水凝胶，又一篇Biomaterials！
水凝胶简介
水凝胶简介水凝胶是一种具有亲水性的三维网状交联结构的高分子网络体系。
水凝胶性质柔软，能保持一定的形状，能吸收大量的水，具有良好的生物相容性和生物降解性。
自从20世纪50年代由Wichterle等首次报道后，就被广泛地应用于组织工程、药物输送、3D细胞培养等医药学领域。
[1]水凝胶根据交联方式不同，分为物理交联水凝胶和化学交联水凝胶。
物理凝胶是指通过静电力、氢键、疏水相互作用等分子间作用力交联形成的水凝胶。
这种水凝胶力学强度低，温度升高会转变成溶胶。
化学交联水凝胶是指通过共价键将聚合物交联成网络的凝胶。
其中，共价键通过“点击”反应生成，比如硫醇-烯/炔加成、硫醇-环氧反应、叠氮-炔环加成、席夫碱反应、环氧-胺反应、硫醇-二硫化物交换反应等。
Gao Lilong等在生理条件下将N,N-二甲基丙烯酰胺、甲基丙烯酸缩水甘油酯和聚低聚乙二醇巯基丁二酸通过巯基-环氧“点击”反应制备得到可注射水凝胶。
[2]和物理凝胶相比，化学交联水凝胶稳定性较好，力学性能优异。
根据来源不同，水凝胶又可分为天然水凝胶和合成水凝胶。
天然水凝胶包括琼脂、壳聚糖、胶原、明胶等，它们大都通过氢键交联形成。
合成水凝胶包括聚乙二醇、丙烯酸及其衍生物类（聚丙烯酸，聚甲基丙烯酸，聚丙烯酰胺，聚N-聚代丙烯酰胺等）。
和合成水凝胶相比，天然水凝胶生物相容性较好，环境敏感性好，价格低廉，但稳定性较差。
目前，有学者将天然高分子和合成高分子交联制备杂化水凝胶。
比如，Lei Wang等将壳聚糖和聚异丙基丙烯酰胺交联得到热敏性杂化水凝胶用于体内药物输送，并利用近红外光引发药物释放。
[3]水凝胶凭借良好的生物相容性广泛地应用于药物输送、组织再生等医药学领域。
药物可以通过化学接枝和包埋等方式实现负载。
负载药物的水凝胶通过移植或注射进入生物体内，然后在体内逐渐降解实现药物的缓慢释放。
为了更好地实现药物的输送和释放，智能水凝胶应运而生，所谓智能水凝胶，是指能够对外界环境的变化，比如pH、温度等做出反应的水凝胶，从而实现药物的可控释放。
水凝胶 骨修复Development of tailored and self-mineralizing citric acid-crosslinked hydrogels
Development of tailored and self-mineralizing citric acid-crosslinked hydrogels for in situ bone regenerationAitor S a nchez-Ferrero a,b, Alvaro Mata c,Miguel A.Mateos-Timoneda a,b,e,Jos e C.Rodríguez-Cabello b,d,Matilde Alonso b,d,Josep Planell a,Elisabeth Engel a,b,e,*a Biomaterials for Regenerative Therapies Group,Institute for Bioengineering of Catalonia(IBEC),Barcelona,08028,Spainb Biomedical Research Networking Center in Bioengineering,Biomaterials,and Nanomedicine(CIBER-BBN),Spainc School of Engineering&Materials Science,Queen Mary,University of London,London,E14NS,UKd G.I.R.Bioforge,University of Valladolid,Valladolid,47001,Spaine Department of Materials Science and Metallurgical Engineering,Technical University of Catalonia(UPC),Barcelona,08028,Spaina r t i c l e i n f oArticle history:Received10February2015 Received in revised form30July2015Accepted31July2015 Available online3August2015Keywords:Biomimetic material BiomineralisationBone tissue engineeringCross-linkingHydrogelMesenchymal stem cell a b s t r a c tBone tissue engineering demands alternatives overcoming the limitations of traditional approaches in the context of a constantly aging global population.In the present study,elastin-like recombinamers hydrogels were produced by means of carbodiimide-catalyzed crosslinking with citric acid,a molecule suggested to be essential for bone nanostructure.By systematically studying the effect of the relative abundance of reactive species on gelation and hydrogel properties such as functional groups content, degradation and structure,we were able to understand and to control the crosslinking reaction to achieve hydrogels mimicking thefibrillary nature of the extracellular matrix.By studying the effect of polymer concentration on scaffold mechanical properties,we were able to produce hydrogels with a stiffness value of36.13±10.72kPa,previously suggested to be osteoinductive.Microstructured and mechanically-tailored hydrogels supported the growth of human mesenchymal stem cells and led to higher osteopontin expression in comparison to their non-tailored counterparts.Additionally,tailored hydrogels were able to rapidly self-mineralize in biomimetic conditions,evidencing that citric acid was successfully used both as a crosslinker and a bioactive molecule providing polymers with calcium phosphate nucleation capacity.©2015Elsevier Ltd.All rights reserved.1.IntroductionBiomimicry has become the cornerstone of bone tissue engi-neering strategies involving the use of scaffolds.The extracellular matrix(ECM)is the tissue-specific[1]nanofibrillar platform sup-porting cells and regulating their behavior in vivo[2].Thus,it is the archetype for the design of materials aiming to recapitulate skeletal development and to ultimately achieve tissue regeneration.Matrix properties such as structure[3],stiffness[4],surface chemistry[5], and ligand nature[6]have proved useful in promoting the osteo-blastic differentiation of mesenchymal stem cells(MSCs).However, combinatorial studies[7,8]suggest that their synergistic effect must be considered,evidencing that complex scaffold designs are required to more accurately direct cell behavior.The soft and tailorable nature of hydrogels make them an ideal platform to induce bone formation by providing cells with com-bined ECM-mimicking signals while being remodeled and degraded.Among the many polymers suitable to produce hydro-gels,elastin-like recombinamers(ELRs)stand out as a powerful tool given their recombinant nature.This confers them great versatility regarding the inclusion of particular sequences to control processes such as cell adhesion[9],mineralization[10]and degradation[11]. Although ELRs inherit elastin's reversible self-aggregation capacity, covalent crosslinking is required to produce stable hydrogels.The crosslinking conditions used to prepare hydrogels influence their structure and mechanical properties[12],so crosslinking is a useful tool to achieve hydrogels with tuned properties.Water-soluble carbodiimide(WSC)is a non-integrative cross-linker widely used to produce protein-based hydrogels.It catalyzes the formation of peptide bonds by condensation of primary amines (e NH2)and carboxyl groups(e COOH)[13]and can be easily*Corresponding author.Biomaterials for regenerative therapies group,Institute for Bioengineering of Catalonia(IBEC),Barcelona,08028,Spain.E-mail address:eengel@ibecbarcelona.eu(E.Engel).Contents lists available at ScienceDirect Biomaterialsjournal h omepage:/locate/biomaterials/10.1016/j.biomaterials.2015.07.0620142-9612/©2015Elsevier Ltd.All rights reserved.Biomaterials68(2015)42e53washed out from scaffolds,thus minimally compromising cyto-compatibility.Although ELRs have been designed to include lysine residues as a source of e NH2,they are short on e COOH,so carboxyl-donor molecules are required to achieve the carbodiimide-catalyzed crosslinking of ELRs.Donor molecules,ideally polycarboxylic acids such as citric acid,would then be incorporated into the polymeric matrix and might potentially provide hydrogels with new functionalities.Up to the80%of citric acid in the human body is found in bones [14].This tricarboxylic acid,long known