1,720,970 research outputs found
A new viscosupplement based on partially hydrophobic hyaluronic acid: A comparative study
No full textA novel partially hydrophobized derivative of hyaluronic acid (HYADD® 4), containing a low number of C16 side-chains per polysaccharide backbone, provides injectable hydrogels stabilized by side-chain hydrophobic interactions. The rheological properties of Hymovis®, a physical hydrogel based on the hyaluronic acid derivative HYADD® 4, were evaluated using as reference a solution of the parent natural polysaccharide, hyaluronic acid. The rheological measurements were performed both in flow and oscillation regimes at the physiological frequency values of the knee, typically spanning the range from 0.5 Hz (walking frequency) to 3 Hz (running frequency). Moreover, the viscoelastic features of Hymovis® were compared with the market-available viscosupplementation products in view of its use in joint diseases.The different behavior of the investigated materials in crossover frequency measurements and in structure recovery experiments can be explained on the basis of the structural and dynamic properties of the polymeric systems
Viscoelastic properties and elastic recovery of HYADD®4 hydrogel compared to crosslinked HA-based commercial viscosupplements
No full textHyaluronic acid auto-crosslinked polymer (ACP): Reaction monitoring, process investigation and hyaluronidase stability
No full textHyaluronic Acid (HA) is a non-sulphated glycosaminoglycan that, despite its high molecular weight, is soluble in water and is not resistant to enzymatic degradation, the latter of which hinders its wider application as a biomedical material. Auto-crosslinked polymer (ACP) gels of HA are fully biocompatible hydrogels that exhibit improved viscoelastic properties and prolonged in vivo residence times compared to the native polymer. Crosslinking is achieved through a base-catalysed reaction consisting of the activation of HA carboxyl groups by 2-chloro-1-methylpyridinium iodide (CMPI) and subsequent nucleophilic acyl substitution by the hydroxyl groups of HA in organic solvent. In this study, a number of ACP hydrogels have been obtained via reactions using varying ratios of CMPI to HA. The crosslinking reaction was monitored by rheological measurements in organic solvents during CMPI addition to the reaction mixture. The ACP intermediates, powders and hydrogels were characterized, helping to elucidate the crosslinking process. A two-step mechanism was proposed to explain the observed trends in viscosity and particle size. Syntheses were carried out by varying the reaction temperature, respectively at 0 °C, 25 °C and 45 °C in N-Methyl-2-Pyrrolidone (NMP), as well as the solvent respectively in NMP, DMSO and DMF at 25 °C. Interestingly, varying these parameters did not substantially affect the degree of crosslinking but likely did influence the intra/inter-molecular crosslinking ratio and, therefore, the viscoelastic properties. A wide range of crosslinking densities was confirmed through ESEM analysis. Finally, a comparative hyaluronidase degradation assay revealed that the ACPs exhibited a higher resistance toward enzymatic cleavage at low elastic modulus compared to other more chemically resistant, crosslinked HAs. These observations demonstrated the importance of crosslinking density of matrix structures on substrate availability
Hyaluronan: molecular size-dependent signaling and biological functions in inflammation and cancer.
No full textHyaluronan (HA) is a linear nonsulfated glycosaminoglycan of the extracellular matrix that plays a pivotal role in a variety of biological processes. High-molecular weight HA exhibits different biological properties than oligomers and low-molecular weight HA. Depending on their molecular size, HA fragments can influence cellular behavior in a different mode of action. This phenomenon is attributed to the different manner of interaction with the HA receptors, especially CD44 and RHAMM. Both receptors can trigger signaling cascades that regulate cell functional properties, such as proliferation migration, angiogenesis, and wound healing. HA fragments are able to enhance or attenuate the HA receptor-mediated signaling pathways, as they compete with the endogenous HA for binding to the receptors. The modulation of these pathways could be crucial for the development of pathological conditions, such as inflammation and cancer. The primary goal of this review is to critically present the importance of HA molecular size on cellular signaling, functional cell properties, and morphology in normal and pathological conditions, including inflammation and cancer. A deeper understanding of these mechanisms could contribute to the development of novel therapeutic strategies
Dopamine-functionalized sulphated hyaluronic acid as a titanium implant coating enhances biofilm prevention and promotes osseointegration
No full textA series of new hyaluronan derivatives was synthesized and tested as an antibiotic release system by antibacterial and osseointegration assays. Specifically, partially sulphated hyaluronic acid (sHA) was functionalized with dopamine (DA). The DA moiety guarantees good performance as a binding agent for coating a titanium alloy surface; furthermore, the negatively charged sHA has bone regenerative effects and a high binding affinity for positively charged antibiotics. A sHA scaffold with a defined degree of sulphation (DS =2) was selected as a good compromise between a high negative charge density and poor heparin-like anticoagulant activity, while the degree of DA derivatization (17.1%mol) was chosen based on the absence of cytotoxic activity and the promotion of osteoblast proliferation. The titanium alloy coating was investigated indirectly using a fluorescent probe and directly by environmental scanning electron microscope (ESEM) analysis. Long-duration antibiotic release was demonstrated in vitro, and antibacterial efficacy against a Staphylococcus aureus culture was shown
Synthesis and NMR characterization of new hyaluronan based no-donors
No full textNitric oxide (NO) and hyaluronic acid (HA), two species widely different in terms of molecular complexity and
biological competence, are both known to play an important role in the wound healing process. To combine the
properties of HA and NO, we synthesized new NO-donors based on hyaluronic acid derivatives exhibiting a
controlled NO-release under physiological conditions (in vitro tests). Since two molecules of NO can form a
covalent bond with secondary amines to yield structures, named NONO-ates, able to release NO in solution, we
used spermidine bound to HA as the NO-linker. The HA-spermidine derivative was obtained by controlled HA
amidation in aqueous media, activating the biopolymer carboxylate groups with a water soluble carbodiimide.
The resulting derivative, soluble in water, was fully characterized by high field 1H and 13C NMR spectroscopy.
The amount of grafting of spermidine on HA was determined by integration of suitable 1H NMR signals. In
addition, cross-linked derivatives of HA were synthesized by the Ugi’s four-component reaction using formaldehyde,
cyclohexylisocyanide, and spermidine. The HA-spermidine networks were characterized by 13C CP-MAS NMR
spectroscopy. The degree of cross-linking of the networks was also determined. Finally, the release of NO from
the swollen hydrogels freshly saturated with NO, in contact with aqueous media, was monitored by means of UV
spectrophotometric measurements
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Collective Dynamics and Transient Behavior of Partially Hydrophobic Hyaluronic Acid Chains
No full textThe unique performance of a partially hydrophobic derivative of hyaluronic acid, HYADD4, bearing 2–3 hexadecylic side chains every 100 repeating units, enables hydrogels based on this polymer to be suitably used as a viscosupplement to replace synovial fluid in stressed or injured articular joints. This contribution addresses: i) as to whether there is a self-assembly process driving the HYADD4 hydrogel stabilization and ii) what the characteristics of the long-range dynamics governing the macroscopic viscoelastic behavior are, and to what extent these features are different from those present in the parent polymer (i.e., hyaluronic acid). Mesoscale dynamic and static properties are interpreted in the light of “sticky reptation theory” and evaluated in combination with small-angle neutron scattering results
Gel-like structure of a hexadecyl derivative of hyaluronic acid for the treatment of osteoarthritis
No full textHyaluronic 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
- …
