Patent Application: US-49515306-A

Abstract:
hydrogels are described which have delayed swelling properties . a hydrogel is formed by reacting a hydrophilic monomer , a first crosslinker , and a second crosslinker . the first crosslinker defines the volume expansion of the hydrogel in an aqueous environment , and the second crosslinker , which is biodegradable , can modulate the swelling rate of the hydrogel in aqueous solution . in its dry state , the hydrogel is flexible and elastic . it can also be cut with a knife or scissors , or molded or shaped by hand . the ready shapeability of the xerogel by trimming or compression affords a superior hydrogel for medical applications .

Description:
the present invention entails synthesis of a new class of hydrogels that exhibit flexible and elastic properties in the dried state ( xerogels ). such hydrogels are able to be reshaped in the dried state , e . g ., by cutting or molding , and exhibit controlled swelling behavior in an aqueous environment . to overcome the limitations of the approaches described hereinabove , hydrogels have been designed and synthesized with degradable cross - linkers along with non - degradable cross - linkers , which permits delayed swelling with retention of hydrogel properties . novel hydrogels are prepared using hydrophilic polymers in the presence of chemical crosslinking agents . at least two types of crosslinking agents are incorporated into the hydrogels : ( 1 ) a first crosslinker determines the final degree of swelling in an aqueous solution ; and ( 2 ) a second crosslinker modulates swelling at a predetermined rate . the first crosslinker is not biodegradable and limits the volumetric expansion of hydrogel , which depends on the crosslinking density . the second crosslinker is biodegradable and can be provided as a biodegradable chemical moiety , monomer or oligomer . a biodegradable crosslinker and / or monomer function as a swelling / degradation controller ( sdc ), which exhibits different degradation rates depending on chemical structure . the degradation rate of sdcs plays a critical role in controlling the delay time before a hydrogel swells , e . g ., in excess of 30 days . numerous hydrophilic monomers , oligomers , and polymers are available with various crosslinkers to synthesize a hydrogel of the present invention , which exhibits controlled swelling kinetics . some of the synthetic routes of hydrogels made with different hydrophilic monomers , oligomers , polymers and crosslinkers are described herein . in general , the hydrogels are synthesized using hydrophilic vinyl monomers for the polymer backbone , conventional crosslinking agents , and sdcs . preferred hydrophilic monomers for this synthesis include , but not limited to , acrylic acid , acrylamide , n - vinyl - 2 - pyrrolidone , 2 - hydroxyethyl methacrylate , n - isopropylacrylamide , and n -( 2 - hydroxylpropyl ) methacryl amide . exemplary first crosslinkers include n , n ′- methylenebisacrylamide ( bis ), ethylene glycol dimethacrylate , and poly ( ethylene glycol ) di ( meth ) acrylates with different molecular weights in the range of 200 - 2 , 000 kda . additional examples of suitable monomers and crosslinkers are disclosed in u . s . pat . nos . 5 , 750 , 585 and 6 , 271 , 278 ( issued to park et al . ), and u . s . pat . no . 6 , 018 , 033 ( issued to chen et al . ), the disclosures of which are incorporated herein by reference . the chemical structures of some of the non - degradable monomers and crosslinkers that can be employed in the synthesis of a hydrogel of the present invention are shown in table 1 . different combinations of the monomers and crosslinkers listed in table 1 permit synthesis of various hydrogels having different chemical structures and , thus , different final degrees of volumetric expansion ( swelling ). an sdc of the present invention preferably has a polymerizable group at both or one end of the polymer chain and hydrolyzable ester groups in the chain backbone , such as oligomers of poly ( lactic acid ) ( pla ), poly ( glycolic acid ) ( pga ), poly ( lactic acid - co - glycolic acid ) ( plga ), and poly ( ε - caprolactone ) ( pcl ). see table 2 . such moieties exhibit