Macromolecules modified with electrophilic groups and methods of making and using thereof

Abstract

Described herein are macromolecules modified with electrophilic groups and methods of making and using thereof. The preparation of a thiol-reactive, electrophililic derivative of HA in order to prepare ''crosslinker-free'' hydrogels are described as well as compounds and methods that are capable of coupling two or more molecules, such as macromolecules, under mild conditions. Specifically disclosed is the introduction of reactive bromo- and iodoacetate functionalities at the hydroxyl groups that are abundantly present on the HA polymer. The ''crosslinker-free'' hydrogels described have numerous applications including, but not limited to, drug delivery, small molecule delivery, wound healing, burn injury healing, tissue regeneration / engineering, cell culturing, and bio-artificial materials.

Description

Background technique [0001] The use of macromolecules has received considerable attention in pharmaceutical applications. Sometimes, it is necessary to couple more than two kinds of macromolecules to prepare new macromolecular scaffolds with multiple activities. However, existing techniques for coupling more than two macromolecules present many difficulties. For example, alkaline conditions or high temperatures required to prepare hydrogels with high mechanical strength are cumbersome and harsh. Although there has been some success using crosslinkers to prepare macromolecular scaffolds, crosslinkers are typically relatively small, cytotoxic molecules, and the resulting scaffolds must be extracted or washed extensively to remove traces of unreacted reactants and by-products (Hennink, W.E.; van Nostrum, C.F. Adv. Drug Del. Rev. 2002, 54, 13-36), thus precluding its use in many medical applications. Physiologically compatible macromolecular scaffolds that can be prepared in a ...

AI Technical Summary

Problems solved by technology

Although there has been some success using crosslinkers to prepare macromolecular scaffolds, crosslinkers are typically relatively small, cytotoxic molecules, and the resulting scaffolds must be extracted or washed extensively to remove traces of unreacted reactants and by-products (Hennink, W.E.; van Nostrum, C.F. Adv. Drug Del. Rev. 2002, 54, 13-36), thus precluding its use in many medical applications

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