Preparation And Properties Of Polysaccharide Components Smart Hydrogels

Smart hydrogels are materials that can response to changes of external environment.They are promising in emerging fields such as regenerative medicine,precision medicine,and 3D printing.However,insufficient mechanical performance,slow response to external stimuli,and poor biocompatibility greatly hinder their practical applications.Therefore,it is important to design new types of smart hydrogels and investigate their structures and properties in depth.In this work,a series of smart hydrogels were fabricated by cooperating a novel polysaccharide------Salecan and stimuli-responsive polymers through semi-IPN networks and graft polymerization.The smart hydrogels can response to one or more factors such as temperature,pH,and ionic strength.Their physicochemical properties were comprehensively characterized,and their stimuli-responsive behaviors to the external environment were systematically studied as well.In addition,the cell adhesion and drug release behavior of these smart hydrogels were studied in order to explore their potential application in biomedical field.The main contents and results are as follows:(1)A novel thermo-responsive hydrogel based on Salecan and poly(N-isopropylacrylamide):synthesis and characterizationSalecan were firstly introduced into poly(N-isopropylacrylamide)(PNIPAm)network to form novel thermo-sensitive semi-interpenetrating polymer networks(semi-IPNs).The structure of Salecan/PNIPAm semi-IPNs was confirmed by Fourier transformation infrared spectroscopy(FTIR)and X-ray diffraction(XRD).Thermogravimetric analysis(TGA)proved the stability of the semi-IPNs.Rheological and compressive tests revealed an elastic solid-like behavior and good mechanical properties of the hydrogels.SEM images showed these hydrogels porous structure and the pore-size was in the range of 150-300 ?m.Swelling behavior test showed the hydrogels possessed high water content at room temperature.An excellent thermo-sensitive property of fast response rates to temperature had been demonstrated as well.In vitro degradation measurements ensured the semi-IPNs were degradable.Cytotoxicity and cell adhesion study suggested the synthesized Salecan/PNIPAm hydrogels were non-cytotoxic and biocompatibility.The results indicated the novel thermo-responsive hydrogels could be a suitable candidate for biomedical applications.(2)Smart macro-porous Salecan/poly(N,N-diethylacrylamide)semi-IPN hydrogel for anti-inflammatory drug deliveryPoly(N,N-diethylacrylamide)is not only a thermo-sensitive polymer,but a good hydrogen bond acceptor as well.Therefore,drugs with carboxyl groups can serve as hydrogen bond donors and form interactions with the tertiary amide groups in N,N-diethylacrylamide.Herein,we report a novel drug delivery system for anionic drugs comprised of poly(N,N-diethylacrylamide)and Salecan.Salecan was used to improve the hydrophilicity and accelerate the responsive rate of this system.As expected,Salecan-enriched hydrogels exhibited higher swelling ratios and were more sensitive to temperature.Moreover,scanning electron microscopy images showed that the hydrogels are superporous structures,with pore sizes that increase with Salecan concentration.The swelling ratios decreased continuously with the increase of temperature in the range of 25-37 ?.MTT assay for cell viability and cell adhesion studies confirm the non-cytotoxicity and cell compatibility of the system.Delivery test using diclofenac sodium,an anti-inflammatory drug,indicate that the thermo-sensitive property of this system is favorable for anionic drug delivery.Interestingly,the release rates of diclofenac sodium from the hydrogels were temperature dependent,with higher temperatures contributing toward faster release rates.(3)Synthesis and characterization of a novel pH-thermo dual responsive hydrogel based on Salecan and poly(N,N-diethylacrylamide-co-methacrylic acid)Here,we report a novel pH-thermo dual responsive hydrogel based on Salecan and poly(N,N-diethylacrylamide-co-methacrylic acid)semi-interpenetrating polymer networks(semi-IPNs).It was interesting that the storage modulus(G')and pore size of the hydrogel could be tuned by adjusting the content of Salecan and crosslinker.The pH-thermo dual responsive property was demonstrated by swelling behavior test:the swelling ratio of the hydrogel decreased continuously as the temperature increased from 25? to 37?,while it was pH-dependent as well.Then the hydrogels were used for drug delivery test.Especially,when exposed to a higher temperature(37?)and acidic environment(pH4.0),drug-loaded hydrogel would have a quick release.Finally,the cytotoxicity of drug-free hydrogels was investigated on A549 and HepG2 cells,results showed that it was non-toxic while the DOX released from hydrogels had comparable cytotoxicity with respect to free DOX.In conclusion,the novel Salecan/poly(N,N-diethylacrylamide-co-methacrylic acid)semi-interpenetrating polymer network hydrogels were pH-thermo dual responsive and may be a promising candidate for drug delivery system.(4)Synthesis and characterization of a novel cationic hydrogel base on Salecan-g-PMAPTACHere,we fabricated a novel cationic hydrogel by graft-polymerizing 3-(methacryloylamino)propyl-trimethylammonium chloride(MAPTAC)onto Salecan chains.The obtained hydrogels were transparent,solid-elastic,macro-porous,ion-sensitive,and non-cytotoxic.The swelling ratios increased with Salecan content while decreased with ionic strength.Drug delivery test was studied as a potential application.Diclofenac sodium(DS)and insulin were used as model drugs.Interestingly,in drug loading process,DS molecules exhibited highly affinity to these hydrogels.Almost all the DS molecules in the loading solution were absorbed and concentrated into the hydrogel.For drug release profiles,insulin-loaded hydrogel showed an initial rapid release and a sustained release.As a comparison,DS-loaded hydrogel exhibited a more sustained release profile.Results suggested Salecan-g-PMAPTAC hydrogel could be a good candidate for anionic drug loading and delivery.(5)Synthesis and characterization of smart hydrogels responsive to pH,temperature,and ionic strength for controlled release of drugsA smart hydrogel was prepared by polymerizing and crosslinking dimethylaminoethyl methacrylate(DMAEMA)in aqueous solution of Salecan and N,N'-dimethylbisacrylamide(BIS).The sensitivity of the hydrogel to pH,ionic strength and temperature was studied by measuring the swelling behavior of the hydrogels in PBS with different pH values and different ionic strength at different temperatures.The hydrogels exhibit obvious pH-sensitive property:maximizes the swelling ratios at pH 1.2 and shrinks at pH values greater than 3.In addition,the water absorption of the hydrogel decreases as the ionic strength increases.In terms of temperature,the hydrogel swells at temperatures below 40 ?,above which it contracts to lose water.The hydrogel has a continuous,well-distributed porous morphology with a pore size distribution of 93-249 ?m.The pore size increases with the swelling ratios of the hydrogel.The cytotoxicity test showed that the cell viability of all samples was more than 85%,and the cell morphology was similar to the control group.This indicates the hydrogel is non-cytotoxic to COS-7 cells.Because of the tertiary amino groups in the PDMAEMA structure,hydrogen-bonding can be formed with some negatively charged molecules.Therefore,hydrogels were sopposed to have a certain ability of drug encapsulation.Protein drug insulin was selected was a model drug to test the drug delivery property of the hydrogel.Result showed the hydrogel has a controlled drug releasing behavior for insulin,and the release rate increases with the swelling ratio of the hydrogel.In addition,when temperature is higher than the LCST of PDMAEMA,drug molecules are extruded from the hydrogel and the release rate is faster.When the hydrogel was placed in pH 1.2environment,the release rate and release amount were higher than that of in pH 7.4.In summary,Salecan/PDMAEMA hydrogel has environment-controlled drug release behavior and can be used as drug carriers.