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Thermosensitive hybrid hyaluronan/p(HPMAm‐lac)‐PEG hydrogels enhance cartilage regeneration in a mouse model of osteoarthritis
Author(s) -
Agas Dimitrios,
Laus Fulvio,
Lacava Giovanna,
Marchegiani Andrea,
Deng Siyuan,
Magi Federico,
Silva Guilherme Gusmão,
Di Martino Piera,
Sabbieti Maria Giovanna,
Censi Roberta
Publication year - 2019
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.28598
Subject(s) - self healing hydrogels , hyaluronic acid , proinflammatory cytokine , cartilage , chemistry , osteoarthritis , biophysics , peg ratio , proteoglycan , chondroitin sulfate , microbiology and biotechnology , inflammation , extracellular matrix , glycosaminoglycan , biochemistry , immunology , medicine , anatomy , polymer chemistry , pathology , biology , alternative medicine , finance , economics
Osteoarthritis (OA), due to cartilage degeneration, is one of the leading causes of disability worldwide. Currently, there are not efficacious therapies to reverse cartilage degeneration. In this study we evaluated the potential of hybrid hydrogels, composed of a biodegradable and thermosensitive triblock copolymer cross‐linked via Michael addition to thiolated hyaluronic acid, in contrasting inflammatory processes underlying OA. Hydrogels composed of different w/w % concentrations of hyaluronan were investigated for their degradation behavior and capacity to release the polysaccharide in a sustained fashion. It was found that hyaluronic acid was controllably released during network degradation with a zero‐order release kinetics, and the release rate depended on cross‐link density and degradation kinetics of the hydrogels. When locally administered in vivo in an OA mouse model, the hydrogels demonstrated the ability to restore, to some extent, bone remineralization, proteoglycan production, levels of Sox‐9 and Runx‐2. Furthermore, the downregulation of proinflammatory mediators, such as TNF‐α, NFkB, and RANKL and proinflammatory cytokines was observed. In summary, the investigated hydrogel technology represents an ideal candidate for the potential encapsulation and release of drugs relevant in the field of OA. In this context, the hydrogel matrix could act in synergy with the drug, in reversing phenomena of inflammation, cartilage disruption, and bone demineralization associated with OA.