Thermosensitive hybrid hyaluronan/p(HPMAm‐lac)‐PEG hydrogels enhance cartilage regeneration in a mouse model of osteoarthritis

Abstract

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.

Interpenetrating Hydrogel Networks Enhance Mechanical Stability, Rheological Properties, Release Behavior and Adhesiveness of Platelet-Rich Plasma

“…The proposed hydrogel already showed promising results in the field of protein release and tissue regeneration [6][7][8][9].…”

“…The developed hydrogels were demonstrated to possess the capability to controllably release and protect from degradation a number of model and therapeutic proteins, [7,8] as well as to encapsulate viable cells for cartilage tissue engineering applications. [9] In the present study, a novel interpenetrating hydrogel network composed of two interlaced polymeric networks independently cross-linked via covalent or ionic bonds was designed and synthesized by combining the previously developed thermosensitive hybrid hydrogel with activated platelet-rich plasma (PRP) from equine source. PRP is a sample of plasma with a twofold or more increase in platelet concentration above baseline levels, that acts as a reservoir of an autologous assortment of growth factors collected in α-granules, such as platelet-derived growth factor (PDGF), transforming growth factor (TGF-β), bone morphogenetic protein (BMP), epithelial growth factor (EPG), fibroblast growth factor (FGF), and insulin growth factor I (IGF-I) (Scheme 1).…”

Development of a New Hyaluronic Acid Based Redox-Responsive Nanohydrogel for the Encapsulation of Oncolytic Viruses for Cancer Immunotherapy

“…The synthesis of thiolated hyaluronic acid (HA-SH) was slightly modified according to the procedure described in our previous study [60]. HA was coupled with DTP by carbodiimide chemistry firstly, and then the disulfide bonds were reduced by DTT to obtain free thiol groups as terminal group for HA pending side chains.…”

Narrative review of the choices of stem cell sources and hydrogels for cartilage tissue engineering

“…Hydrogels based on natural polymers can be divided into two groups: (I) polysaccharides, such as hyaluronic acid (HA), chitosan, alginate and agarose; (II) proteins, such as collagen, gelatin, and fibroin (15)(16)(17)(18)(19)(20). A variety of hydrogels based on synthetic polymers, such as polyethylene glycol (PEG), poly N,N-dimethylacrylamide (PDMAAm) and polyvinyl alcohol (PVA), have been reported (21)(22)(23). (27,28).…”