for its central role in cell metabolism,has been recently suggested to play a critical role in limiting the growth of hydroxyapatite(HA)crystals in vivo[15]. Conversely,citrate has been shown to induce the in vitro nucleation of HA on collagen matrices[16].The presence of HA at a surface level provides scaffolds with bone regenerative potential[17],as evidenced by both in vitro[18]and in vivo[19]studies involving the use of premineralized hydrogels.Thus,calcium phosphate-nucleation capacity is an interesting feature to boost the osteo-genic potential of biomimetic hydrogels.The goal of this study was to develop tailored citric acid-crosslinked ELRs hydrogels for in situ bone regeneration.Different crosslinking parameters were used to decipher their contribution to scaffolds'architecture,stiffness,degradation and cytotoxicity, and to ultimately extrapolate the proper set of conditions needed to achieve structurally and mechanically-tailored hydrogels.Poly-meric matrices with tuned properties were assessed to determine their capacity to support cell growth,to induce the osteogenic differentiation of hMSCs and to self-mineralize in vitro.Interest-ingly,our results show that herein developed crosslinking reaction is a versatile and useful tool to both tune hydrogel physical prop-erties and provide polymers with calcium phosphate nucleation capacity,thus avoiding the need of performing functionalization,in the development of scaffolds for bone regeneration.2.Materials and methods2.1.HRGD6ELRHRGD6ELR was synthesized as previously reported[20].This recombinant polymer,based on the repetition of VPGxG(where x is either I or K)elastomeric domains,includes lysine residues as a source ofε-NH2groups to be used for crosslinking purposes and RGD tripeptides for cell adhesion.2.2.Sample preparationHRGD6polymer was crosslinked with citric acid monohydrate (Sigma)through a N-(3-Dimethylaminopropyl)-N0-ethyl-carbodiimide(EDC,Aldrich)-catalyzed reaction in2-(N-Morpho-lino)ethanesulfonic acid(MES,Sigma).Seven different hydrogels, each one characterized by a particular combination of EDC:COOH and COOH:NH2molar ratios,were prepared(Fig.1b).Setups were encoded in the form EXCY,where EX denotes the molar excess(X) of EDC with respect to e COOH groups and CY denotes the molar excess(Y)of e COOH with respect to e NH2groups.In all cases, HRGD6polymer was dissolved overnight at4 C in MES buffer containing citric acid;similarly,EDC was dissolved overnight at4 C in MES buffer.Polymer-citrate and EDC solutions were mixed ataFig.1.(a)Changes in absorbance occurring during crosslinking reaction tracked at750nm(black)and mathematical derivative(gray),from which kinetic parameters were extracted.Inset:citric acid-crosslinked hydrogel at reaction completion;U.A.:Units of absorbance.(b)Detailed relative abundance of reactive species in reaction mixes used to prepare hydrogels.(c)Latency time calculated for all seven different samples.Plotting area was colored to clearly distinguish the separate contribution of the two molar ratios.(d)Quantification of unreacted primary amines after crosslinking with citric acid and EDC.*p value0.05with respect to E2C1samples;**p value0.05with respect to E9C1 samples.A.S a nchez-Ferrero et al./Biomaterials68(2015)42e53431:1volume ratio(polymer concentration:40mg/ml)and pH was adjusted to z6by adding cold NaOH or HCl(Panreac).Crosslinking reactions were carried out at37 C for1h and stopped by incu-bation with0.1M Na2HPO4(Sigma)at room temperature for3h. Samples were then washed by performing5swelling/shrinking incubation cycles in ultrapure water at4 C(swelling)/37 C (shrinking)to allow excess EDC and reaction by-products to be released.2.3.Effect of reaction conditions on the crosslinking reaction2.3.1.GelationReaction mixes for all seven different hydrogels were prepared as previously stated and poured into96-well plates.Absorbance evolution was monitored at37 C and l¼750nm for 62.5min using an Infinite M200Pro multimode reader and i-con-trol software(Tecan,Switzerland).Collected data were treated with Origin(OriginLab,version8.0724);latency time,herein defined as the time lapse between the mixture of reagents and the initial in-crease in turbidity,was calculated using the Spectroscopy Peak Analyzer tool in Origin.2.3.2.Quantification of unreacted e NH2groupsHydrogels were prepared in96-well plates and incubated with 100m l of a10.55mM2,4,6,-trinitrobenzenesulfonic acid(TNBS, Sigma)solution in9:10.1M NaHCO3:0.1M Na2CO3(pH8.93)in the dark at4 C with gentle stirring for30h.200m l of6M HCl were added to completely hydrolyze samples over a75h period and resulting solutions were diluted1/10in ultrapure water.Absor-bance was read at l¼342nm and glycine was used to prepare standard curves to stoichiometrically quantify unreacted primary amines.2.4.Effect of reaction conditions on hydrogels properties2.4.1.Hydrogels structure and polymer-occupied volumeHydrogels structure was assessed by confocal microscopy and Field Emission Scanning Electron Microscopy(FESEM).Samples to be assessed by confocal microscopy were prepared on16-well Lab-Tek glass chamber slides(Nunc)and stained with0.4%Trypan blue (Sigma)for3h at room temperature.Several washing steps with phosphate-buffered saline(PBS;Life technologies)were performed until no apparent dye release was noticed.Samples were then treated withfixative solution(3%paraformaldehyde and40mM sucrose in PBS;reagents from Sigma)for10min at4 C and washed three times with cold0.15%glycine in PBS(PBS-gly).Hydrogels were then mounted with Mowiol40-88(Sigma e Aldrich)and sealed with nailpolish.Images were acquired at an emission wavelength range of579e657nm and a stepsize of80nm by using a TCS SP5confocal microscope(Leica,Germany)and LAS-AF soft-ware(Leica;version2.4.1build6384).The size of polymer aggre-gates was measured with Fiji[21].Hydrogels to be observed by FESEM were prepared in PDMS molds,washed with water several times to remove salts,lyophi-lized and sputtered with graphite.FESEM images were obtained by using a NOVA NANOSEM230microscope(FEI,United States)at a 3.00kV voltage and5mm working distance.Sections obtained by confocal