Bioactivity of immobilized hyaluronic acid derivatives regarding protein adsorption and cell adhesion

Abstract

Hyaluronic acid (HA) was chemically modified either by oxidation to obtain aldehyde-HA (aHA) or 3,3'-dithiobis(propanoic hydrazide) to obtain thiol-HA (tHA) that was covalently immobilized on model substrata such as amino-terminated surfaces or gold. Knowledge about the effect of modification with HA on physicochemical surface properties of these substrata and estimates of the quantities of immobilized HA were obtained by different physical methods such as contact angle measurements, ellipsometry, and atomic force microscopy. The bioactivity of aHA and tHA toward their natural binding partner aggrecan was studied by comparing surface plasmon resonance to native HA; this shows that binding of aggrecan was achieved in a similar way. Dermal human fibroblasts were used as a model cell to study how chemical modification and immobilization of HA impact adhesion and spreading of cells, which also affects cell growth and differentiation. A lower number and spreading of cells were observed on HA-modified surfaces compared to amino- and vinyl-terminated glass and silicon surfaces. Immunofluorescence microscopy also revealed that adhesion of fibroblast plated on HA-modified surfaces was mediated primarily by HA receptor CD44, indicating that bioactivity of HA was not significantly reduced by chemical modification.

Dual functional core–sheath electrospun hyaluronic acid/polycaprolactone nanofibrous membranes embedded with silver nanoparticles for prevention of peritendinous adhesion

“…A lower number and reduced spreading of cells were observed on HA-modified surfaces. The adhesion of fibroblasts plated on HA-modified surfaces was found to be mediated primarily by the HA receptor CD44 located on the cell surface [38]. Silver nanoparticles were shown to suppress the proliferation of fibroblasts in ex vivo cell culture experiments, which was confirmed to be not due to Ag cytotoxicity [39].…”

Study on the potential mechanism of anti‐inflammatory activity of covalently immobilized hyaluronan and heparin

“…The reason beyond the presence of anionic Hep inside macrophages might be due to either endocytosis or anionic transporters (Young, ). Indeed, the preparation of samples was based on covalent binding, which should provide a stable bond formation due to the chemical cross‐linking process of GAG to amino groups on the substratum (Hermanson, ; Köwitsch et al, ). This was also observed here as we found no release of FITC‐labeled GAG after covalent immobilization on NH 2 ‐modified surfaces (see Figure S2) Thus, we assume a partial release of GAG molecules from the samples through the activity of secreted reactive oxygen species (ROS), hyaluronidases and heparinases by macrophages that could be responsible for the mobilisation of HA and Hep (Li & Vlodavsky, ; Puissant & Boonen, ).…”

Effect of Immobilized Thiolated Glycosaminoglycans on Fibronectin Adsorption and Behavior of Fibroblasts

“…High molecular weight HA ( M w 1.3 MDa) was provided by Kraeber & Co. GmbH (Ellerbek, Germany). Low molecular weight HA ( M w 15 kDa) was obtained by acidic hydrolysis as reported previously . Sulfated HA with a sulfation degree (DS S ) of 1.3 was a kind gift from Innovent e.V.…”