Aqueous photo-RAFT polymerization under NIR light

Under NIR light irradiation, tetrasulfonated zinc phthalocyanine (ZnPcS₄⁻), a water-soluble PC (Scheme 1B and Supporting Information, Figure S1), was employed to photosensitize hydrogen peroxide (H₂O₂) in the presence of trithiocarbonate (TTC) RAFT agent, for the photoinitiation of RAFT polymerization in aqueous solution (Scheme 1A). N,N-dimethylacrylamide (DMAm) and 4-((((2-carboxyethyl)thio)carbonothioyl)thio)-4-cyanopentanoic acid (CTCPA) (Scheme 1C) were selected as model monomer and TTC owing to their good solubility in water. Firstly, a series of control experiments were performed with and without deoxygenation, demonstrating the need for NIR light, ZnPcS₄⁻, and H₂O₂. Low monomer conversions were observed in the absence of either these species or light irradiation (Supporting Information, Table S1, #2, 3, 5, 7, 8, and 10). In comparison with the photo-RAFT polymerization after deoxygenation, the reaction without deoxygenation displayed a slower polymerization rate (a lower apparent propagation rate coefficient, k_p^app) (Supporting Information, Figure S2A, k_p^app_non-degas=0.70 h⁻¹ versus k_p^app_degas=0.92 h⁻¹). This result was attributed to the consumption of radicals by the presence of oxygen. However, photo-RAFT with and without deoxygenation exhibited excellent control towards the preparation of poly(N,N-dimethylacrylamide) (PDMAm) polymers (Supporting Information, Table S1, #1 and 6; Figure S2B) as indicated by low dispersity (Đ<1.15) and good agreement between theoretical (M_n, theo) and experimental (M_n, GPC) molecular weights. Moreover, in the absence of the RAFT agent, oxygen inhibition was also observed in the non-degassed reaction, resulting in lower conversions at analogous time points (Supporting Information, Table S1, #4 and 9).

Besides H₂O₂, other peroxides, including tert-butyl hydroperoxide (TBHP), urea hydrogen peroxide (UHP), and di-tert-butyl peroxide (DTBP), were tested (Supporting Information, Scheme S1). Well-defined polymers (Đ<1.2; Supporting Information, Figure S3) were successfully synthesized by photo-RAFT polymerization in the presence of all three peroxides (Supporting Information, Table S2) under NIR light irradiation. In comparison with the polymerization in the presence of UHP and DTBP, TBHP-mediated photo-RAFT polymerization was much faster (Supporting Information, Table S2, #3–5). Overall, H₂O₂ still displayed the fastest rate among these peroxides (Supporting Information, Table S2, #2). Therefore, H₂O₂ was selected in this photo-RAFT system for the following experiments.

To demonstrate the versatility of this system, two other TTC RAFT agents, including 4-cyano-4-[(dodecylsulfanylthiocarbonyl)sulfanyl]pentanoic acid (CDTPA) and 2-(butylthiocarbonothioylthio)propanoic acid (BTPA) (Scheme 1C) were investigated in systems without deoxygenation and using a relatively high monomer concentration (50 v %) in water to enable the solubilization of RAFT agents. BTPA-mediated photopolymerization demonstrated better control (Supporting Information, Table S3 and Figure S4) than CDTPA-mediated system as evidenced by a lower dispersity (Đ _BTPA≈1.1 versus Đ _CDTPA≈1.2). This may be attributed to the more hydrophobic Z-group of CDTPA, i.e., n-dodecyl group, than the n-butyl group of BTPA. However, CTCPA-mediated photopolymerization displayed a much higher monomer conversion than BTPA after 2 h NIR irradiation (Supporting Information, Table S3, #1 and 3). As a result, CTCPA was selected as a RAFT agent in the following experiments.