a degradation behavior that depends upon its hydrophilicity , crystallinity , chemical composition , and molecular weight . various hydrophilic vinyl monomers can be used to prepare the hydrogel . a series of hydrogels with a broad range of physico - chemical properties can be prepared from many combinational choices of building blocks . a systematic alteration in the chemical composition and structure can lead to better control of physical properties of hydrogels . see table 3 . hydrophilic vinyl monomers . the chemical structure and composition of hydrogels can be modified or tailor - made to have desired properties in elasticity , swelling , mechanical strength , degradation , etc . thus , the choice of hydrophilic vinyl monomers for hydrogels is a primary factor in determining the hydrogel properties . representative hydrophilic monomers listed in table 3 can be used as building blocks to construct various kinds of hydrogels with diverse physical properties . however , each monomer may need different conditions for polymerization reaction due to its different reactivity . the hydrogels can also be synthesized using two or more monomers to produce hydrogels composed of copolymers which provide the desired physico - chemical properties . cross - linking agents . not only low molecular weight crosslinking agents but also macromolecules , such as proteins and polysaccharides , can be used as crosslinking agents . usually three kinds of crosslinking agents are used to make the hydrogels . a . bifunctional monomers . n , n ′- methylenebisacrylamide ( bis ) is a commonly used crosslinking agent for making hydrogels . b . peg -( di ) acrylates . poly ( ethylene glycol ) ( peg ) is a well - known hydrophilic polymer , which has been broadly used for biomedical application due to biocompatibility . bifunctionalized pegs such as peg - diacrylate can be used as a crosslinking agent and monofunctionalized peg such as peg - acrylate is useful for introducing grafted structure in hydrogels . this type of cross - linker provides flexibility and elasticity to xerogels . c . vinyl group - containing polysaccharides . various kinds of polysaccharides can be modified to have multi - functional vinyl groups that are available for polymerization and crosslinking reaction . for example , water - soluble hydroxyethyl starch ( he - starch ) can be modified with glycidyl methacrylate . he - starch solution is prepared by dissolving he - starch powder in pbs solution ( 10 % w / v , ph = 8 . 5 ). a predetermined amount of glycidyl methacrylate is added to the solution . the heterogeneous mixture solution is kept at 40 ° c . with stirring for 4 days . the resulting product is precipitated in cold acetone and dried in vacuo overnight . swelling / degradation controllers ( sdcs ). sdcs are biodegradable crosslinkers and monomers that can modulate , i . e ., regulate in a predetermined way , the swelling rate . the degradation rates of sdcs are dependent on their chemical compositions and structures , and may play an important role in controlling the delay time before hydrogels start swelling . a diverse class of hydrogels can be synthesized through different combinations of hydrophilic vinyl monomers , crosslinkers , and sdcs . for radical polymerization , benzoyl peroxide or 2 , 2 ′- azobisisobutyrylnitrile ( aibn ) is preferably used as an initiator . a typical synthetic procedure is shown in scheme i . in general , to make a hydrogel , hydrophilic vinyl monomer is dissolved in the solvent containing crosslinker , sdcs , and initiator . the mixture is stirred until the solution becomes clear and the reaction is maintained , e . g ., at 70 ° c . for 8 h . some particular examples of making flexible , elastic xerogels that use sdcs to firnish a delayed swelling property , are shown below , which illustrate but do not limit the invention . a two - neck flask was purged with dry nitrogen for 20 - 30 min . pcl diol ( 5 g ) was dissolved in 30 ml of anhydrous benzene and 0 . 81 ml of acryloyl chloride ( or methacryloyl chloride ) was dissolved in 20 ml of anhydrous benzene , followed by addition of 1 . 