Meltable Dextran Esters As Biocompatible and Functional Coating Materials

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  • Published: July 08, 2011

    r 2011 American Chemical Society 3107 | Biomacromolecules 2011, 12, 31073113


    Meltable Dextran Esters As Biocompatible and FunctionalCoating MaterialsTim Liebert, Jana Wotschadlo, Peggy Laudeley, and Thomas Heinze*

    Institute of Organic Chemistry and Macromolecular Chemistry, Center of Excellence for Polysaccharide Research, Friedrich SchillerUniversity of Jena, Humboldtstr. 10, 07743 Jena, Germany

    bS Supporting Information


    Hybrid materials consisting of a scaffold and a biocompatiblecoating are in the focus of medical research because long-termimplantation of synthetic polymers or metallic compounds suchas stents or joints might provide a chronic inflammatory stimulus.This may lead to medial atrophy and may cause enhancedthrombotic response.1,2 Moreover, infection is a severe problemduring implantation.3 Biocompatible coating can overcome thisproblem. In addition, modern coatings can act as reservoirs andthereby as controlled release systems for bioactive substancessuch as antibiotics or growth factors imparting defined biologicalactivity to implants.4,5 Different polymeric coatings are used suchas poly(D,L-lactide) (PDLLA) as coating of titanium implantsthat serves as a local drug delivery system for gentamicin.6

    Polysaccharides and their derivatives are well suited for suchapplications because of their biocompatibility and their hightendency toward the formation of defined supramoleculararchitectures.79 Starting materials are today preferably chitosan,alginate, hyaluronic acid or carboxymethylated polysaccharides,most commonly carboxymethyl dextran.10 The polymers areusually applied as hydrogels. A major problem of these water-soluble or swellable hydrophilic materials is the proper fixation tothe carrier and undefined swelling. Symplex formation or acovalent cross-linking may be exploited to overcome suchshortcomings.1114 Nevertheless, these are irreversible processesand the cross-linking is usually combined with the use of toxicreagents limiting or avoiding the application of the resultingmaterial in the medical field.

    A new strategy could be the use of meltable coatings based onpolysaccharides. In this regard fatty acid esters of polysaccharides

    may be considered as promising substances15 but conventionalsynthesis of long chain fatty acid esters (LCE) of polysaccharidesinvolves the use of acid chlorides and bases such as pyridine ortriethylamine yielding derivatives with byproduct. This prohibitsbiomedical application and prevents proper melting of thesubstances. As can be seen in Figure 1, only dark brown meltsare obtained from such esters which form brittle and inhomoge-neous films upon cooling.

    In contrast, it has been shown that the esterification ofpolysaccharides with carboxylic acids after in situ activation is avery useful alternative for the preparation of very purederivatives.15,16 Even sensitive structures such as unsaturatedand heterocyclic acids can be bound to polysaccharides in a veryefficient and gentle manner leading to compounds withoutbyproduct. For the introduction of aliphatic ester moietiesiminium chlorides are well suitable. During the reaction mostlygaseous byproduct are formed and a simple aprotic, polar solvent(Figure 2) making this a proper reaction path for the manufac-ture of pure derivatives which should be applicable in thebiomedical field.

    Therefore, the synthesis of long chain fatty esters of dextranvia in situ activation of the carboxylic acids with iminium chloridewas studied to generate meltable and biocompatible coatingmaterials. The influence of the reaction conditions on the meltingbehavior, and their application for the preparation of homoge-neous, biocompatible and long-lasting films was investigated.

    Received: June 20, 2011Revised: July 6, 2011

    ABSTRACT: The conversion of dextran with in situ synthe-sized iminium chlorides of long chain carboxylic acids was usedto obtain pure and defined melting dextran esters in an efficientone-pot synthesis. The melting point of these esters can betailored by the degree of substitutions (DS), the molecularweight of the starting polymer, and the chain length of the estermoiety. The dextran esters give homogeneous and completelytransparent melts, which form stable films on a broad variety ofmaterials. Even complex geometries, such as implants, can beevenly coated by multiple melting steps. The films do notdisplay any inhomogeneity and have a very low surface roughness. Therefore, no unspecific protein binding is observed. Moreover,the dextran esters are biocompatible as demonstrated for the interaction with three types of cells namely human brain microvascularendothelial cell, primary human fibroblasts, and mouse myoblast cells.

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    In addition first results toward the surface characteristics and theinteraction of these surfaces with biological material such asproteins and cells will be presented.


