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

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Abstract

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.

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

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Publication details

The article was received on 02 Jan 2018, accepted on 08 Mar 2018 and first published on 14 Mar 2018


Article type: Paper
DOI: 10.1039/C8BM00010G
Citation: Biomater. Sci., 2018, Advance Article
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    Intra-articular TSG-6 delivery from heparin-based microparticles reduces cartilage damage in a rat model of osteoarthritis

    L. E. Tellier, E. A. Treviño, A. L. Brimeyer, D. S. Reece, N. J. Willett, R. E. Guldberg and J. S. Temenoff, Biomater. Sci., 2018, Advance Article , DOI: 10.1039/C8BM00010G

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