Large‐Sized Hydrogel Sheet Incorporated with Dual Physical Crosslinkers for Enhanced Mechanical and Adhesive Properties

This work reports the fabrication of a large‐sized hydrogel sheet with enhanced mechanical and adhesive properties. The fabrication involves the introduction of carboxymethyl‐modified cellulose nanofibers (m‐CNFs) and solid silica nanoparticles (SSNs) as physical cross‐linkers into acrylic acid monomer (AA), followed by bar coating and photopolymerization. The addition of the nanomaterials to the monomer solution renders it viscous, enabling the fabrication of A4‐sized hydrogel sheets with uniform thickness and enhanced mechanical and adhesive properties. Interestingly, the combined incorporation of both the nanomaterials generates a synergistic effect to improve the properties much more, which results from the hierarchical rupture of the multiple hydrogen‐bonded interactions among the poly(acrylic acid) (PAA) matrix, m‐CNFs, and SSNs. Under optimal conditions, the hydrogel sheet incorporated with the dual crosslinkers exhibits a sevenfold higher toughness and a sixfold increased peel strength than plain PAA, together with good biocompatibility. Furthermore, when mesoporous silica nanoparticles (MSNs) with active agent loading into their pores are incorporated instead of SSNs, the active agent can be released from the hydrogel sheet in a sustained or temperature‐sensitive manner, indicating that the system is potentially applicable to transdermal drug delivery system with no additional adhesive.


Introduction
[3] Owing to their unique properties, such as biocompatibility, flexibility, and responsiveness to stimuli (pH, solvent, electric/magnetic field, light, temperature, and so on), hydrogels can be applied in diverse fields, including tissue engineering, [4,5] filtration/separation, [6] catalysis, [7] and sensor system. [8,9]Additionally, the introduction of adhesiveness to hydrogels has expanded their application to biomedical sectors, such as biomedical devices, [10] wound healing, [11] and transdermal drug delivery. [12]However, the mechanical and adhesive properties of hydrogels need to be optimized for these applications to be successful in practice.
The mechanical properties of hydrogels are considerably affected by crosslinker activity.When chemical crosslinkers are used, the toughness and modulus of hydrogels are enhanced, at the expense of their extensibility, due to the formation of irreversible covalent bonds between the polymer chains. [3]The introduction of physical crosslinkers, which can induce friction in polymer chain movement and provide energy dissipation mechanisms during deformation, confers high toughness and extensibility on hydrogels. [13]16][17] The weak physical crosslinks, which are generated by hydrogen bonds, [18,19] ionic coordination bonds, [20] and hydrophobic interactions, [16] dissipate energy through their rupturing during deformation, while the high elasticity provided by the reversibility of physical crosslinks combined with chemically covalent crosslinks can maintain the structural integrity of hydrogels after deformation.
The adhesiveness of hydrogels can be given by introducing carboxyl groups into them because the groups form hydrogen bonds with other functional groups, including hydroxyl, amide, carboxyl, and amine. [21]Among various hydrogels, poly(acrylic acid) (PAA) hydrogels with numerous carboxyl groups have attracted research attention owing to their instant adhesion with diverse materials. [13,22]][25] However, the practical application of these bio-adhesive hydrogels is limited because of the inadequate combination of their mechanical and adhesive properties.Furthermore, the fabrication of hydrogels with large size, which is essential for shaping them into different shapes for various applications, remains a challenging issue.
Herein we have introduced an easy approach to fabricating a large-sized hydrogel sheet with high mechanical and adhesive properties.The fabrication begins with the introduction of carboxymethyl-modified cellulose nanofibers (m-CNFs) and solid silica nanoparticles (SSNs) as physical crosslinkers into acrylic acid (AA), followed by uniform spreading of the mixture solution via bar coating method and photopolymerization.The addition of the physical crosslinkers leads to an increase in viscosity of the mixture solution, which makes the spread mixture solution stable after bar coating and consequently allows the fabrication of A4-sized hydrogel sheets with uniform thickness.Various properties of the sheets, including mechanical and adhesive properties, are investigated.Interestingly, the use of the dual physical crosslinkers has a synergistic effect on the adhesion and mechanical properties of the hydrogel sheet, as compared with the single physical crosslinkers.Furthermore, when mesoporous silica nanoparticles (MSNs) with the loading of drugs into their pores are used instead of SSNs, sustained or temperaturesensitive drug release from the hydrogels can be demonstrated, which indicates that the system is potentially applicable to transdermal drug delivery systems.