    Materials. Dextran from Leuconostoc mesenteroides ssp. (1, Mw6000 g/mol, Fluka) was treated in vacuum at 105 C for 2 h prior to use.Oxalyl chloride,N,N-dimethylacetamide (DMAc),N,N-dimethylforma-mide (DMF), and the fatty acids were obtained from Fluka and wereused without further purification. Lithium chloride was supplied bySigma Aldrich and was treated in vacuum for 24 h at 100 C to guaranteethe absence of water.Dissolution of Dextran in DMAc/LiCl (2). A total of 1.0 g (6.2 mmol)

    of dried dextran (1), 1 g anhydrous LiCl, and 40 mL of DMAc wereheated to 100 C for about 30 min under stirring until completedissolution occurs. The solution became completely clear during coolingdown to room temperature under stirring.Preparation of Palmitic Acid Iminium Chloride (3; Typical Exam-

    ple). In a 100mL flask equipped with amagnetic stirrer, a thermometer, abubble counter, and a SUBA-SEAL septum 30 mL DMF were cooledwith a mixture of isopropanol and dry ice to20 C. At this temperature2.7 mL (31 mmol) oxalyl chloride were added very carefully. Gasformation and a white precipitate were observed. The reaction mixturewas kept at 20 C until the gas formation stopped. 7.9 g (31 mmol)palmitic acid was added to the mixture. After 20 min stirring undercooling the temperature was increased to 0 C. A clear solution of theacid iminium chloride is formed.

    Synthesis of Dextran Palmitate (E7; Typical Example). A solution ofthe iminium chloride (3) was carefully added to the dextran solution (2).This mixture was kept for 16 h at 60 C. After cooling to room tem-perature the product was precipitated by addition of 300mL isopropanol.The product was isolated by filtration and washed three times with50 mL isopropanol. After drying in vacuum at room temperature a puredextran palmitate (E7) was obtained. It is soluble in CHCl3, THF,toluene, and diethylether. The melting point is 46 C.

    Yield: 1.66 g (88.8%); DS (determined by 1H NMR afterperpropionylation): 2.7; FTIR (KBr; cm1): 3483 (OH), 2925, 2892(CH alkyl), 1742 (CdO ester), 1227 (COC ester); 13CNMR(DMSO-d6): (ppm) = 172.3 (CO), 100.9 (C-1), 95.8 (C-1),66.170.6 (C-2 to C-6), 34.1143.4 (alkyl C-atoms).

    Peracetylation of the Dextran Palmitate for 1H NMR Analysis(According to Ref 16). A mixture of 6 mL of pyridine, 6 mL of acetic acidanhydride, and 50mg 4-(dimethylamino)pyridine was added to 0.3 g dextranpalmitate (E7). After 24 h at 80 C, the reactionmixture was cooled to roomtemperature andprecipitated in50mLof ethanol. For purification the isolatedproduct was reprecipitated from chloroform in 50 mL of ethanol, filtered off,washed with ethanol, and dried in vacuum at room temperature.

    Yield: 0.31 g (86.1%); FTIR (KBr; cm1): no (OH), 2910, 2854(CH), 1758, 1737 (CdOester); 1H NMR (of the peracetylateddextran palmitate dissolved in CDCl3): (ppm) = 3.495.48 (HAGU),2.04 (CH3-acetate), 0.771.93, 2.122.24 (CH3 and CH2-palmitate).DSpalmitate = 2.7, DSacetyl = 0.3.

    Coating of Surfaces with the Meltable Dextran Esters. For thecoating of glass surfaces, the flat substrates were evenly covered with thesolid material and placed on a heating plate. Within a few minutes, thedextran ester didmelt and gave very uniform layers on the substrate. Afterannealing for 20min, the air bubbles disappeared. For objects with amorecomplex geometry, the coating was done by dipping the object in a melt.If necessary, a second heat treatment of the precoated material in a waterbath yields very homogeneous and even films.

    Cell Cultures. Different cell types were used for testing cell compat-ibility of the dextran ester coating in vitro, namely, endothelial cell lineHBMEC (human brain microvascular endothelial cell), primary humanfibroblasts, and mouse myoblast cells C2C12. Dextran ester coatedmicroscope slides were dipped into 96% ethanol and were flamedshortly. A total of 6 104 cells (primary human fibroblasts, C2C12)and 1 105 cells (HBMEC) per well (9.6 cm2) were grown on thecoated microscope slides in six-well plates (37 C in a humidifiedatmosphere of 5% CO2 in air) in phenol red-free DMEM or RPMI-1640supplemented with 10% heat inactivated fetal calf serum.