40 ml of triethylamine . after 20 - 30 min , the nitrogen purge was stopped and the reaction solution was stirred at 80 ° c . for 3 h . to remove triethylamine hydrochloride , a side product from the reaction , the reaction solution was filtered . finally the filtrate was precipitated in an excess of n - hexane and the precipitated product was collected and dried in a vacuum oven for 24 h . the overall reaction is depicted in scheme 1 . a polymerizable plga unit was synthesized by introducing a vinyl group at the chain end of plga , e . g ., by reacting hydroxyl - terminated plga with acryloyl chloride , as shown in scheme 2 . one gram of hydroxy - terminated plga was dissolved in 10 ml of dichloromethane . acryloyl chloride ( 2 equiv . of [ oh ] in plga ) was slowly added and the mixture was stirred for 3 h at room temperature . the resulting solution was poured into the excess amount of cold diethyl ether , and the precipitate was filtered , followed by drying under vacuum for 2 days at room temperature . in addition to the sdcs listed in table 2 , copolymers with two or more different repeating units are useful to precisely control the swelling kinetics and other physical properties of the hydrogel . one example is peg - plga - peg triblock copolymer . incorporation of peg , which has a low glass transition temperature (˜− 60 ° c . ), is expected to improve the softness of a xerogel , a dried hydrogel . the overall synthetic scheme for peg - plga - peg triblock copolymer as an sdc is shown in scheme 3 . one gram of carboxylic acid - terminated plga was dissolved in 10 ml of dichloromethane containing 1 , 3 - dicyclohexyl carbodiimide ( dcc , 1 . 2 equiv . of [ cooh ]) and 4 - dimethyl aminopyridine ( dmap , 1 . 2 equiv . of [ cooh ]). after adding peg ( 2 equiv . of [ cooh ]), the reaction mixture was stirred for 12 h at room temperature . the precipitated dicyclohexyl urea was filtered off , the solution was poured into cold diethyl ether , and the precipitates were filtered and washed with excess ethyl alcohol . after drying under vacuum at room temperature for 2 days , the peg - plga - peg terminated with hydroxyl end groups ( p — oh ) is obtained . p — oh was then dissolved in dichloromethane , to which acryloyl chloride ( 2 equiv . of [ oh ] in p — oh ) was slowly added . the reaction mixture is stirred for 3 h at room temperature , and poured into cold diethyl ether . the precipitate was filtered , followed by drying under vacuum . pla - peg - pla is another example of an sdc of the invention . a suitable synthetic route is shown in scheme 4 . prior to the synthesis , peg was dried for one day at 80 ° c . under vacuum to remove any moisture . thereafter , appropriate amounts of peg and lactide were placed in a one - neck flask . after adding one drop of stannous octoate , the reaction mixture was heated to 150 ° c . and stirred for 15 h under n 2 atmosphere . the resulting mixture was poured into cold hexane , and the precipitates were filtered and dried for 2 days at room temperature under vacuum to obtain a white powder of pla - peg - pla terminated with hydroxyl end groups ( pl - oh ). pl - oh was then dissolved in dichloromethane and acryloyl chloride ( 2 equiv . of [ oh ] in p — oh ) was slowly added . the reaction mixture was stirred for 3 h at room temperature , and poured into cold diethyl ether . the precipitate was filtered , followed by drying under vacuum . a suitable synthetic route is shown in scheme 5 . peg ( 5 g ) was stirred at 150 ° c . for 3 h under vacuum to remove any moisture . the predetermined amounts of lactide and glycolide were added to the reaction flask and then the mixture was evacuated for 30 min . subsequently 0 . 