Results and Discussion
Figure 1A shows a schematic of the procedure for preparing a large-sized, adhesive hydrogel sheet.A mixture solution comprising monomer (AA), photo-initiator (Irgacure2959), and crosslinker (N,N'-methylenebisacrylamide, MBAA) was dropped on a backing substrate.A bar was then lowered to generate a meniscus over the solution, followed by its horizontal movement over the substrate to form a uniform layer of the solution.Finally, UV light was irradiated to initiate polymerization.The use of a viscous mixture solution, which ensured the stability of the barcoated mixture solution during photopolymerization, was critical for the successful production of the hydrogel sheet.This was achieved by adding nanomaterials to the mixture solution.We chose to work with m-CNFs and SSNs owing to the abundance of functional groups on their surfaces as well as their excellent mechanical properties.The surface functional groups of the nanomaterials, particularly ─OH and ─COOH groups, may form hydrogen bonds with the AA monomer molecules, increasing the viscosity of the mixture solution.
When bar coating and photopolymerization were carried out using a solution containing m-CNFs (0.25 wt.%), an A4-sized PAA hydrogel sheet was successfully formed on a polyurethane backing substrate, as shown in Figure 1B.The hydrogel was peeled off from the backing substrate (Figure 1C), obtaining a free-standing PAA sheet (Figure 1D) that was devoid of damage and tearing.This free-standing sheet denoted as PAA/m-CNF 0.25 , was stretchable without any breakage in response to an external force, as shown in Figure 1E.In contrast, the bar-coated solution without any nanomaterials ran out of the backing substrate owing to its low viscosity.Consequently, a hydrogel sheet considerably smaller than the A4 size was created, coupled with rough surfaces.
The Fourier transform infrared (FTIR) spectrum of the PAA/m-CNF 0.25 sheet in Figure 1D is shown in Figure 2A.The spectrum exhibited a characteristic band at 1015 cm −1 that was attributed to the C-O stretching vibrations of glucopyranose rings in m-CNFs. [26]When a mixture solution containing SSNs (0.25 wt.%) was used instead of m-CNFs, an A4-sized hydrogel sheet (denoted as PAA/SSN 0.25 ) was successfully fabricated, and its FTIR spectrum contained a characteristic band at 1068 cm −1 corresponding to the Si-O-Si symmetric stretching vibration of SSNs. [27]These results indicate that the nanomaterials used to increase the viscosity of the mixture solution were incorporated in the hydrogel sheets after bar coating and photopolymerization.There was no significant difference between the FTIR spectra of the nanomaterial-incorporated PAA sheets and plain PAA hydro-gel, except that the band at 3380 cm −1 for the plain sample, which was assigned to O-H groups, was shifted to 3377 and 3370 cm −1 for the PAA/m-CNF 0.25 and PAA/SSN 0.25 hydrogel sheets, respectively.This shift implies that the nanomaterials formed hydrogen bonds with the PAA chains. [28]o assess the thermal stability of the nanomaterialincorporated sheets, thermogravimetric analysis (TGA) measurements were performed.As shown in Figure 2B, the residual weights of the PAA/m-CNF 0.25 and PAA/SSN 0.25 hydrogel sheets were greater than that of the plain PAA hydrogel.This improved thermal stability resulted from the existence of physical interactions between the nanomaterials and the PAA matrix, such as hydrogen bonding. [20]he interactions had a direct impact on the interior morphology of the hydrogel sheet.As shown in Figure 3A-C, all the hydrogel samples exhibited interconnected pore structures due to the water loss during freeze-drying.However, their pore sizes were different from each other.The average pore diameters of the plain PAA, PAA/m-CNF 0.25 , and PAA/SSN 0.25 sheets were 1.98, 1.94, and 1.73 μm, respectively.The pore size decrease in the nanomaterial-incorporated sheets was due to an increase in physical crosslinking density, which was driven by hydrogen bonding generated between the nanomaterials and PAA chains (Figures S1 and S2, Supporting Information). [29]The smaller pore size in the PAA/SSN 0.25 sheet indicates that the NPs interacted more strongly with the PAA chains, which was also supported by the improved thermal stability and the larger shift of the O-H band in the hydrogel sheet (Figure 2).Similar trends were observed in the swelling test.The swelling ratio at equilibrium state (SRE) values of the hydrogel sheets with the incorporation of the nanomaterials were lower than that of the plain hydrogel sheet (Figure 3D,E), which was prepared through the photopolymerization of a mixture solution with no nanomaterials pre-placed in a stainless-steel mold.Furthermore, higher concentration of the nanomaterials resulted in lower SRE value owing to the increased crosslinking density.In particular, the incorporation of SSNs having stronger interaction with the PAA matrix resulted in substantially lower SRE values.