microscopy were used to quantify the percentage of polymer-occupied volume(i.e.polymer volume/ total volume;PV/TV)by using the Volume Fraction tool(BoneJ[22] plugin v.1.3.11for Fiji).Calculations were performed with a surface resampling value of2and a specific threshold for each set of im-ages.3D reconstructions of quantified volumes were analyzed to assure proper thresholding was used for each single calculation.2.4.2.Resistance to enzymatic degradationSelected samples were prepared in96-well plates and incubated with 2.82$10À3U/ml porcine pancreatic elastase(Worthington Biochemical Corporation,United States)in PBS at37 C for1,3and 7days.Hydrogels not exposed to elastase were used to set sample weight at day0.At every time point,samples were washed with ultrapure water,dried at37 C and weighted.2.4.3.Surface stiffnessSamples were prepared in6mm-diameter PDMS molds and kept in PBS at37 C until use.Molds were mounted on glass slides using double-sided tape and ten force curves per sample were ac-quired in Force Mode using IGOR Pro software(Wavemetrics, version6.2.2.2A)and a MFP-3D stand alone unit(Asylum Research, United States).Measurements were made in PBS at37 C using chromium and gold-coated,pyramidal silicon nitride cantilevers (NanoWorld)with a nominal spring constant of0.08N/nm and assuming Poisson's ratio to be0.5.A custom-made script consid-ering cone-shaped tip was used to calculate Young's modulus by means of Hertz model.2.5.Effect of reaction conditions on hydrogels cytotoxicity and RGD integrity2.5.1.CytotoxicityBone marrow-derived rat MSCs(rMSCs)were cultured in 75cm2flasks at37 C in a5%CO2atmosphere.Cell expansion was carried out in complete medium:Advanced Dulbecco's modified Eagle's medium(AdvDMEM;Gibco)supplemented with15%fetal bovine serum(FBS;Gibco),2mM L-glutamine(Gibco),100U/ml Penicillin and100m g/ml Streptomycin(Gibco).Cells at passage6e8 were detached at a confluence of about80%with Tryp-LE Express (Gibco)and the number of viable cells was determined after staining with Trypan blue.104viable cells/well were seeded on24-well plates and allowed to adhere for4h.Non-adhered cells were washed out with PBS and attached cells were quantified with10% Alamar blue(TREK Diagnostic Systems)in complete medium to verify homogenous adhesion in all wells.Cells were then washed with PBS and wells were subsequently replenished with complete medium.Selected hydrogels were tested for cytotoxicity by indirect contact.Samples prepared in PDMS molds were sterilized with70% ethanol under UV irradiation for1h,washed thrice with PBS and kept in the buffer at37 C until use.PET Millicell Inserts(Millipore) with a0.4m m pore size were placed into wells and300m l of culture medium were added to each insert.Hydrogels were then washed twice with PBS to remove remaining ethanol and transferred to inserts.Negative controls(TCPS)consisted on inserts containing just complete medium;positive controls consisted on the use of complete medium supplemented with1%phenol(Sigma e Aldrich) in both the wells and the inserts.After a42.5h incubation period at37 C and5%CO2,cytotoxicity by indirect contact was assessed by cell quantification with Alamar blue and cell morphology examination.For cell shape visualization, cells were washed with Dulbecco's phosphate-buffered saline (DPBS,Gibco),stained in the dark with2m M Calcein AM(Sigma-e Aldrich)for20min at37 C and washed with the buffer to removeexcess dye.Images were acquired using an Eclipse TE200inverted microscope(Nikon,Japan)and MetaMorph Microscopy Automa-tion&Image Analysis Software(Molecular Devices,version5.0r1).2.5.2.Cell adhesionSamples were prepared on16-well Lab-Tek glass chamber slides,stained with Trypan blue and washed until no apparent dye release was noticed.rMSCs were cultured as previously stated,A.S a nchez-Ferrero et al./Biomaterials68(2015)42e53 44seeded at afinal density of2.5$103viable cells/sample and kept in complete medium for24h.Samples werefixed with para-formaldehyde,permeabilized with0.1%Triton X-100(Sigma-e Aldrich)for5min,blocked with PBS-gly supplemented with6% bovine serum albumin(BSA;Sigma)for45min and stained in the dark at room temperature for vinculin and nuclei observation. Briefly,cell staining consisted on:(i)incubation with mouse anti-vinculin primary antibody(Sigma)at a1/400dilution in PBS-gly supplemented with3%BSA(PBS-gly-BSA3%)for1h,(ii)incuba-tion with Alexa488-conjugated goat anti-mouse secondary anti-body(Molecular Probes)at a1/300dilution in PBS-gly-BSA3%for 1h,and(iii)incubation with4m g/ml40,6-diamino-2-phenylindole dihydrochloride(DAPI,Sigma)for2min.Hydrogels were then mounted,sealed and observed by confocal microscopy.Volocity3D Image Analysis Software(Perkin Elmer,version6.2.1)was used to obtain3D reconstructions.2.6.Design of hydrogels with combined tailored properties2.6.1.Surface stiffnessAn EDC:COOH9.3:1,COOH:NH21.06:1combination of molar ratios was selected to test the influence of polymer concentration on stiffness.Samples were prepared at40,54,80and160mg/ml polymer concentrations and stiffness was quantified as previously stated.2.6.2.Structure of mechanically-tailored hydrogelsHydrogels were prepared at a polymer concentration of54mg/ ml using the EDC:COOH9.3:1,COOH:NH21.06:1combination of molar ratios(from now on,RGD-C samples),incubated with0.1M Na2HPO4for3h at RT and washed with PBS by performing swelling/shrinking cycles.Samples to be observed by confocal mi-croscopy were stained with Trypan blue,and mounted and visu-alized as previously stated.Hydrogels to be visualized by FESEM were subjected to serial dehydration in ethanol and critical point drying with CO2.A voltage of5kV and a working distance of6mm were used to acquire images.The diameter of polymeric trabeculae was quantified using Fiji.2.6.3.Cell proliferation on tailored hydrogelsHuman MSCs(Lonza,Switzerland)were expanded in complete medium up to passage8.2$103cells/scaffold were seeded on RGD-C samples and on their40mg/ml,non-tailored counterparts.Seeded scaffolds were kept in culture for1,7,14and21days.For qualita-tively assessing proliferation,samples were washed with PBS,cells werefixed with3%paraformaldehyde