# Fileset

[Nanoscale24_16_13230.pdf](https://mdr.nims.go.jp/filesets/35334eb9-9242-4c72-9a52-10cc10c9b696/download)

## Creator

[Jingwen Song](https://orcid.org/0000-0003-1910-9287), [Wenyan Lyu](https://orcid.org/0000-0002-4109-6817), [Kohsaku Kawakami](https://orcid.org/0000-0002-3466-9365), [Katsuhiko Ariga](https://orcid.org/0000-0002-2445-2955)

## Rights



## Other metadata

[Bio-gel nanoarchitectonics in tissue engineering](https://mdr.nims.go.jp/datasets/2fe69cd5-e41d-4758-b811-a7625ba75892)

## Fulltext

Bio-gel nanoarchitectonics in tissue engineeringNanoscaleREVIEWCite this: Nanoscale, 2024, 16, 13230Received 10th February 2024,Accepted 13th June 2024DOI: 10.1039/d4nr00609grsc.li/nanoscaleBio-gel nanoarchitectonics in tissue engineeringJingwen Song, *a Wenyan Lyu, b,c Kohsaku Kawakami a,d and Katsuhiko Ariga *b,cGiven the creation of materials based on nanoscale science, nanotechnology must be combined withother disciplines. This role is played by the new concept of nanoarchitectonics, the process of construct-ing functional materials from nanocomponents. Nanoarchitectonics may be highly compatible with appli-cations in biological systems. Conversely, it would be meaningful to consider nanoarchitectonics researchoriented toward biological applications with a focus on materials systems. Perhaps, hydrogels are promis-ing as a model medium to realize nanoarchitectonics in biofunctional materials science. In this review, wewill provide an overview of some of the defined targets, especially for tissue engineering. Specifically, wewill discuss (i) hydrogel bio-inks for 3D bioprinting, (ii) dynamic hydrogels as an artificial extracellularmatrix (ECM), and (iii) topographical hydrogels for tissue organization. Based on these backgrounds andconceptual evolution, the construction strategies and functions of bio-gel nanoarchitectonics in medicalapplications and tissue engineering will be discussed.1. IntroductionThe development of mankind has been accompanied by thedevelopment of available functional materials. As humansocial life has become larger and more diverse, socialdemands have increased dramatically. For example, functionalmaterials have been developed to confront many problemssuch as energy production,1 energy storage,2 various sensing,3environmental protection,4 carbon neutrality,5 device develop-ment,6 drug delivery,7 regenerative medicine,8 pathogencontrol,9 and cancer treatment.10 Most of them do not rely onthe inherent performance of the material itself. The key to theexpression of advanced functions is the control of sophisti-cated structures that extend to the nanoscale. The develop-ment of the concept of nanotechnology has clarified thistrend. It has made it possible to observe11 and manipulate12structures at the atomic and molecular levels. Nanotechnologyhas allowed us to elucidate scientific phenomena and prin-Jingwen SongJingwen Song received her Ph.D.degree from The University ofTokyo under the guidance ofProfessor Katsuhiko Ariga in2021. She also studied in theSupermolecules Group at theWorld Premier International(WPI) Research Centre forMaterials Nanoarchitectonics(MANA), National Institute forMaterials Science (NIMS), from2018 to 2021. She is currently apostdoctoral researcher in theMedical Soft Matter group,NIMS.Wenyan LyuWenyan Lyu is a PhD studentat The University of Tokyo underthe supervision of ProfessorKatsuhiko Ariga. She completedher master’s degree from the SunYat-Sen University in 2023. Herresearch focuses on theManipulation of cellular beha-viors and fates based on liquid–liquid interfaces.aResearch Center for Functional Materials, National Institute for Materials Science(NIMS), 1-1 Namiki, Tsukuba 305-0044, Ibaraki, Japan.E-mail: SONG.Jingwen@nims.go.jpbGraduate School of Frontier Sciences, The University of Tokyo, 5-1-5 Kashiwa-no-ha,Kashiwa 277-8561, JapancResearch Center for Materials Nanoarchitectonics, National Institute for MaterialsScience (NIMS), 1-1 Namiki, Tsukuba 305-0044, Japan.E-mail: ARIGA.Katsuhiko@nims.go.jpdGraduate School of Pure and Applied Sciences, University of Tsukuba,1-1-1 Tennodai, Tsukuba 305-8577, Ibaraki, Japan13230 | Nanoscale, 2024, 16, 13230–13246 This journal is © The Royal Society of Chemistry 2024http://rsc.li/nanoscalehttp://orcid.org/0000-0003-1910-9287http://orcid.org/0000-0002-4109-6817http://orcid.org/0000-0002-3466-9365http://orcid.org/0000-0002-2445-2955http://crossmark.crossref.org/dialog/?doi=10.1039/d4nr00609g&domain=pdf&date_stamp=2024-07-15ciples at the nanoscale. Given the creation of materials basedon nanoscale science, nanotechnology must be combined withother disciplines. This role is played