Synthesis And Properties Of Degradable Antibacterial Hydrogels

Bacterial infection is a serious problem in biomedicine. The application of antibacterial materials is expected to meet this challenge Antibacterial hydrogel is one of the most important antibacterial materials, which has bee widely investigated and applied in wound dressings, medical device coatings, tissue engineering and so on. However, the reported antibacterial hydrogels could hardly combine the biocompatibility, biodegradability and injectability, which greatly reduced their clinical applications. In this dissertation, we designed and prepared a series of injectable, biodegradable and biocompatible antibacterial hydrogels by a combination of polycondensation and thiol-ene "click" chemistry, which could be promising biomaterials in clinic.Degradable multifunctional poly(ethylene glycol) (PEG) derivatives were first synthesized by polycondensation of oligo(ethylene glycol) (OEG) with functional diacid, such as maleic acid and malic acid. Afterwards, they were further modified by living/controlled radical polymerization or thiol-ene "click" chemistry, resulting in POEGM-g-QPDMAEMA and POEGMS-g-QDMAEA with degradable backbone and quaternary ammonium salt (QAS) side groups. These polymers showed good antibacterial properties against both S.aureus and E.coli.As mentioned above, water soluble and biodegradable multifunctional PEG derivatives could be facilely synthesized by polycondensation using OEG as macromonomer, which provides the possibililty to further crosslink these PEG derivatives by the reaction between the functional groups, resulting in biodegradable PEG hydrogels. Based on this concept, we synthesized a hydrogel precursor containing multiple enes and quaternary ammoniums (POEGDMAM) by the polycondensation of OEG, fumaryl chloride and dodecyl bis(2-hydroxyethyl) methylammonium chloride. At the same time, another hydrogel precursor with multiple thiols (POEGMS) was synthesized by the polycondensation of OEG and malic acid. Then injectable hydrogels were prepared by simply mixing the two hydrogel precursors through the thiol-ene "click" reaction. The gelation time of the hydrogels could be controlled by adjusting the pH, OEG/ammonium molar ratio and polymer concentration. The hydrogels basically reached equilibrium swelling within 9 h, and the hydrogels could completely degrade after 30 days. This kind of cationic hydrogels exhibits excellent antibacterial activity against both Gram-negative and Gram-positive bacteria. The hydrogel with fewer QAS moieties possesses both strong antibacterial abilities and low toxicity.In order to improve the biocompatibility of antibacterial hydrogels, guanidine hydrochlorides were used as the alternatives of quaternary ammoniums, and introduced into the backbone of hydrogels.We used glycidyl methacrylate (GMA) to modify polyhexamethylene guanidine hydrochloride (PHMG), resulting in PHMGGMA with multiple enes. Injectable PEG-PHMG hydrogels could be prepared by thiol-ene "click" reaction between PHMGGMA and POEGMS under physiological conditions. The gelation time of hydrogels could be adjusted by changing the concentration of precursors. PEG-PHMG hydrogel could be degraded within 12 days. SEM images showed that the inner structure of PEG-PHMG hydrogel was 3D-network and porous. This PEG-PHMG hydrogel possesses both good antibacterial property and excellent blood compatibility.Introducing PHMG directly into hydrogels to simplify the preparation process, another novel polyguanidine hydrogels were prepared by the reaction of oxidized dextran and PHMG. The inner morphology of hydrogels was also porous. All these hydrogels with different polyguanidine fractions are biodegradable and have excellent antimicrobial abilities.