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Thermo-responsive and covalently cross-linkable hydrogels for intra-articular drug delivery
ACS Applied Bio Materials
  • Andy Prince, The University of Western Ontario
  • Ian J. Villamagna, Western University
  • Aneta Borecki, Western University
  • Frank Beier, Western University
  • John R. de Bruyn, Western University
  • Mark Hurtig, Ontario Veterinary College
  • Elizabeth Gillies, Western University
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The local delivery of drugs to joints is a recognized strategy in the treatment of osteoarthritis. Hydrogels, particularly those that can be injected as liquids but undergo gelation in the joint, are promising platforms for intra-articular drug delivery. However, their properties must be carefully designed and tuned to achieve sustained drug release, which has been a challenge with previous hydrogels. We describe here the use of a combination of non-covalent thermal gelation and covalent cross-linking with poly(caprolactone-co-lactide)(PCLA)-poly(ethylene glycol)(PEG)-PCLA triblock copolymers to achieve hydrogels with sustained drug release in joints. The hybrid cross-linking approach afforded higher viscoelastic and compression moduli compared to non-covalent cross-linking alone and enabled celecoxib as well as other drugs to be loaded without substantially compromising the mechanical properties. Celecoxib release in vitro was much slower for the hybrid cross-linked hydrogel, with only 20% released over 22 days, compared to 90% released over 22 days for a non-covalently cross-linked hydrogel. Furthermore, the burst release of celecoxib was reduced in vivo in horse joints compared to non-covalent systems, and drug was detected in synovial fluid for a period of two months. Overall, this new hydrogel system shows significant promise as a platform for further development in intra-articular delivery.


A correction is submitted as an additional file.

This document is the Accepted Manuscript version of a Published Work that appeared in final form in ASC Applied Bio Materials, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see

Citation Information
Andy Prince, Ian J. Villamagna, Aneta Borecki, Frank Beier, et al.. "Thermo-responsive and covalently cross-linkable hydrogels for intra-articular drug delivery" ACS Applied Bio Materials Vol. 2 (2019) p. 3498-3507 - 3498
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