Exceptionally fast temperature-responsive, mechanically strong, tough and extensible monolithic non-porous hydrogels were synthesized. They are based on divinyl-crosslinked poly(N-isopropyl-acrylamide) (PNIPAm) intercalated by hydroxypropyl methylcellulose (HPMC). HPMC was largely extracted after polymerization, thus yielding a 'template-modified' PNIPAm network intercalated with a modest residue of HPMC. High contents of divinyl crosslinker and of HPMC caused a varying degree of micro-phase-separation in some products, but without detriment to mechanical or tensile properties. After extraction of non-fixed HPMC, the micro-phase-separated products combine superior mechanical properties with ultra-fast T-response (in 30 s). Their PNIPAm network was highly regular and extensible (intercalation effect), toughened by hydrogen bonds to HPMC, and interpenetrated by a network of nano-channels (left behind by extracted HPMC), which ensured the water transport rates needed for ultra-fast deswelling. Moreover, the T-response rate could be widely tuned by the degree of heterogeneity during synthesis. The fastest-responsive among our hydrogels could be of practical interest as soft actuators with very good mechanical properties (soft robotics), while the slower ones offer applications in drug delivery systems (as tested on the example of Theophylline), or in related biomedical engineering applications.

Cellulose and Paper Department National Research Centre 33 El Bohouth Str Dokki Giza 12622 Egypt

Institute of Macromolecular Chemistry Academy of Sciences of the Czech Republic Heyrovskeho nam 2 162 00 Praha Czech Republic

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Bashir S., Hina M., Iqbal J., Rajpar A.H., Mujtaba M.A., Alghamdi N.A., Wageh S., Ramesh K., Ramesh S. Fundamental Concepts of Hydrogels: Synthesis, Properties, and Their Applications. Polymers. 2020;12:2702. doi: 10.3390/polym12112702. PubMed DOI PMC

El-Husseiny H.M., Mady E.A., Hamabe L., Abugomaa A., Shimada K., Yoshida T., Tanaka T., Yokoi A., Elbadawy M., Tanaka R. Smart/stimuli-responsive hydrogels: Cutting-edge platforms for tissue engineering and other biomedical applications. Mater. Today Bio. 2022;13:100186. doi: 10.1016/j.mtbio.2021.100186. PubMed DOI PMC

Ebara M., Kotsuchibashi Y., Uto K., Aoyagi T., Kim Y.J., Narain R., Idota N., Hoffman J.M. Smart Biomaterials. Springer; Tokyo, Japan: 2014. Smart Hydrogels; pp. 9–65. NIMS Monographs. DOI

Schild H. Poly(N-isopropylacrylamide): Experiment, theory and application. Prog. Polym. Sci. 1992;17:163–249. doi: 10.1016/0079-6700(92)90023-R. DOI

Heskins M., Guillet J.E. Solution Properties of Poly(N-isopropylacrylamide) J. Macromol. Sci. Part A Chem. 1968;2:1441–1455. doi: 10.1080/10601326808051910. DOI

Haq M.A., Su Y., Wang D. Mechanical properties of PNIPAM based hydrogels: A review. Mater. Sci. Eng. C. 2017;70:842–855. doi: 10.1016/j.msec.2016.09.081. PubMed DOI

Sakai T., Matsunaga T., Yamamoto Y., Ito C., Yoshida R., Suzuki S., Sasaki N., Shibayama M., Chung U.-I. Design and Fabrication of a High-Strength Hydrogel with Ideally Homogeneous Network Structure from Tetrahedron-like Macromonomers. Macromolecules. 2008;41:5379–5384. doi: 10.1021/ma800476x. DOI

Sun J.-Y., Zhao X., Illeperuma W.R.K., Chaudhuri O., Oh K.H., Mooney D.J., Vlassak J.J., Suo Z. Highly stretchable and tough hydrogels. Nature. 2012;489:133–136. doi: 10.1038/nature11409. PubMed DOI PMC

Bin Imran A., Esaki K., Gotoh H., Seki T., Ito K., Sakai Y., Takeoka Y. Extremely stretchable thermosensitive hydrogels by introducing slide-ring polyrotaxane cross-linkers and ionic groups into the polymer network. Nat. Commun. 2014;5:5124. doi: 10.1038/ncomms6124. PubMed DOI PMC

Kalkan B., Orakdogen N. Anionically modified N-(alkyl)acrylamide-based semi-IPN hybrid gels reinforced with SiO2 for enhanced on–off switching and responsive properties. Soft Matter. 2022;18:4582–4603. doi: 10.1039/D2SM00319H. PubMed DOI

Gong J.P., Katsuyama Y., Kurokawa T., Osada Y. Double-Network Hydrogels with Extremely High Mechanical Strength. Adv. Mater. 2003;15:1155–1158. doi: 10.1002/adma.200304907. DOI

Song K., Zhu W., Li X., Yu Z. A novel mechanical robust, self-healing and shape memory hydrogel based on PVA reinforced by cellulose nanocrystal. Mater. Lett. 2020;260:126884. doi: 10.1016/j.matlet.2019.126884. DOI

