Synthesis and in Vitro Degradation of New Polyvalent Hydrazide Cross-Linked Hydrogels of Hyaluronic Acid

Abstract

New polyvalent hydrazide cross-linkers were synthesized, characterized, and used to prepare hydrazide cross-linked hydrogels derived from hyaluronic acid (HA). First, the chemical synthesis and characterization of the di-, tri-, tetra-, penta-, and hexahydrazides are presented. Second, HA concentration, buffer type and concentration, and ratio of HA to carbodiimide to cross-linker were varied to obtain HA-hydrogels with different chemical and physical properties. Third, two new assays are described to monitor the stability of HA-hydrogels toward hyaluronidase (HAse) and other media. These assays were used to evaluate the stability of cross-linked HA-hydrogels to HAse solutions and different pH values. Hydrophobic cross-linkers gave the most stable gels, and the susceptibility of the gels to HAse was independent of cross-linker concentration. HAse does not significantly penetrate the HA-hydrogels and acts primarily at the gel-solution interface. The HA-hydrogels are stable in acid environments and dissolve gradually above pH 7.0.

Biomimetic Topography: Bioinspired Cell Culture Substrates and Scaffolds

“…Gelatin is a derivative of collagen that can also form gels when the temperature of its solution changes. Hyaluronate is one of the ECM glycosaminoglycans; it can form gels by covalently crosslinking with various hydrazide derivatives, and be degraded by hyaluronidase (Pouyani et al, 1994, Vercruysse et al, 1997. Fibrin can be collected from blood, and forms gels by the enzymatic polymerization of fibrinogen at room temperature in the presence of thrombin (Ikari et al, 2000).…”

Hydrogels from Biopolymer Hybrid for Biomedical, Food, and Functional Food Applications

“…To be used as implants for tissue engineering applications, such as artificial skin, would healing, facial intradermal implants, cartilage repair, and soft tissue augmentation [42][43][44], stable HA hydrogels are required. This can be achieved by covalent cross-linking the polysaccharide with various multifunctional reagents, such as a group of epoxides, tresyl chloride, divinyl sulfone, or hydrazide derivatives [45,46], or to form hybrids with other biopolymer, such as collagen (COL; type I, II), and mineralized collagen. The resultant hybrid hydrogels have been shown to possess some functional properties of the extracellular matrix of human tissues [47][48][49].…”

Effect of Gelatin on Heparin Regulation of Cytokine Release from Hyaluronan-Based Hydrogels

“…Thiol-modified HA, gelatin, and heparin (HA-DTPH, Gtn-DTPH, and HP-DTPH) were prepared by EDCI-mediated condensation with DTP (3,3 -dithiolbis (propanoic hydrazide)) followed by DTT reduction and dialysis as previously described (Vercruysse et al 1997;Shu et al 2002;, and their structures confirmed by 1 H-NMR. The thiol substitution percentages of HA-DTPH, Gtn-DTPH, and Gtn-DTPH were determined using a modified DTNB method (Butterworth et al 1967).…”