Studies On The Synthesis And Properties Of Schiff Base Hydrogels Based On Chitosan And PEG-Derivated Dialdehydes

Due to the presence of hydrophilic three-dimensional crosslinked structure,hydrogel may hold a substantial quantity of water or biological fluid,and appear as low-modulus ductile state resembling real biological tissues,therefore extensively used in bio-medical fields,such as drug delivery,wound dressing,tissue engineering,and biosensors.Crosslinking mechanism influences processing performance,and by adjusting properly,some hydrogel crosslinked by ionic or radical pathway could become injectable.The scaffold materials play important role in biomedical properties,and natural macromolecule chitosan（CS）and synthetic macromolecule polyethylene glycol（PEG）have drawn considerable interest because of their biocompatibility,low cytotoxicity,and biodegradability.Rapidly developing CS hydrogels have enabled novel drug delivery systems that are able to release their payloads in response to a variety of environmental stimuli.These smart hydrogels that are environmentally sensitive may be utilized for wound dressings and medication delivery.The purpose of this work is to prepare a schiff base biomedical hydrogels based on CS and PEG-derivated dialdehyde,and investigate their wound dressing-related capabilities.This dissertation consists of two following parts.In the first part,2,5-dihydroxybenzoic acid was reacted with p-fluorobenzaldehyde to offer 5-（4-aldehydephenoxy）-2-hydroxybenzoic acid,followed by nucleophilic substituting with sulfonated PEG to generate polyethylene glycol carboxylic dialdehyde（FPEG）.Similarly,the natural compound eugenol was reacted with sulfonated PEG to produce eugenol terminated polyethylene glycol（SPEG）.Dialdehyde-containing FPEG and SPEG were used to crosslink CS by Schiff base（C=N）to form hydrogels coded as FPEG-CS and SPEG-CS,respectively.The in vitro gel time,swelling degree,degradation,self-repairing,p H responsiveness,drug release,and rheological characteristics of two hydrogels were examined.The results showed that higher concentration of PEG-derivated dialdehyde,leads to shorter the gel time.The swelling degree of PEG dialdehyde derived CS hydrogel is larger than that of glutaraldehyde derived CS hydrogel,with the maximum swelling degree of137%.Under acidic environment C=N could be hydrolytically degraded into C=O and NH₂-,which could be restored into C=N under neutral or alkaline environment,therefore,the dynamic reversible cleavage and formation of C=N impart Schiff base CS hydrogel with desired properties including degradability,PH responsiveness,self-repair,and controlled drug release.Rheological study indicated that the presence of aromatic ring adjacent to crosslinking bond C=N influences the modulus of CS hydrogels.By comparing SPEG-CS hydrogel whose modulus is around 2-3 KPa with FPEG-CS hydrogel whose modulus is approximately 4-5 KPa,two more benzene rings of FPEG than SPEG increase the rigidity of FPEG-CS hydrogel.The second part of this thesis focused on antibacterial properties of Schiff base CS hydrogels.The above FPEG-CS and SPEG-CS hydrogels lack antibacterial functional structure.In the second part,we synthesized PEG aldehyde-terminated PEG containing antibacterial imidazole quaternary salt structure（IPEG）.Experimentally,imidazole-terminated polyethylene glycol is produced by reacting sulfonated polyethylene glycol with imidazole.Meanwhile,chlorobenzyl aldehyde is produced by reacting p-hydroxybenzaldehyde with 4-chloromethylbenzoyl chloride.IPEG is facilely generated by reacting chlorobenzyl aldehyde with imidazole-terminated polyethylene glycol.The IPEG-CS hydrogel was prepared by20%aqueous IPEG crosslinking with CS,and evaluated in terms of rheological properties,antibacterial properties,swelling degree,degradation,self-repair,p H responsiveness.The rheological test results indicate that the mechanical characteristics of the hydrogel（IPEG-CS）are excellent with maximal storage modulus around 2 KPa.