Agency for Science, Technology and Research

Fan Lee

Motoichi Kurisawa

Joo Eun Chung

Li Wang

Pui Yik Peggy Chan

Ki Hyun Bae

Pui Yik Chan

Keming Xu

Hirohisa Yano

There is provided a polymer-flavonoid conjugate, or a pharmaceutically acceptable salt thereof, uses thereof, and methods of making thereof. The disclosed polymer-flavonoid conjugates may be useful in the therapeutic and/or prophylactic treatment of a joint condition in a subject.

Polymer-flavonoid conjugate and uses thereof

The present disclosure relates to a polymeric system for release of an active agent, comprising a first polymeric phase containing the active agent, the first polymeric phase forming discrete regions of a set size range and being dispersed within a second polymeric phase comprising a cross-linked polymer-phenol conjugate for release of the active agent therein. The present disclosure further provides an injectable hydrogel comprising the disclosed polymeric system, a carrier for delivering a biologically active substance or a drug comprising the injectable hydrogel, and a method for producing the disclosed polymeric system.

Polymeric system for release of an active agent

There is provided methods for producing a hydrogel comprising conjugates of a hydrogel forming agent and a flavonoid including a method for producing a hydrogel that is capable of adhesion of cells and which comprises enzymatically cross-linked conjugates of a hydrogel forming agent and a flavonoid. There is also provided a method for producing a hydrogel comprising conjugates of a hydrogel forming agent and a flavonoid without the addition of an exogenous peroxide or peroxidase or without the addition of an exogenous peroxide. Hydrogels produced by such methods and methods of using the hydrogels are also described herein.

Methods for producing crosslinked flavonoid hydrogels

There are provided methods for producing a hydrogel that is capable of adhesion of cells and which comprises enzymatically cross-linked conjugates of a hydrogel forming agent and a flavonoid, formed from a reaction using peroxide and peroxidase. Hydrogels produced by such methods and methods of using the hydrogels are also provided.

Cell-adhesive, enzymatically crosslinked flavonoid hydrogels and methods for making same

There is provided a method of forming a hydrogel, the method comprising: providing a mixture of a polymer comprising a cross-linkable pendant phenolic group, peroxidase, HO, fibrinogen, and thrombin, at concentration sufficient to enzymatically cross-link the polymer and to cleave the fibrinogen to yield fibrin; and allowing the mixture to form a hydrogel. There is also provided a hydrogel comprising a cross-linked network of a polymer interpenetrated by fibrin fibers, the polymer cross-linked by oxidative coupling between phenolic groups pendant on the polymer.

Interpenetrating polymer network comprising fibrin

In a process of forming a hydrogel from a mixture comprising hydrogen peroxide (HO), horseradish peroxidase (HRP), and a polymer comprising a crosslinkable phenol group, the gelation rate in the solution and the crosslinking density in the hydrogel can be independently adjusted or controlled by selection of the molarity of HOand concentration of HRP in the solution when the molarity of HOis limited to be within a range and the concentration of HRP is limited to be above a threshold. A method for determining the range and threshold is disclosed. The hydrogel may be used to grow cells, in which case, the molarity of HOmay be selected to affect the differentiation or growth rate of the cells in the hydrogel. Also, the hydrogel system may be used for sustained delivery of a therapeutic protein, for example in the treatment of liver cancer, fibrosis or hepatitis.

Formation of hydrogel in the presence of peroxidase and low concentration of hydrogen peroxide

In a process of forming a hydrogel from a mixture comprising hydrogen peroxide (HO), horseradish peroxidase (HRP), and a polymer comprising a crosslinkable phenol group, the gelation rate in the solution and the crosslinking density in the hydrogel can be independently adjusted or controlled by selection of the molarity of HOand concentration of HRP in the solution when the molarity of HOis limited to be within a range and the concentration of HRP is limited to be above a threshold. A method for determining the range and threshold is disclosed. The hydrogel may be used to grow cells, in which case, the molarity of HOmay be selected to affect the differentiation or growth rate of the cells in the hydrogel.

Growing community of inventors

Singapore, Singapore

Fan Lee