Nanoconfining Cation-π Interactions as a Modular Strategy to Construct Injectable Self-Healing Hydrogel

Open AccessCCS ChemistryRESEARCH ARTICLE5 Aug 2022Nanoconfining Cation-π Interactions as a Modular Strategy to Construct Injectable Self-Healing Hydrogel Bin Yan, Changyuan He, Sheng Chen, Li Xiang, Lu Gong, Yingchun Gu and Hongbo Zeng Bin Yan National Engineering Laboratory for Clean Technology of Leather Manufacture, College of Biomass Science and Engineering, Sichuan University, Chengdu 610065 Google Scholar More articles by this author , Changyuan He National Engineering Laboratory for Clean Technology of Leather Manufacture, College of Biomass Science and Engineering, Sichuan University, Chengdu 610065 Google Scholar More articles by this author , Sheng Chen National Engineering Laboratory for Clean Technology of Leather Manufacture, College of Biomass Science and Engineering, Sichuan University, Chengdu 610065 Google Scholar More articles by this author , Li Xiang Department of Chemical and Materials Engineering, University of Alberta, Edmonton AB T6G 1H9 Google Scholar More articles by this author , Lu Gong Department of Chemical and Materials Engineering, University of Alberta, Edmonton AB T6G 1H9 Google Scholar More articles by this author , Yingchun Gu *Corresponding authors: E-mail Address: [email protected] E-mail Address: [email protected] National Engineering Laboratory for Clean Technology of Leather Manufacture, College of Biomass Science and Engineering, Sichuan University, Chengdu 610065 Google Scholar More articles by this author and Hongbo Zeng *Corresponding authors: E-mail Address: [email protected] E-mail Address: [email protected] Department of Chemical and Materials Engineering, University of Alberta, Edmonton AB T6G 1H9 Google Scholar More articles by this author https://doi.org/10.31635/ccschem.021.202101274 SectionsSupplemental MaterialAboutAbstractPDF ToolsAdd to favoritesDownload CitationsTrack Citations ShareFacebookTwitterLinked InEmail Cation-π interaction is considered one of the strongest noncovalent interactions in aqueous solutions, which endows natural biomolecules (e.g., proteins) with robust wet adhesion and cohesion in humid/underwater environments. However, it remains a challenge to construct synthetic functional materials (e.g., self-healing hydrogels) by adopting the cation-π interactions rationally. Herein, we present a facile and novel strategy to fabricate injectable self-healing synthetic hydrogel from self-assembly of a thermoresponsive ABA triblock copolymer via cation-π interactions. This triblock comprised a modified poly(N-isopropylacrylamide) (PNIPAM) incorporated with cationic and aromatic components as the A block and a hydrophilic poly(ethylene oxide) (PEO) as B block. Upon thermally induced gelation, the cationic and aromatic components are closely and densely packed into nanoconfined micelles to provide reversible and strong cation-π interactions, thereby endowing the resulting hydrogel with an eye-catching self-healing performance upon the hydrogel damage. The hydrogel also exhibited an excellent thermoresponsive reversible sol–gel transition and clear shear-thinning property that offers the developed hydrogel injectability. This work demonstrates a new strategy for developing self-healing materials by incorporating cation-π interaction that renders various engineering and bioengineering applications. Download figure Download PowerPoint Introduction Most biological living tissues are gel-like materials with high water content and have an intrinsic ability to heal upon damages autonomously.1 Nature adopts a delicate combination of noncovalent interactions such as hydrogen bonding, hydrophobic interaction, and π–π stacking to tune the self-healing properties of these tissues and mediate their biological functions after recovery.2–6 Inspired by nature, researchers have developed various strategies to confer their synthetic counterpart hydrogels with self-healing ability using these noncovalent interactions.3,7–12 To date, different noncovalent interactions such as hydrogen bonding, π–π stacking, hydrophobic interaction, ionic interactions, and metal–ligand interactions have been selected and combined in successful fabrications of self-healing hydrogels.13–21 Cation-π interaction is another important noncovalent interaction