Construction Of Dynamic Hydrogel Based On Knoevenagel Condensation Reaction

Hydrogel is a biocompatible material with a 3D network structure that can absorb a large amount of water while maintaining a certain mechanical strength.Therefore,it can simulate the extracellular matrix and has applications in the fields of drug delivery,tissue engineering,wound dressing,and cell therapy in biomedicine.One of the main reasons for the widespread use of hydrogels is the variety of raw materials available,as well as the different physical and chemical crosslinking methods that can be used.The Knoevenagel condensation(KC)is a classical organic chemical reaction that involves the condensation of aldehydes(or ketones)with compounds containing active α-hydrogen atoms in the presence of a weak base catalyst such as an amine or pyridine.In recent years,the KC has been used to prepare hydrogels that can form dynamic C=C bonds in aqueous medium.However,only the reaction between phenylformaldehyde and ethyl cyanoacetate has been reported to form hydrogels,and it is unknown whether other types of aldehyde compounds can form hydrogels through the KC.In this paper,we designed two systems for forming hydrogels using the KC and studied their rheological properties,self-healing,injectability,molding plasticity,and applications in the field of biomedicine.The main research contents are as follows:Part 1: Research has proved that the five-membered heterocyclic compound 5-hydroxymethylfurfural(5-HMF)can undergo KC to form a C=C dynamic covalent bond.Using methoxy poly(m PEG)modified with 5-HMF and cyanoacetate,denoted as m PEG-SA-5-HMF and m PEG-CA,it was confirmed that the C=C double bond formed based on this reaction is a dynamic covalent bond and is reversible.Furthermore,4-arm poly(ethylene glycol)(4-arm-PEG)end-capped with cyanoacetate,denoted as 4-arm PEG-CA and 5-HMFmodified poly(γ-glutamic acid)(γ-PGA),denoted as γ-PGA-5-HMF,were prepared and used for preparation of dynamic hydrogel.The hydrogel is injectable,self-healing and biocompatibility,and has the potential to serve as a hydrogel scaffold for 3D cell culture.Part 2: Research has proved that aldehyde polysaccharide polymer: oxidized dextran(ODex)can undergo KC reaction and form a hydrogel.Under the action of biocompatible catalyst,the injectability of hydrogel is improved,so that hydrogel can be used as cell transplantation material.The hydrogel protects cells from mechanical damage during injection and can maintain the 3D network structure to disperse and proliferate cells after injection.In the experiment,hydrogels were formed by using ODex with different oxidation degrees and4-arm-PEG-CA with different grafting ratios.Then 9 catalysts with different p Ka values were designed.Through orthogonal experiments,it was finally proved that the ionic liquid catalyst:choline hydroxide-histidine could significantly enhance the stress relaxation effect of the hydrogel.It plays a role in protecting cells in the process of injecting hydrogel,and does not change the mechanical strength of hydrogel.This kind of hydrogel is expected to be used as a cell transplantation material.