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Intra-articular administration of gelatin hydrogels incorporating rapamycin–micelles reduces the development of experimental osteoarthritis in a murine model

Paper ID Volume ID Publish Year Pages File Format Full-Text
5953 450 2014 8 PDF Available
Title
Intra-articular administration of gelatin hydrogels incorporating rapamycin–micelles reduces the development of experimental osteoarthritis in a murine model
Abstract

Autophagy is a cellular homeostasis mechanism that may have a protective role against osteoarthritis (OA). The present study investigated the therapeutic effect of local administration of rapamycin, a potent activator of autophagy, against OA. To achieve controlled intra-articular administration of rapamycin, gelatin hydrogels incorporating rapamycin-micelles were created and the release profile was evaluated in vitro. The therapeutic effects of gelatin hydrogels incorporating rapamycin-micelles were then tested in a murine OA model. Mice were divided into four groups: Group 1, gelatin hydrogels alone; Group 2, single injection of 1 μg rapamycin; and Groups 3 and 4, gelatin hydrogels incorporating 100 ng or 1 μg rapamycin-micelles, respectively. Immunohistochemical analysis revealed that autophagic marker-positive chondrocytes were increased in the rapamycin-treated mice at 10 weeks after surgery. The histologic score was better in Groups 3 and 4 than in Groups 1 and 2, and Group 2 had a better score than Group 1. Delayed OA progression was maintained even at 16 weeks after surgery in Group 4. Microarray and real-time polymerase chain reaction analysis indicated that OA mediator genes were downregulated in the rapamycin-treated mice. Our novel system for intra-articular administration of rapamycin could be a novel therapeutic approach for treating patients with OA.

Keywords
Animal model; Arthritis; Cartilage; Biodegradation; Matrix metalloproteinase
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Intra-articular administration of gelatin hydrogels incorporating rapamycin–micelles reduces the development of experimental osteoarthritis in a murine model
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Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 35, Issue 37, December 2014, Pages 9904–9911
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us