Surface Functionalization Of Titanium Substrate And PEG-based Hydrogel For Antibacterial/Antifouling Applications

The demand for biomedical materials is increasing,not only because of the aging population,natural disasters,traffic accidents and complicated diseases,but also due to our ardent love for a good life.Scientific and technological advances are continuously made in biomedical materials to meet that expectation.Titanium and titanium alloys as well as hydrogels have been widely used in biomedical fields due to their excellent biocompatibility and other intriguing properties.However,their surfaces are prone to be adhered by bacteria,proteins and other biomolecules in the body.The subsequent microbial colonization and biofilm formation on biomedical materials could cause infection and inflammation in the host,and malfunction and failure of the devices and components.The biomedical material centered infections are now a serious threat to human health.On the other hand,they have limited the applications and further developments of biomedical materials.To solve these problems,it is necessary to introduce surface functionalities on biomedical materials and endow them with antibacterial/antifouling properties.Firstly,the antifouling titanium surfaces were constructed via mussel-inspired anchoring and host-guest interaction.Two catecholic derivatives,dopamine 4-?phenylazo?benzamide?AZODopa?and dopamine 1-adamantanecarboxamide?AdaDopa?were synthesized via ester-amine reaction and amidation.The as-synthesized AZODopa and AdaDopa were then anchored onto the Ti?oxide?surfaces to form guest molecule monolayers for the subsequent host-guest interactions with zwitterionic heptakis[6-deoxy-6-?N-3-sulfopropyl-N,N-dimethylammonium ethyl sulfanyl?]-?-cyclodextrin?SBCD?and hydrophilic?-CD polymer?CDP?.The surface elemental compositions and hydrophobic/hydrophilic properties of the Ti?oxide?surfaces before and after modification were characterized by X-ray photoelectron spectroscopy?XPS?and static water contact angle measurements,respectively.The antifouling properties of the modified Ti?oxide?surfaces were evaluated by the protein adsorption and bacterial adhesion assays.The zwitterionic SBCD-and hydrophilic CDP-functionalized Ti?oxide?surfaces can reduce the adsorption of bovine plasma fibrinogen and adhesion of Escherichia coli,as compared to the pristine and guest molecules-anchored Ti?oxide?surface.Secondly,the PEG hydrogel was prepared via nucleophilic thiol-yne addition between thiolated 4-arm PEG(PEG_10k-4-SH)and propiolated 4-arm PEG(PEG_10k-4-PP).The as-fabricated hydrogels still possess residual functionalities,enabling a second nucleophilic thiol-yne addition on the gel matrix.A thiol-containing antimicrobial peptide?AMP-SH?was also embedded into the gel matrix via nucleophilic thiol-yne addition to build the antibacterial hydrogel.The inhibition of bacterial growth in suspensions and contaminated substrate surfaces by the AMP-embedded hydrogels was studied.The results indicate that AMP-embedded hydrogels possess good antimicrobial activities against various bacteria and the growth inhibition of gram-positive bacteria by the AMP-embedded hydrogels is better than that of gram-negative bacteria.The cytotoxicity of PEG-based hydrogels against 3T3 fibroblasts was investigated by 3-?4,5-dimathylthiazol-2-yl?-2,5-diphenyl-tetrazoliumbromide?MTT?viability assay.The MTT viability assay shows that the unmodified PEG-based hydrogels have negligible cytotoxicity against 3T3fibroblasts.The AMP-embedded PEG-based hydrogels exhibit a low cytotoxicity against3T3 fibroblasts and can be potentially used in wound dressing.