in biological systems, which, however, has been significantly underappreciated and has only been quantified experimentally recently via molecular force measurements.22–24 Nevertheless, it remains a challenge to construct self-healing synthetic hydrogels by rationally adopting the cation-π interactions. Essentially, cation-π interactions are electrostatic attraction between positively charged cations and negatively charged electron-rich π systems, and are widely employed in nature to tune and stabilize the structures and functions of a variety of biological molecules.25–27 In general, they show higher strength than hydrogen bonding, and in some cases, even charge–charge interactions, which are arguably one of the strongest noncovalent interactions in aqueous solutions.22,24,26 Therefore, since its discovery, cation-π interaction has attracted tremendous interest in a wide variety of fields,28–35 including biology, chemistry, and materials science. Recently, cation-π interaction has been included in molecular designs to imbue developed functional materials with robust wet adhesion and cohesion in humid/underwater environments. For example, it was demonstrated that an adaptive synergy between aromatic catechol and cationic moieties such as lysine could promote wet adhesion by displacing surface salt from the surface with their cationic groups.22,23,36,37 In our previous studies, we measured the adhesion of a 3,4-dihydroxyphenylalanine (DOPA)-deficient foot protein from green mussels using a surface forces apparatus (SFA), which demonstrated the significant contribution of cation-π interaction to the adhesion properties.22,23 Cation-π interactions between various hydrogels and electron-rich π systems in aqueous solutions were then quantified directly via force measurements using SFA.24 The strength of cohesion of the films composed of lysine- and aromatic-rich peptides, measured further by SFA, demonstrating that cation-π interaction could endow films composed of lysine- and aromatic-rich peptides with powerful underwater cohesion.25 Inspired by these fundamental force measurements, we discovered further that the cation-π interaction could successfully drive the complexation and coacervation of like-charged polyelectrolytes, as well as single polyelectrolyte containing positively charged ions (cations) and electron-rich π groups.38,39 Recently, sequence-controlled polymers with adjacent cationic-aromatic sequences were synthesized via cation-π complexation-aided copolymerization. Then a series of hydrogels from these polymers were developed that exhibited fast, strong, and yet reversible adhesion to negatively charged surfaces in saline water.40–42 Very recently, a common pressure-sensitive adhesive polymer (PSA) incorporated with cationic amine and aromatic groups was developed; it was verified that the cooperativity between aromatic catechol and amines could endow the developed PSA with high-performance dry/wet adhesion.43 Encouraged by these promising findings, we surmised that introducing cation-π interactions into hydrophilic polymer networks would provide an effective strategy to fabricate hydrogels with excellent self-healing properties, as well as reversible and robust underwater cohesion and adhesion. The greatest challenge in achieving this proposed approach for self-healing hydrogels is the construction of a polymeric hydrogel with suitable amounts of cationic and aromatic groups next to each other to enable reversible and strong cation-π interactions. Previous studies demonstrated that the strength of cation-π interactions was highly dependent on the distance between the cationic and aromatic components and were effective only when these two were in close proximity.24,26 However, similar to most reported hydrogels,44–51 the reported hydrogels with cation-π interactions were highly swollen polymeric networks.40–42 In these cases, the distance between the incorporated cationic and aromatic groups increased dramatically, which markedly weakened the cation-π interactions in the hydrogels, and thus, were unable to achieve their self-healing performance. Meanwhile, the preparation of these hydrogels involved specific monomer selection, toxic solvents, and additional laborious solvent exchange, thereby limiting their widespread biomedical applications. Herein, we have