    Characterization of Actin Cytoskeleton. After growing for 3 days,slides with adherent cells were washed three times with phosphate

    Figure 1. Microscopic image of a dextran palmitate (degree of substitution = 1.7, synthesized according to the conventional esterification method withthe acid chloride and pyridine as a base) on glass with human fibroblasts after 2 days: (A) transmitted light microscopy image; (B) fluorescencemicroscopic image.

    Figure 2. Synthesis path for the preparation of dextran esters (in thisexample, a dextran palmitate) via iminium chloride.

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    buffered saline (PBS) and fixed in 4% neutral buffered paraformalde-hyde for 20 min. Subsequently, the cell membrane was permeabilized in0.1% Tween-20/PBS for 30 min. For visualization and microscopiccharacterization of cells, the cytoskeleton was fluorescently labeled withAlexa Fluor488 phalloidin (Invitrogen) for 90 min. The cell nucleus wasstained with 40,6-diamidino-2-phenylindole (DAPI, Vysis Inc.). Micro-scope slides were completely washed in PBS and prepared with Immu-Mount (Thermo Shandon) for fluorescence microscopy (Axiocam,Zeiss). All incubations were operated at room temperature.Protein Affinity to Dextran Esters. Dextran ester-coated glass slides

    were incubated for 24 h in a complete protein lysat solution of cellculture cells (breast cancer cell line MCF-7). After washing several timeswith PBS, staining for 15 min with a 0.1% coomassie brilliant bluesolution (5% acetic acid, 50% ethanol, 45% dest. water) and discolora-tion (10% acidic acid, 20% isopropanol, 80% dest. water) differences indye staining could be observed with a microscope.Measurements. FTIR spectra were recorded on a Nicolet Protege

    460 spectrometer with the KBr technique. KBr tablets were dried at100 C for 1 h to remove moisture prior to the measurement. NMRspectra were acquired on a Bruker AMX 250 spectrometer with 16 scansfor 1H NMR and 1500089000 scans for 13C NMR measurements(Bruker AMX 400, 50 mg sample/mL). 1H NMR spectra of the esterswere acquired in dimethyl sulfoxide (DMSO)-d6 after peracetylation ofthe unmodified hydroxyl groups.17,18 Elemental analyses were performedwith a CHNS 932 Analyzer (Leco). UVvis spectroscopy was carriedout with a Genesys 6 (Thermospectronic). AFM was conducted in thenoncontact mode with a DualScope C-21 (DME) and silicon nitride tips(60.0 N 3m

    1, 0.20 nN). Rheological characterizations of the melts werecarried out with a Haake MARS rheometer equipped with coneplategeometry (35 mm radius, cone angle 1). Differential scanning calorim-etry (DSC) measurements were performed with a Mettler Toledo DSC822e using a heating rate of 10 C/min in the range20 to 300 C afterdrying all the samples at 40 C for 24 h in vacuum (except samples E2andE4). All the fluorescence images were takenwith an Axioplan 2 imagingfluorescence microscope, transmitted light images with an Axiovert 25microscope and an AxioCam HRc (all from Zeiss). Images wereprocessed with an AxioVision 3.1 program (Zeiss). Objectives: Ph2Plan-NEOFLUAR 20/0.5 and Ph1 CP-ACHROMAT 10x/0.25.


    Iminium chlorides are simply formed by conversion of N,N-dimethylformamide (DMF) with a variety of chlorinating agentsincluding phosphoryl chloride, phosphorus trichloride or oxalyl

    chloride.11 In this study, oxalyl chloride was used. The formationof the iminium chloride and the conversion with the carboxylicacid were carried out as a simple one-pot-reaction, that is, DMFwas cooled to 20 C, oxalyl chloride was added very carefully,and after the gas formation has stopped, the carboxylic acid wasadded. The conversion occurred with quantitative yield at thistemperature. Esterification of the polysaccharide was simplyachieved by mixing the solution of the acid iminium chloridewith dextran dissolved in DMAc/LiCl. The purification of thedextran ester was rather easy because most of the products aregaseous and during the last step DMF is reformed making this avery efficient reaction path toward the preparation of highly puredextran esters (Figure 2).

