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Hyaluronan (HA)-based hydrogels obtained by crosslinking the biopolymer via ether bonds are widely used in clinical practice. There is interest in improving the design of these gels to match specific properties. Here, the possibility to tune HA-hydrogel behavior by adjusting the molecular weight distribution of the biopolymer undergoing crosslinking was investigated. Three HA samples (500, 1100 and 1600 kDa) underwent reaction with 1,4-butandioldiglycidyl-ether(BDDE) under reported conditions and the crosslinked products were characterized for chemical modification extent, swelling, rheological behavior, cohesivity, sensitivity to enzymatic degradation and effect on Human Dermal Fibroblasts (HDF). HA hydrolysis, under the highly alkaline crosslinking conditions, was also studied for the first time. The main achievements are that 1) varying HA chain length affects hydrogel behavior less than expected, due to the de-polymerization occurring alongside crosslinking, that reduces the differences in sample size 2) when differences in chain length persist notwithstanding hydrolysis, lowering HA size is a means to prepare more concentrated formulations, expected to exhibit longer duration and better cohesivity in vivo, while retaining a certain rigidity, preserving biocompatibility and slightly influencing HDF behavior in relation to CollagenI production. The study shed light on aspects concerning BDDE-HA gel manufacturing and contributed to the improvement of their design.
This article was published in the following journal.
Name: International journal of biological macromolecules
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Heparin fractions with a molecular weight usually between 4000 and 6000 kD. These low-molecular-weight fractions are effective antithrombotic agents. Their administration reduces the risk of hemorrhage, they have a longer half-life, and their platelet interactions are reduced in comparison to unfractionated heparin. They also provide an effective prophylaxis against postoperative major pulmonary embolism.
Membrane-associated glucuronosyltransferases that catalyze the reaction of UDP-N-acetyl-D-glucosamine and UDP-D-glucuronate to produce HYALURONAN. HYALURONAN SYNTHASE 2 (HAS2) is essential for embryogenesis and its expression by tumor cells is associated with metastasis.
Any of various enzymatically catalyzed post-translational modifications of PEPTIDES or PROTEINS in the cell of origin. These modifications include carboxylation; HYDROXYLATION; ACETYLATION; PHOSPHORYLATION; METHYLATION; GLYCOSYLATION; ubiquitination; oxidation; proteolysis; and crosslinking and result in changes in molecular weight and electrophoretic motility.
A protein, molecular weight 50 kD, located in various normal tissues. Upon cleavage by KALLIKREINS, it forms KALLIDIN. Kallidin, in turn, is converted into BRADYKININ. (From Stedman, 25th ed)
A low-molecular-weight fragment of heparin, prepared by nitrous acid depolymerization of porcine mucosal heparin. The mean molecular weight is 4000-6000 daltons. It is used therapeutically as an antithrombotic agent. (From Merck Index, 11th ed)