developed a facile and viable strategy to fabricate self-healing hydrogel based on reversible and robust cation-π interactions between cationic amine and aromatic phenyl groups. To ensure that the cation-π interactions could provide sufficient healing ability upon hydrogel damage, cationic amine, and aromatic phenyl groups were incorporated in the A blocks of an ABA triblock copolymer (PLOPL) possessing thermoresponsive reversible sol–gel transitions. The chemical structure of the PLOPL is shown in Figure 1a. Upon heating the hydrogel above its lower critical solution temperature (LCST), the triblock copolymer PLOPL self-assembled into an injectable hydrogel and simultaneously formed nanoconfined micelles of A blocks containing both cationic and aromatic components. As illustrated in Figure 1b, such self-assembly phenomenon coupled with the formation of cation-π interactions between the cationic and aromatic groups confined in these micellar spaces, thereby offering the hydrogel reversible and strong cohesion and adhesion. Thus, the resulting hydrogel exhibited an eye-catching self-healing performance, as it autonomously healed after repeated damage. In addition, developed hydrogel demonstrated a clear shear-thinning property that endowed it with injectability. Figure 1 | Chemical structure of (a) ABA triblock copolymer PLOPL and its precursor triblock polymer PBOPB. (b) Schematic representation of the proposed structure of PLOPL hydrogel. Download figure Download PowerPoint Experimental Section Materials Poly(ethylene oxide) (PEO; average Mn 20,000, PEO455, Sigma-Aldrich, Shanghai, China), acryloyl chloride (Shanghai Darui Fine Chemicals, Shanghai, China), N-Boc-ethylenediamine (Huaxia Reagent, Chengdu, China), triethylamine (TEA; Adamas-Beta, Shanghai, China), and phenylethylamine (Shanghai Darui Fine Chemicals, Shanghai, China) are used as received. 2,2′-Azobisisobutyronitrile (AIBN) and N-isopropylacrylamide (NIPAM) were purchased from Sigma-Aldrich and purified by recrystallization from methanol and benzene/n-hexane (65/35 v/v), respectively. Tetrahydrofuran (THF), trifluoroacetic acid (TFA), stearyl trimethyl ammonium chloride (STAC), sodium dodecyl sulfate (SDS), acetic acid (HAc), and other reagents were of analytical grade and purchased from Chengdu Kelong Chemical Reagent Co., Ltd. (Chengdu, China). The chain transfer agent (CTA), (S)-1-dodecyl-(S′)-(α,α′-dimethyl-α″-acetic acid)-trithiocarbonate, was synthesized according to a reported procedure.52 Macro-CTA agent reversible additional fragmental transfer (RAFT)-PEO455-RAFT was synthesized following a reported procedure by attaching (S)-1-dodecyl-(S′)-(α,α′-dimethyl-α″-acetic acid) trithiocarbonate to both ends of PEO455.53 Synthesis of 2-phenylethyl acrylamide (NPA) NPA was synthesized following a reported procedure54 with some modifications. Briefly, phenylethylamine (2.057 g, 17 mmol) was dissolved in THF (100 mL) with TEA (20 mmol). Then acryloyl chloride (1.674 g, 18.5 mmol) was added to this solution dropwise in an ice bath with N2 bubbling. The resulting mixture was stirred at room temperature for 4 h. After that, the mixture was concentrated using a rotary evaporator, followed by dissolving in chloroform (150 mL) and subsequent washing with 0.1 M HCl solution (1 × 75 mL), saturated NaHCO3 (1 × 75 mL), and brine (1 × 75 mL). The organic phase was dried using MgSO4, filtered, and dried in a vacuum to deliver a yellow oil product (yield: 72%). 1H NMR characterization: (CDCl3, 400 MHz, δ) (ppm) 7.36–7.16 (m, –CH2C6H5), 6.3–6.2 (dd, CH2=C H), 6.1–6.0 (q, C H2=CH), 5.65–-5.6 (dd, C H2=CH), 3.65–3.55 (q, O=C–NH–C H2), 2.90–2.80 (t, C H2C6H5). Synthesis of tert-butyl(2-acrylamidoethyl)carbamate (TBAMCA) TBAMCA was synthesized following a reported procedure53 with some modifications. Typically, N-Boc-Ethylenediamine (3.845 g, 24 mmol) was added to THF (100 mL). Triethylamine (TEA) (3.643 g, 36 mmol) and acryloyl chloride (2.851 g, 31.5 mmol) were added dropwise to the solution at ice bath with N2 bubbling. The reaction mixture was then stirred at room temperature for 2 h. THF was then dried off in vacuo. The crude product was then dissolved in chloroform (150 mL) and washed against 0.1 M HCl solution (1 × 75 mL), saturated NaHCO3 (1 × 75 mL), brine (1 × 75 mL). The organic phase was dried using MgSO4, filtered and concentrated in vacuo. The product was precipitated with hexane twice and further dried in vacuo. The product was obtained as a fine white powder (yield: 76%). 