Gel‐Like Structure of a Hexadecyl Derivative of Hyaluronic Acid for the Treatment of Osteoarthritis

Abstract

Hyaluronic acid is a polysaccharide with viscoelastic and mechanical properties that are crucial for the normal functioning of osteoarticular junctions. It is demonstrated that introduction of a hexadecyl side chain into HA yields an injectable polysaccharide capable of forming physical hydrogels, which are stable at very low polymer concentrations, whereas native hyaluronic acid forms viscous solutions at concentrations that are ten times higher. Characterization of this system showed that the driving force for its gel-like behavior is the occurrence of hydrophobic interactions involving aliphatic side chains, despite the low degree of substitution, as confirmed by molecular dynamics simulations of HYADD4 and HA hydrogels.

Enhancing hyaluronan pseudoplasticity via 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride-mediated conjugation with short alkyl moieties

“…Therefore, the grafting of small alkyl amines is a viable method for the tuning of HA rheological properties. A similar associative behavior was previously reported in presence of long alkyl chains either directly grafted to HA (Finelli, Chiessi, Galesso, Renier & Paradossi, 2009) or via pre-derivatization with spacer arm of adipic dihydrazide (Creuzet, Kadi, Rinaudo & Auzély-Velty, 2006).…”

“…This linear polysaccharide and its derivatives have been extensively applied in tissue augmentation (Yeom et al, 2010), tissue engineering (Collins & Birkinshaw, 2013), treatment of osteoarthritis (Finelli, Chiessi, Galesso, Renier & Paradossi, 2009;Listrat et al, 1997;Lo, LaValley, McAlindon & Felson, 2003) and drug delivery (Pitarresi et al, 2010;Saravanakumar et al, 2010). HA is extremely hydrophilic, biocompatible and rapidly degradable in vivo.…”

Degradation alters the lubrication of articular cartilage by high viscosity, hyaluronic acid‐based lubricants

“…Cylindrical cartilage ( n = 4–6) samples were mated against a polished glass flat counterface while bathed in lubricant baths of varying viscosities. The lubricants were PBS (1 mPa · s), 10 mg/ml 700 kDa HA (156 mPa · s, Hyalgan ® ), and 8 mg/ml HYADD4 (partial hexadecylamide of 700 kDa HA, 72,000 mPa · s, Hymovis®) . To lessen the effects of interstitial fluid pressurization on friction coefficient measurements, samples were tested in a stationary contact area configuratio .…”

Carbohydrate force fields

“…The procedure yielded 99 papers124–222 in which a classical FF, which was not necessarily a CarbFF, was applied to a carbohydrate. Studies that considered only DNA or RNA were excluded.…”