2 ml of stannous octoate diluted with toluene was added and then the reaction mixture was heated up to 155 ° c . after the reaction for 8 h , the product was poured into cold hexane , and the precipitates were filtered and dried for 2 days at room temperature under vacuum to obtain a white powder of plga - peg - plga terminated with hydroxyl end groups ( plga - oh ). plga - oh was dissolved in dried dichloromethane containing triethylamine , and acryloyl chloride ( 2 30 equiv . of [ oh ]) was slowly added . the reaction solution was stirred at 0 ° c . for 12 h and then at room temperature for 12 h . the resulting solution was filtered to remove triethylamine hydrochloride and the filtrate was precipitated in cold ether . the precipitate was filtered , followed by drying under vacuum at room temperature for one day . some low molecular weight mono - acrylate polymers , such as pla - monoacrylate and plga monoacrylate , can be used as good sdcs . their hydrophobicity can suppress swelling although they cannot work as a cross - linker . after degradation of hydrophobic moieties , however , hydrogels can start to swell due to enhanced hydrophilicity . pla ( or plga ) was dissolved in dried dichloromethane and acryloyl chloride ( 1 . 5 equiv . of [ oh ] in pla or plga ) was added to the solution . the reaction solution was stirred 12 h at 0 ° c . and then 12 h at room temperature . the mixture solution was filtered to remove triethylamine hydrochloride and the filtrate was precipitated in cold ether , filtered , and dried under vacuum for 24 h . peg - pla - monoacrylate is another example of an sdc of the invention . a suitable synthetic route is shown in scheme 6 . prior to the synthesis , monomethoxy peg ( mpeg ) was dried for one day at 80 ° c . under vacuum to remove any moisture . thereafter , appropriate amounts of peg and lactide were placed in a one - neck flask . after adding one drop of stannous octoate , the reaction mixture was heated to 150 ° c . and stirred for 15 h under n 2 atmosphere . the resulting mixture was poured into cold hexane , and the precipitates were filtered and dried for 2 days at room temperature under vacuum to obtain a white powder of mpeg - pla terminated with hydroxyl end groups ( mpl - oh ). mpl - oh was then dissolved in dichloromethane and acryloyl chloride ( 2 equiv . of [ oh ]) was slowly added . the reaction mixture was stirred for 3 h at room temperature , and poured into cold diethyl ether . the precipitate was filtered , followed by drying under vacuum . in this example , the hydrophilic vinyl monomer , crosslinker , and sdc units are acrylic acid , bis , and plga , respectively . the vinyl - terminated plga ( plga - da ) obtained above and acrylic acid were dissolved in dimethyl sulfoxide . to this solution , the appropriate amounts of bis as a crosslinker and aibn as an initiator were added . the mixture solution was heated to 70 ° c . and allowed to react for 8 h . the hydrogel obtained was washed with excess amounts of diethyl ether and ethyl alcohol , respectively . it was then dried under vacuum at room temperature for 2 days . the crosslinking density of hydrogel was controlled by the amount of bis added , whereas the swelling / degradation kinetic was adjusted by varying the amount of plga - vinyl and its molecular weight . it should be noted that numerous hydrogels can be prepared in this fashion , in which their characteristics are dependent on the type of monomer , crosslinker , and sdc selected . for example , pcl can be used to prepare hydrogels that show slower swelling than plga and pla . the incorporation of two or more different sdcs can afford two or more onsets of swelling , respectively . in this example , peg - da was used for both hydrophilic monomer and crosslinker . pcl is expected to improve the flexibility of dried hydrogel due to its low glass transition temperature ( t g ) property and also afford biodegradable properties . 0 . 1 g of diacrylated pcl ( mw . 1250 ), 0 . 1 g of peg - da ( mw . 575 , 700 ) and 0 . 007 g of aibn were dissolved in 2 ml of dmso and placed into 2 ml microcentrifuge tubes for reaction . the reaction tubes were kept at 65 ° c . for 12 h . after the reaction , the resultant hydrogels were pulled out gently from the tubes and dried in a vacuum oven for 2 - 3 days . the mws and the molar ratios of peg - da and pcl - da can be modulated to control swelling , mechanical , and degradation properties of the hydrogels . table 4 shows various compositions of hydrogels based on peg - da and pcl - da . in this example , the hydrophilic vinyl monomer , crosslinker , and sdc units are acrylic acid , peg - da , and pcl - da , respectively . 0 . 1 g of pcl - da ( mw . 1250 ) and 0 . 1 gram of peg - da ( mw . 575 ) were dissolved in 2 ml of dmso in 2 ml microcentrifuge tubes . 