In situ photocrosslinkable nanohybrids based on poly(ε-caprolactone fumarate)/polyhedral oligomeric silsesquioxane: synthesis and characterization

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<ul><li><p>ORIGINAL PAPER</p><p>In situ photocrosslinkable nanohybrids basedon poly(-caprolactone fumarate)/polyhedral oligomericsilsesquioxane: synthesis and characterization</p><p>Seyed Amin Mirmohammadi &amp; Mohammad Imani &amp;Hiroshi Uyama &amp; Mohammad Atai</p><p>Received: 1 July 2013 /Accepted: 6 October 2013 /Published online: 3 November 2013# Springer Science+Business Media Dordrecht 2013</p><p>Abstrac t Two types of b iodegradable , in s i tuphotocrosslinkable macromers were synthesized consisting alinear copolyester i.e., PCLF based on fumaric acid (FA) andpoly(-caprolactone diol) (PCL diol), and its nanohybrid coun-terpart (POSS-PCLF) composed of FA, PCL diol and polyhe-dral oligomeric silsesquioxane (POSS). Chemical structure ofthe macromers was characterized by 1HNMR and FTIR spec-troscopy. The synthesized macromers were photocrosslinkedby visible light irradiation in the presence of camphorquinoneand N,N-dimethylaminoethyl methacrylate as a photoinitiatorand accelerator, respectively. Photocrosslinking characteristicsof the compositions were investigated as a function of the initialPCL diol molecular weight, presence of POSS nanoparticles orN-vinylpyrrolidone (NVP, as a reactive diluent) by tracingdegree of conversion by FTIR spectroscopy, equilibrium swell-ing studies. Thermal and dynamical properties of themacromers and the resulting networks were studied by TGA,DSC and DMA techniques pre- and post-photocrosslinking. Incontrast to the self-crosslinkability of the macromers, thecrosslinking reaction was promoted more efficiently in thepresence of NVP as a reactive diluent. This scrutiny showedthat there is an optimum point for POSS concentration to obtainthe maximum improvement in the network properties.</p><p>Keywords Nanohybrids . Fumarate-basedmacromers .</p><p>Polyhedral Oligomeric Silsesquioxane (POSS) .</p><p>Photocrosslinking . In situ forming . Visible light</p><p>Introduction</p><p>During the past few decades, researchers in the area of tissueengineering have done all of their best to discover novelmethods and materials for renewing the injured tissues. De-livery of cells, using a carrier, to the injured tissues has beenreported as one of the successful strategies to attain this goal[16]. It is noteworthy that the selected cell carrier should bebiocompatible with no degradation product possessing toxiceffect on the body tissues. The material should also exhibitgood mechanical properties with clinically relevant handlingproperties [711].</p><p>To provide more convenience to patients than using theconventional tissue scaffolds, injectable and in situcrosslinkable materials have been recently developed. So,several unsaturated fumarate-based polymers like polyethyl-ene glycol fumarate (PEGF), poly( -caprolactone fumarate)(PCLF) and polypropylene fumarate (PPF) have been exam-ined for tissue engineering applications until now. Some ofthese fumarate-based macromers may exhibit self-crosslinkable properties and can be cured in different waysusing thermal, redox or photo-initiated crosslinking capability.The named polyesters biodegrade to biocompatible residuesby hydrolysis to the corresponding constituent monomers thatare easily excreted from human body hence, they have recent-ly attracted the scientific community interest to develop im-plantable tissue engineering scaffolds or drug delivery carriersas implantable devices. Thus, injectable and in situcrosslinkable polyesters with a wide range of mechanicaland biodegradation properties have been reported to havemore potential for some special purposes like drug deliveryapplications [9, 1215].