    A summary of reaction conditions and results is given inTable 1. The DS values were determined by 1H NMR spectros-copy after peracetylation of the remaining hydroxyl groupsaccording to ref 16. The degree of substitution (DS) wascalculated by the following equation (DSLCE = 3 (7 IH,acetyl)/(3 IH,AGU).

    The esterification method is suitable for the synthesis of alltypes of aliphatic carboxylic acids (samples E1E10). Esterifica-tion succeeds with comparable efficiency for all acids applied. Arather good control of the DS values is possible via the amount ofreagent used. For the myristate even complete conversion of allOH moieties was observed. The esters prepared are whitesubstances, which are well soluble in DMSO, THF, acetone,toluene, or chloroform, depending on the DS values.

    No chlorine was determined by elemental analysis. In FTIRspectra (KBr) of the products, the typical absorption bands forthe polysaccharide backbone (3620, 2920, and 1140 cm1) andsignals for the carbonyl function of the ester moiety at17451760 cm1 were found. The representative 1H,1H COSYNMR spectrum (CDCl3) of a highly functionalized dextranpalmitate depicted in Figure 3 shows signals for the anhydroglu-cose unit (AGU) at = 3.45.5 ppm (H-1H-6) and for thealiphatic protons of the palmitoyl moiety at 0.82.3 ppm (H-7, 8).Assignment of the cross peaks gave no hints for side reactions orimpurities, which would lead to substructures such as deoxy-chloro functions. Elemental analysis confirmed the DS calculatedfrom the 1H NMR spectra.

    Further evidence for the purity of the dextran esters was gainedfrom 13C NMR spectra of the products. In a typical spectrum

    Table 1. Summary of ReactionConditions andProductCharacteristics of LongChainAliphatic Esters ofDextran (Mw 6000 g/mol)Synthesized via the Acid Iminium Chlorides

    reaction conditions product

    No. carboxylic acid (C-number) molar ratiob DSc solubility melting pointd (C)

    E1 lauric (12)- 1:3 1.3 DMSO, THF 65

    E2 lauric- 1:5 2.8 CHCl3, THF, acetone, toluene 25e

    E3 myristic (14)- 1:2 1.0 DMSO, THF 58

    E4 myristic- 1:5 3.0 CHCl3, THF, acetone, toluene 42

    E5 palmitic (16)- 1:2 1.0 DMSO, THF 59

    E6 palmitic- 1:3 1.7 DMSO, THF 53

    E7 palmitic- 1:5 2.7 CHCl3, THF, acetone, toluene 46

    E8a palmitic- 1:5 2.2 CHCl3, THF, acetone 61

    E9 stearic (18)- 1:3 1.6 DMSO, THF 71

    E10 stearic- 1:5 2.7 CHCl3, THF, acetone, toluene 53a Starting dextran had a Mw of 20000 g/mol.

    bMol anhydroglucose unit dextran/mol reagent. cDetermined by 1H NMR spectroscopy afterperacetylation. dDetermined with DSC measurements, last DSC transition. eWaxy material.

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    (Figure 4, spectrum of dextran palmitate with DS = 2.7) onlysignals for the ester moiety in the range 1236 ppm (aliphaticregion) and 172 ppm (carbonyl signal) and for the AGU(6698 ppm) were detected. Formation of a chlorodeoxy unitcan be excluded because there are no signals in the region4060 ppm.

    The dextran esters were characterized by means of thermo-gravimetry (TG) to evaluate their stability during heat treatmentfrom 25 to 600 C. The compounds were thermally stable up to230 C and showed partial degradation between 240 and 300 Cfollowed by an almost complete decomposition step as illustratedfor the dextran palmitate in Figure 5. Thus, the esters are wellsuitable for coating via a melting process.

    For the esters synthesized, DSC measurements were con-ducted. In the DSC experiments, numerous thermal transi-tions can be observed (see Supporting Information, Figure S3).

    According to Sealey,19 these thermal transitions in long chainesters of polysaccharides are caused by glass-to-rubber and rubber-to-melt transitions both of the waxy phase and the polysaccharidebackbone. The first transition can be attributed to the rearrange-ment of the long side chains because with increasing DS theserearrangements are more pronounced. The last endothermic peakwas assigned to be the rubber-to-melt transition of the polymer. Itcoincides with the visible clarification of the material duringthermal treatment as can be observed with a hot-stagemicroscope.Thus, themelting points determined byDSC, given in Table 1, arethis last thermal transition. Clarification temperatures in the rangeof 25 to 70 Cwere determined for the esters with thismethod andby means of a hot stage microscope. The data illustrate thatmelting depends on the ester function introduced, the DS and themolecular weight of the starting polymer. Nevertheless, the mostpronounced influence is the DS as displayed for the differentlaurates. Increase of the DS value from 1.3 to 2.8 resulted in adecrease of the clarification temperature of 40 C. Thus, themelting range can be easily adjusted with the DS.