0 . 1 gram of aa and 0 . 007 gram of aibn were added to the mixture . after sealing with teflon tape , the mixture tube was placed into a heating oven at 65 ° c . for 12 h . the resultant hydrogels were dried in a vacuum oven at room temperature for 2 - 3 days . various compositions can be applied by varying the mw and the feed ratio of hydrophilic monomer , peg - da and pcl - da to modulate the hydrogel properties . some examples are listed in table 5 . various hydrophilic monomers listed in the previous tables can be used instead of acrylic acid . in this example , peg - da acts as both hydrophilic monomer and crosslinker , and pla - peg - pla is used as sdc . 0 . 25 gram of pla - peg - pla diacrylate and 0 . 25 gram of peg - da were dissolved in 5 ml of dmso and placed into 15 ml of conical centrifuge tube ( 17 mm × 120 mm ). 0 . 0175 gram of aibn was added to the solution and then the mixture was poured separately to 2 ml microcentrifuge tubes . the tubes were placed in a vacuum oven at 65 ° c . for 12 h . the hydrogel was taken out and dried in a vacuum oven at room temperature for 2 - 3 days . the mws and the molar ratios of peg - da and pla - peg - pla - da can be modulated to control swelling , mechanical , and degradation properties of the hydrogels . also , other similar types of biodegradable triblock copolymers such as plga - peg - plga and pcl - peg - pcl can be used instead of pla - peg - pla - da predetermined amounts of pla - peg - pla - da ( each pla block length : 747 ) and 0 . 25 gram of peg - da ( mw . 575 ) were dissolved in 5 ml dmso . 0 . 1 gram of acrylic acid and 0 . 0175 gram of aibn were added to the mixture . the mixture was poured separately into 2 ml microcentrifuge tubes . the tubes were placed in vacuum oven at 65 ° c . for 12 h . the resultant hydrogels were taken out and dried in a vacuum oven at room temperature for 2 - 3 days . various compositions can be applied by varying the mw and the feed ratio of hydrophilic monomer , peg - da and pcl - da to modulate the hydrogel properties . also , various hydrophilic monomers mention previously can be used instead of acrylic acid . synthesis of hydrogels based on poly ( vinyl alchol ) ( pva ) glycidyl methacrylate ( gma ), and plga . hydrophilic monomer units , which can introduce functional groups into the polymer backbone , can be used for hydrogel synthesis in the presence of a crosslinker and a sdc . scheme 7 shows a synthetic scheme for such a hydrogel , which is composed of pva , gma , and peg - plga - peg as hydrophilic polymer , crosslinker , and sdc , respectively . first , pva and gma were dissolved in water . after being stirred for 12 h , the solution was dialyzed against excess amount of water for 2 days and freeze - dried for 2 days . pva - gma and peg - plga - peg terminated with vinyl groups , synthesized as described hereinabove , were dissolved in distilled water containing bis . ammonium persulfate ( aps ) and n , n , n ′ n ′- tetramethylethylenediamine ( temed ) were added to initiate the polymerization . the reaction was continued for 1 h , and the hydrogel synthesized was washed with an excess amount of water , followed by drying under vacuum at room temperature for 3 days . hydrogels may show a ph - sensitive swelling behavior when the sdc contains a linkage cleavable at a certain ph . one example is to introduce a cis - aconityl linkage into the sdc , which is susceptible to hydrolysis at low ph (& lt ;˜ 6 . 0 ). scheme 8 shows a synthetic route for making a peg - based sdc bearing cis - aconityl acid ( sdc - ca ). since there are many hydrophilic polymers possessing hydroxyl and amino groups capable of reacting with carboxylic acid , sdc - ca is useful to be incorporated into a hydrogel intended to exhibit rapid swelling at low ph . a few examples of hydrophilic polymers for this purpose include synthetic polymers , such as pva , and natural polysaccharides , such as chitosan , alginate , dextran , and hyaluronate . the backbone of a hydrophilic polymer can be biodegradable . degradation of hydrogel in biological environments is often very important for biomedical applications , since the hydrogel can be removed without