1H NMR characterization: (CDCl3, 400 MHz, δ) (ppm) 6.3–6.2 (d, CH2=C H), 6.15–6.05 (q, C H2=CH), 5.7–5.6 (d, C H2=CH), 3.48–2.58 (m, O=C–NH–(C H2)2–NH–C=O), 1.44 (s, O–C(C H3)3). Synthesis of poly(NIPAM-co-TBAMCA-co-NPA)-b-PEO-b-poly(NIPAM-co-TBAMCA-co-NPA) (PBOPB) The PBOPB triblock copolymer was synthesized following a one-pot protocol in dioxane by RAFT polymerization. Briefly, RAFT-PEO455-RAFT agent (0.518 g, 0.025 mmol), NIPAM (1.045 g, 9.25 mmol), TBAMCA (0.080 g, 0.375 mmol), NPA (0.066 g,0.375mmol), and AIBN (0.002 g, 0.0125 mmol) were dissolved in 5 mL dioxane. After N2 purging for 15 min, the entire system was stirred at 70 °C for 12 h. The polymerization was quenched by adding 5 mL THF, and the resulting solution was added dropwise into a high volume of ethyl ether to precipitate the polymer out; this purification process was repeated twice. Then the product was filtered and dried under vacuum overnight. The composition of the resulting polymer was characterized by 1H NMR and was determined as poly (NIPAM204-co-TBAMCA13-co-NPA8)-b-PEO455-b-(NIPAM204-co-TBAMCA13-co-NPA8). Synthesis of poly(NIPAM-co-NAA-co-NPA)-b-PEO-b-poly(NIPAM-co-NAA-co-NPA) (PLOPL) The PLOPL triblock copolymer was synthesized by removing the Boc protecting groups of PBOPB following a reported procedure54 with some modifications. In general, PBOPB (2 g) was dissolved in 30 mL THF, followed by adding TFA (1 mL). The mixture was stirred at room temperature for 3 h and precipitated twice in ethyl ether. The precipitate was dried under vacuum overnight, and a white powder solid was obtained. The complete removal of the Boc protection groups was confirmed by 1H NMR, and the composition of the resulting PLOPL triblock copolymer was determined as poly(NIPAM204-co-NAA13-co-NPA8)-b-PEO455-b-poly(NIPAM204-co-NAA13-co-NPA8). Synthesis of dealkylated poly(NIPAM-co-NAA-co-NPA)-b-PEO-b-poly(NIPAM-co-NAA-co-NPA) (PLOPL-dealk) The CTA end-groups of dealkylated PLOPL (PLOPL-dealk) triblock copolymer were removed following a reported procedure55 with some modifications. Briefly, the PLOPL polymer (1 g) and AIBN (0.12 g, 0.1 mmol) were dissolved in 10 mL ethanol. The solution was degassed with N2 for 15 min then heated to 80 °C for 12 h. The solution was cooled and precipitated twice in ethyl ether. The precipitate was dried under a vacuum overnight to obtain a white solid. Synthesis of poly(NIPAM-co-NPA)-b-PEO-b-poly(NIPAM-co-NPA) (PNOPN) The PNOPN was synthesized as follows: RAFT-PEO455-RAFT agent (0.518 g, 0.025 mmol), NIPAM (1.045 g, 9.25 mmol), NPA (0.066 g, 0.375 mmol), and AIBN (0.002 g, 0.0125 mmol) were dissolved in 5 mL dioxane. After N2 purging for 15 min, the whole system was stirred at 70 °C for 12 h. After that, the polymer was purified and collected using the same procedure as PBOPB. The composition of the resulting PNOPN polymer was characterized by 1H NMR and was determined as poly(NIPAM186-co-NPA9)-b-PEO455-b-poly(NIPAM186-co-NPA9). Synthesis of poly(NIPAM-co-TBAMCA)-b-PEO-b-poly(NIPAM-co-TBAMCA) (PAOPA-Boc) Briefly, RAFT-PEO455-RAFT agent (0.518 g, 0.025 mmol), NIPAM (1.045 g, 9.25 mmol), TBAMCA (0.080 g, 0.375 mmol), and AIBN (0.002 g, 0.0125 mmol) were dissolved in 5 mL dioxane. After N2 purging for 15 min, the whole system was stirred at 70 °C for 12 h. The polymerization was quenched by adding 5 mL THF into the above mixture, and the resulting solution was added dropwise into a great amount of ethyl ether to precipitate the polymer out. The purification process was repeated twice, and the collected product was dried under a vacuum overnight. The composition of the resulting PAOPA-Boc triblock copolymer was characterized by 1H NMR and was determined as poly(NIPAM192-co-TBAMCA9)-b-PEO455-b-(NIPAM192-co-TBAMCA9). Synthesis of poly(NPA-co-NAA)-b-PEO-b-Poly(NPA-co-NAA) (NAONA) Briefly, RAFT-PEO455-RAFT agent (0.518 g, 0.025 mmol), TBAMCA (1.067 g, 5 mmol), NPA (0.88 g, 5 mmol), and AIBN (0.002 g, 0.0125 mmol) were dissolved in 5 mL dioxane. After N2 purging for 15 min, the whole system was stirred at 70 °C for 12 h. The polymerization was quenched by adding 5 mL THF into the above mixture, and the resulting solution was added dropwise into an