To investigate the role of H₂O₂ in this photo-RAFT system, we conducted a series of experiments using different ratios of H₂O₂ relative to CTCPA from 0.05 to 0.5 (Supporting Information, Figure S5 and Table S4). Using 0.05 equivalents of H₂O₂, a long induction period was observed (Supporting Information, Figure S5, orange line), with no monomer conversion within 1 h and sluggish polymerization thereafter. The conversion reached a plateau at ≈29 % monomer conversion after 3 h. Interestingly, a shorter inhibition period (≈0.5 h) and a faster polymerization rate were observed when using an H₂O₂ ratio of 0.1 (Supporting Information, Figure S5, purple line). These results indicated that a higher H₂O₂ concentration promoted photo-RAFT polymerization with a faster rate and a shorter inhibition period. However, the kinetic plot deviated from pseudo-first order behavior, indicating a low radical concentration in these conditions. At 0.5 and 1.0 equivalents of H₂O₂, a linear relationship between ln([M]₀/[M]_t) and irradiation time was observed, indicating a constant concentration of radicals (Supporting Information, Figure S5).

The consumption of H₂O₂ was also monitored in situ by ¹H NMR spectroscopy using DMF as an internal standard during the photo-RAFT polymerization (Figure 1A; Supporting Information, Figure S6). Interestingly, H₂O₂ consumption only occurred under NIR light irradiation (Figure 1A). As observed via ¹H NMR spectroscopy, the integral of the peak corresponding to H₂O₂ decreased from 0.96 to 0.72 after 1 h of NIR light irradiation, then stayed essentially constant (integral=0.71) throughout a 2 h dark period. Upon reexposure to NIR light for 1 h, the H₂O₂ consumption resumed as indicated by a further decrease in the H₂O₂ peak integral from 0.71 to 0.39 (Figure 1A and Supporting Information, Figure S6). This result is consistent with previous publications examining zinc phthalocyanines for photodynamic therapy: the ability of zinc phthalocyanines to photosensitize peroxides and generate hydroxyl radicals was demonstrated in these works.¹² To further confirm the formation of hydroxyl radicals, terephthalic acid (TA), which is commonly used as the probe to detect hydroxyl radicals (Supporting Information, Figure S7A),¹³ was added into reaction mixtures containing ZnPcS₄⁻ and H₂O₂ in water. After NIR light irradiation, the fluorescence spectrum of this mixture displayed a significantly increased peak at ≈440 nm (Supporting Information, Figure S7B, green curve), which corresponds to the fluorescent product of the reaction between TA and hydroxyl radicals. Meanwhile, no change in fluorescence was observed in the control experiment in the dark (Supporting Information, Figure S7, orange curve), indicating that hydroxyl radicals were only generated under light irradiation in the presence of H₂O₂ and ZnPcS₄⁻ (Scheme 1A).

Temporal control over the aqueous photo-RAFT polymerization process was also demonstrated, as evidenced by the absence of monomer conversion when the light was turned off (Figure 1B). As the reaction was placed again under NIR light, photopolymerization resumed with little change in k_p^app (k_p^app _before=0.62 h⁻¹ versus k_p^app _after=0.65 h⁻¹). This temporal control can be explained by the absence of formation of initiating species in the dark, as H₂O₂ can only be photosensitized by the excited state of ZnPcS₄⁻ under light (Scheme 1A). Furthermore, we observed a good agreement between M_n, theo and M_n, GPC and a decreasing Đ from ≈1.2 to ≈1.1 with increasing monomer conversion (Figure 1C). Additionally, with increasing light irradiation time, molecular weight distributions (MWDs) of the synthesized PDMAm shifted toward higher molecular weights, indicating the controlled character of this photo-RAFT system (Figure 1D). Moreover, the chain extension of a PDMAm macroRAFT agent was performed by adding fresh DMAm to the reaction mixture and exposing the new mixture to NIR light. A clear shift in the MWD for PDMAm-b-PDMAm compared to the initial PDMAm was observed by GPC (Supporting Information, Figure S8), indicating the high fidelity of thiocarbonylthio groups during the photopolymerization. The high end group fidelity was also supported by ¹H NMR spectroscopy with retention of the characteristic signal at 5.1 ppm attributed to the CH adjacent to the thiocarbonylthio group. The ratio of the CH signal to the CH₃ protons from the n-dodecyl Z-group is close to the expected value (Supporting Information, Figure S9).