by the new concept ofnanoarchitectonics,13 the process of constructing functionalmaterials from nanocomponents. It can be called a post-nano-technology concept.14 The ultimate goal of nanoarchitectonicsis to construct functional materials systems with many func-tional units, such as biological systems.15While Richard Feynman proposed nanotechnology in themid-20th century,16 Masakazu Aono initiated nano-architectonics at the beginning of the 21st century.17Nanoarchitectonics combines various processes that have beenmainly formulated in the field of materials science, with theaim of architecting functional materials systems from nano-units such as atoms and molecules (Fig. 1).18 It selects andcombines atomic and molecular manipulation, chemical/physical material creation and transformation, self-assembly/self-organization, arrangement/organization by external fieldsand forces, nano- and micro-fabrication, biochemical pro-cesses, etc. to architect functional materials.19 Thus, unlikeself-assembly,20 which is based on simple equilibrium,nanoarchitectonics is suited to creating asymmetric and hier-archical materials structures.21 Nanoscale processes aresubject to uncertainties such as thermal fluctuations, stochas-tic distributions, and quantum effects. Therefore, functionalmaterials systems are built in such a way that effects are har-monized.22 The form in which functional molecules are orga-nized hierarchically and the mode in which they work symbio-tically with thermal fluctuations is similar to those of biofunc-tional systems.23 Therefore, the ultimate goal of nanoarchitec-tonics is to construct advanced functional systems like biologi-cal systems and to architect materials systems that interactwith biofunctional systems. For example, exploration of func-tional systems based on bio-gels would be a good researchtarget.Nanoarchitectonics is a methodology for architecting func-tional materials systems from atoms and molecules. Since allmaterials are in principle made of atoms and molecules, themethodology of nanoarchitectonics applies to all materials. Itis an integrative concept that can be likened to the theory ofeverything in physics24 and can be called the method for every-thing in materials science.25 The endeavor of nanoarchitec-tonics will provide new insights and deeper thinkings in thefield of materials chemistry in general. In fact, researchstudies advocating nanoarchitectonics are being conducted ina wide range of fields, not only in fields related to chemistry26and physics,27 but also many related to biology and bio-chem-istry.28 Nanoarchitectonics is expected to contribute to manyareas, including those related to basic bio-chemistry,29 biosen-sing,30 drug delivery,31 cell control,32 and therapeutic areas.33Nanoarchitectonics may be highly compatible with appli-cations in biological systems. Conversely, it would be meaning-ful to consider nanoarchitectonics research oriented towardbiological applications with a focus on materials systems.The methodology of nanoarchitectonics is not aboutlaunching an entirely new concept. Rather, it is an integrationof existing fields. Therefore, there are many examples ofKohsaku KawakamiKohsaku Kawakami received hisPhD in Chemical Engineering in2000 from Kyoto University.After working for pharmaceuticalcompanies including Shionogiand Merck, he joined theNational Institute for MaterialsScience in 2006. He is currentlya group leader of the MedicalSoft Matter group and a directorof the Material Open Platformfor Pharmaceutical Science. Healso serves as a professor at theUniversity of Tsukuba.Katsuhiko ArigaKatsuhiko Ariga received hisPh.D. degree from the TokyoInstitute of Technology in 1990.He joined the National Institutefor Materials Science (NIMS) in2004 and is currently the leaderof the Supermolecules Groupand a senior scientist withspecial missions of the ResearchCentre for MaterialsNanoarchitectonics (MANA),NIMS. He has also beenappointed as a professor in TheUniversity of Tokyo.Fig. 1 Outline of the nanoarchitectonics concept and approach.Nanoscale ReviewThis journal is © The Royal Society of Chemistry 2024 Nanoscale, 2024, 16, 13230–13246 | 13231research that have characteristics of nanoarchitectonics even ifthey do not advocate nanoarchitectonics. From this perspec-tive, we will consider how conventional technologies can con-tribute to nanoarchitectonics. The point is to assemblerational three-dimensional (3D) structures from nano-unitssuch as atoms, molecules, and ions. One methodology is toorganize two-dimensional (2D) structures and then assemblethem into an organized 3D functional structure.34 Functionalintegration in biological