To investigate the mechanical properties of the hydrogel sheets, tensile tests were performed using a universal testing machine (UTM).The modulus, tensile strength, elongation at break, toughness, and modulus of the hydrogel sheets could be determined using the obtained stress-strain curves (Figure S3A,B, Supporting Information).For the plain hydrogel with no incorporation of m-CNFs, the existence of many covalent crosslinks, which were generated by the use of MBAA, elasticized it, leading to small viscoelastic energy dissipation and consequently inducing its short elongation, [3] as shown in Figure 4A.In contrast, the m-CNF-incorporated hydrogels exhibited an enhancement in the mechanical properties.The enhancement became more pronounced as the concentration of m-CNFs increased to 0.5 wt.% (Figure 4A,B).This result was because the hydrogen bonds formed between the PAA matrix and m-CNFs increased the crosslinking density within the hydrogel sheet.The short chain segment length between the m-CNF-induced crosslinking points could make the network of the hydrogel uniform, allowing an even stress distribution in the hydrogel network. [30]urthermore, the intrinsic rigidity of nanomaterials and the reversibility of hydrogen-bonded crosslinks might contribute to the improvement of the mechanical properties. [31,32]When the concentration exceeded 0.5 wt.%, the mechanical properties deteriorated, which might result from a reduction in the homogeneity of the hydrogel network caused by the agglomeration of the nanomaterials. [30]hen SSNs were used, the behavior of the mechanical properties as a function of their concentration was different.An increase in the nanomaterial concentration up to 2 wt.% improved all the mechanical properties (Figure 4C,D).For concentrations greater than 2 wt.%, the mixture solutions were too viscous for the nanomaterials to be dispersed evenly.The stronger interaction be-tween the PAA matrix and SSNs allowed the SSN-incorporated sheets to have better mechanical properties than the m-CNFloaded ones, even though the sheets were prepared from mixture solutions with the same nanomaterial concentrations (Tables S1  and S2, Supporting Information).
Additionally, we examined the adhesive properties of the hydrogel sheets in Figure 4.The tack, peel strength, and lab shear strength of the m-CNF-incorporated sheets, which were measured using the probe tack, peel, and lap shear tests, respectively, are shown in Figure 5A-C.The use of m-CNFs up to 0.5 wt.% increased the tack, peel strength, and lab shear strength, which was consistent with the modulus trend in Figure 4C.Adhesion is determined by an interplay between the cohesion of an adhesive and its wettability on an adherent for excellent contact between both of them. [33,34]It is well known that the stronger is the cohesion of an adhesive, the higher is its modulus. [33]These results suggest that cohesion was crucial in determining the adhesive properties of the m-CNF-incorporated hydrogel sheets.
Similarly, the hydrogel sheets with the incorporation of SSNs exhibited maximum tack and peel strength at 0.5 wt.% of the nanomaterial concentration (Figure 5D,E), except for the lap shear strength with a maximum value at a nanomaterial concentration of 1.5 wt.% (Figure 5F).Considering the monotonous increase in modulus as a function of the SSN concentration (Figure 4C), it is believed that there was a competition between cohesion and wettability to determine the adhesive properties. [35,36]At low concentrations, the SSNs evenly distributed in the sheets acted as physical crosslinkers to increase the cohesion of the hydrogel sheets, [33] consequently   enhancing the adhesive properties.In contrast, introducing excessive crosslinking points through the high concentrations caused a low wettability of the sheets, [37] which worsened the mechanical performances.