as previously described, subjected to serial dehydration in ethanol and to critical point drying in CO2.Hydrogels were then graphite-sputtered and visu-alized under a Quanta200Scanning Electron Microscope(SEM; FEI)at a10mm working distance and a20kV voltage.For the quantitative assessment of cell proliferation in complete medium,hydrogels prepared in96-well plates were degraded at days1,3,7,14and21by using2mg/ml porcine pancreatic elastase in PBS for3h at37 C.After hydrogel degradation,M-PER(Thermos Scientific)was added to a1:1volume ratio and samples were subjected to three freezing/thawing cycles atÀ80 C/RT.Cell lysates were transferred to microtubes and centrifuged at2500g for 10min at4 C using an Eppendorf5415R(Eppendorf,Germany) centrifuge.Cell debris were discarded and cleared cell lysates were used to quantify cell number by using the LDH-based Cytotoxicity detection kit plus(Roche)according to manufacturer's instructions. Briefly,cell lysates were incubated with reaction solution at a1:1 volume ratio.Mixtures were incubated for20min at RT and absorbance was read at490nm using a reference wavelength of 600nm.2.6.4.Preliminary cell differentiation assaysFor the assessment of alkaline phosphatase(ALP)expression, RGD-C hydrogels and their40mg/ml counterparts were prepared in96-well plates and sterilized as previously stated.hMSCs were seeded at2$103cells/scaffold density and cultured in osteogenic medium(plete medium supplemented with50m g/ml ascorbic acid,10mM b-glycerophosphate and10nM dexametha-sone;osteogenic supplements from Sigma).At selected time points, scaffolds were degraded and cells were lysed as abovementioned. The expression of alkaline phosphatase(ALP)was quantified by using the SensoLyte pNPP alkaline phosphatase assay kit(AnaSpec). Briefly,cleared lysates were incubated with the p-Nitrophenyl phosphate(pNPP)substrate at a1:1volume ratio.Reagents were homogenized for few seconds and incubated at37 C for40min, and absorbance was read at450nm.ALP expression results were normalized to cell number.For the assessment of osteopontin(OPN)expression,samples were prepared on16-well Lab-Tek glass chamber slides,stained with Trypan blue,washed until no apparent dye release was noticed,and sterilized as previously mentioned.hMSCs up to pas-sage8were seeded at2$103cells/scaffold density and cultured in osteogenic medium.At selected time points,cells werefixed,per-meabilized and blocked as previously stated,and stained in the dark at room temperature for osteopontin(OPN)and nuclei visu-alization.Briefly,cell staining consisted on:(i)incubation with rabbit anti-OPN primary antibody(Abcam)at a1/600dilution in PBS-gly-BSA3%for1h,(ii)incubation with Alexa488-conjugated goat anti-rabbit secondary antibody(Molecular Probes)at a1/300 dilution in PBS-gly-BSA3%for1h,and(iii)incubation with DAPI for 2min.Cells were then mounted with Mowiol40-88,sealed and visualized by confocal microscopy.2.6.5.In vitro mineralizationTo assess citrate-related calcium phosphate nucleation capacity, citric acid-crosslinked hydrogels with tailored stiffness(RGD-C) were compared to samples crosslinked with glutaraldehyde(RGD-G).RGD-G hydrogels were prepared at a polymer concentration of 54mg/ml.Briefly,HRGD6polymer was crosslinked with5% glutaraldehyde(Sigma)for7:30h at4 C,reduced with5%NaBH4 (Aldrich)for2h on ice and washed with ultrapure water to remove remaining NaBH4.RGD-C hydrogels were prepared as previously stated and washed several times with water to remove remaining reagents,by-products and salts.All samples were prepared in 6mm-diameter PDMS molds.Simulated bodyfluids(SBF)were prepared as specified in the literature[17].Samples were incubated withfiltered,pre-warmed SBF at37 C for1,7,14and28days;SBF was replaced every3days.At endpoints,hydrogels were washed3 times with ultrapure water and kept at37 C until the end of the experiment.RGD-C samples were subjected to serial dehydration in ethanol and critical point drying with CO2;RGD-G samples were frozen with liquid N2and lyophilized for two days.Hydrogels were then graphite-sputtered and analyzed using a Quanta200Scanning Electron Microscope equipped with a Genesis Energy Dispersive X-Ray Spectroscopy(EDS)system(EDAX,United States).A voltage of 20kV and a working distance of10mm were used.2.7.Statistical analysisData were analyzed by means of t-test or one-way ANOVA with Dunnett's post hoc test.All analyses were performed using Prism (GraphPad,version6.01).Results were considered significant when p0.05unless otherwise specified.A.S a nchez-Ferrero et al./Biomaterials68(2015)42e53453.Results3.1.Effect of reaction conditions on the crosslinking reaction3.1.1.GelationPreliminary tests showed crosslinking was consistently ach-ieved when reaction mixes prepared at4 C in MES buffer at an initial pH of ca.6were let to react for1h at37 C(Data not shown). Under these conditions,hydrogels became gradually opaque during reticulation(Fig.1a).This phenomenon made possible the moni-toring of absorbance changes at a wavelength of750nm,at which none of the components showed remarkable light absorption.The increase in absorbance followed a sigmoidal curve that was mathematically derived to calculate latency time.This parameter was used to investigate how the relative abundance of reactive species(EDC and,e COOH and e NH2groups)involved in the re-action kinetically affect polymer aggregation.With this purpose, seven different hydrogels were prepared using particular combi-nations of EDC:COOH and COOH:NH2molar ratios(Fig.1b).Latency time was found to be clearly influenced by the relative abundance of reactive species:increasing any of the two molar ratios led to a reduction in latency time(EDC:COOH,from568.33±91.45s to 371.11±6.97s;COOH:NH2,from371.11±6.97s to120.77±26.37s; Fig.1c).3.1.2.Quantification of unreacted e NH2groupsThe number of primary amines remaining unreacted after reticulation was quantified by using TNBS[23].Although HRGD6 polymer was designed to displayε-amino groups from lysine res-idues to be used for crosslinking purposes,a-amino groups from the N-terminus of polymeric chains may also participate in the EDC-mediated