Subsequently, we tested different targeted degrees of polymerization (DPs) in this oxygen-tolerant photo-RAFT system by fixing the concentrations of monomer, ZnPcS₄⁻ and H₂O₂ and changing RAFT agent concentrations. Well-defined PDMAm was successfully synthesized with narrow MWDs (Đ<1.25) at target DPs of 200, 600, and 2000 (Supporting Information, Table S5 and Figure S10). However, the synthesized polymers displayed a broad MWD (Đ=1.51) when the target DP was 5000. This can be attributed to the low concentration (0.87 mM) of RAFT agents used in this experiment. To investigate the versatility of this photo-RAFT system toward various monomers, the family and type of water-soluble monomers were expanded. Under NIR light irradiation without requiring prior deoxygenation, N,N-diethylacrylamide (DEAm), 2-hydroxyethyl acrylate (HEA), oligo(ethylene glycol)methyl ether acrylate (OEGA, M_n=480 g mol⁻¹), and oligo(ethylene glycol) methyl ether methacrylate (OEGMA, M_n=300 g mol⁻¹) were successfully polymerized with narrow MWDs (Đ<1.25) in the presence of ZnPcS₄⁻, H₂O₂ and CTCPA in water (Supporting Information, Table S6 and Figure S11).

Hydrogel synthesis regulated by NIR light

After establishing aqueous photo-RAFT polymerization, we decided to exploit these systems for the fabrication of hydrogels owing to their good performance in the presence of oxygen. A polyacrylamide TTC macroRAFT agent (Scheme 1C, PAm₃₉-bis-TTC) was synthesized (Supporting Information, Figure S12) and used as macroRAFT in photo-RAFT polymerization of hydrogels, owing to its high water solubility. As PAm₃₉-bis-TTC did not dissolve in most organic solvents, a chain extension experiment (Supporting Information, Table S4, #4) was performed on PAm₃₉-bis-TTC using DMAm as a monomer to enhance solubility in dimethylacetamide (DMAc) for GPC characterization. A well-controlled block copolymer PAm-b-PDMAm was observed with symmetric MWDs (Supporting Information, Figure S4) and low Đ (1.11), indicating the living character of the original PAm₃₉-bis-TTC macroRAFT agent. Hydrogels were prepared by chain extension of PAm₃₉-bis-TTC using oligo(ethylene glycol) methyl ether acrylate (OEGA) as the monomer and poly(ethylene glycol) diacrylate (PEGDA) as the crosslinker in the presence of H₂O₂, and ZnPcS₄⁻ without deoxygenation in water under NIR light irradiation (Scheme 1C). Although successful gelation was observed in 40 mins (Figure 2A, yellow line), the top layer of the reaction remained liquid. Under light irradiation for 100 mins, the monomer conversion of the bottom gel layer (≈800 μL) reached over 80 % as indicated by FTNIR spectroscopy, while the monomer conversion of the top liquid layer (≈200 μL) stayed below 10 % (Figure 2A, top right; Supporting Information, Figure S13A). This incomplete gelation can be attributed to the diffusion of oxygen from the vial headspace to the top layer of the reaction, leading to the partial inhibition of the photopolymerization. For the photopolymerization of DMAm in the previous section, a 0.8 mL flat cuvette with a cross-section of 1 cm×2 mm was employed, whereas a 5 mL cylindrical glass vial with a diameter of 1.0 cm was used for the synthesis of hydrogels. Although photo-RAFT polymerization of DMAm displayed a good oxygen tolerance in flat cuvettes, the rapid diffusion of oxygen from the headspace resulted in more significant inhibition and retardation of the polymerization (Supporting Information, Figure S14) in the top layer using the glass vial for hydrogel synthesis. To confirm this assumption, the same reaction after deoxygenation was performed. As expected, a faster polymerization was achieved with 90 % monomer conversion obtained after 60 mins, resulting in the formation of complete hydrogel without the presence of a liquid layer (Supporting Information, Figure S13B). However, deoxygenation requires stringent protocols such as the use of a glovebox, which limits the applicability of these approaches. We also tried to synthesize hydrogel without deoxygenation in a silicone mold rather than in a glass vial. After exposure to NIR light for 10 h, partial gelation was still observed (Supporting Information, Figure S15A), indicating that the oxygen diffusion hindered the gelation.