</p><p>Using inorganic nanoparticles such as hydroxyapatite (HA)or polyhedral oligomeric silsesquioxane (POSS) to modify un-saturated aliphatic polyesters are reported to yield in enhancedmechanical properties, thermal stability, biocompatibility profile</p><p>S. A. Mirmohammadi :H. UyamaDepartment of Applied Chemistry, Graduate School of Engineering,Suita, Osaka 565-0871, Japan</p><p>S. A. Mirmohammadi (*) :M. Imani (*) :M. AtaiNovel Drug Delivery Systems Department, Iran Polymer andPetrochemical Institute, P.O.Box 14965/115, Tehran, Irane-mail:</p><p>J Polym Res (2013) 20:297DOI 10.1007/s10965-013-0297-z</p></li><li><p>[1621]. The recent investigations showed that POSS, anorganosilicon oligomer existing as a nanoscale hollow cage witha generic empirical formula (RSiO1.5)n and 13 nm in diameter,can be incorporated into polymers as a building block to providehybrid organicinorganic nanocomposites [2233]. Further-more, the POSS-based materials have been reported to be non-toxic and cytocompatible [34, 35]. POSS nanoparticles canimprove biostability ofmaterials due to their hydrophobic natureand create an inert porous network which is more resistant tohydrolysis for tissue engineering applications. These nanocages,due to the presence of hydrophobic forces and intermolecularinteractions between themselves, can create physical network inthe polymer matrix providing some POSS crystalline aggregateswith globular or spherical morphology [3642]. For instance,Yaseen et al. synthesized a novel flexible nanohybrid by graftingPOSS nanocage to poly(carbonate-urea)urethane via the trans-cyclohexanediol substituent group [38]. Bai et al. also preparedtwo uniform inorganicorganic core-shell hybrid latex particlesbased on POSS/polystyrene-butylacrylate-fluorinated acrylate[36] and POSS/polyacrylonitrile/polydimethylsiloxane [37] byseeded emulsion polymerization with POSS as the core.</p><p>The purpose of this study is to synthesize a new in situphoto-crosslinkable nanohybrid, based on PCL fumarate(PCLF) and POSS nanocages containing various contents ofthe nanofiller capable to form chemical network. The authorshave been previously focused on developing drug elutingbiomedical devices including cochlear implant electrodes[43], bone cement and recently stents [44]. It is expected toobserve high endothelialization potential from thesenanohybridmaterials when coated on endovascular biomedicaldevices. Self crosslinkable character of these unsaturatedmacromers was investigated and compared with PCLF. NVP,a reactive diluent, was also examined to provide highcrosslinking ratio. The NVP monomer is commonly used asa reactive diluent in ultraviolet (UV), electron beam and visiblelight curing of polymers applied as inks, coatings or adhesives.These three dimensional organicinorganic nanohybrids canbe used as suitable candidates in tissue engineering applica-tions. The density of physical networks (formed by POSSnanoparticles) and chemical networks (formed by radical po-lymerization of C = C double bonds) can affect some importantproperties of the crosslinked nanohybrids especially the me-chanical ones as reported here in this research. To the best ofour knowledge, synthesis and characterization of thesemacromers are not reported elsewhere.</p><p>Experimental</p><p>Materials</p><p>Trans-cyclohexanediol isobutyl POSS (POSS diol) was pur-chased from Hybrid Plastics Co., (Hattiesburg, USA) and used</p><p>as received. Tetrahydrofuran (THF) (Merck Chemicals Co.,Darmstadt, Germany) was dried by adding sodium wire for48 h and consequent distillation under reduced pressure. -Caprolactone (-CL) monomer (99 %, Fluka, Munchen, Ger-many) and ethylene glycol (EG) (Merck, Germany) were driedover calcium hydride for 48 h and distilled under reducedpressure. Potassium (synthesis grade) was purchased fromMerck, Germany. N-vinylpyrrolidone (NVP), camphorquinone(CQ), calcium hydride, fumaryl chloride (FuCl), potassiumcarbonate (K2CO3), N,N -dimethylaminoethyl methacrylate(DMAEMA), methanol, dichloromethane (DCM), n-hexane,toluene, chloroform (CHCl3) and acetone were purchased fromWako Pure Chemical Industries Ltd., Osaka, Japan. FuCl waspurified by distillation at 161 C under ambient pressure. An-hydrous potassium carbonate (K2CO3) was grinded into a finepowder before application and kept desiccated before any fur-ther application. Anhydrous DCM was obtained by distillationafter reflux for 1 h in the presence of calcium hydride. All otherreagents were used as received without further purification.</p><p>Methods</p><p>Synthesis of linear OH-PCL-EG-PCL-OHand OH-PCL-POSS-PCL-OH nanohybrid copolyester</p><p>In this research, POSS diol nanoparticles and EG were sepa-rately used as initiators for anionic ring opening polymeriza-tion (AROP) of -CL to obtain HO-PCL-POSS-PCL-OH(POSS-PCL diol) and HO-PCL-EG-PCL-OH (PCL diol) co-polymers. In a typical batch, EG or POSS diol (0.16 mmole)was dissolved in freshly double-distilled and dried THF(7 mL) charged into a two-necked glass reactor. The mixturewas kept stirred for 5 h in an oil bath at 63 C after addingpotassium metal wire. After extracting the residual potassiumparticles, a definite amount of -CL monomer (withmonomer/initiator molar ratio of 100, 151 and 202) was addedto the reaction flask. Upon completion of the reaction, themixture was poured into a large volume of deionized water.The precipitate was purified two times by solvent (THF)/non-solvent (n -hexane) addition method and dried at 40 C invacuo (EYELAVos-201SD, Tokyo, Japan). The characteris-tics of synthesized macromers were summarized in Table 1.</p><p>Synthesis of PCLF and POSS-PCLF macromers</p><p>The procedure of PCLF and POSS-PCLF macromers synthe-sis is adopted from the works of Sharifi et al., with minormodifications as illustrated in Scheme 1 [14]. The purifiedFuCl and PCL diol (or POSS-PCL diol) were reacted in 1:0.99molar ratios. To this end, the dried PCL diol or POSS-PCLdiol macromers were dissolved in 100 mL of anhydrousdichloromethane (DCM) and charged into a reaction flaskequipped with magnetic stirrer. Potassium carbonate powder</p><p>297, Page 2 of 13 J Polym Res (2013) 20:297</p></li><li><p>was added to the reaction mixture in 5:1 molar ratio respectiveto the diol macromer. The FuCl was separately dissolved in50 mL anhydrous DCM and added dropwise to stirredmacromer/DCM/K2CO3 suspension while the reaction mix-ture was maintained at boiling temperature of DCM under</p><p>reflux condensation under nitrogen atmosphere. After addingall the FuCl-DCM solution (30 min) the reaction mixture wasallowed to stir for an additional 12 h. Upon completion of thereaction, the organic phase was washed with water and cen-trifuged at 6,000 rpm for 45 min (hamic CF 15RX, Tokyo,Japan) to remove all particulate matters also aqueous solubleresidues like K2CO3. The solvent was then removed byrotovaporation and the residue was dissolved in smallamounts of acetone/methanol (90 %V/V) mixture then anappropriate amount of water (as a non-solvent) was added toprecipitate the macromers. The product was re-dissolved inTHF and dropped into an excess volume of n-hexane to bepurified. The purification stages were repeated several timesto obtain a pure, transparent mass of polymer. The resultingmacromers were vacuum-dried at 35 C for 24 h and storedat 20 C for further use.