Synthesis of Thermo-Responsive Block-Graft Copolymer Based on PCL and PEG Analogs, and Preparation of Hydrogel via Click Chemistry

Thermo-responsive cross-linkable mPEG-b-[PCL-g-(MEO2MA-co-OEGMA)]-b-mPEG was synthesized by ring-opening polymerization (ROP) and atom transfer radical polymerization (ATRP). Then, the cross-linkable block-graft copolymer was used to prepare hydrogel via a copper-catalyzed 1,3-dipolar azide-alkyne cycloaddition reaction. The chemical structure and composition of copolymer were characterized by proton nuclear magnetic resonance (1H NMR), Fourier-transform infrared (FT-IR) and gel permeation chromatography (GPC). The self-assembly behaviors of the copolymer in aqueous solution were studied by UV spectrophotometer, fluorescence probes, the surface tension method, dynamic light scattering, and transmission electron microscopy. The results proved that the copolymer has excellent solubility and better temperature response. The three-dimensional network structure of the gels, observed by scanning electron microscopy at different temperatures, indicated that the gels have temperature response.


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The use of chemical techniques to synthesize biomimetic materials such as biological tissues and 34 carriers has become one of the hotspots of research [1,2]. Hydrogel with three-dimensional network 35 structure stands out among many chemical synthetic materials because of their good 36 biodegradability, low immunogenicity, and the micro-environment that can truly simulate human 37 tissues and cells on a three-dimensional scale [3][4][5]. Environmentally responsive hydrogels are a class 38 of hydrogels that produce corresponding reversible changes depending on small changes in their 39 environment, such as temperature, pH, and ion concentration [6,7]. This special property makes

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The specific operations are as follows: Weigh a certain amount of mPEG into a three-necked flask 95 containing dry toluene and stir. Weigh a certain molar ratio of α-Chloro-ε-caprolactone (αClεCL) and 96 ε-Caprolactone (εCL) in a small flask, completely dissolved in a small amount of toluene and added 97 to the reaction vessel. Add three drops of catalyst stannous octoate, under a nitrogen atmosphere, the 98 reaction was heated in a 120 °C oil bath for 12 h. The diblock copolymer mPEG-b-PCL was obtained. 99 Then, the system was cooled to 60 °C and nitrogen gas was still introduced. The diblock copolymer 100 mPEG-b-PCL was reacted with Hexamethylene diisocyanate (HMDI) in a ratio of 2:1 for 6 hours, and 101 then the reaction was terminated by cooling, and the product was precipitated with cold methanol.

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Dissolve in dichloromethane, precipitate with cold diethyl ether, and finally dry in a vacuum oven.

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The α-chloro-ε-caprolactone used in this step was synthesized according to the method of the

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The infrared spectrum was measured by a Tensor 27 Fourier transform infrared spectrometer.

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The sample should be mixed with KBr, ground into a powder and dried before being tableted.   The preliminary determination of water solubility and temperature sensitivity was carried out 181 by disposing a 2 mg/mL aqueous copolymer solution in a transparent glass vial at room temperature, 182 and after fully stirred, photographed the digital photos at 25 °C, 35 °C and 45 °C respectively.

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In addition, the water solubility and temperature sensitivity of the copolymers aqueous

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The particle size and particle size distribution were measured by dynamic light scattering 206 instrument: configured 1 mg/mL copolymers aqueous solution, and used a water filter with a pore 207 size of 0.45 μm to remove impurities. The particle size of the copolymer aqueous solution in the 208 temperature range of 20-45 °C was measured using a ZS90 type dynamic light scattering instrument.

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The micelle morphology was observed by transmission electron microscopy: the copolymers   The two different gels synthesized were fully swelled in water, and then freeze-dried to obtain 222 dry gels, and the surface morphology of the two dry hydrogels was taken by a uniform scanning 223 cross section in an environmental scanning electron microscope.

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In this study, the diblock copolymer mPEG-b-PCL was synthesized by ring-opening reaction of  271 Figure S5 shows the infrared spectrum of the azided triblock-graft copolymer, the crosslinker 272 alkynylated P(GMA-co-MEO2MA-co-OEGMA), the crosslinker TPOM and the two gels. Figure S5(a) 273 same with Figure S2(b), is the infrared spectrum of the azided triblock-graft copolymer. Figure S5

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Therefore, the molecular weight of the copolymers also differs. The molecular weight of each polymer 285 was measured by gel permeation chromatography as shown in Table S1. The measured molecular 286 weight of the polymer is consistent with the molecular weight of the experimental design basically.

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these two substances give the copolymer of corresponding temperature sensitivity [31].

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The specific case is illustrated by the transmittance curve measured by an ultraviolet 306 spectrophotometer. As shown in Figure 2(a), the transmittance of the tBG1 to tBG4 solution gradually 307 increases at room temperature because the density of the characteristic functional group Cl of the 308 tBG1 to tBG4 is increased with the same polymerization degree. That is, from tBG1 to tBG4, the water-

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Transmission electron microscopy is one of the most common methods for studying the 394 morphology of copolymer micelles. This method can not only clearly observe the morphology of the 395 micelles, but also measure the particle size of the micelles. In order to more intuitively introduce the 396 micelles formed by the self-assembly in the copolymer aqueous solution, taken tBG4 as an example, 397 the transmission electron micrographs of the tBG4 copolymer micelles measured at 25 °C and 37 °C, 398 as shown in Figure 4 (c). The morphology of the micelles formed by the copolymer can be clearly 399 seen from the figure. The copolymer aqueous solution is very homogeneous at 25 °C, therefore，the 400 prepared micelles are evenly dispersed on the copper mesh. In this situation, the particle diameter of 401 the micelle was about 50 nm. When the copolymer aqueous solution was preheated to 37 °C, the 402 hydrogen bond between the graft chain P(MEO2MA-co-OEGMA) and the water molecules began to 403 be destroyed, the copolymer aqueous solution was not as uniform as at 25 °C, and began to become 404 cloudy. The micelles sample prepared in this case can be observed the larger particle size, but these 405 micelles no longer a regular spherical shape and the particle diameter of the micelles were 160 nm.

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Comparing Figure 4 (a) with Figure 4 (b), it can be found that the particle size of the micelles 407 measured by the dynamic light scattering instrument is slightly larger than the micelles diameter 408 observed by the transmission electron microscope, it is because the particle size measured by the