Under light irradiation and in the presence of excited ZnPcS₄⁻ (³PC*), oxygen (O₂) can be transformed into singlet oxygen (¹O₂) by triplet-triplet annihilation (TTA; Figure 2B).¹⁴ Previous investigations have demonstrated that the addition of triethanolamine (TEOA) can react with ¹O₂ producing superoxide (O₂⋅⁻) and H₂O₂ species.^{4a, 15} As a result, dissolved oxygen can be rapidly eliminated via this mechanism. Inspired by these early contributions, TEOA was added to the hydrogel solution to improve oxygen tolerance. Excitingly, after placing the reaction mixture under NIR light irradiation for 40 mins, complete gelation was observed in the presence of TEOA and ZnPcS₄⁻ (Figure 2A, green line). A similar result was observed for the hydrogel synthesis in a silicone mold where no liquid remained (Supporting Information, Figure S15B). To investigate the role of TEOA in this photo-RAFT system, various control experiments were conducted (Supporting Information, Table S7). In the absence of ZnPcS₄⁻ or NIR light irradiation (Supporting Information, Table S7, #2 and 7), no monomer conversion was observed in the presence of TEOA, which is consistent with previous control experiments (Supporting Information, Table S1, #7 and 8). This means ZnPcS₄⁻ and light are required for the activation of this photo-RAFT polymerization rather than TEOA. Interestingly, in the absence of H₂O₂, photopolymerization in the presence of ZnPcS₄⁻ and TEOA reached 30 % monomer conversion in 2 h under NIR light irradiation (Figure 2A, red line; Supporting Information, Table S7, #3). Compared with the fast polymerization with H₂O₂ (k_p^app=0.68 h⁻¹; Supporting Information, Figure S16A), photo-RAFT polymerization in the presence of TEOA without deoxygenation displayed a slower apparent polymerization rate (k_p^app=0.38 h⁻¹). As H₂O₂ can be photosensitized by ZnPcS₄⁻ to generate initiating species (Figure 2B), the slower polymerization rate in the TEOA system can be attributed to the generation of a small amount of H₂O₂ by the reaction between TEOA and ¹O₂ (Figure 2B, bottom).^{4a, 15} This was confirmed by a slow formation of H₂O₂ determined by ¹H NMR spectroscopy (Supporting Information, Figure S16).

In addition to PAm₃₉-bis-TTC, PDMAm macroRAFT agent (M_n=15 100; Đ=1.13) was also tested (Supporting Information, Figure S17A) for the synthesis of hydrogel in the presence of ZnPcS₄⁻, H₂O₂, and TEOA under NIR irradiation. Successful gelations were observed after 1 h light irradiation when using the PDMAm macroRAFT agent (Supporting Information, Figure S17B).

