Preparation And Performance Study Of Nucleotide Modified Graphene Oxide

With the rapid development of modern technology and living quality,and the lengthening of human average life,biomaterials have become one of the most important section in present medical treating.Wound dressing has played an irreplaceable role in biomedical materials,because of its extensive usage and growing market demand.Wound dressing usually works as a temporary substitute of lost skin to protect wound from pathogene infection and reduce the risk of serious inner-body complications.Suitable wound dressing is extremely helpful for those patients with chronic wounds or large-area skin injury,which would also provide ideal wound environment for follow-up treatments.Graphene oxide(GO)is one important carbon-based materials with excellent chemical activity,biocompatibility and relative low cost.For its unique two-dimensional structure,abundant oxygen containing groups and lage specific surface area,GO has been widely used in cell imaging,biosensor,drug delivery and tissue engineering.To improve the dispersing ability and achieve functionalization of GO,proper non-covalent or covalent modification is quite necessary.Nucleotide is the basic unit of nucleic acid and works as one of the most vital substances in human body,like conditioning cellular morphology,metabolic activities and protein biosynthesis.Citicoline and adenosine triphosphate are two common endogenous nucleotides,which have been proven to have the function of promoting human cell repair and regeneration.In this study,two sodium salts of nucleotides:citicoline sodium(CDPC)and disodium adenosine triphosphate(ATP),along with lanthanum ion(La3+)were chosen in the modification GO sheets,in order to improve the dispersibility,antibacterial property and biocompatibility of GO-based materials.Then the PVA/modified GO nano composite films were prepared as a novel wound dressing material.The detailed research process are described as follows:(1)CDPC with zwitterionic structure were adopted to functionalize GO via the activation of EDS·HCl/EDS system to obtain GO-CDPC nano compound.The structure properties of GO-CDPC with different mass rations were characterized by XRD,TGA and Raman techniques.According to the results,when the mass ratio of GO and CDPC was 1:4,most CDPC molecules could insert into the interlayers of GO and exhibited maximum property enhancement.La3+ was then added into GO-CDPC synthesized under this ratio to prepare GO-CDPC-La nano compound.Results of FTIR,EDS,XPS,TEM and SCA analysis indicated that GO-CDPC and GO-CDPC-La have been successfully prepared.CDPC molecules could bind to GO sheets through amido bonds,while La3+ was loaded on those nano sheets by both electrostatic adsorption and coordination effect.Moreover,the hydrophilicity of GO-CDPC and GO-CDPC-La was greatly improved,leading to better dispersing in aqueous medium.MTT assay showed that the cell toxicity grades of GO-CDPC and GO-CDPC-La with different concentrations were distributed between 0?1 level,suggesting all the modified functional GO nano composites were equipped with good biocompatibility and suitable for biomedical application.Antibacterial experiments showed that compared with GO-CDPC,GO-CDPC-La displayed better antibacterial ability and more significant inhibitory effect on S.aureus than E.coli.(2)To further improve the dispersibility,anti-microbial ability and biocompatibility of GO-based materials,negative-charged ATP and La3+ were adopted to functionalize GO.The structure properties of GO-ATP with different mass ration were characterized by XRD,TGA and Raman.According to the results,when the mass ratio of GO and ATP was 1:4,most ATP molecules could insert into the interlayers of GO and exhibited maximum property enhancement.La3+ was then added into GO-ATP compound synthesized under this ratio to prepare GO-ATP-La nano composite.Results of FTIR,EDS,XPS,TEM and SCA analysis indicated that GO-ATP and GO-ATP-La have been successfully prepared.The amino groups in ATP molecules could react with carboxyl groups on GO surface,while La3+ was loaded on those nano sheets by electrostatic adsorption and coordination effect.Morever,the hydrophilicity of GO-ATP and GO-ATP-La was greatly improved,leading to better dispersing in aqueous medium.Vitro cytotoxicity test proved that the cell toxicity grades of GO-ATP and GO-ATP-La with different concentrations were distributed between 0?1 level,suggesting all the obtained modified functional GO nano composites were equipped with good biocompatibility and suitable for biomedical application.Antibacterial experiments showed that compared with GO-ATP,GO-ATP-La displayed better antibactrial ability and more significant inhibitory effect can be observed on S.aureus than E.coli.(3)On the basis of above work,to explore the application prospect of modified GO as a novel kind of nano filler for polymeric medical materials,we prepares a series of PVA/modified GO nano composite films including PVA/GO-CDPC,PVA/GO-CDPC-La,PVA/GO-ATP and PVA/GO-ATP-La,by filling PVA chains into modified GO interlayers through solution intercalation method.The physical and chemical Properties and biomedical functions as wound dressing of these PVA/modified GO nano composite films were further estimated.XRD results testified that the modified GO were well dispersed in the polymer matrix by nanoscale.Thermo analysis found that due to the heat and oxygen insulation function of GO sheet and La3+,the thermo stability of prepared PVA films was increased with the introduction of GO-CDPC,GO-CDPC-La,GO-ATP and GO-ATP-La.Results of SCA and water absorption test showed that the hydrophily of PVA/modified GO nano composite films was enhanced compared with pristine PVA and exhibited excellent ability to absorb wound exudate while keeping wound moist.Vitro cytotoxicity assay and cell proliferation experiments showed that the relative growth rate of all PVA/modified GO nano composite were outnumbered 80%and normal growth of NIH3T3 cells on prepared nano composite films could be observed,implying low cytotoxic and good biocompatibility.Bacterial adhesion experiments showed that PVA/GO-ATP have better ability to prevent bacterial adhesion than PVA/GO-CDPC,since the electronegativity of GO-ATP could provide repulsive force against bacteria.Bacterial growth on PVA/GO-CDPC-La and PVA/GO-ATP-La films was further inhibited with the outstanding bacteria-killing efficiency of La3+,making it possible to reduce the risk of infection and promote wound healing.