reaction.Thus,results presented herein correspond to the sum of unreacted a-andε-amino groups.As shown in Fig.1d,increasing the EDC-to-COOH ratio did not have an effect on the percentage of primary amines involved in the reticulation reaction(all samples displayed ca.46%free e NH2), suggesting EDC is efficient even at a2-fold molar excess respect to carboxyl groups for afixed COOH:NH2ratio.In contrast,increasing the COOH:NH2ratio led to a remarkable decrease in the amount of unreacted amines,leading to an almost total consumption of e NH2 groups in samples E9C5(6.01±4.48%free e NH2).3.2.Effect of reaction conditions on hydrogel properties3.2.1.Hydrogels structure and polymer-occupied volumeThe effect of molar ratios on hydrogel architecture was studied both by confocal microscopy and FESEM.Observation of the structure by confocal microscopy was possible due to hydrogels' inner autofluorescence,which was red-shifted and intensified by staining with Trypan blue(Data not shown).This phenomenon allowed the visualization of three different architectures(globular, globulo-fibrillar and dense)and structural changes regarding polymer aggregation,aggregate size and matrix density.Polymer in E2C1samples assembled in the form of globules with a diameter of ca.3m m(Fig.2a).Increasing EDC:COOH to obtain E3C1samples led to a transitional structure in which large aggregates and nascent elongated entities(trabeculae)formed by smaller aggregates (diameter of ca.1.5m m)were observed(Fig.2b).E5C1and E9C1 samples displayed architectures enriched withfiber-like structures where polymer aggregates had a diameter of ca.1.3m m and1.2m m, respectively(Fig.2c and d).Although it was not possible measuring the size of aggregates in E9C2,E9C3and E9C5samples,increasing COOH:NH2seemingly led to a reduction of the aggregate and trabeculae size down to the nanoscale(Fig.2f e h).This latter phe-nomenon was accompanied by an increase in hydrogels density.FESEM was used to confirm what was observed by confocal microscopy.No globules were observed in any of the samples. However,changes in the density of the structure and in polymer aggregation were confirmed.Increasing EDC:COOH molar ratio led to mesh constituents transitioning from irregular-shaped(Fig.2a2) to thin connectingfiber-like entities or trabeculae(Fig.2b2e d2). Increasing the COOH-to-NH2ratio led to obtaining hydrogels with dense structures displaying sublimation-derived pores typical of lyophilized hydrogels[24](Fig.2f2e h2).In order to confirm the apparent effect of excess e COOH with respect to e NH2on scaffold density,sections obtained by confocal microscopy were processed to quantify the volume occupied by HRGD6polymer(3D reconstructions of calculated volumes compared to the original3D sections can be seen in Fig.S1).The EDC:COOH ratio was found not to affect PV/TV;in contrast, COOH:NH2had a strong effect on reducing the void volume(from 31.56±0.69%to74.09±7.33%of polymer-occupied volume;Fig.3a) in such a way that the higher the COOH-to-NH2ratio,the more dense the scaffold.3.2.2.Resistance to enzymatic degradationTo investigate differences between samples regarding resistance to enzymatic degradation,hydrogels were incubated with porcine pancreatic elastase.In order to simplify the experiments and to provide a proof of concept,3out of the7different hydrogels were chosen to be used in this part of the study:E2C1,E9C1and E9C5. E2C1samples were found to degrade quickly,losing ca.50%of their mass within thefirst day and being completely dissolved by day3 (Fig.3b,left).In contrast,E9C1hydrogels showed reduced degra-dation at day1and sustained mass loss along the experiment,by the end of which ca.75%of the material had been digested.E9C5 samples showed a significantly reduced mass loss rate from day3 to day7,at which ca.55%of the material had been enzymatically processed(Fig.3b,right).3.2.3.Surface stiffnessAn interesting question to answer was whether the apparent differences regarding crosslinking yield and structure between samples would influence their mechanical properties at a surface level.As it is shown in Table1,stiffness was seemingly unaffected by molar ratios,none of which proved useful to mechanically tailor citric acid-crosslinked hydrogels.Additionally,none of the samples was shown to possess a Young's modulus value in the range of interest(25e40kPa[4]).3.3.Effect of reaction conditions on hydrogels cytotoxicity and RGD integrity3.3.1.CytotoxicityIndirect contact experiments were performed to test hydrogels for the release of excess EDC and its toxic by-product,N-acylurea. Again,E2C1,E9C1and E9C5samples were selected to simplify the experiment.Cells were seeded on tissue culture polystyrene (TCPS),let to adhere for4h and quantified.Results were normalized to cell number in the negative control.No differences in cell number were observed(Fig.4a),assuring all wells used in the experiment had approximately the same initial cell density, thus avoiding artifacts due to uneven adhesion.Cells were exposed to different agents for42.5h and quantified again.After normalization,it was found E2C1and E9C1samples led to an increased number of cells when compared to that in TCPS.In contrast,E9C5hydrogels produced a decrease in cell number of about70%.No cell survival was observed in those wells treated with culture medium supplemented with1%phenol.After stain-ing with Calcein AM,cells exposed to culture medium and samplesA.S a nchez-Ferrero et al./Biomaterials68(2015)42e53 46。
【doc】水凝胶医用敷料的研究概况
