Biomedical subjects

Frédéric Chaubet

Publications and source records attributed to Frédéric Chaubet.

3 recordsLinked to original sources

PubMed2005

Retention of transforming growth factor beta1 using functionalized dextran-based hydrogels.

Functionalized dextrans (FD) are anionic water-soluble polymers bearing carboxylate, benzylamide and sulfate groups, which exhibit binding capacity to transforming growth factor-beta1 (TGF-beta1). In this paper, we have investigated the ability of dextran-based hydrogels containing FD, to bind and release recombinant human TGF-beta1. Hydrogels were prepared by chemical crosslink native dextran and FD with sodium trimetaphosphate in 1m NaOH at 50 degrees C. A wide range of hydrogels were prepared as particles ranging of 1-1.6mm of diameter and characterized with various amounts of FD and with different crosslinker feeding ratios (CFR). Dried particles were soaked with recombinant human transforming growth factor-beta1 (rhTGF-beta1) to determine their capacity to deliver the growth factor. Results indicated that the in vitro kinetics releases of rhTGF-beta1 were related to FD and CFR. Retention capacity of rhTGF-beta1 increases with an increase of negative charges of the matrices brought by both phosphate linkages and FD as demonstrated by an additional release of growth factor in high ionic strength solution. Highly crosslinked hydrogels that contained the highest amount of FD (18% (w/w)) retained up to 88% of rhTGF-beta1. Bioactivity of released growth factor was confirmed in a cell assay. These functionalized hydrogels may have important uses for the stabilization and the protection of rhTGF-beta1 as entrapment systems and could be applied to other proteins of clinical interest.

Absorption↗

PubMed2002

Heparin-like polymers modulate proinflammatory cytokine production by lipopolysaccharide-stimulated human monocytes.

The search for heparin-like materials remains an intensive field of research. In this context, we studied the immunomodulatory properties of semisynthetic dextran derivatives and naturally occurring sulfated polysaccharides present in brown seaweed (fucans). In this study, we investigated the functional potencies of fucan and dextran derivatives by analyzing their effects on the release of proinflammatory cytokines by resting or lipopolysaccharide (LPS)-stimulated human monocytes and their interactions on monocyte surfaces. The results showed that fucan, dextran derivatives, and heparin differentially (1) triggered interleukin-1alpha, tumor necrosis factor alpha, interleukin-6, and interleukin-8 production by monocytes in a dose-dependent manner, (2) modulated cytokine production by LPS-stimulated monocytes, and (3) specifically inhibited the binding of biotinylated LPS to monocyte membranes. Taken together, these data indicated that fucan and dextran derivatives displayed interesting immunomodulatory effects on human blood cells that could be relevant as new drugs or biomaterial coatings. Indeed, such polysaccharides, by regulating monocyte activation, could contribute to the improved biocompatibility of implants.

Flow Cytometry↗

PubMed2002

Heparin and non-heparin-like dextrans differentially modulate endothelial cell proliferation: in vitro evaluation with soluble and crosslinked polysaccharide matrices.

Proliferation of endothelial cells (ECs) is a cellular step of particular importance for implanted cardiovascular biomaterials. Heparin and some synthetic water-soluble non-anticoagulant polysaccharides derived from dextran and bearing anionic carboxymethyl and hydrophobic benzylamine groups were first investigated for their effects on EC proliferation in vitro. The results assessed by cell counting, 3H-thymidine uptake, and flow cytometry analysis, showed that the derivatized dextran-bearing hydrophobic groups stimulated the EC growth in the presence of serum, whereas native dextran or dextran-bearing anionic carboxymethyl groups were inactive and heparin was slightly inhibitory. Then, we showed that the derivatized dextran enhanced EC proliferation by potentiation of the mitogenic activities of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (FGF-2), two potent EC growth factors. In the presence of 2 nM of derivatized dextran, a 3-fold and 13-fold increase of 3H-thymidine uptake was obtained with VEGF and FGF-2, respectively. Finally, proliferation of ECs was investigated on crosslinked gels made of polysaccharides. It is of interest that EC proliferation was higher on gels containing the derivatized dextran than on plain hydrogels, and heparinized gels inhibited cell proliferation. From the obtained results, we propose that the synthetic non-heparin-like dextran may be of interest as a coating for the endothelialization of cardiovascular biomaterials.

Anticoagulants↗