    The esters synthesized via the iminium chloride method canbe molten into clear and transparent liquids (Figure 6) withoutany degradation or decomposition as observed by FTIR afterdifferent melting steps. No hints for degradation products or asplitting of the ester can be found. In contrast dextran estersprepared with the conventional methods give brown and in-homogeneous layers with cracks (see Figure 1).

    Dextran esters synthesized from a starting dextran with Mw6000 g/mol exhibit melt viscosities in the range 50 to 70 Pa 3 saccording to rheological measurements on the melts at 75 C.For a dextran laurate melt (E1; DS 1.3, Fp 65 C) a value of56 Pa 3 s was found at shear rates up to 20 s

    1. At higher shearrates, a non-Newtonian behavior is observed (see Figure S1,Supporting Information). Thus, the esters can be processed viacommonly used methods for low viscous polymer melts such as

    Figure 3. 1H,1H COSY NMR spectrum of a dextran palmitate (E7, degree of substitution = 2.7, in CDCl3).

    Figure 4. 13C NMR spectrum of a dextran palmitate (E7, degree ofsubstitution = 2.7, in CDCl3).

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    dip coating.20 After annealing the melts for 20 min and cooling toroom temperature, they give transparent and homogeneous filmswithout cracks or bubbles. For more complex geometries, dipcoating and multiple melting steps can be used for complete andeven coating, as shown for a nitrided titan implant in Figure 7.After coating, the whole implant is covered with the glossy surfaceof the dextran ester film.

    To investigate the surface morphology of such films on thesubmicrometer scale, AFM measurements were carried out. Forthis purpose a film was prepared by simply melting a dextranstearate (E10) at 65 C on a freshly cleaved mica surface,annealing and cooling the liquefied material to room tempera-ture. In AFM images a homogeneous layer of the dextran esterwas observed covering the complete mica surface (Figure 8).These layers usually have a surface roughness of less than 10 nm ifan area of 1 1 m is scanned. In all the experiments, no hints ofcracks or fissures were found even at high resolution.

    This low surface roughness should avoid unspecific proteinbinding. To study the unspecific protein affinity to dextran esterfilms, ester-coated glass slides were incubated for 24 h at roomtemperature in a protein mixture consisting of a complete celllysate from the cell line MCF-7. After washing several times withPBS, staining for 15 min with coomassie brilliant blue solutionand discoloration differences in dye staining could be observed(see Figure S2, Supporting Information). On the completelycoated glass slides no blue stainingwas visible, that is, no unspecific

    protein binding was detectable. Only on the cutting line of glassslides, where the films are not homogeneous, a light blue colorshows unspecific binding and therefore staining. Coomassiebrilliant blue solution was added to a solution of the cell lysateas positive control for the staining.

    The biocompatibility of the material was investigated bymeans of cell growth experiments on dextran esters with threedifferent cell types, namely, endothelial cell line HBMEC(human brain microvascular endothelial cell), primary humanfibroblasts and mouse myoblast cells C2C12. Dextran estercoated microscope slides were treated with ethanol and shortlyflamed to allow cell cultivation under sterile and non infectiousconditions. All incubations were operated at room temperature.After growing for 3 days, slides with adherent cells were washed

    Figure 5. Thermogram of a dextran palmitate (E7, degree of substitution = 2.7).

    Figure 6. Melting behavior of a dextran laurate (E2, degree of substitution = 2.8) during temperature increase to 50 C within 10 min (A: 25 C, B:45 C, C: 50 C).

    Figure 7. Nitrided titanium implant before (A) and after (B) coatingwith a dextran laurate (E2, degree of substitution = 2.8).

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    and fixed in 4% neutral buffered paraformaldehyde. Due to thetransparent character of dextran ester layers, cells can be visua-lized in transmitted light microscopy with a high contrast. For allcell types, an unhindered growth is observed (Figure 9).