【doc】水凝胶医用敷料的研究概况水凝胶医用敷料的研究概况轻纺工业与技2011年第40卷第1期水凝胶医用敷料的研究概况陈向标(五邑大学纺织服装学院,广东江门529020) 【摘要】介绍水凝胶敷料在医疗卫生领域的应用,叙述了水凝胶医用敷料的制备原料,制备方法以及水凝胶医用敷料的诸多优点.【关键词】水凝胶;医用敷料;静电纺丝中图分类号:TQ342+.87,R318.08文献标识码:B文章编号:2095—0101(2011)0l 一0066—03水凝胶是功能高分子材料的一种,内部带有强烈的亲水基团,因而对水有特殊吸附作用,通过分子间交联,形成网状结构.吸水性凝胶材料吸水的特点不同于海绵,棉布等吸附材料,它可以吸收是自身质量成百上千倍的水,并与水牢固结合,然后膨胀形成水凝胶.这种凝胶中的水即使受到相当大的压力也很少被挤出.这一特殊功能使得吸水性高分子凝胶材料在被发现之后就得到了快速发展.水凝胶医用敷料是近年来发展起来的一种新型的创伤敷料.与传统的敷料相比,水凝胶能促进伤口更好地愈合,减轻患者的疼痛,它能改善创面的微环境,抑制细菌的生长.水凝胶特别适用于常见的体表创伤,如擦伤,划伤,褥疮等各种皮肤损伤.对于这些伤口,传统上医生一般用无菌纱布及外用抗生素处理.纱布易与皮肤伤口组织粘连,换药时常常破坏新生的上皮和肉芽组织,引起出血,这不但不利于伤口的愈合,而且使病人疼痛难忍.用水凝胶敷料敷贴在伤口上时,它不但不粘连伤口,不破坏新生组织,而且能杀死各种细菌,避免伤口感染f".1制备水凝胶的原料制备水凝胶一般采用高分子材料,包括天然高分子材料和合成高分子材料.天然高分子材料因其生物相容性较好而常被选用, 但是天然高分子也存在一些缺点:比如材料性能的重复性差,机械强度较差,而且结构与性能可调范围窄,致使收稿日期:2010—11-03作者简介:陈向标(1985.3一),男,广东省陆丰市人,在读研究生.研究方向:生物医用纺织品.其难以满足医学上的各种实际要求.合成高分子用来制备敷料用水凝胶具有诸多优点: 合成材料通过控制条件,其生产重复性好,可根据需要大量生产,通过简单的物理,化学改性,获得广泛的性能,以满足不同需要121.但合成高分子的生物相容性一般较差,可用来制备敷料用水凝胶的原料种类也有限. 因此研究利用天然高分子与合成高分子合成杂化高分子水凝胶引起人们更为广泛的重视,这种方法将两者的优点结合起来,以提高水凝胶的性能.既能保留人工合成高分子材料基质的力学强度,又能具有天然高分子材料的良好生物相容性.常用于制备敷料用水凝胶的聚合物原料如表1. 表1常用来制备敷料用水凝胶的聚合物材料类别聚合物天然高分子藉嚣概鼬'嗽衙艨,合成高分子詈篙卿峭.烷酮'聚天然一合成壳聚糖一聚乙二醇,壳聚糖一聚乙烯吡咯烷酮,胶原蛋复合高分子白一聚丙烯酸2水凝胶的制备方法水凝胶的合成主要分为物理方法和化学方法.物理方法主要有共混法,冻融法,纺丝法等.作用的机理主要是通过静电作用,氢键,链的缠结等物理交联作用形成凝胶.化学方法主要有:接枝共聚,高能辐射(如电子辐射,射线)交联等.作用的机理主要是由通过化学键交联形成三维网络聚合物.2.1冻融法主要是通过多次冷冻熔融循环使高分子在低温下 2011年第4O卷第1期轻纺工业与技67 结晶,这种结晶作用可促使聚合物内部形成微晶,其功能类似于物理凝胶网络交联点嘲.Park等人采用冻融法合成了PVA/PVP共聚物水凝胶以用于敷料,在合成过程中加入了芦荟成分,发现随着聚合物中芦荟含量的增加,凝胶的强度下降,但敷料中的芦荟成分可加快伤口的愈合[41.2.2静电纺丝法采用静电纺丝技术制备水凝胶纤维,可以得到直径可低至几十纳米超细纤维,因此具有很高的比表面积, 使其在水中溶胀快,吸液量大,同时得到的纳米纤维膜具有较好的孔隙结构,可以透湿透气.这样的结构和功能特点使其非常适合于制备医用敷料,所以近年来人们开始采用静电纺丝的方法制备纳米纤维敷料[51. 用静电纺丝的方法制备纳米纤维要求水凝胶的材料能溶于一定的溶剂,形成均匀的溶液,并可以进行静电纺丝,而且要制得的纳米纤维在水中应有一定的溶胀性.据目前的文献报道,能制成纳米纤维水凝胶的材料主要有:壳聚糖及其衍生物,纤维素,明胶,透明质酸等.MilenaIgnatova等人将壳聚糖和季胺化的壳聚糖分别与聚乳酸混合,然后静电纺丝,制得壳聚糖一聚乳酸和季胺化壳聚糖一聚乳酸纳米纤维,并用戊二醛蒸汽对纳米纤维组成的无纺毡进行交联,形成的水凝胶在水中溶胀度达170%,纤维毡对大肠杆菌,金黄色和葡萄球菌具有较强的抑菌作用,因此可以用来制备医用敷料嘲. Chong等人将PCL与明胶的共混,然后利用静电纺丝将共混物放到3M公司生产的Tegadem聚氨酯敷料上面,形成一层具有孔隙结构的三维支架层,这种敷料应用于创面上时可促进纤维原细胞的迁移和繁殖,加快伤口处真皮层的愈合同.2.3共混法共混法是比较简捷的方法,可以产生物理交联效果,在共混过程中产生相分离,制成的水凝胶可用作医用敷料,可促进生长因子的产生,加快伤口愈合. 将海藻酸钠与羧甲基壳聚糖共混后可以制成水凝胶膜,羧甲基壳聚糖中的一NH与海藻酸钠中的一COO一的强静电作用,使共混制得的水凝胶膜在湿的状态下具有较好的强度,优于单一的海藻酸水凝胶膜田. 2.4接枝共聚接技共聚指大分子链上通过化学键结合适当的支链或功能性侧基的反应.通过共聚,可将两种性质不同的聚合物接枝在一起,形成性能特殊的接枝物. Siriporn 等人研究了以丙烯酸接枝甲壳素制备水凝胶于敷料.以重量比chitin:PAA=I:4时制成的水凝胶膜的溶胀度达30,60%,且具有较好的机械强度和细胞相容性,可以用作水凝胶敷料I91.2.5高能辐射交联电子辐射交联和射线交联是合成医用水凝胶的最常用方法,具有反应条件温和,不使用有毒交联剂等优点【.Lugao等人用PVP,PEG与琼脂共混,采用电子辐射交联制成水凝胶,并用于制备水凝胶敷料,该水凝胶通过吸水和脱水实验,发现水通过扩散作用进入到凝胶基质中,松散地结合在PVP网络中,这有助于了解敷料吸水和脱水的过程.水凝胶敷料中,不仅要考虑水凝胶对伤口渗出液的吸收,还要考虑水凝胶脱水的速率,防止水分的快速蒸发而导致伤口变干燥Il1】. 3水凝胶医用敷料的优点水凝胶医用敷料具有很好的亲水性,能吸收伤口的渗出液,而且不与伤口粘连,因此换药时不会破坏新生的肉芽或上皮组织.敷用时,医生将水凝胶敷料粘贴在患者的皮肤表面上,然后再用胶布或聚氨酯薄膜固定在伤口上.更换的时候,只要将水凝胶轻轻地揭掉,或用生理盐水冲洗掉.更换过程对创面的影响很小,这是各种医用纱布所无法比拟的.与其他常用的敷料相比,水凝胶不会在伤口上脱落纤维等杂质.在伤口愈合时,可以很方便地把水凝胶从伤口上冲洗去.在一些有皮肤组织损失的伤口,例如植皮,擦伤,烧伤等,适合使用片状水凝胶.在这些伤口上, 水凝胶片保护了伤口,避免伤口的脱水干燥.这也是水凝胶的最大优点——它能在伤口上产生一个湿润的环境,促使伤口上的坏死组织被酶分解,因而为伤口的愈合创造了一个良好的环境n1.总的来讲,与其他种类的功能性医用敷料相比,水凝胶敷料有如下一些优点: 有利于维持创面的湿润环境,使伤口不易结痴.避免了使用纱布时,纱布常常与伤口粘在一起,更换时易引起伤口开裂,不利于伤口愈合,给患者造成痛苦的状况:由于水凝胶是透明的,有利于患者和医生透过凝胶随时观察伤口的变化情况;可根据需要,将不同药物包埋在水凝胶内,药物可缓缓持续地释放到病变区,可以促进伤口的愈合或减轻伤口的疼痛;水凝胶不与伤口作用,伤口渗出物可通过凝胶排出:水凝胶较柔软,弹性好,机械性能好,透水透气,并且无毒副作用;轻纺工业与技2011年第4O卷第1期原料来源广,水凝胶由90%左右的水组成,成本低, 制备水凝胶的亲水性高分子,如海藻酸钠,果胶等价格也相对较低;生产的流程短,工艺简单方便【ll.临床上,水凝胶医用敷料已经被证明具有很好的疗效.4结语水凝胶医用敷料具有传统敷料所无可比拟的诸多优点,因此我们要加强具有自主产权,性能优良,价格低廉的水凝胶医用敷料的研究和开发,减少对国外进口敷料的依赖,这对减轻病人的经济负担和痛苦,对我国敷料工业的发展,都具有重要意义.参考文献【1】秦益民.功能性医用敷料【M】.北京:中国纺织出版社.2007.[2】傅杰,李世普.生物可降解材料在生物医学领域的应用【JJ.武汉工业大学.1999,21(2):l一4.[3】MatsudaK,SuzukiS,IsshikiN.Re—frezzedriedbi—layerartifieialskin[J].Biomaterials,1993,14:1030—1035.【4】ParkKyoungRan,NhoYoungChang.Preparation andcharacterizationbyradiationofHydrogelsofPVPand PVPcontainingAloeveraIJI.JournalofAppliedPolymerScienee,2004,91(3):1612—1618.[5]SeemaAgarwal,JoaehimH.Wendofff,AndreaseofelectrosPinningteehniqueforbiomedicalapplications,Polymer,2008,49:5603—5621.【6】MilenaIgnatova,NevenaManolova,NadyaMarko—va,eta1.Electrospunnon—wovenNanofibroushyoridmatsbasedonchitosanandPLAforwound-dressingapplicationsfJ1.Macromolecular,Bioscienee,2009,9(1):102—111.【7】ChongEJ,PhanTT,LimIJ.Evaluationofelectro—spunPCL/gelatinnanofibrousscaffolds[J].Forwoundhealing andlayereddermalreconstitution,2007,3(3):321—330.[8】ZhangLina,Guoji.Blendmembranesfromear-boxymethylatedehitosan/alginateinaqueoussolution[J]. JournalofAppliedPolymerSeience,2000,77:610—616.【9】SiripornTanodekaew,SomruethaiChannasanon.Xylan/Polyvinylalcoholblendanditsperformanceashydro-gel[J].JournalofAppliedPolymerScience,2006,100: 1914-l918.【10】ChmielewskiAG,Haji—saeidM.Radiationtech—nologies:Past,Presentandfuture[J].Radiationphysicsandchemistry,2004,71:16-20.【11】LugaoAB,MachadoLDB.Studyofwounddressingstructureandhydration/dehydrationProperities【J].RadiaionPhysicsChemistry,1998.52:319—322.(上接第65页)源匮乏,污染越来越严重的今天,必然会得到越来越多的关注.参考文献【1】柯勤飞,靳向煜.非织造学【M].上海:东华大学出版社,2004.29.[2]刘晓华.大麻纤维毡汽车内饰基材阻燃性能的研究[D】.合肥:安徽农业大学,2008.[3】徐磊,王瑞.麻非织造复合材料的开发和应用IJ]. 非织造布,2005,13(4):24. 【4】兰红艳,靳向煜.天然纤维非织造物增强复合材料概述『J]冲国麻业科学,2007,29(1):45—46. 【5】曲丽君.麻纤维在汽车装饰材料中的应用『J1.产业用纺织品,2002,143(20):37. 【6]兰红艳,靳向煜,张彤彤.麻类纤维在非织造领域的应用[J].中国麻业,2006,28(1):26. 【7】P1asticreinforcedwithnaturalfibersfortrimcompo—nents[J].HighPerformanceTextiles,1998,(12):6-7.[8]马建伟,毕克鲁,郭秉臣等.非织造布实用教程 [M].北京:中国纺织出版社,1994.【9]李清华,李铁忠等.大麻纤维在非织造布领域的应用初探【J].非织造布,2009,17(3):31.。
细菌纤维素水凝胶肿瘤标志物
细菌纤维素水凝胶肿瘤标志物哎呀，今天咱们聊一个既神秘又令人期待的话题——细菌纤维素水凝胶和肿瘤标志物。
看这标题，估计大家会觉得好像有点高深莫测，哎呀，别担心，今天我就给你讲讲这个听起来又复杂又陌生的东西。
其实吧，细菌纤维素水凝胶，听着有点像某种科幻电影里的超级武器，其实它也就是一种超厉害的材料，能从细菌身上“借”来的。
这个“借”法啊，真的是高大上！这些细菌一旦生长起来，就能分泌出一种非常特别的纤维，这种纤维跟咱们平时说的“纤维素”差不多，但它要比普通的纤维更坚固、更有弹性，甚至比人类手工制作的某些纤维还要好。
神奇吧？想象一下，细菌竟然能做这么厉害的事。
细菌纤维素水凝胶，这个名字呢，说白了，就是用细菌纤维素和水做成的一种超级有弹性的凝胶。
它不仅可以像海绵一样吸水，而且在很多医疗领域都能派上用场。
别小看它，这玩意儿可是有着超强的“修复”能力。
比方说，它能帮助伤口愈合，甚至在一些特殊情况下，还能用来作为人工皮肤呢！这玩意儿能这么厉害，咱们还真得好好琢磨琢磨它的秘密。
你说，细菌啊，能做这些事，简直让人大开眼界！可是，它的用途不仅仅止于此。
它的神奇之处，还在于能和一些特殊的肿瘤标志物“打交道”。
肿瘤标志物？你别急，这玩意儿跟咱们的健康息息相关。
就像一个人的身份证一样，肿瘤标志物是咱们身体里某些细胞或物质的“标志”。
这些标志物一旦在体内出现异常，很有可能就意味着咱们的身体出了问题，可能是某个地方长了肿瘤。
咋一听，有点吓人吧？不过，你要知道，早期发现肿瘤是非常关键的。
如果肿瘤标志物能被及时发现，咱们就能早点采取措施，给病魔下“封印”！你可能会问，这个细菌纤维素水凝胶和肿瘤标志物有什么关系？好问题！其实啊，这两者结合起来，可是能大大提高癌症早期检测的准确性和效率。
怎么做到的呢？咱们的细菌纤维素水凝胶，可以通过特殊的方式，吸附到体内的肿瘤标志物上。
你想啊，细菌纤维素就像个大扫帚，能把体内的肿瘤标志物扫过来。
只要这些肿瘤标志物进入了水凝胶，它就能在检测时被轻松识别出来。
水凝胶简介
水凝胶简介水凝胶就是一种具有亲水性的三维网状交联结构的高分子网络体系。
水凝胶性质柔软,能保持一定的形状,能吸收大量的水,具有良好的生物相容性与生物降解性。
自从20世纪50年代由Wichterle等首次报道后,就被广泛地应用于组织工程、药物输送、3D细胞培养等医药学领域。
[1]水凝胶根据交联方式不同,分为物理交联水凝胶与化学交联水凝胶。
物理凝胶就是指通过静电力、氢键、疏水相互作用等分子间作用力交联形成的水凝胶。
这种水凝胶力学强度低,温度升高会转变成溶胶。
化学交联水凝胶就是指通过共价键将聚合物交联成网络的凝胶。
其中,共价键通过“点击”反应生成,比如硫醇-烯/炔加成、硫醇-环氧反应、叠氮-炔环加成、席夫碱反应、环氧-胺反应、硫醇-二硫化物交换反应等。
Gao Lilong等在生理条件下将N,N-二甲基丙烯酰胺、甲基丙烯酸缩水甘油酯与聚低聚乙二醇巯基丁二酸通过巯基-环氧“点击”反应制备得到可注射水凝胶。
[2]与物理凝胶相比,化学交联水凝胶稳定性较好,力学性能优异。
根据来源不同,水凝胶又可分为天然水凝胶与合成水凝胶。
天然水凝胶包括琼脂、壳聚糖、胶原、明胶等,它们大都通过氢键交联形成。
合成水凝胶包括聚乙二醇、丙烯酸及其衍生物类(聚丙烯酸,聚甲基丙烯酸,聚丙烯酰胺,聚N-聚代丙烯酰胺等)。
与合成水凝胶相比,天然水凝胶生物相容性较好,环境敏感性好,价格低廉,但稳定性较差。
目前,有学者将天然高分子与合成高分子交联制备杂化水凝胶。
