Preparation,Bioactivities And Biomedical Applications Of Acetylated Konjac Glucomannan

Konjac glucomannan(KGM)has good cytocompatibility,and macrophage immunomodulating activities,but its application in biomedical engineering is greatly limited due to its poor processing performance and poor stability in the physiological environment.In this paper,KGM was acetylated to improve the processing and stability properties,as well as keeping its biological activity,and to expand its application in biomedical engineering.Acetylated KGM(Ace KGM)with different acetylation degree was prepared in trifluoroacetic anhydride and acetic acid.The results of DSC and XRD showed that Ace KGM was an amorphous polymer with a high glass transition temperature and could dissolve in organic solvents.In addition,the results of cell experiments showed that Ace KGM could significantly improve cell adhesion and proliferation.The results of subcutaneous implantation in rat showed that Ace KGM was stable in physiological environment and could decrease the inflammatory reaction.It was found that Ace KGM can self-assemble into nanoparticles in aqueous solution.The Ace KGM nanoparticles loaded with curcumin were prepared by an emulsion solvent evaporation technique,and the optimal parameters for the preparation of nanoparticles were obtained.The results of DLS,AFM,and SEM showed that the particle size was about 200 nm.In vitro cell experiments showed that nanoparticles loaded with curcumin had good cellular compatibility,and could be?adhered? and enriched around by M1 phenotype macrophages,so as to prolong the existence time of drugs in inflammatory sites and improve drug utilization.In vitro,drug release experiments showed that Ace KGM could protect the activity of curcumin in simulated gastric juice and release curcumin in simulated colon juice.In colitis model experiment,the Ace KGM nanoparticles loaded with curcumin had a certain therapeutic effect,which was specifically reflected in comparatively complete colon morphology by HE staining.In short,the Ace KGM could be used as a novel nano-drug carrier,which could be used for colon-targeting drug delivery system.Growth factors(GFs)and cytokines play key roles in regulating inflammation,granulation tissue formation,re-epithelialization,matrix formation,and tissue remodeling.Wound healing could be accelerated by regulation and utilization of endogenous growth factors.It was found that there was good cell compatibility and macrophage immunomodulation activity of Ace KGM.Cell adherence and AFM-SCFS assay statistically suggested that there was a specific interaction between Ace KGM and M2 phenotype macrophage.Elisa results showed that Ace KGM could up-regulate the secretion of anti-inflammatory cytokines IL-10 and TGF-?1 on M2-phenotype macrophages.The Ace KGM nanofibrous membranes were prepared by electrostatic spinning.SEM results showed that the average diameters of the nanofibers were about 200 nm.Mechanical testing results showed that the membranes had a certain tensile strength,which could meet the needs of wound repair.To demonstrate the bioactivity of Ace KGM in vivo,a dorsal full-thickness skin defect mouse model was designed.The experimental groups with Ace KGM contained membranes showed a mild inflammatory response,faster formation and deposition of new collagen and rapid wound closure.These results demonstrated that Ace KGM could stimulate M2 macrophages of the host innate immunity to express GFs for improving wound regeneration.In summary,Ace KGM could be degradable in colon and had immunomodulation activity,and had potential in colon-targeting drug delivery system and for designing immunomodulating scaffold for wound regeneration.