Although these results demonstrate that the incorporation of SSNs into the hydrogel sheets could further improve their mechanical and adhesive properties, the use of only the nanomaterials did not confer good swelling ability (Figure 3E).For this reason, we chose to use the dual physical crosslinkers of m-CNFs and SSNs.When mechanical and adhesive properties as well as SRE were comprehensively concerned, the concentration of m-CNFs was set at 0.5 wt.%, while varying concentrations of SSNs were added.Figure 6A shows the change in SRE of the hydrogel sheets depending on the concentration of SSNs with a fixed concentration of m-CNFs at 0.5 wt.%.The inclusion of more SSNs in the hydrogel sheets, which was achieved by using higher concentrations of SSNs, decreased the SRE.Interestingly, the values were greater than the results of the hydrogels prepared with only SSNs at the same concentrations (Tables S3 and S4, Supporting Information).For example, the hydrogel sheet made from a mixture solution containing 0.5 wt.% of m-CNFs and 0.5 wt.% of SSNs (PAA/m-CNF 0.5 /SSN 0.5 ) exhibited an SRE of 550.0 ± 8.2%, whereas the SRE value of the sample (PAA/SSN 0.5 ), which was prepared using a mixture solution containing only 0.5 wt.% of SSNs, was 499.1 ± 5.7%.These results were attributable to ─COOH groups on the surfaces of the incorporated m-CNFs, which could be dissociated to increase the concentration of ─COO -groups in the hydrogel. [38]The electrostatic repulsion between the negatively charged groups on the m-CNFs and the ─COO − groups tethered to the PAA matrix could contribute to the expansion of the hydrogel sheet with the dual physical crosslinkers. [39]urthermore, we examined the mechanical and adhesive properties of the hydrogel sheets including the dual physical crosslinkers.Similar to the swelling test results, the PAA/m-CNF 0.5 /SSN 0.5 hydrogel sheet outperformed the PAA/SSN 0.5 sheet in terms of mechanical performance (Tables S2-S5, Supporting Information).The highest values of the tensile strength, elongation at break, and toughness were observed in the PAA/m-CNF 0.5 /SSN 1.5 hydrogel (Figure 6B,C).The incorporation of the dual crosslinkers could develop multiple physical interactions in the hydrogel sheet, thus improving the mechanical characteristics.The well-dispersed m-CNFs induced the formation of hydrogen bonds with the PAA chains, while the stronger interactions were further introduced by inserting SSNs, including their hydrogen-bonded interactions with the functional groups on the polymer and m-CNFs.External deformation would preferentially sacrifice the weaker interactions among these multiple physical interactions, followed by the subsequent breakage of the stronger interactions.This hierarchical breakdown of sacrificial interactions could allow the maximized energy dissipation. [40,41]he adhesive properties were also improved through the use of the dual crosslinker.The incorporation of more SSNs improved the tack and peel strength as well as the lap shear strength of the dual crosslinker-loaded hydrogels owing to the stronger cohesion through the increased modulus (Figure 6C), as shown in Figure 6D-F.However, the loss in wettability, which stemmed from the excessive increase in crosslinking density, reduced their adhesive performances.Considering the SRE, mechanical performance, and adhesive performances in conjunction reveals that an optimal hydrogel sheet can be created using 0.5 wt.% m-CNFs together with 0.5 wt.% SSNs.
Figure 7A shows the lap shear strength of the optimal sheet (PAA/m-CNF 0.5 /SSN 0.5 ) on several substrates, such as porcine skin, rubber, polyethylene terephthalate (PET), and glass.The sheet exhibited a lap shear strength exceeding 25 kPa, irrespective of the type of substrate, and its strength was highest on the porcine skin (49.8 kPa), which is well known to be markedly similar to human skin.Furthermore, the cytotoxicity of the sheet was tested.The sheet with the dual crosslinkers, along with the plain sheet and the samples loaded with the single crosslinkers, exhib-ited cell viability above 85% (Figure 7B), demonstrating good biocompatibility.These results suggest that the sheet can be applied to an epidermal patch without requiring an extra adhesive.