比如,Lei Wang等将壳聚糖与聚异丙基丙烯酰胺交联得到热敏性杂化水凝胶用于体内药物输送,并利用近红外光引发药物释放。
[3]水凝胶凭借良好的生物相容性广泛地应用于药物输送、组织再生等医药学领域。
药物可以通过化学接枝与包埋等方式实现负载。
负载药物的水凝胶通过移植或注射进入生物体内,然后在体内逐渐降解实现药物的缓慢释放。
为了更好地实现药物的输送与释放,智能水凝胶应运而生,所谓智能水凝胶,就是指能够对外界环境的变化,比如pH、温度等做出反应的水凝胶,从而实现药物的可控释放。
水凝胶的简介
结论
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磁性水凝胶在 药物载体靶向 释药研究领域 有望能进一步 发展，并广泛 应用
磁性水凝胶在 处理污水重金 属、有机染料 等上有优良的 吸附回收性
磁性水凝胶还 存在磁性强度 控制上的问题 有待提高。
参考文献
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开发多功能水凝胶伤口敷料方面取得新进展
开发多功能水凝胶伤口敷料方面取得新进展皮肤损伤是人体最为常见的损伤之一，而不合理的治疗方案常会危害人体健康，例如引发细菌感染，组织脱水，甚至更为严重的二次创伤。
因此，设计可以加快伤口封闭、促进伤口愈合的新型伤口敷料在现代医学中具有重要的临床意义。
水凝胶医用敷料是近年来发展起来的一种新型的创伤敷料，但是目前常见的水凝胶敷料仍然存在缺乏固有抗菌性能从而引发伤口感染、机械性能较弱为病患带来不适感、粘合性能较弱无法贴合皮肤等一系列问题，在治疗效果和使用体验方面都限制其进一步应用。
近日，西安交通大学前沿院郭保林课题组合成的季胺化壳聚糖(QCS)与芳香醛基功能化的Pluronic? F127三嵌段共聚物(PF127-CHO)进行动态化学键交联，报道了同时具有快速自愈合、良好机械性能、高粘合力、抗菌性能的可注射水凝胶敷料。
该水凝胶的原位成胶和组织粘合性能可以快速的封闭任意形状的伤口、并与伤口轮廓粘合为其提供物理屏障并模拟皮肤的湿润环境，同时凝胶的止血性能和抗菌性能可以让伤口快速止血并防止伤口感染。
同时，基于动态席夫碱键和共聚物的胶术交联两种作用，水凝胶敷料被赋予与人体皮肤相似的模量，展示出易延展，易压缩的机械性能，极大降低传统敷料捆绑伤口而带来的不适感。
最后，负载活性药物姜黄素后的凝胶表现出抗氧化性与凝胶本身多种性能结合从而促进全皮层缺损伤口快速愈合。
因此，该水凝胶作为生物活性敷料在伤口愈合应用中具有巨大潜力。
以上研究结果以论文形式发表在国际知名期刊Biomaterials（影响因子8.806）上，西安交大前沿院硕士生屈锦和博士生赵鑫为本论文的共同第一作者，西安交大前沿院为本文的第一作者单位和通讯作者单位。
这是郭保林课题组在多功能水凝胶敷料领域继Nature Communications, 2018, 9:2784; Biomaterials, 2017, 122, 34 后的又一重要进展。
该项工作得到了国家自然科学基金面上项目（51673155），金属材料强度国家重点实验室（20182002）和中央高校基本科研专项资金基金的支持。
【doc】水凝胶医用敷料的研究概况
【doc】水凝胶医用敷料的研究概况水凝胶医用敷料的研究概况轻纺工业与技2011年第40卷第1期水凝胶医用敷料的研究概况陈向标(五邑大学纺织服装学院,广东江门529020) 【摘要】介绍水凝胶敷料在医疗卫生领域的应用,叙述了水凝胶医用敷料的制备原料,制备方法以及水凝胶医用敷料的诸多优点.【关键词】水凝胶;医用敷料;静电纺丝中图分类号:TQ342+.87,R318.08文献标识码:B文章编号:2095—0101(2011)0l 一0066—03水凝胶是功能高分子材料的一种,内部带有强烈的亲水基团,因而对水有特殊吸附作用,通过分子间交联,形成网状结构.吸水性凝胶材料吸水的特点不同于海绵,棉布等吸附材料,它可以吸收是自身质量成百上千倍的水,并与水牢固结合,然后膨胀形成水凝胶.这种凝胶中的水即使受到相当大的压力也很少被挤出.这一特殊功能使得吸水性高分子凝胶材料在被发现之后就得到了快速发展.水凝胶医用敷料是近年来发展起来的一种新型的创伤敷料.与传统的敷料相比,水凝胶能促进伤口更好地愈合,减轻患者的疼痛,它能改善创面的微环境,抑制细菌的生长.水凝胶特别适用于常见的体表创伤,如擦伤,划伤,褥疮等各种皮肤损伤.对于这些伤口,传统上医生一般用无菌纱布及外用抗生素处理.纱布易与皮肤伤口组织粘连,换药时常常破坏新生的上皮和肉芽组织,引起出血,这不但不利于伤口的愈合,而且使病人疼痛难忍.用水凝胶敷料敷贴在伤口上时,它不但不粘连伤口,不破坏新生组织,而且能杀死各种细菌,避免伤口感染f".1制备水凝胶的原料制备水凝胶一般采用高分子材料,包括天然高分子材料和合成高分子材料.天然高分子材料因其生物相容性较好而常被选用, 但是天然高分子也存在一些缺点:比如材料性能的重复性差,机械强度较差,而且结构与性能可调范围窄,致使收稿日期:2010—11-03作者简介:陈向标(1985.3一),男,广东省陆丰市人,在读研究生.研究方向:生物医用纺织品.其难以满足医学上的各种实际要求.合成高分子用来制备敷料用水凝胶具有诸多优点: 合成材料通过控制条件,其生产重复性好,可根据需要大量生产,通过简单的物理,化学改性,获得广泛的性能,以满足不同需要121.但合成高分子的生物相容性一般较差,可用来制备敷料用水凝胶的原料种类也有限. 因此研究利用天然高分子与合成高分子合成杂化高分子水凝胶引起人们更为广泛的重视,这种方法将两者的优点结合起来,以提高水凝胶的性能.既能保留人工合成高分子材料基质的力学强度,又能具有天然高分子材料的良好生物相容性.常用于制备敷料用水凝胶的聚合物原料如表1. 表1常用来制备敷料用水凝胶的聚合物材料类别聚合物天然高分子藉嚣概鼬'嗽衙艨,合成高分子詈篙卿峭.烷酮'聚天然一合成壳聚糖一聚乙二醇,壳聚糖一聚乙烯吡咯烷酮,胶原蛋复合高分子白一聚丙烯酸2水凝胶的制备方法水凝胶的合成主要分为物理方法和化学方法.物理方法主要有共混法,冻融法,纺丝法等.作用的机理主要是通过静电作用,氢键,链的缠结等物理交联作用形成凝胶.化学方法主要有:接枝共聚,高能辐射(如电子辐射,射线)交联等.作用的机理主要是由通过化学键交联形成三维网络聚合物.2.1冻融法主要是通过多次冷冻熔融循环使高分子在低温下 2011年第4O卷第1期轻纺工业与技67 结晶,这种结晶作用可促使聚合物内部形成微晶,其功能类似于物理凝胶网络交联点嘲.Park等人采用冻融法合成了PVA/PVP共聚物水凝胶以用于敷料,在合成过程中加入了芦荟成分,发现随着聚合物中芦荟含量的增加,凝胶的强度下降,但敷料中的芦荟成分可加快伤口的愈合[41.2.2静电纺丝法采用静电纺丝技术制备水凝胶纤维,可以得到直径可低至几十纳米超细纤维,因此具有很高的比表面积, 使其在水中溶胀快,吸液量大,同时得到的纳米纤维膜具有较好的孔隙结构,可以透湿透气.这样的结构和功能特点使其非常适合于制备医用敷料,所以近年来人们开始采用静电纺丝的方法制备纳米纤维敷料[51. 用静电纺丝的方法制备纳米纤维要求水凝胶的材料能溶于一定的溶剂,形成均匀的溶液,并可以进行静电纺丝,而且要制得的纳米纤维在水中应有一定的溶胀性.据目前的文献报道,能制成纳米纤维水凝胶的材料主要有:壳聚糖及其衍生物,纤维素,明胶,透明质酸等.MilenaIgnatova等人将壳聚糖和季胺化的壳聚糖分别与聚乳酸混合,然后静电纺丝,制得壳聚糖一聚乳酸和季胺化壳聚糖一聚乳酸纳米纤维,并用戊二醛蒸汽对纳米纤维组成的无纺毡进行交联,形成的水凝胶在水中溶胀度达170%,纤维毡对大肠杆菌,金黄色和葡萄球菌具有较强的抑菌作用,因此可以用来制备医用敷料嘲. Chong等人将PCL与明胶的共混,然后利用静电纺丝将共混物放到3M公司生产的Tegadem聚氨酯敷料上面,形成一层具有孔隙结构的三维支架层,这种敷料应用于创面上时可促进纤维原细胞的迁移和繁殖,加快伤口处真皮层的愈合同.2.3共混法共混法是比较简捷的方法,可以产生物理交联效果,在共混过程中产生相分离,制成的水凝胶可用作医用敷料,可促进生长因子的产生,加快伤口愈合. 将海藻酸钠与羧甲基壳聚糖共混后可以制成水凝胶膜,羧甲基壳聚糖中的一NH与海藻酸钠中的一COO一的强静电作用,使共混制得的水凝胶膜在湿的状态下具有较好的强度,优于单一的海藻酸水凝胶膜田. 2.4接枝共聚接技共聚指大分子链上通过化学键结合适当的支链或功能性侧基的反应.通过共聚,可将两种性质不同的聚合物接枝在一起,形成性能特殊的接枝物. Siriporn 等人研究了以丙烯酸接枝甲壳素制备水凝胶于敷料.以重量比chitin:PAA=I:4时制成的水凝胶膜的溶胀度达30,60%,且具有较好的机械强度和细胞相容性,可以用作水凝胶敷料I91.2.5高能辐射交联电子辐射交联和射线交联是合成医用水凝胶的最常用方法,具有反应条件温和,不使用有毒交联剂等优点【.Lugao等人用PVP,PEG与琼脂共混,采用电子辐射交联制成水凝胶,并用于制备水凝胶敷料,该水凝胶通过吸水和脱水实验,发现水通过扩散作用进入到凝胶基质中,松散地结合在PVP网络中,这有助于了解敷料吸水和脱水的过程.水凝胶敷料中,不仅要考虑水凝胶对伤口渗出液的吸收,还要考虑水凝胶脱水的速率,防止水分的快速蒸发而导致伤口变干燥Il1】. 3水凝胶医用敷料的优点水凝胶医用敷料具有很好的亲水性,能吸收伤口的渗出液,而且不与伤口粘连,因此换药时不会破坏新生的肉芽或上皮组织.敷用时,医生将水凝胶敷料粘贴在患者的皮肤表面上,然后再用胶布或聚氨酯薄膜固定在伤口上.更换的时候,只要将水凝胶轻轻地揭掉,或用生理盐水冲洗掉.更换过程对创面的影响很小,这是各种医用纱布所无法比拟的.与其他常用的敷料相比,水凝胶不会在伤口上脱落纤维等杂质.在伤口愈合时,可以很方便地把水凝胶从伤口上冲洗去.在一些有皮肤组织损失的伤口,例如植皮,擦伤,烧伤等,适合使用片状水凝胶.在这些伤口上, 水凝胶片保护了伤口,避免伤口的脱水干燥.这也是水凝胶的最大优点——它能在伤口上产生一个湿润的环境,促使伤口上的坏死组织被酶分解,因而为伤口的愈合创造了一个良好的环境n1.总的来讲,与其他种类的功能性医用敷料相比,水凝胶敷料有如下一些优点: 有利于维持创面的湿润环境,使伤口不易结痴.避免了使用纱布时,纱布常常与伤口粘在一起,更换时易引起伤口开裂,不利于伤口愈合,给患者造成痛苦的状况:由于水凝胶是透明的,有利于患者和医生透过凝胶随时观察伤口的变化情况;可根据需要,将不同药物包埋在水凝胶内,药物可缓缓持续地释放到病变区,可以促进伤口的愈合或减轻伤口的疼痛;水凝胶不与伤口作用,伤口渗出物可通过凝胶排出:水凝胶较柔软,弹性好,机械性能好,透水透气,并且无毒副作用;轻纺工业与技2011年第4O卷第1期原料来源广,水凝胶由90%左右的水组成,成本低, 制备水凝胶的亲水性高分子,如海藻酸钠,果胶等价格也相对较低;生产的流程短,工艺简单方便【ll.临床上,水凝胶医用敷料已经被证明具有很好的疗效.4结语水凝胶医用敷料具有传统敷料所无可比拟的诸多优点,因此我们要加强具有自主产权,性能优良,价格低廉的水凝胶医用敷料的研究和开发,减少对国外进口敷料的依赖,这对减轻病人的经济负担和痛苦,对我国敷料工业的发展,都具有重要意义.参考文献【1】秦益民.功能性医用敷料【M】.北京:中国纺织出版社.2007.[2】傅杰,李世普.生物可降解材料在生物医学领域的应用【JJ.武汉工业大学.1999,21(2):l一4.[3】MatsudaK,SuzukiS,IsshikiN.Re—frezzedriedbi—layerartifieialskin[J].Biomaterials,1993,14:1030—1035.【4】ParkKyoungRan,NhoYoungChang.Preparation andcharacterizationbyradiationofHydrogelsofPVPand PVPcontainingAloeveraIJI.JournalofAppliedPolymerScienee,2004,91(3):1612—1618.[5]SeemaAgarwal,JoaehimH.Wendofff,AndreaseofelectrosPinningteehniqueforbiomedicalapplications,Polymer,2008,49:5603—5621.【6】MilenaIgnatova,NevenaManolova,NadyaMarko—va,eta1.Electrospunnon—wovenNanofibroushyoridmatsbasedonchitosanandPLAforwound-dressingapplicationsfJ1.Macromolecular,Bioscienee,2009,9(1):102—111.【7】ChongEJ,PhanTT,LimIJ.Evaluationofelectro—spunPCL/gelatinnanofibrousscaffolds[J].Forwoundhealing andlayereddermalreconstitution,2007,3(3):321—330.[8】ZhangLina,Guoji.Blendmembranesfromear-boxymethylatedehitosan/alginateinaqueoussolution[J]. JournalofAppliedPolymerSeience,2000,77:610—616.【9】SiripornTanodekaew,SomruethaiChannasanon.Xylan/Polyvinylalcoholblendanditsperformanceashydro-gel[J].JournalofAppliedPolymerScience,2006,100: 1914-l918.【10】ChmielewskiAG,Haji—saeidM.Radiationtech—nologies:Past,Presentandfuture[J].Radiationphysicsandchemistry,2004,71:16-20.【11】LugaoAB,MachadoLDB.Studyofwounddressingstructureandhydration/dehydrationProperities【J].RadiaionPhysicsChemistry,1998.52:319—322.(上接第65页)源匮乏,污染越来越严重的今天,必然会得到越来越多的关注.参考文献【1】柯勤飞,靳向煜.非织造学【M].上海:东华大学出版社,2004.29.[2]刘晓华.大麻纤维毡汽车内饰基材阻燃性能的研究[D】.合肥:安徽农业大学,2008.[3】徐磊,王瑞.麻非织造复合材料的开发和应用IJ]. 非织造布,2005,13(4):24. 【4】兰红艳,靳向煜.天然纤维非织造物增强复合材料概述『J]冲国麻业科学,2007,29(1):45—46. 【5】曲丽君.麻纤维在汽车装饰材料中的应用『J1.产业用纺织品,2002,143(20):37. 【6]兰红艳,靳向煜,张彤彤.麻类纤维在非织造领域的应用[J].中国麻业,2006,28(1):26. 【7】P1asticreinforcedwithnaturalfibersfortrimcompo—nents[J].HighPerformanceTextiles,1998,(12):6-7.[8]马建伟,毕克鲁,郭秉臣等.非织造布实用教程 [M].北京:中国纺织出版社,1994.【9]李清华,李铁忠等.大麻纤维在非织造布领域的应用初探【J].非织造布,2009,17(3):31.。