excess volume of ethyl ether to precipitate the polymer out. The purification process was repeated twice, and the collected product was dried overnight under a vacuum. Synthesis of poly(NIPAM-co-NAA)-b-PEO-b-poly(NIPAM-co-NAA) (PAOPA) and poly(NPA-co-NAA)-b-PEO-b-poly(NPA-co-NAA) (NAONA) The PAOPA and ppNAONA were synthesized by removing the Boc protecting groups of PAOPA-Boc and NAONA-Boc, following the same procedure as PLOPL. Synthesis of PNIPAM-b-PEO-b-PNIPAM (NON) The NON was synthesized following the same method shown above, except that no TBAMCA and NPA were added during the polymerization process. The obtained polymer was characterized by 1H NMR and determined to be PNIPAM197-b-PEO455-b-PNIPAM197. Hydrogel preparation To fabricate the PLOPL hydrogels, the triblock copolymer was first dissolved in a pH 2.5 buffer solution of 100 mM HAc and 250 mM KNO3 at a concentration of 15 wt % at 5 °C overnight. The polymer solutions were heated for 3 min above the sol–gel transition temperature (TSG) of the corresponding triblock copolymers to induce hydrogel formation. The PLOPL-d hydrogel was also prepared by dissolving the PLOPL polymers in phosphate-buffered saline solution (PBS; 0.1 M, pH 7.4) to deprotonate the cationic amine groups in the micelles. To confirm the critical contribution of cation-π interaction on the self-healing properties of the PLOPL hydrogel, four different hydrogel types were prepared using PBOPB, PNOPN, PAOPA, and NON triblock copolymers employing the same procedure as PLOPL hydrogel. Among these hydrogels, PBOPB and PNOPN hydrogels involve π–π interaction and hydrogen bonding; while the PAOPA one involved electrostatic interaction and hydrogen bonding; the NON one only offered hydrogen bonding. Meanwhile, STAC and SDS were used as competitive species to R-NMe3+ and π components, and were introduced into the PLOPL hydrogel at a concentration of 0.1 mg/mL to deprive the cation-π interactions from the hydrogel network. The formulation of all the hydrogels is presented in Supporting Information Table S1. Monomer and polymer characterizations The chemical structures of the synthesized monomers and copolymers were confirmed by nuclear magnetic resonance (NMR; AV III HD 400 MHz, Bruker, German), where CDCl3 and D2O were used as the deuterated solvents for the monomers and polymers. The 1H NMR data of the polymers are shown in Supporting Information Figures S1–S7. The weight-average and number-average molecular weights, Mw and Mn, of the synthetic ABA triblock copolymers were characterized by size exclusion chromatography (SEC; Waters 2414 refractive index detector, USA) at 40 °C using dimethylformamide (DMF) containing 10 mM lithium bromide as the eluent at a flow rate of 1 mL/min. The SEC system was calibrated using monodisperse polystyrene standards. The molecular characteristics and chemical compositions of the polymers are summarized in Table 1. Table 1 | Molecular Characterizations of the Synthesized Triblock Copolymers Polymer Mn (KDa) Mw (KDa) Ð π (NPA) Cation (TBAMCA/NAA) NIPAM PEO 25.4 28.5 1.12 — — — Macro-CTA 26.1 29.3 1.12 — — — NON 68.2 81.8 1.20 — — 394 PAOPA-Boc 73.6 91.3 1.24 — 30 384 PAOPA — — — — 30a 384 PNOPN 70.8 88.5 1.25 18 — 372 PBOPB 76.6 95.8 1.25 16 26 408 PLOPL — — — 16 26a 408 PLOPL-dealk — — — 16 26a 408 NAONA — — — 226 200a — aThe polymerization degree of NAA. Rheological characterizations of polymer hydrogels The rheological properties of all hydrogels were tested on a rheometer (MCR 302; Anton Paar Trading Co., Ltd., Shanghai, China) with a 20-mm parallel-plate configuration. Temperature ramp experiments were carried out in the range of 4–50 °C to study the temperature-dependent sol–gel transition behavior of the hydrogels with a heating rate of 1 °C/min. The thermal responsiveness of the hydrogels was verified by the temperature cycle test, where the modulus values of most hydrogels were measured between 15 and 37 °C at a constant angular frequency (ω = 10 rad/s) and strain (γ = 5%). For NON hydrogel, the temperature cycle test was varied from 37 to 45 °C. The self-healing performance of the hydrogels was characterized by an amplitude vibration test and a dynamic strain cyclic test. The amplitude vibration test was performed at 37 °C and a fixed frequency of 10 rad/s, where the strain was increased from 0.1% to 1000% to achieve