Cysteine-hyaluronic acid conjugates prepared by freeze-drying and thiol-ene click chemistry, and synthetic methods and applications thereof

Abstract

The present invention discloses a cysteine functionalized hyaluronic acid conjugate prepared through freeze drying and thiol-ene click chemistry, and a synthesis method thereof, and discloses applications of the hyaluronic acid conjugate in preparation of an injectable in-situ hydrogel, and applications of the formed injectable in-situ hydrogel in islet cell culture and insulin secretion. According to the present invention, a series of cysteine functionalized hyaluronic acid conjugates having different modification rates and stable ether bonds are obtained through freeze drying and thiol-ene click chemistry, wherein the cysteine functionalized hyaluronic acid conjugate has the thiol active group, such that the further functionalized modification can be performed; and the hyaluronic acid conjugates having different modification rates and the polyethylene glycol conjugate can be subjected to the oxo ester-mediated natural chemical link reaction to obtain the an injectable in-situ formed hydrogel, wherein the obtained hydrogel has the good rheological property, the free thiol group can increase the cell adhesion of the hyaluronic acid and can be adopted as the cell scaffold material so as to be used in the islet cell culture and the insulin secretion stimulation, and the broad biomedical prospects are provided.

Description

technical field [0001] The invention relates to a cysteine-functionalized hyaluronic acid conjugate formed by freeze-drying and thiol-ene click modification and its synthesis method, as well as its application in the preparation of injectable in-situ hydrogel, belonging to the field of biomedicine . Background technique [0002] Bioscaffold materials are key to tissue engineering and regenerative medicine research. Because the scaffold material not only provides structural support for cells, but also acts as a template to guide tissue regeneration and control tissue structure. Among them, hydrogel-based bioscaffolds are particularly widely used in tissue engineering and regenerative medicine. [0003] Hydrogel is a hydrophilic polymer network that can absorb a large amount of water and has good biocompatibility. Although the application of hydrogels in biomedicine has made great progress, however, the development of covalently cross-linked hydrogels that meet the clinical...

AI Technical Summary

Problems solved by technology

It overcomes the shortcomings of natural hyaluronic acid being cleared quickly in the body and low mechanical strength

However, the cross-linked hydrogel prepared by the carboxyl group of hyaluronic acid may produce some side reactions

Studies have shown that if its carboxyl group is chemically modified, it will reduce the negative charge of hyaluronic acid, which will cause CD44 receptors to not recognize normally

Cellular CD44 receptors are considered to be reduced by the negative charge of hyaluronic acid and hyaluronic acid (Morra M. Engineering of biomaterials surfaces by hyaluronan. [J]. Biomacromolecules, 2005, 6 (3): 1205-1223. The negative charge of hyaluronic acid will affect the interaction between cell CD44 receptors and hyaluronic acid, thereby reducing the ability of cells to repair damage (Herrera MB, Bussolati B, Bruno S, et al. Exogenous mesenchymal stem cells localize to the kidney by means of CD44 following acute tubular injury[J].KidneyInternational, 2007, 72(4):430-441.), so hyaluronic acid has lost its superiority as a biological material

However, the hyaluronic acid hydrogel obtained through the reaction of its hydroxyl group often needs to react with ultraviolet light or use other methods to pre-form the hydrogel, so that in situ injection cannot be achieved.

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