any surgical operation . the biodegradable hydrogel was prepared using biodegradable / hydrophilic polymer ( bhp ), crosslinker , and sdc . a plurality of bhp products are available for such synthesis , including a synthetic polymer bearing hydrolyzable linkage and natural polysaccharides , such as chitosan , alginate , dextran , and hyaluronate . one example is to use glycol chitosan as the hydrophilic polymer . scheme 9 shows a chemical modification of glycol chitosan . glycol chitosan is dissolved in water / acetone ( 1 : 1 v / v ) to give a polymer concentration of 1w / v %. acryloyl chloride is slowly added and the solution is stirred for 3 h . the impurities are removed by dialysis against the excess amount of water for 2 days . glycol chitosan bearing vinyl group ( gc - vinyl ) is then obtained after being freeze - dried for 3 days . a number of biodegradable hydrogels can be produced using gc - vinyl by varying the composition of crosslinkers and sdcs , as listed in tables 1 and 2 . another example is to use alginate as a hydrophilic backbone , as shown in scheme 10 . since alginate does not have a primary amino group in the backbone , the chemistry to introduce a vinyl group is different from ( glycol ) chitosan . in brief , alginate and gma is dissolved in distilled water , and the solution is stirred for 12 h . the resulting solution is dialyzed against excess amount of water and freeze - dried for 2 days . the alginate - gma obtained is also useful for syntheses of a plurality of hydrogel systems using different crosslinkers and sdcs . to measure the weight swelling ratio , the hydrogels were cut into disk shape ( 2 mm in diameter and 3 mm in thickness ) and then dried in a vacuum oven for 24 hrs to remove any residual moisture . after immersion in an excessive amount of distilled water at room temperature or 37 ° c . for fixed time periods , the weights of the swollen hydrogels were measured after removal of excess surface water by patting the samples with filter paper . the weight swelling ratio ( sr ) of the hydrogels was calculated from the following equation : where w s and w d are the weights of the swollen and dried hydrogels , respectively . fig1 - 4 show the results of swelling tests of several hydrogels . the degradation rates of sdcs were dependent upon the mw and the chemical composition . the degradation rates of sdcs with the same chemical compositions increased with decreasing mw . on the other hand , in case of sdcs with similar mws the degradation rate increased in the order of plga , pga , pla , and pcl . so , the delayed time for swelling can be modulated by choosing a sdc with a suitable degradation rate for specific applications . in cases of using pla - peg - pla - da as a sdc , hydrogels showed the delayed time ranging from 20 to 30 days for swelling ( fig3 and 4 ). as shown in fig4 , the hydrogels made of only pla - peg - pla showed a delayed swelling after 25 days and then dissolved in aqueous media due their complete degradation . because pcl required a much longer time for degradation , their hydrogels did not show a delayed swelling even after 45 days . considering the slow degradation nature of pcl , probably more than 2 months is required for delayed swelling . usually , hydrogels take a long time to swell to their equilibrium state . the hydrogels showing delayed swelling behaviors also require several hours to days for their equilibrium swelling . one way to enhance the swelling rate and increase the swelling size is to make them superporous . because superporous hydrogels ( sphs ) can show much faster swelling with higher swelling ratio than other nonporous hydrogels , they can be very useful for demonstrating a hydrogel showing a delayed swelling with fast initial swelling and high osmotic pressure at final swelling stage . here , two general methods , the gas blowing technique and the salt leaching method , were used for the preparation of superporous hydrogels . when water - soluble sdcs were used , superporous hydrogels were prepared using the gas blowing technique in aqueous media . in cases of using water - insoluble sdcs , the hydrogels were prepared using the salt leaching method in organic phase . a . preparation of superporous hydrogels based on aa / aam using gas blowing technique the sphs were prepared by polymerization of water - soluble monomers , aa and aam , in the presence of bis ( 0 . 