Previous NIR polymerization systems employed for the fabrication of hydrogels used lasers with high light intensity, which led to noticeable photothermal effects with an increase in the reaction temperature that can exceed 40 °C.^{8a, 11b} On the contrary, our system employs LEDs with low light intensity, promoting NIR photopolymerization under mild conditions (Figure 2C). Experimentally, the reaction temperature went up from ≈22 to ≈26 °C under irradiation (λ_max=730 nm; I=61.6 mW cm⁻²) for 5 mins, followed by a slow increase to ≈28 °C in the next 10 mins. Then, the reaction temperature dropped slightly and stayed at ≈28 °C between 15 and 30 mins. In addition, temporal control over photoinduced gelation was demonstrated by turning OFF the light (Figure 2D), displaying negligible monomer conversion during the dark period (Figure 2E). Photopolymerization resumed when the NIR light was turned ON again with no significant change in polymerization rate (k_p^app _before=0.83 h⁻¹ versus k_p^app _after=0.89 h⁻¹).

Photoinduced gelation through non-transparent barriers

Notably, in comparison with visible light (λ=400–700 nm), NIR wavelengths possess enhanced light penetration (Figure 3A),^{1k, 1o, 2g, 9} which can be exploited to mediate polymerization through non-transparent barriers for the fabrication of hydrogels with potential biomedical applications. To emphasize the enhanced penetration of NIR wavelengths compared to visible light, the light intensity of green (λ_max=530 nm) and NIR light (λ_max=730 nm) was measured before and after passing through barriers with different thicknesses (Figure 3B). Through 2.5 and 5.0 mm pig skin, the light intensity (I) of green light decreased to 2.3 % and 0.3 % of the initial value (I₀). By contrast, in the case of 730 nm NIR light, 21.3 % and 10.6 % of the initial light intensity were able to pass through 2.5 and 5.0 mm pig skin, respectively.

To demonstrate the applicability of this system to produce hydrogels through thick barriers, photo-RAFT polymerization was performed through biological barriers with various thicknesses (Figure 3C). In the presence of 2.5 mm pig skin, k_p^app of Erythrosin B (EB) mediated photo-RAFT polymerization (Supporting Information, Scheme S2) under green light decreased from 20.38 to 0.44 h⁻¹ (Figure 3E), which corresponds to 2 % of the original polymerization rate. By contrast, ZnPcS₄⁻-mediated NIR photo-RAFT system through 2.5 mm pig skin (Figure 3D) displayed 58 % of the k_p^app without barrier (k_p^app _{(with barrier)}=0.83 vs k_p^app _{(without barrier)} 0.48 h⁻¹). Therefore, NIR photopolymerization system exhibited a much smaller decrease in k_p^app than the green light system when pig skin was placed between the light source and the reaction. Upon increasing the barrier thickness to 5.0 mm (pig skin), k_p^app of the EB system under green light was determined to be 0.03 h⁻¹ which corresponds to only 0.015 % of the original k_p^app, while the NIR system exhibited a k_p^app equal to 0.31 h⁻¹, corresponding to 37 % of the value without barrier. For the NIR photopolymerization through 5.0 mm thick pig skin, hydrogels were successfully prepared despite an increase in gelation time from ≈40 to ≈80 mins (Figure 3C, red lines). By contrast, the green light mediated hydrogel system (Supporting Information, Scheme S2) using EB and TEOA performed poorly in the presence of thick barriers. Although there is rapid gelation (Figure 3E, green line; k_p^app=20.38 h⁻¹; 80 % monomer conversion in 5 mins) without barriers under green light exposure which is expected as our previous results,¹⁶ the polymerization under green light passing through 5.0 mm pig skin performed at a sluggish rate (Figure 3E, red line; k_p^app=0.03 h⁻¹) and no gelation was observed under irradiation after 7 h (Figure 3E, right).