To demonstrate its potential for epidermal patches, we endowed it with drug-releasing capability by incorporating MSNs that could load drug molecules into their nanopores, instead of SSNs.A transmission electron microscopy (TEM) image of the synthesized MSNs is shown in Figure 8A.They were nearly spherical and their mean diameter, which was evaluated from the TEM image, was 132 nm similar to that of the SSNs.The magnified TEM image in the inset demonstrates their mesoporous structure clearly.The presence of the mesoporous structure was also confirmed by their nitrogen adsorption-desorption isotherm with a typical type IV (Figure S4A, Supporting Information). [42]he pore volume and Brunauer-Emmett-Teller (BET) surface area of the MSNs were measured to be 1.53 cm 3 g −1 and 397 m 2 g −1 , respectively.Their mean pore size was 5.1 nm, as shown in the density functional theory (DFT) pore size distribution of the inset.
These mesopores of the MSNs were useful for loading active agent molecules.When the MSNs loaded with rhodamine B, a model agent in this study, were incorporated into the hydrogel sheet together with m-CNFs, rhodamine B molecules were released from the sheet.At 37 °C, ≈52% of the agent molecules were released over 48 h (Figure 8B), which confirms the release capability of the MSN-incorporated sheet.However, similar release behaviors were observed at 25 and 43 °C, indicating a premature release or leakage of the agent molecules in an inactive state because of open MSN pores.To prevent unwanted premature or leakage, lauric acid (LA), a temperature gatekeeper was introduced to block the open entrances of rhodamine B-loaded MSNs. [42]A TEM image of the MSNs treated with LA is shown in Figure 8C, demonstrating the highly blurred interfaces between the mesopores and silica.Furthermore, the treatment with LA flattened the nitrogen adsorption-desorption isotherm (Figure S4B, Supporting Information), accompanied by a decrease in pore volume (0.95 cm 3 g −1 ), surface area (247 cm 3 g −1 ), and pore size (2.4 nm).These results support the successful incorporation of LA into the MSNs.The incorporation was more directly confirmed by a peak at 42.4 °C on the differential scanning calorimetry (DSC) thermogram of the treated sample (Figure S5, Supporting Information), which corresponded to a melting point of LA. [43] Because the LA in solid form inhibited the out-diffusion of rhodamine B from the MSNs, the inclusion of this temperaturesensitive gatekeeper substantially reduced rhodamine B leakage from the hydrogel sheet containing the LA-incorporated MSNs in inactivated states (25 and 37 °C).In contrast, the thermal annealing for 10 min at 43 °C, which was higher than the melting point of LA, led to the solid-liquid transition of LA, [43] melting out the gatekeeping material.Consequently, the dramatic release of rhodamine B from the hydrogel sheet with the inclusion of the LA-incorporated MSNs could be activated at 37 °C, which demonstrates the great potential of the hydrogel sheet for application in a transdermal on-demand drug delivery system.

Conclusion
In this work, we fabricated a large-sized hydrogel sheet with enhanced mechanical and adhesive properties.The use of m-CNFs and SSNs was critical in achieving this because they increased the viscosity of the AA monomer solution, enabling the successful preparation of large-sized PAA hydrogel sheets via a series of bar coating and photopolymerization processes.In addition, they served as physical crosslinkers within the sheets to achieve enhanced mechanical and adhesive properties.Further, when both the physical crosslinkers were used together, the mechanical and adhesive properties were substantially improved through the hierarchical rupture of the multiple hydrogen-bonded interactions between the PAA matrix, m-CNFs, and SSNs.This synergistic effect of the dual physical crosslinkers was optimized in the PAA/m-CNF 0.5 /SSN 0.5 hydrogel sheet, allowing a sevenfold higher toughness and a sixfold enhanced peel strength than plain PAA, without a significant loss in SRE.Furthermore, the incorporation of MSNs capable of loading active agent molecules into their pores, instead of SSNs, enabled the sustained or on-demand release of the active agent from the hydrogel sheet.This feature and its good biocompatibility in conjunction with the improved mechanical and adhesive properties suggest that the fabricated hydrogel sheets can be potentially applied in transdermal drug delivery systems without requiring additional adhesive.

Experimental Section
Materials: AA and m-CNF with a mean diameter of 35 nm were purchased from Daejung Chemicals and Asia Nanotech, respectively.SSNs with a mean diameter of 120 nm, Irgacure2959, MBAA, triethanolamine (TEA), tetraethyl orthosilicate (TEOS), cetyltrimethylammonium bromide (CTAB), trifluoroacetate anions (FC 2 ), phosphate buffer saline (PBS) solution (pH 7.4), LA, and water-soluble tetrazolium solution (WST-1) were obtained from Sigma-Aldrich.Absolute ethanol and hydrochloric acid (HCl) were purchased from Ducksan Chemicals.All the chemicals were used as received without extra purification process.