25 % w / v ) as a cross - linking agent . aa ( 10 % w / v ), aam ( 15 % w / v ), bis ( 0 . 25 % w / v ), and pf127 ( 0 . 5 % w / v ) were dissolved in distilled water . the predetermined amount of a biodegradable sdc was added to the monomer solution . the ph value of the solution was adjusted to 4 . 5 by adding 8 m naoh solution . the monomer solutions ( 8 ml ) were placed into polypropylene conical tubes ( 50 ml ) and then aps ( 0 . 6 % w / v ) and temed ( 0 . 4 % w / v ) were added . after 3 . 5 min , sodium bicarbonate powder ( 5 % w / v ) was added to the solutions with vigorous stirring using a spatula to generate and distribute gas bubbles evenly throughout the reaction solution . the solutions were kept for 30 min to ensure complete polymerization . the resultant sphs were dehydrated in ethyl alcohol and placed in a drying oven at 60 ° c . for 12 h . b . preparation of superporous hydrogels based on aa / aam using salt leaching method the sphs were prepared by polymerization of water - soluble monomers , aa and aam , in the presence of bis ( 0 . 25 % w / v ) as a cross - linking agent . aa ( 10 % w / v ) and aam ( 15 % w / v ), and bis ( 0 . 25 % w / v ) were dissolved in dmso . the predetermined amounts of a biodegradable sdc ( pcl - da , peg - pla - peg - da , or plga - da ) and aibn were added to the monomer solution . the monomer solution ( 8 ml ) was poured into a polypropylene conical tube ( 50 ml ) containing sodium chloride salt particulates ( several hundred micrometers ). the reaction solution was placed into in a heating oven at 60 ° c . for 12 h . the resultant hydrogel was removed from the tube and placed in distilled water to dissolve the salt out . finally , the hydrogel was dried in a drying oven . fig5 shows the relative swelling ratios of hydrogels based on aa , aam , bis , and pcl - da . the hydrogels show a lower swelling ratio as the amount of pcl - da used as a sdc increase . but their swelling ratios are much higher than other typical hydrogels and ranged from several tens to hundreds . so , making the hydrogels superporous can be a good method to enhance the swelling ratio and pressure . peg - da ( 5 % w / v ) and pcl - da ( 5 % w / v ) were dissolved in dmso . aibn were added to the solution and placed into 50 ml of polypropylene conical tube containing sodium chloride salt particulates ( several hundred micrometers ). the reaction solution was placed in a heating oven at 60 ° c . for 12 h . the resultant hydrogel was taken out of the tube and placed in distilled water to dissolve the salt out , following by drying in a vacuum oven for 2 - 3 days . the mws and the molar ratios of peg - da and pcl - da blocks can be modulated to control swelling , mechanical , and degradation properties of the hydrogels . typical hydrogels , such as those based on aac , aam , hema , etc ., are glassy and brittle in the dry state and thus it is very difficult to change the shape and size of the dried state . even though the hydrogels can show elastic behavior to some degree in swollen state , their mechanical strength in the swollen state becomes too weak to change their shape by using physical forces or devices such as scissors , knives or scalpels . therefore , it is very useful to make flexible and elastic hydrogels even in the dried state so that they can be reshaped and adjusted as necessary for each application . peg is a hydrophilic polymer and its glass transition temperature is very low due to the flexible chain structure . when peg was used as a building block for preparing hydrogels with other biodegradable polyesters such as pga , pla and pcl , the hydrogels can show flexible and / or elastic properties even in the dried state . for instance , a hydrogel , and its xerogel , made of peg and pcl was flexible and elastic , and remained intact even after application of repeated bending or stretching . the xerogel can be stretched to almost twice the original length without breaking . 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