Effect of RAFT polymerization on hydrogel properties

Previous investigations indicate that polymer networks prepared by RAFT polymerizations possess more homogeneous microstructures than networks made by FRP.¹⁷ Highly crosslinked polymeric nanogels with compact structures are generated at the early stages of FRP (Figure 4A, top first), due to the rapid consumption of pendant double bonds via intramolecular polymerization in the presence of propagating radicals. As demonstrated in previous work by atomic force microscopy (AFM), scanning electron microscope (SEM), and light scattering,¹⁸ these nanogels first remain isolated at the early stage of the polymerization. In a later stage of the polymerization, they can react via intermolecular crosslinking, eventually forming a heterogeneous network (Figure 4A, top second). In contrast to FRP, RAFT polymerization allows an equilibrium between propagating species and dormant polymer chains to be established, which enables more even growth of all polymer chains throughout the polymerization (Figure 4A, bottom top). The efficient chain transfer in the RAFT system allows diffusion of polymer chains and intermolecular crosslinking, producing more homogeneous polymer networks (Figure 4A, bottom second).¹⁹

To investigate the effect of the RAFT agent on the mechanical properties of hydrogels, samples containing various concentrations of RAFT agent were synthesized and analyzed via tensile testing. A hydrogel system consisting of acrylamide (Am) and N,N′-methylenebis(acrylamide) (MBAm) was selected, owing to its higher strength than the previously used polyacrylate networks. ZnPcS₄⁻ mediated photo-RAFT polymerizations were performed under NIR light for 10 h, enabling nearly full vinyl bond conversions (>99 % by FTNIR spectroscopy). Meanwhile, due to the sluggish FRP observed in ZnPcS₄⁻ system (Supporting Information, Table S1, #9; Table S7, #6), FRP-mediated hydrogels with comparable vinyl bond conversion (>99 %) were synthesized using EB and TEOA under green light irradiation. The tensile strength of hydrogel samples increased with decreasing concentration in thiocarbonylthio groups (1.0 ratio of TTC RAFT agent relative to 300 Am units: 68.0±4.2 kPa, 0.5 ratio of TTC: 89.2±9.4 kPa; Figure 4B; Supporting Information, Table S8), and the sample without addition of RAFT agent possessed the highest tensile strength at 106.0±6.0 kPa. In contrast, the elongation at break increased for hydrogels with higher RAFT agent concentrations (1.0 TTC RAFT agent: 92.0±7.7 %; 0.5 TTC: 61.4±3.4 % versus 0 TTC: 45.0±2.3 %; Figure 4B; Supporting Information, Table S8). Overall, lower tensile strength and higher elongation at break were observed in RAFT-mediated hydrogel networks compared to FRP-mediated networks, which was in agreement with the property of RAFT-mediated 3D printed materials in previous contributions.^3c Owing to the efficient chain transfer and diffusion in RAFT polymerization, more homogeneous polymer networks were prepared (Figure 4A, bottom second), benefiting the polymer chains uncoiling.^17a In addition, previous contributions reported that the addition of RAFT agents into hydrogel networks significantly reduces shrinkage stress and enhances relaxation of the polymer networks.²⁰

The swelling properties of hydrogels containing various concentrations of the RAFT agent were determined. Hydrogels prepared by NIR photo-RAFT were swollen in 1× PBS (pH=7.4) for 24 h to obtain the equilibrium swollen weight (Supporting Information, Figure S18), and the dry weights of samples were obtained after freeze-drying. Overall, in comparison with FRP-mediated networks, polymer networks containing thiocarbonylthio groups showed no evident change in swelling ratios (Figure 4C), which was consistent with the previous reports by Takai group^17b and Konkolewicz group.²¹ In addition, the effect of crosslinker concentrations on swelling ratios of RAFT-mediated hydrogel networks was investigated. As expected, swelling ratios of hydrogel networks decreased with increasing concentrations of crosslinkers (Supporting Information, Figure S19).