Fabrication of Adhesive Hydrogel Sheet: AA (10 g) was first mixed with a photo-initiator, Irgacure2959 (0.2 g), followed by the addition of MBAA (30 mg) as a chemical crosslinker.After mechanical agitation, an aqueous dispersion (10 g) of m-CNFs and/or SSNs was added as physical crosslinkers.Each sample was sonicated for 1 min using an ultrasonic homogenizer (UW3200, Bandelin) to disperse the nanomaterials uniformly.The resulting mixed solution was dropped on a polyurethane film that served as a backing substrate, followed by bar coating.To conduct the bar coating step, a 30 cm long stainless-steal applicator with 250 μm space was placed on the mixed solution without additional pressure and moved at a speed of 10 cm s −1 .This process was meticulously executed to fabricate hydrogel films of A4 size.Subsequently, UV light, which was generated by a TL 18 W BLB (Philips), was irradiated to the solution layer for 30 min.The resulting hydrogel sheet was then rinsed with deionized (DI) water to remove unreacted and residual reagents before cutting into dumbbell and rectangular shapes for further testing.The hydrogel sheets were named PAA/m-CNF X /SSN Y , where the subscripts X and Y denote the concentrations (wt.%) of m-CNFs and SSNs present in the mixture solutions used for their preparation, respectively.
Swelling Behavior Test: Small pieces of the as-prepared hydrogel sheets (2 g) were immersed in DI water at room temperature until their swelling reached equilibrium.After the samples were taken out, the residual water on their surfaces was carefully removed using filter paper.The SRE was calculated using the following equation: where W s and W d denote the weights of the fully swollen and dry hydrogels, respectively.Three tests for each sample were carried out and the mean value was represented together with its standard deviation.Mechanical Test: Tensile tests were performed on the hydrogel sheets using a UTM (ST-1001, SALT Corp.) at a constant stretching rate of 100 mm min −1 .Each specimen was prepared in a dumbbell shape according to the ASTM D882 standard, with dimensions of 5.0 × 75.0 × 1.0 mm.The obtained stress-strain curves were used to determine the modulus, tensile strength, elongation at break, and toughness of the hydrogels.
Adhesive Property Test: Probe tack test, peel test, and lab shear test were performed using a TA.XTplus100C texture analyzer (Stable Micro Systems).In the probe tack test, a cylindrical stainless steel probe with a diameter of 5 mm was used at room temperature with a probe speed of 10 mm s −1 , a separation speed of 10 mm s −1 , an applied pressure of 500 gf cm −2 , and a contact time of 1 s.The measured tack values were obtained based on the maximum forces applied to pull apart the samples.For the peel test, each hydrogel sheet, which was cut in a dimension of 2.5 cm × 2.5 cm, was placed on a stainless steel plate, followed by pressing twice with a 2 kg rubber roller.After its storage at room temperature for 1 h, the 180°peel strength was measured at room temperature at a speed of 300 mm min −1 .The lab shear test was carried out at a crosshead rate of 5 mm min −1 , with the hydrogel sheets (2.5 cm × 2.5 cm) mounted on the stainless steel plates.In all the tests, five test pieces for each sample were examined.
Cytotoxicity Test: Each hydrogel sheet was immersed in PBS buffer solution at 37 °C for 24 h to obtain its eluate.Separately, osteoblast cells were seeded at a density of 10 000 cells per well in a 24-well cell culture plate.After 24 h, the medium was replaced with fresh medium containing the eluate (1, 5, and 10 vol%).Afterward, the cells were incubated for an additional 24 h to conduct WST-1 assay, as previously reported. [42]As a control group, the cells that had not been treated with the eluate were used.
Preparation of MSNs and MSN-Loaded Hydrogel Sheets: CTAB (380 mg), FC 2 (179 mg), and TEA (68 mg) were dissolved in 25 mL of DI water.The mixture solution was heated to 80 °C for 1 h, followed by adding 4 mL of TEOS.After 24 h of reaction, the resulting particles were collected via centrifugation (5,000 rpm, 30 min), washed with ethanol three times, and then dried in vacuum.The dried MSNs (10 mg) were mixed with 2 mL of acetone in a 20 mL vial, followed by subsequently introducing a rhodamine B solution in acetone (2 mL, 0.1 wt.%) together with LA (200 mg).
