 21 days, cartilage thickness, volume, and attenuation were significantly increased with soluble TSG-6, indicating degenerative changes. In contrast, no significant differences were observed with TSG-6 loaded MP treatment, demonstrating that TSG-6 loaded MPs reduced cartilage damage following MMT injury. Ultimately, our results indicate that Hep-N can enhance TSG-6 anti-plasmin activity and that Hep-N-based biomaterials may be an effective method for TSG-6 delivery to treat OA.
ISSN:2047-4830
2047-4849
DOI:10.1039/c8bm00010g