Strachotová B., Strachota A., Uchman M., Šlouf M., Brus J., Pleštil J., Matějka L. Super porous organic–inorganic poly(N-isopropylacrylamide)-based hydrogel with a very fast temperature response. Polymer. 2007;48:1471–1482. doi: 10.1016/j.polymer.2007.01.042. DOI

Depa K., Strachota A., Šlouf M., Hromádková J. Fast temperature-responsive nanocomposite PNIPAM hydrogels with controlled pore wall thickness: Force and rate of T-response. Eur. Polym. J. 2012;48:1997–2007. doi: 10.1016/j.eurpolymj.2012.09.007. DOI

Strachota B., Šlouf M., Matějka L. Tremendous reinforcing, pore-stabilizing and response-accelerating effect of in situ generated nanosilica in thermoresponsive poly(N-isopropylacrylamide) cryogels. Polym. Int. 2017;66:1510–1521. doi: 10.1002/pi.5406. DOI

Huerta-Angeles G., Hishchak K., Strachota A., Strachota B., Šlouf M., Matějka L. Super-porous nanocomposite PNIPAm hydrogels reinforced with titania nanoparticles, displaying a very fast temperature response as well as pH-sensitivity. Eur. Polym. J. 2014;59:341–352. doi: 10.1016/j.eurpolymj.2014.07.033. DOI

Strachota B., Matějka L., Zhigunov A., Konefał R., Spěváček J., Dybal J., Puffr R. Poly(N-isopropylacrylamide)–clay based hydrogels controlled by the initiating conditions: Evolution of structure and gel formation. Soft Matter. 2015;11:9291–9306. doi: 10.1039/C5SM01996F. PubMed DOI

Strachota B., Hodan J., Matějka L. Poly(N-isopropylacrylamide)–clay hydrogels: Control of mechanical properties and structure by the initiating conditions of polymerization. Eur. Polym. J. 2016;77:1–15. doi: 10.1016/j.eurpolymj.2016.02.011. DOI

Strachota B., Šlouf M., Hodan J., Matějka L. Advanced two-step cryopolymerization to form superporous thermosensitive PNIPA/clay gels with unique mechanical properties and ultrafast swelling-deswelling kinetics. Colloid Polym. Sci. 2018;296:753–769. doi: 10.1007/s00396-018-4289-8. DOI

Haraguchi K., Takehisa T. Nanocomposite Hydrogels: A Unique Organic–Inorganic Network Structure with Extraordinary Mechanical, Optical, and Swelling/De-swelling Properties. Adv. Mater. 2002;14:1120. doi: 10.1002/1521-4095(20020816)14:16<1120::AID-ADMA1120>3.0.CO;2-9. DOI

Strachota B., Matějka L., Sikora A., Spěváček J., Konefał R., Zhigunov A., Šlouf M. Insight into the cryopolymerization to form a poly(N-isopropylacrylamide)/clay macroporous gel: Structure and phase evolution. Soft Matter. 2017;13:1244–1256. doi: 10.1039/C6SM02278B. PubMed DOI

Yoshida R., Sakai K., Okano T., Sakurai Y. Surface-modulated skin layers of thermal responsive hydrogels as on-off switches: II. Drug permeation. J. Biomater. Sci. Polym. Ed. 1992;3:243–252. doi: 10.1163/156856292X00150. PubMed DOI

Zhang J.-T., Huang S.-W., Zhuo R.-X. Temperature-Sensitive Polyamidoamine Dendrimer/Poly(N-isopropylacrylamide) Hydrogels with Improved Responsive Properties. Macromol. Biosci. 2004;4:575–578. doi: 10.1002/mabi.200400003. PubMed DOI

Liu Q., Zhang P., Qing A., Lan Y., Lu M. Poly(N-isopropylacrylamide) hydrogels with improved shrinking kinetics by RAFT polymerization. Polymer. 2006;47:2330–2336. doi: 10.1016/j.polymer.2006.02.006. DOI

Depa K., Strachota A., Šlouf M., Brus J. Poly(N-isopropylacrylamide)-SiO2 nanocomposites interpenetrated by starch: Stimuli-responsive hydrogels with attractive tensile properties. Eur. Polym. J. 2017;88:349–372. doi: 10.1016/j.eurpolymj.2017.01.038. DOI

Strachota B., Strachota A., Šlouf M., Brus J., Cimrová V. Monolithic intercalated PNIPAm/starch hydrogels with very fast and extensive one-way volume and swelling responses to temperature and pH: Prospective actuators and drug release systems. Soft Matter. 2019;15:752–769. doi: 10.1039/C8SM02153H. PubMed DOI

Strachota B., Strachota A., Horodecka S., Šlouf M., Dybal J. Monolithic nanocomposite hydrogels with fast dual T- and pH- stimuli responsiveness combined with high mechanical properties. J. Mater. Res. Technol. 2021;15:6079–6097. doi: 10.1016/j.jmrt.2021.11.018. DOI

Zhang L.-M. Cellulosic associative thickeners. Carbohydr. Polym. 2001;45:1–10. doi: 10.1016/S0144-8617(00)00276-9. DOI