After stirring for 1 h, the system was heated at 80 °C for additional 1 h to evaporate acetone, with no capping.Thereafter, 10 mL of hot DI water was added into the vial to produce two separate phases, one containing LA/rhodamine B and the other containing LA/rhodamine B-loaded MSNs.The latter was collected via centrifugation at 6,000 rpm for 5 min and then dried in air before being incorporated into the hydrogel sheet.In the incorporation, a series of bar coating and UV polymerization processes were performed, as previously described.
In-Vitro Release Test: The hydrogel sheet (60 mg) was placed in 4 mL in PBS buffer solution at pH 7.4 and then kept in a water bath set at 25, 37, and 43 °C.For the hydrogel sheet containing the LA-incorporated MSNs, thermal treatment at 43 °C for 10 min was carried out, followed by immersion in a water bath at 37 °C.At certain time intervals, 1 mL of the solution was extracted for UV-vis spectral measurement.The solution was poured back for the next measurement and the tests were repeated three times.The release percentage was calculated by dividing the cumulative amount of rhodamine B released at a given time by the initial amount loaded.
Characterization: The FTIR spectra of the hydrogel sheets containing m-CNFs and/or SSNs were acquired in the range of 4000-400 cm −1 using an FT/IR-4100 FTIR spectrometer (Jasco).Their cross-sectional morphologies were studied with SEM (JSM-6360LV, JEOL) at an acceleration voltage of 5 kV.To achieve this, the water-swollen hydrogel sheets, which were cut into discs with a diameter of 1 cm, were immediately frozen in liquid nitrogen, followed by freeze-drying for 24 h.The thermal properties of the hydrogels were also measured via TGA (Q500, TA Instruments) ranging from 25 to 800 °C in a nitrogen atmosphere.The TEM images of the MSNs were taken using an HT-7700 (Hitachi) operated at 75 kV.The nitrogen adsorption-desorption isotherms on the MSNs were measured using a surface area and porosity analyzer (Quadrasorb evo, Quantachrome).The BET and DFT techniques were used to determine the surface area and pore size distribution, respectively.

Figure 1 .
Figure 1.A) Schematic of the procedure for preparing a large-sized, adhesive hydrogel sheet.B) Photograph of the PAA hydrogel on a polyurethane backing substrate, which was made using a mixture solution with the inclusion of m-CNFs.C) Photograph of the PAA hydrogel sheet being peeled off from the backing substrate.D) Photograph of the free-standing PAA hydrogel sheet.E) Photograph of the free-standing PAA hydrogel sheet under stretching.

Figure 3 .
Figure 3. A-C) Scanning electron microscopy (SEM) images showing the cross-sectional morphologies of A) the plain PAA hydrogel, B) the PAA/m-CNF 0.25 sheet, and C) the PAA/SSN 0.25 hydrogel sheet.D,E) Changes in SRE as a function of the concentration of m-CNFs and SSNs.

Figure 4 .
Figure 4. Changes in tensile and elongation at the break of the hydrogel sheets depending on the concentration of: A) m-CNFs and C) SSNs.Changes in toughness and modulus of the hydrogel sheets as a function of the concentration of B) m-CNFs and D) SSNs.

Figure 5 .
Figure 5. Adhesive properties of the hydrogel sheets incorporated with m-CNFs: A) tack, B) peel strength, and C) lab shear strength.Adhesive properties of the hydrogel sheets incorporated with SSNs: D) tack, E) peel strength, and F) lab shear strength.

Figure 6 .
Figure 6.A-C) SRE and mechanical performance of the hydrogel sheets incorporated with m-CNFs and SSNs: SRE, tensile strength and elongation at break, and toughness and modulus.D-F) Adhesive properties of the dual crosslinker-incorporated sheets: tack, peel strength, and lab shear strength.

Figure 8 .
Figure 8. A) TEM image of the as-synthesized MSNs.B) Release profiles of rhodamine B from the hydrogel sheet containing the m-CNFs and MSNs.C) TEM image of the MSNs treated with LA.D) Release profiles of rhodamine B from the hydrogel sheet with the inclusion of the m-CNFs and LA-treated MSNs.