NIR light mediated hydrogel healing

A unique advantage of RAFT polymerization is the facile reactivation of RAFT agents embedded in polymer networks. In the presence of fresh monomers, the polymer chains can be extended, resulting in the modification of materials synthesized by RAFT polymerizations.^{2b, 3c, 10a, 22} The living property conferred by the RAFT group has also been exploited to self-heal damaged polymer networks. Although self-healing hydrogel systems have been established widely,²³ many of them suffer from complex experimental procedures or low recovery of mechanical strength.²⁴ In this study, hydrogel networks were healed efficiently under NIR light irradiation by reactivation of thiocarbonylthio groups in the presence of PC, monomers, and crosslinkers, achieving high tensile strength recovery. Although previous contributions demonstrated the self-healing of polymer network under UV light by reactivation of RAFT agents,^{3c, 10a, 10b} these high-energy photons lead to unwanted side reactions, such as the degradation of thiocarbonylthio groups.²⁵ Besides UV light, Johnson's group developed a hydrogel system that was healed under blue light in the presence of PC.^2b However, compared with NIR wavelengths, blue light displays low penetration through barriers, limiting its applicability to non-transparent systems.

We performed hydrogel healing experiments by reactivating RAFT agents under NIR light (Figure 5A). Taking advantage of enhanced light penetration of these longer wavelengths, the photoinduced-healing process of hydrogels is accessible through thick barriers (Figure 3A), which may present potential applications in broad fields. In addition, as previously demonstrated, difunctional RAFT agents consisting of symmetric leaving R groups can display more efficient healing capability owing to the location of the thiocarbonylthio group within the polymer chains.^{3c, 10a, 22a} Therefore, PAm₃₉-bis-TTC (Scheme 1C), a difunctional macroRAFT agent with great water solubility was used for hydrogel fabrication. Experimentally, hydrogel samples containing a 1 ratio of TTC RAFT agent relative to 300 Am units were synthesized by ZnPcS₄⁻-mediated photo-RAFT polymerization under NIR light with nearly complete conversion of vinyl bonds (>99 %). Subsequently, the sample was cut into two pieces. In our first attempts, the healing process was performed by placing the two parts in contact in the hydrogel mold consisting of a silicone frame and two glass plates under NIR light irradiation at room temperature and in an open-air environment. Unfortunately, we only observed moderate healing under NIR light for 3 h, as indicated by 17±3 % recovery of tensile strength and 9±1 % recovery of elongation at break (Supporting Information, Table S8, #3). This can be attributed to the low amount of residual monomers and crosslinkers in the hydrogel sample limiting the healing process, although some thiocarbonylthio units can be reactivated under NIR light. This result was in agreement with Johnson and co-workers’ work, which reported poor healing capability of a RAFT-mediated hydrogel under blue light in the presence of the PC only.^2b Consequently, a small amount (≈20 μL) of hydrogel precursor solution consisting of [Am]: [MBAm]: [H₂O₂]: [TEOA]: [ZnPcS₄⁻]=300 : 2 : 8 : 8 : 0.015 at [Am]=5 M without RAFT agent was introduced at the cut interface prior to healing under NIR light for 3 h (Figure 5C). Excitingly, tensile testing of the healed hydrogel samples (Figure 5F; Supporting Information, supplementary video) revealed 84±4 % recovery of tensile strength and 76±2 % recovery of elongation at break (Figure 5D, green curve; Figure 5E; Supporting Information, Table S8, #2). The proposed mechanism of healing process is presented in Scheme S3. In our process, we added a solution containing ZnPcS₄⁻ and H₂O₂ to the interfaces of cut hydrogels. Under NIR irradiation, the initiating hydroxyl radicals can be generated, which can propagate in the presence of residual monomers (Supporting Information, Scheme S3A) to generate propagating radicals (P_n⋅ and P_m⋅). These radicals can enter into the RAFT process (Supporting Information, Scheme S3A–B), leading to the formation of intermediate radical species. Upon fragmentation of these intermediate radical species, the polymer networks containing thiocarbonylthio groups are reactivated to yield radicals (Supporting Information, Scheme S3B–C). These radicals can propagate (Supporting Information, Scheme S3C–D) or transfer to thiocarbonylthio groups. The healing process is induced by the crosslinking between polymer chains (Supporting Information, Scheme S3D–E) and the RAFT chain transfer process (Supporting Information, Scheme S3E–F) between active chains and dormant chains, resulting in the formation of new networks. Moreover, a lower healing efficiency with 41±7 % recovery of tensile strength and 29±5 % recovery of elongation at break (Figure 5D, blue curve; Figure 5E; Supporting Information, Table S8, #5) was observed in the samples prepared using a lower ratio of RAFT agents (the 0.5 ratio of thiocarbonylthio units). This decreased healing capability can be attributed to a lower concentration of thiocarbonylthio groups embedded in polymer networks, resulting in less reactivation of polymer chains at hydrogel interfaces, which is consistent with previous results.^{3c, 10c} Tensile tests of healed samples demonstrated that high concentrations of RAFT agents in hydrogel networks were essential to improve tensile strength recovery (Figure 5D, blue and green curves). In contrast to samples containing thiocarbonylthio units, FRP-mediated hydrogels (Figure 5B) displayed minimal healing ability in the presence of the same hydrogel precursor solution, displaying only less than 16±4 % and 13±2 % recovery of stress and elongation at break (Figure 5D, red curve; Figure 5E; Supporting Information, Table S8, #7). This poor healing capability demonstrates that the polymer chains produced in FRP-mediated hydrogels cannot be reactivated under NIR irradiation and the RAFT end group is necessary for the healing process (Supporting Information, Scheme S3).