Moussa E., Siepmann F., Flament M., Benzine Y., Penz F., Siepmann J., Karrout Y. Controlled release tablets based on HPMC:lactose blends. J. Drug Deliv. Sci. Technol. 2019;52:607–617. doi: 10.1016/j.jddst.2019.05.028. DOI

Wu Z., Hong Y. Combination of the Silver–Ethylene Interaction and 3D Printing To Develop Antibacterial Superporous Hydrogels for Wound Management. ACS Appl. Mater. Interfaces. 2019;11:33734–33747. doi: 10.1021/acsami.9b14090. PubMed DOI

Kato N., Gehrke S.H. Microporous, fast response cellulose ether hydrogel prepared by freeze-drying. Colloids Surf. B Biointerfaces. 2004;38:191–196. doi: 10.1016/j.colsurfb.2004.01.018. PubMed DOI

Marsano E., Bianchi E., Viscardi A. Stimuli responsive gels based on interpenetrating network of hydroxy propylcellulose and poly(N-isopropylacrylamide) Polymer. 2004;45:157–163. doi: 10.1016/j.polymer.2003.10.088. DOI

Liu Z., Zhang S., Gao C., Meng X., Wang S., Kong F. Temperature/pH-Responsive Carboxymethyl Cellulose/Poly (N-isopropyl acrylamide) Interpenetrating Polymer Network Aerogels for Drug Delivery Systems. Polymers. 2022;14:1578. doi: 10.3390/polym14081578. PubMed DOI PMC

Liu Z., Zhang S., He B., Wang S., Kong F. Temperature-responsive hydroxypropyl methylcellulose-N-isopropylacrylamide aerogels for drug delivery systems. Cellulose. 2020;27:9493–9504. doi: 10.1007/s10570-020-03426-w. DOI

Wang J., Zhou X., Xiao H. Structure and properties of cellulose/poly(N-isopropylacrylamide) hydrogels prepared by SIPN strategy. Carbohydr. Polym. 2013;94:749–754. doi: 10.1016/j.carbpol.2013.01.036. PubMed DOI

Wei W., Hu X., Qi X., Yu H., Liu Y., Li J., Zhang J., Dong W. A novel thermo-responsive hydrogel based on salecan and poly(N-isopropylacrylamide): Synthesis and characterization. Colloids Surf. B Biointerfaces. 2015;125:1–11. doi: 10.1016/j.colsurfb.2014.10.057. PubMed DOI

Hu Y., Kim Y., Jeong J.-P., Park S., Shin Y., Hong I.K., Kim M.S., Jung S. Novel temperature/pH-responsive hydrogels based on succinoglycan/poly(N-isopropylacrylamide) with improved mechanical and swelling properties. Eur. Polym. J. 2022;174:111308. doi: 10.1016/j.eurpolymj.2022.111308. DOI

Wan T., Huang R., Zhao Q., Xiong L., Qin L., Tan X., Cai G. Synthesis of wheat straw composite superabsorbent. J. Appl. Polym. Sci. 2013;130:3404–3410. doi: 10.1002/app.39573. DOI

Mirzakhanian Z., Faghihi K., Barati A., Momeni H.R. Synthesis and characterization of fast-swelling porous superabsorbent hydrogel based on starch as a hemostatic agent. J. Biomater. Sci. Polym. Ed. 2015;26:1439–1451. doi: 10.1080/09205063.2015.1100496. PubMed DOI

Yi G., Huang Y., Xiong F., Liao B., Yang J., Chen X. Preparation and swelling behaviors of rapid responsive semi-IPN NaCMC/PNIPAm hydrogels. J. Wuhan Univ. Technol. Sci. Ed. 2011;26:1073–1078. doi: 10.1007/s11595-011-0365-3. DOI

Alvarez-Lorenzo C., Concheiro A., Dubovik A.S., Grinberg N.V., Burova T.V., Grinberg V.Y. Temperature-sensitive chitosan-poly(N-isopropylacrylamide) interpenetrated networks with enhanced loading capacity and controlled release properties. J. Control. Release. 2005;102:629–641. doi: 10.1016/j.jconrel.2004.10.021. PubMed DOI

Zhang G.-Q., Zha L.-S., Zhou M.-H., Ma J.-H., Liang B.-R. Rapid deswelling of sodium alginate/poly(N-isopropylacrylamide) semi-interpenetrating polymer network hydrogels in response to temperature and pH changes. Colloid Polym. Sci. 2004;283:431–438. doi: 10.1007/s00396-004-1172-6. DOI

Ilavský M. Responsive Gels: Volume Transitions I. Springer; Berlin/Heidelberg, Germany: 1993. Effect of phase transition on swelling and mechanical behavior of synthetic hydrogels; pp. 173–206. DOI

Yoshida R., Sakai K., Okano T., Sakurai Y. Drug release profiles in the shrinking process of thermoresponsive poly(N-isopropylacrylamide-co-alkyl methacrylate) gels. Ind. Eng. Chem. Res. 1992;31:2339–2345. doi: 10.1021/ie00010a013. DOI