科学家新研发“水凝胶”材质纤维材料或可用来止痛
科学家新研发“水凝胶”材质纤维材料或可用来止痛科学家们有更好的方法来“照亮”全身的神经细胞吗？当研究人员Xinyue Liu和Siyuan Rao第一次在麻省理工学院开始合作时，他们认真研究了这个问题。
光遗传学是一个跨学科的科学分支，在该分支中，细胞被基因改变为光敏细胞，从而有可能抑制或激发细胞，并通过应用彩色光来研究其功能。
通常，到达目标细胞的光传输线是由在大脑中静止时工作良好的材料制成的。
然而，如果它们被植入试验动物体内的其他地方，它们可能会破坏、损伤组织或影响行为，从而难以研究外周神经系统，尤其是疼痛。
“This flexible fiber expands the toolbox of approaches we have.”—ROB BONIN, UNIVERSITY OF TORONTO现在，Liu、Rao和同事们开发了一种柔软、灵活、耐用的光纤，使用这种新材料后，水凝胶将光遗传学光信号从大脑或脊椎传递出去。
该细丝由两种不同折射性能的水凝胶的内芯和外包层组成，但纤维直径只有约一毫米。
研究人员在10月19日发表在《自然方法》杂志上的一篇论文中描述了这种光纤及其在模型小鼠中的各种测试方法。
这项工作为光遗传学、外周神经系统研究以及未来可能的转化医学（包括疼痛、慢性疼痛和神经疾病的治疗）增添了另一项技术和一点灵活性。
多伦多大学疼痛研究员Rob Bonin没有参与这项研究，他说：“这种柔性纤维扩展了我们用于外周光遗传学工作的方法工具箱。
”他指出，灵活性和耐用性是新方法的两大优势。
广义上讲，水凝胶是聚合物和水的软网络，如豆腐或果冻。
“我们的身体也是由水凝胶组成的。
除了骨骼和牙齿，我们的肌肉和其他器官实际上都是水凝胶，”现就职于密歇根州立大学的材料科学家Liu说。
该纤维使用聚乙烯醇水凝胶，因其在重复机械应力下的光学性能和耐用性而被选中。
软材料的研究是在考虑到外周神经系统的光遗传学疼痛研究的情况下开始的。
水凝胶 心肌 临床 biomaterials -回复
水凝胶心肌临床biomaterials -回复在医学领域中，生物材料在诊断、治疗和修复方面起着至关重要的作用。
其中，水凝胶作为一种多功能的生物材料，具有出色的生物相容性和生物活性，被广泛应用于心肌临床治疗领域。
本文将介绍水凝胶在心肌临床应用中的作用、制备技术及其对心肌修复的效果。
首先，我们来了解什么是水凝胶。
水凝胶是一种高度水合的凝胶材料，通常由水和聚合物网络组成。
其特点是能够吸附大量水分，同时保持其形状稳定。
这种独特的结构使得水凝胶在渗透性、生物相容性和生物降解性方面表现出优异的性能。
因此，水凝胶在心肌临床应用中具有广阔的前景。
水凝胶在心肌临床应用中的作用包括：支持组织和细胞生长、缓解心肌纤维化、调控心脏功能等。
首先，其三维结构可以模拟心肌组织的特性，为心肌细胞提供良好的支撑，并促进组织生长与修复。
其次，水凝胶具有良好的水分保持能力，可以提高心肌细胞的存活率，并减少炎症反应。
同时，水凝胶还能够释放生物活性物质，如生长因子、细胞因子等，促进心肌再生和修复。
因此，水凝胶在心肌临床应用中具有广泛的潜力。
接下来，我们将介绍水凝胶的制备技术。
水凝胶的制备主要有自由基聚合法、溶液聚合法、电化学方法等。
其中，自由基聚合法是最常用的制备方法之一。
在这种方法中，首先需要选择合适的聚合物，如明胶、聚乙二醇、聚乳酸等。
然后，在聚合物溶液中加入交联剂，如二烯丙基化四氢呋喃（TTBIF）等。
最后，通过加热、辐照或化学反应等方式进行交联，形成具有三维结构的水凝胶。
此外，溶液聚合法和电化学方法也具有一定的应用潜力，可以根据具体需要选择适合的制备方法。
最后，让我们来看一下水凝胶在心肌临床应用中的效果。
目前，水凝胶已经在心肌修复和康复中取得了一些令人鼓舞的结果。
例如，研究表明，将水凝胶植入心肌梗死部位可以促进心肌细胞的再生和血管生成，从而改善心肌功能。
此外，水凝胶还可以用于修复心肌缺损和血管病变，提高心肌组织的弹性和功能。
然而，目前水凝胶在心肌临床应用中还存在一些挑战，如长期稳定性、降解产物对机体的影响等。
水凝胶nature文章
水凝胶nature文章水凝胶是一种特殊的材料，它具有许多有趣的性质和潜在的应用。
以下是一篇关于水凝胶的Nature文章，希望能够帮助到您。
题目：生物材料的增强剂：高强度、可拉伸的水凝胶摘要：水凝胶是一种广泛应用于生物医学、工程和环境科学领域的材料，但由于其力学性能的限制，其应用受到了一定的限制。
本文报道了一种高强度、可拉伸的水凝胶，该水凝胶通过利用长链聚合物和具有可逆物理性质的交联聚合物制备而成。
这种水凝胶的力学性能得到了显著提高，其拉伸能力可以超过原长的几倍，而且其断裂能量也大大增加。
这种水凝胶在生物材料、可穿戴设备等领域具有广阔的应用前景。
一、引言水凝胶是一种特殊的材料，它能够吸收大量的水分而不会溶解，因此被广泛应用于许多领域。
然而，传统水凝胶的力学性能较差，限制了其应用范围。
为了克服这一限制，研究者们一直在探索制备高强度、可拉伸的水凝胶的方法。
本文报道了一种利用长链聚合物和具有可逆物理性质的交联聚合物制备的水凝胶，其力学性能得到了显著提高。
二、水凝胶的制备水凝胶的制备通常是通过将聚合物溶液混合并添加交联剂来实现的。
然而，传统的水凝胶制备方法通常只使用短链聚合物和不可逆的化学交联剂，导致水凝胶的力学性能较差。
为了制备高强度、可拉伸的水凝胶，研究者们将长链聚合物和具有可逆物理性质的交联聚合物结合使用。
这种制备方法可以产生一种具有高度交联的网络结构的水凝胶，其力学性能得到了显著提高。
三、水凝胶的力学性能与传统水凝胶相比，这种新型水凝胶的力学性能得到了显著提高。
其拉伸能力可以超过原长的几倍，而且其断裂能量也大大增加。
这种水凝胶的优异力学性能归功于其独特的网络结构和交联机制。
此外，这种水凝胶还具有良好的自修复能力和响应性质，使其在各种领域中具有广泛的应用前景。
四、水凝胶的应用前景由于这种新型水凝胶具有优异的力学性能和良好的生物相容性，因此它在许多领域中都具有广泛的应用前景。
例如，它可以被用作生物材料的增强剂，以提高材料的力学性能和耐用性。
水凝胶相变材料
水凝胶相变材料水凝胶相变材料可是个很有趣又非常实用的东西呢。
咱们先来说说水凝胶吧。
水凝胶啊，就像是一种超级能吸水的“海绵”，不过它比普通海绵可神奇多了。
它是由高分子聚合物交联形成的三维网络结构，这个网络结构就像一个小房子一样，里面可以容纳很多的水。
水凝胶有个特别的地方，就是它的亲水性非常强，这就使得它能够大量地吸收水分并且还能保持一定的形状。
比如说，有些水凝胶可以吸收自身重量几十倍甚至上百倍的水，你能想象到这种强大的吸水能力吗？在日常生活中，像一些婴儿的尿不湿里就用到了水凝胶，宝宝尿了之后，水凝胶就把尿液吸收起来，让宝宝的小屁屁保持干爽。
再来说说相变材料。
相变材料有一种特殊的本领，那就是在温度发生变化的时候，它能够改变自身的相态，比如从固态变成液态，或者从液态变成固态。
这种相态的变化伴随着热量的吸收或者释放。
就像是冰融化成水的时候需要吸收热量，水结冰的时候会释放热量一样。
相变材料利用这个原理，可以用来调节温度呢。
比如说在建筑领域，如果把相变材料用在墙壁里，白天温度升高的时候，它可以吸收热量，让室内不会变得太热；到了晚上温度降低的时候，它又可以释放热量，让室内保持温暖。
那当水凝胶和相变材料结合在一起的时候，就产生了水凝胶相变材料。
这种材料结合了两者的优点。
一方面，水凝胶的网络结构可以为相变材料提供一个很好的支撑和容纳的环境。
另一方面，相变材料的相变特性又给了水凝胶更多的功能。
比如说在医疗领域，水凝胶相变材料就有很大的潜力。
想象一下，当病人受伤需要冷敷或者热敷的时候，如果有一种水凝胶相变材料做成的敷贴，它可以根据设定的温度变化，自动进行冷敷或者热敷的转换，既方便又能达到很好的治疗效果。
在农业方面，水凝胶相变材料也有用武之地。
在一些干旱地区，水分是非常宝贵的。
水凝胶相变材料可以用来储存水分，并且根据土壤温度的变化来调节水分的释放。
当土壤温度升高，作物需要更多水分的时候，它可以释放出储存的水分来滋润作物；当温度降低，作物对水分需求减少的时候，它又可以减少水分的释放，这样就可以更有效地利用水资源，提高农作物的产量。
水凝胶软骨修复原理
水凝胶软骨修复原理
《水凝胶软骨修复原理》
嘿，咱今天就来聊聊水凝胶软骨修复这档子事儿哈。
你知道吗，我有一次去看我爷爷，他年纪大了，关节不咋好。
我就看着他走路的时候一瘸一拐的，心里可难受了。
然后我就问医生这是咋回事呀，医生就说爷爷的软骨有点损伤啦。
这软骨就像是我们身体里的小零件，时间长了就会磨损。
这时候水凝胶就派上用场啦！水凝胶呢，就像是一种神奇的胶水，但它可不是普通的胶水哦。
它可以跑到软骨损伤的地方，然后把那里给填补起来，就好像给破了洞的衣服打个补丁一样。
而且呀，它还很柔软，能随着我们的关节活动而变形，可乖啦！
它是怎么做到的呢？原来水凝胶有很多小缝隙，就像一个个小口袋似的，能把营养物质啊啥的都装进去，然后慢慢地释放出来，给软骨提供养分，让软骨能慢慢地修复。
就好像我们给花浇水施肥，让花能茁壮成长一样。
我就想着呀，如果有了水凝胶，爷爷是不是就能走路不那么难受了呢。
真希望这种神奇的东西能快点发挥大作用，让像爷爷这样的人都能重新健步如飞呀！
总之呢，水凝胶软骨修复就是这么一个神奇又有趣的原理，就像一个小小的魔法，在我们身体里施展着它的魔力，让我们的软骨能重新变得健康有活力哟！
哎呀，我现在一想到爷爷，就觉得水凝胶真的太重要啦，希望它能快快帮助更多的人呢！这就是我对水凝胶软骨修复原理的一点小感受啦，嘿嘿。
水凝胶可将癌细胞还原为癌症干细胞
水凝胶可将癌细胞还原为癌症干细胞北海道大学开发的一种水凝胶（一种软物质）在24小时内成功地将6种不同类型的人类癌症的癌细胞还原为癌症干细胞。
这可能带来抗癌干细胞药物和个性化药物的开发进展。
北海道大学和国立癌症中心研究所的研究人员在《自然生物医学工程》杂志上报告说，一种创新的水凝胶--称为双网络(DN)凝胶--可以将分化的癌细胞迅速还原为癌症干细胞。
这种水凝胶可用于帮助开发新的癌症疗法和针对癌症干细胞的个性化药物。
癌症是发达国家的主要死因，全球每年有超过860万人死于癌症。
尽管治疗方法不断进步，但晚期癌症患者的5年生存率仍然很低。
其中一个原因是癌症组织中含有癌症干细胞，这些细胞对化疗和放疗有抵抗力。
这些细胞会以 "根"的形式隐藏起来，或者在体内循环，导致癌症复发。
"癌症干细胞是抗癌药物的主要靶点，但由于它们在癌症组织中存在的数量非常少，因此难以识别。
"北海道大学医学部的田中伸弥教授解释说。
"了解癌症干细胞的分子机制对于开发更好的癌症治疗方法至关重要。
"癌症干细胞需要一个非常特殊的微环境。
在这项研究中，研究小组调查了他们的DN凝胶是否可以重新创造合适的条件来诱导癌症干细胞。
DN凝胶由两种化学物质组成的网络，并加入了大量的水，使其具有类似生物组织的软、湿特性。
在研究中，DN凝胶在短短24小时内就将6种不同的人类癌症细胞系--脑癌、子宫癌、肺癌、结肠癌、膀胱癌和肉瘤的分化癌细胞迅速重编程为癌症干细胞。
癌细胞被放置在DN凝胶上后，它们开始形成球形结构，并产生已知是癌症干细胞标记的特定分子，如SOX2和Oct3/4，又名山中因子，它以诺贝尔奖得主的名字命名，表明它们已经被重新编程。
研究人员还发现了一些参与癌细胞重编程的分子机制。
他们发现，钙通道受体和蛋白骨素是诱导癌症干细胞的关键。
他们还发现，来自患者的脑癌细胞在DN凝胶上培养后，产生了名为血小板衍生生长因子受体的受体。
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水凝胶，又一篇Biomaterials！
烧伤创面是最具破坏性的皮肤创伤之一，每年导致超过一百万人的死亡。
烧伤创面大、且不规则烧伤创口的患者愈合较为缓慢。
动态烧伤伤口由于其高频运动而对水凝胶敷料有着特殊要求。
为了研究研究动态烧伤创面，西北大学范代娣、Shihong Shen、Yang Yuan等人设计了一种由席夫碱和邻苯二酚-Fe3 螯合键制备的新型双交联水凝胶。
本文要点：1）水凝胶独特的双交联结构，使其具有较好的理化性能和增强了凝胶的药效。
凝胶化时间（52±2s）、机械性能（535kpa/G'）、粘接强度（19.3kPa）和较好的自愈性等物理化学性能的增强，使水凝胶更适合于动态创面。
该水凝胶具有良好的形状适应性（97.1±1.3%的恢复率），适合于形状不规则的创面。
2）水凝胶在创面愈合过程中不仅具有生物降解性，而且具有优良的固有抗菌活性（100%的杀灭率）和止血性能。
结果表明，水凝胶能使烧伤创面愈合时间缩短到13天，促进皮肤结构和功能的重建。
这种双交联的多功能水凝胶作为动态烧伤创面敷料是有希望的候选材料。
参考文献：Yang Yuan, et al., A physicochemical double cross-linked multifunctional hydrogel for dynamic burn wound healing: shape adaptability, injectable self-healing property and enhanced adhesion, Biomaterials 2021./10.1016/j.biomaterials.2021.120838。