After drying, healed hydrogel samples were characterized by scanning electron microscopy (SEM; Figure 6B–D). The top view of sample interfaces indicated successful healing (Figure 6B). To further demonstrate the success of the healing process, cross-sectional views of healed interfaces were imaged in SEM (Figure 6C–D) by cutting the samples in the direction perpendicular to the healing line (Figure 6A). The successful binding of the two separated hydrogel pieces was evidenced by the absence of cracks in the cross-sectional view of the healed material. Moreover, after swelling in PBS for 24 h, the healed hydrogels effectively swelled and showed no signs of rupture at the healed interface or elsewhere. (Supporting Information, Figure S20).

The effect of NIR light irradiation time on the recovery of tensile properties was also investigated (Figure 7A–B and Table S9). As expected, tensile strength and elongation at break of the healed samples exhibited higher recovery with increasing NIR light irradiation time. Under NIR light irradiation for 1 h, 44±4 % of strength and 30±2 % elongation were recovered (Figure 7A, red curve). These were increased further to 68±3 % and 59±3 %, respectively, after 2 h NIR irradiation (Figure 7A, yellow curve). Pleasingly, near quantitative recovery of strength (99±8 %) and elongation at break (93±5 %) were observed after 5 h irradiation (Supporting Information, Figure S7A, blue curve).

In the previous sections, the preparation of hydrogels through barriers (Figure 3) and NIR-mediated hydrogel healing (Figure 5) were demonstrated. Owing to the enhanced penetration of NIR light and the reactivation capability of thiocarbonylthio groups, we decided to investigate the photoinduced healing of hydrogels through non-transparent barriers using paper and pig skin as the synthetic and biological barriers (Figure 7C). In the presence of barriers, the photoinduced healing method was the same as the previous method and was performed by adding 20 μL reaction solution to the gel interfaces in a mold consisting of a silicone frame and two glass plates, then irradiating with NIR light. Excitingly, 81±5 % recovery of tensile strength and 73±3 % recovery of elongation at break were observed for healing performed through a 2.5 mm pig skin barrier (Figure 7D; Supporting Information, Table S10) under NIR irradiation for 5 h. When 0.2 mm print paper was placed between the sample and light source after 5 h, tensile strength and elongation at break of healed samples were 72±4 % and 65±8 % of the original values, respectively (Figure 7D; Supporting Information, Table S10). The photoinduced healing process allowed high recovery of hydrogel tensile strength through various non-transparent barriers, providing an avenue for potential applications in manufacturing and biomedical fields.