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Open Access Highly Accessed Research article

Injectable hyaluronic-acid-doxycycline hydrogel therapy in experimental rabbit osteoarthritis

Hsien-Tsung Lu15, Ming-Thau Sheu2, Yung-Feng Lin3, Jai Lan3, Yi-Ping Chin4, Ming-Shium Hsieh15, Chao-Wen Cheng1* and Chien-Ho Chen3*

Author Affiliations

1 Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, No. 250 Wu-Hsing Street, , Taipei City, Xinyi District, 110, Taiwan

2 School of Pharmacy, College of Pharmacy, Taipei Medical University, No. 250 Wu-Hsing Street, , Taipei City, Xinyi District, 110, Taiwan

3 Department of Medical Technology, School of Medical Laboratory Science & Biotechnology, Taipei Medical University, No. 250 Wu-Hsing Street, , Taipei City, Xinyi District, 110, Taiwan

4 Department of Microbiology and Immunology, School of Medicine, Taipei Medical University, No. 250 Wu-Hsing Street, , Taipei City, Xinyi District, 110, Taiwan

5 Department of Orthopedics and Traumatology, Taipei Medical University Hospital, No. 250 Wu-Hsing Street, , Taipei City, Xinyi District, 110, Taiwan

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BMC Veterinary Research 2013, 9:68  doi:10.1186/1746-6148-9-68

Published: 10 April 2013

Abstract

Background

Osteoarthritis (OA) is a common joint disease that causes disabilities in elderly adults. However, few long-lasting pharmacotherapeutic agents with low side effects have been developed to treat OA. We evaluated the therapeutic effects of intra-articular injections of hydrogels containing hyaluronic acid (HA) and doxycycline (DOX) in a rabbit OA model.

Results

Thirteen week old New Zealand White rabbits undergone a partial meniscectomy and unilateral fibular ligament transection were administered with either normal saline (NT), HA, DOX or HA-DOX hydrogels on day 0, 3, 6, 9 and 12; animals were also examined the pain assessment in every three days. The joint samples were taken at day 14 post-surgery for further histopathological evaluation. The degree of pain was significantly attenuated after day 7 post-treatment with both HA and HA-DOX hydrogels. In macroscopic appearance, HA-DOX hydrogel group showed a smoother cartilage surface, no or minimal signs of ulceration, smaller osteophytes, and less fissure formation in compare to HA or DOX treatment alone. In the areas with slight OA changes, HA-DOX hydrogel group exhibited normal distribution of chondrocytes, indicating the existence of cartilage regeneration. In addition, HA-DOX hydrogels also ameliorated the progression of OA by protecting the injury of articular cartilage layer and restoring the elastoviscosity.

Conclusion

Overall, from both macroscopic and microscopic data of this study indicate the injectable HA-DOX hydrogels presented as a long-lasting pharmacotherapeutic agent to apply for OA therapy.

Keywords:
Osteoarthritis; Disease-modifying osteoarthritis drugs; Connective tissue structure-modifying agents; Hyaluronic acid; Doxycycline