strain fracture, then a low strain of 1% was applied. The dynamic strain cycling tests were performed between 1% and 370% at 37 °C and a frequency of 10 rad/s. Dynamic light scattering (DLS) measurement The hydrodynamic diameters of the block copolymers in a pH 2.5 buffer solution of 100 mM HAc and 250 mM KNO3 were measured using a Malvern Zetasizer, UK (Nano ZSP). The experiments were performed with an accuracy of ±0.1 °C at temperatures from 4 to 45 °C. Samples were equilibrated at each temperature for at least 2 min before data collection. The temperature at which the particle size increased abruptly, which was determined to be the LCST. Transmission electron microscopy (TEM) The micellar formation of the triblock copolymer above LCST was confirmed by electron microscopy at an of To of the the were by for 15 the the were negatively with a acid aqueous and to our that introducing cation-π interactions into hydrophilic polymer networks would confer an effective strategy to fabricate hydrogels with excellent with robust underwater cohesion and adhesion Thus, we and synthesized an ABA triblock copolymer Figure composed of a modified incorporated with cationic and aromatic components as thermoresponsive A block and a hydrophilic PEO as B and it to an injectable self-healing hydrogel as shown in Figure This triblock copolymer PLOPL was prepared a its precursor triblock polymer PBOPB was prepared by RAFT polymerization using NPA as the aromatic and TBAMCA as the cationic After removing the protecting groups from the cationic the cationic amine groups were from PBOPB triblock and the PBOPB was into the PLOPL For ABA triblock copolymers were PAOPA and PNOPN triblock copolymers only cationic and aromatic components in the A while the A blocks of NON are the and of these ABA triblock copolymers are shown in Supporting Information and Figure 1H NMR and SEC of PBOPB, and PLOPL are shown in Figures and The NON copolymer the of PEO at and at and while PBOPB polymers show the of Boc and aromatic phenyl groups at and in to that of PEO and After removing the Boc PLOPL no for the Boc at the successful of PLOPL The SEC data of PBOPB, and Macro-CTA further confirmed the successful of the Macro-CTA As shown in Figure with that of the SEC of NON and PBOPB are to higher molecular and a size with a low index further the of our to triblock The of all the triblock copolymers are summarized in Table 1. Figure 2 | (a) Synthesis of the PBOPB, and NON ABA triblock (b) 1H NMR of the PBOPB, and NON ABA triblock SEC of the PBOPB, and Macro-CTA polymers. Download figure Download PowerPoint To a hydrogel, the PLOPL polymer was first dissolved in a pH 2.5 solution of 100 mM HAc and 250 mM KNO3 overnight to obtain a solution of 15 wt The prepared PLOPL hydrogel demonstrated an excellent verified by a temperature ramp test, where the modulus and modulus of the hydrogel was during temperature from 4 to °C with a rate of 1 °C Figure that the hydrogel a of by the between and The of PLOPL was in with the LCST of their thermoresponsive block Supporting Information Figure measurements that the PLOPL polymer into micelles with hydrodynamic diameters of above determined as the LCST. The micellar formation was further confirmed by Supporting Information Figure After with formed micelles were as with an average of the temperature was lower than the values were higher than and the PLOPL mixture exhibited a while upon heating the solution its and with the solution a gel-like Thus, upon heating to 37 the PLOPL solution a 1 min, while it to a solution when cooled to a lower temperature (e.g., 4 This transition was reversible and could be repeated for and verified that PLOPL triblock could a hydrogel above where the A block formed the and micellar and the hydrophilic B block PEO as Meanwhile, the low modulus at low combined with the excellent endowed the PLOPL hydrogel with injectable As shown in Figure using a × the polymer at 4 °C could be into a water bath at 37 °C to a hydrogel Figure 3 | (a) with temperature for a 15 wt % PLOPL hydrogel in and heating (b) of a 15 wt % PLOPL hydrogel with of thermal heating and the thermal of 15 wt % PLOPL hydrogel and the corresponding phase of a 15 wt % PLOPL into 37 °C water with Download figure Download PowerPoint demonstrated that the developed PLOPL hydrogel could the cationic amine an