</p><p>Synthesis of photocrosslinked networks</p><p>The macromers were crosslinked by visible light irradiation atblue region ( =430500 nm) in the presence of CQ andDMAEMA as a photoinitiator-accelerator system (Scheme 1).Therefore, an appropriate amount of melted macromer (T =60 C) was mixed with NVP (10 %w/w) on a glass slide by aspatula. DMAEMA (2%w/w to macromer) and a correspond-ing amount of CQ (1:1 w/w to DMAEMA) was added to themixture. The specimens were made as thin films in the sameway as FTIR samples were prepared (see Fourier-transforminfrared (FTIR) spectroscopy section). The samples werethen cured for 50, 75 and 100 s using a blue light source withan irradiation circa of 2,000 (G-Light Prima-II; GCCo., Tokyo, Japan) at 60 C. To investigate self crosslinkingproperty of the macromers, the same procedure was also</p><p>Table 1 Synthesis medium compositions alongwith the molecular weight, thermal and dynamical characteristics of the linear diol macromers includingdiol and fumarate-based compounds</p><p>Macromer type Samplecode</p><p>Initiator Initiator/monomermolar ratio</p><p>Initiatorcontent(%w/w)</p><p>Mn (g.mol1) PDI Tg</p><p>a (C) Tm (C) Hm (J/g) Crystallinity(%)</p><p>Td (C) Tan</p><p>PCL diol LPCL1 EG 100 0.56 17830 1.73 66.7 54.4 91.7 65.97 363.2 6.83LPCL2 151 0.37 23980 1.43 67.3 53.3 86.4 62.16 360.0 6.29LPCL3 202 0.28 31770 1.62 68.7 53.1 74.2 53.39 361.4 6.18</p><p>POSS-PCL diol PPCL1 POSS diol 100 8.33 18850 2.18 73.8 51.6 59.3 42.66 403.7 7.12PPCL2 151 5.52 27130 1.78 73.3 51.8 60.2 43.31 399.5 7.73PPCL3 202 4.13 34130 1.87 69.0 53.7 69.2 49.78 394.1 8.56</p><p>PCLF LPCLF1 EG 100 0.56 33290 2.76 60.6 51.7 82.4 59.24 378.7 7.27LPCLF2 151 0.37 43800 2.34 62.5 51.2 80.1 57.50 371.7 6.85LPCLF3 202 0.28 57550 2.35 64.0 49.4 68.0. 48.82 374.4 6.93</p><p>POSS-PCLF PPCLF1 POSS diol 100 8.33 35250 2.67 68.4 51.0 54.2 38.91 409.5 8.07PPCLF2 151 5.52 48430 2.16 67.5 51.2 57.7 41.42 397.2 7.17PPCLF3 202 4.13 60100 2.37 65.7 52.6 64.8 46.52 401.1.6 7.67</p><p>a Obtained from DSC experiments</p><p>Scheme 1 Synthesis of fumarate-based PCL-POSS macromers andschematic representation of its crosslinking reaction</p><p>J Polym Res (2013) 20:297 Page 3 of 13, 297</p></li><li><p>applied without adding NVP to the samples. In this case, theinitiator and accelerator were only dissolved in the moltenmacromers.</p><p>Characterizations</p><p>Nuclear magnetic resonance (NMR)</p><p>Proton NMR (1HNMR) spectra were recorded on a BrukerDPX400 spectrometer (Bruker, Germany) at room tempera-ture. CDCl3 was used as a solvent and chemical shifts wererecorded in ppm from the signal of tetramethylsilane.</p><p>Fourier-transform infrared (FTIR) spectroscopy</p><p>FTIR spectra (4,000400 cm1) were acquired on a ThermoScientific, NICOLET IS5 spectrophotometer, Madison, USA.The samples were placed between two polyethylene films,pressed to form a very thin film and the absorbance peaks ofuncured samples were recorded. The specimens were exam-ined at 4 cm1 resolution and 32 scans at room temperature.</p><p>Gel permeation chromatography (GPC)</p><p>GPC analysis is carried out by using a Tosoh GPC-8020 appa-ratus equipped with refractive index (RI) and UV detectors. Theinstrument was equipped by TSKgel GMHHR-L and GMHHR-M columns. Chloroform (LC grade) was run as an eluent at aflow rate of 1.0 mL.min1 at 40 C through the column.</p><p>Thermal behavior and mechanical properties</p><p>Thermal behavior of the synthesized macromers (PCL diol,POSS-PCL nanohybrids and their corresponding copolymerswith FuCl) was studied by differential scanning calorimetry(DSC) and thermogravimetric analysis (TGA) measurementsusing a DSC 6020 and a TG/DTA 7200 (Seiko InstrumentsInc., Tokyo, Japan) instruments, respectively. Thermal stabil-ity of the crosslinked samples was studied by TGA. All of themeasurements (DSC and TGA) were performed at the heatingrate of 10 C.min1 under nitrogen atmosphere. Degree ofcrystallinity of the samples was calculated using Eq. 1 asfollows:</p><p>Crystallinity % Hm=Hm 100 1</p><p>where, Hm stands for the heat of melting determined byintegrating the area (J.g1) under the DSC melting signalobtained from the second heating cycle. To eliminate thethermal history, the specimens were heated from room tem-perature to 100 C (first heating cycle), then cooled to 200 Cand for the second...</p></li></ul>