    For detailed visualization and microscopic characterization ofcells, the cytoskeleton was fluorescently labeled with an irrever-sible and high affine marker for actin. The cell nucleus wasstained with a fluorescent dye that binds selectively to DNA. Theactin cytoskeleton of the cells in Figure 9 is colored green and fornavigation the nucleus is stained blue. This technique confirmsthat cells grow unhindered on the coating materials and form thetypical cell network. Apparently, no difference in growth on thecoating materials is visible compared to the glass as controlsurface. The typical spindle form of the fibroblasts with actinstrands is visible on both surfaces in Figure 9A. The sameobservation was made for the other cell types (Figure 9BE).Moreover, cell growth on a titan implant coated with a dextranpalmitate (E7) was investigated. In this case, primary osteoblastswere cultured with additionally 1% antibiotics. Obviously, the

    dextran ester coating on the implant has no influence on thegrowth rate (Figure 10). No incompatible substances were elutedunder cell culture condition. After 3 days the cell growth ondextran palmitate was as well compared to the growth on plasticsurface of the cell culture flask with fluorescence microscopy.Cells were attached to the coating material surface and show thetypical spindle form with extensions.

    For comparison, the same experiments were carried out onsupports coated with a conventionally prepared dextran palmi-tate, that is, synthesized with the acid chloride in the presence ofpyridine. As can be seen in Figure 1, the layer becomes brown andinhomogeneous during themelting process and almost no growthof cells is observed on this material. Consequently, it is shown thatthe new dextran esters synthesized via the iminium chlorides oflong chain aliphatic acids are biocompatible and do not influencecell growth and should be well suitable for the coating of cytotoxicsurfaces such as the binary Ti alloy Ti15Mo.21


    Themethod described is very efficient for the synthesis of purealiphatic dextran esters with adjustableDS values. The high product

    Figure 8. AFM image of a dextran stearate (E10, degree of substitution = 2.7) on mica.

    Figure 9. Different cell types on dextran palmitate (E7, degree ofsubstitution = 2.7) coated glass slides in fluorescent and transmitted lightmicroscopy: (A) primary human fibroblasts; (B, C) myoblast cellsC2C12; (D, E) HBMEC (human brain microvascular endothelial cell).The red dashed line in image A represents the border of glass slide andester coating (light blue shadow, dextran palmitate with primary humanfibroblasts).

    Figure 10. Osteoblasts grown on polyethylene support with dextranpalmitate (E7, degree of substitution = 2.7, image A) observed withtransmitted light microscopy and on a nitrided titan implant coated withdextran palmitate (image B) observed with fluorescent light microscopy.

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    quality is responsible for the defined melting behaviors. Thus, thematerial is well suitable for the coatings of a variety of materials. Itwas shown that the dextran esters are biocompatible in the sensethat they do not influence cell growth. The stability of the coatingon the support is still a matter of ongoing research. Preliminaryexperiments have shown that such dextran esters can also act asadhesive exhibiting a tensile strength between two glass slides in therange of 120 mN/mm2 (120 kPa). This value can certainly beincreased by a proper pretreatment of the surface.

    Coating with meltable dextran esters offers a wide variety ofapplications in the biomedical field because it has a number ofadvantages in comparison to conventional systems. The coatingcan be carried out without additional chemicals or equipment,and it can even be performed on site because it is a very easyprocess. An advantage of the resulting hybrid material is thereversibility of the process. Adjustment of the film thickness andthe size can be carried out in subsequent steps. Besides thebiocompatible modification of problematic surfaces, the coatingis able to act as matrix for various functional materials. Evenloading with biomolecules seems reasonable because the meltingpoint can be adjusted to a range where embedding of, forexample, proteins occurs without denaturation.


    bS Supporting Information. Rheological behavior of a dextranlaurate. Visualization of unspecific protein binding on surface coatingwith coomassie staining. DSC measurements on dextran palmi-tate. This material is available free of charge via the Internet at


    Corresponding Author*Tel.: +49 3641948270. Fax: +49 364148272. E-mail:


    The authors thankMatildeC. V. Nagel for the help concerningDSC measurements. The authors acknowledge the financialsupport of the Bundesministerium fur Wirtschaft und Techno-logie and the Arbeitsgemeinschaft industrieller Forschungsver-einigungen Otto von Guericke e.V. (ZIM Project VP2258001AK9). The majority of the data published in this paperis part of the patent: Liebert, T.; Wotschadlo, J; Heinze, T. DE 102008 003 271 A1 (09.07.2009).


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