systems is the rational integration offunctional molecules based on various membrane structures.35Therefore, organizing functional molecules intrinsically into2D systems such as thin films may be one of the best strategiesof nanoarchitectonics for creating highly functional materials.On this basis, building 3D structures is a suitable way to creatematerials for bio-applications. Typical methodologies are theLangmuir–Blodgett (LB) method36 and layer-by-layer (LbL)assembly.37 These methods are rational methods for buildingfunctional structures from two to three dimensions, but theyonly synthesize structures at the thin-film level. They are notalways suitable as methods for building macroscopicmaterials.A methodology for creating well-defined structures in twoor three dimensions from molecules or ions is the synthesis ofmetal–organic frameworks (MOFs)38 and covalent organicframeworks (COFs).39 In this case, crystal structures withprecise pore structures are formed. 3D precise structures canbe made, but with a few exceptions,40 most are rigid structures.Also, large structures at the level of animal experiments arenot always possible. In addition, there are many other meth-odologies to create 3D structures by supramolecular assem-bly. Among them, gel creation is a methodology that incor-porates a large amount of solvent molecules to form macro-scopic structures using only a small amount of constituentmolecules.41 The characteristic feature of this method is thatit produces very soft structures due to the large amount ofsolvent. Hydrogels in which the solvent material is watermolecules are particularly suitable for biological applications.When considering biological applications through 3Dnanoarchitectonics, it is useful to consider gels as targetmaterials.First, a brief look at some recent examples of gel researchshows that gels, which are already widely studied materials,are also being investigated for controlling fundamental physi-cal properties, such as mechanical properties are controlledthrough structural design, while the order and disorder charac-teristics are regulated using physicochemical procedures.42This indicates that there remains ample room for nanoarchi-tectonics to contribute to the field of gels as well. Mayumi, Ito,and co-workers are investigating gels with sliding ring struc-tures.43 Recently, they found that moderate cross-linking ofpoly(ethylene glycol) hydrogels led to parallel orientation ofthe chains during elongation and rapid and reversible strain-induced crystallization.44 The resulting toughness was anorder of magnitude greater than that of covalently crosslinkedpoly(ethylene glycol) homogeneous gels. Sekine and Nankawaexamined carboxymethylcellulose nanofiber hydrogels formedby solid–liquid phase separation.45 Kubota discussed supra-molecular-polymer composite hydrogels as multi-networkhydrogels in his recent review.46 The design of this compo-site hydrogel can rationally integrate the stimulus-responseof the supramolecular gel with the stiffness of the poly-meric gel. Yamanaka and co-workers investigated theadsorption of silica, polystyrene, and titania particles ontopolyacrylamide and polydimethylacrylamide hydrogels.47 Thevan der Waals force was again found to be a strongenough driving force for particles absorbed on the surfaceof polymer hydrogels in water. Supramolecular polymer-based hydrogels typically exhibit highly ordered structures,which are stable and in a thermodynamic equilibriumstate. Recently, Xing, Yan, and their co-workers preparedlong-range disordered biomolecular glasses using aminoacid and peptide nanoarchitectonics. These glasses demon-strate biocompatibility, biodegradability, and biorecyclability,surpassing the properties of currently used commercialglasses and plastic materials.48In addition to the basic studies of physical properties,several advanced applications have been reported. Li, Gao, andco-workers discussed in a recent review flexible sensors basedon biohydrogels of bacterial cellulose as natural biomass.49Potential applications include human–machine interfaces,wearable medicine, and bionic intelligent robotics. Masud,Hossain, Kaneti, and co-workers developed κ-carrageenanhydrogel-coated mesoporous gold electrodes.50 These wereuseful for the chronocoulometric detection of microRNA. Lu,Gu, and co-workers developed a conductive polymer hydrogelstrain sensor that exhibited both extreme strain and negligiblehysteresis.51 It was created by a micro-phase semi-separatednetwork design of the polymer and a fabrication techniquethat combined 3D printing and continuous freeze–thawing.The technology could be directed toward stretchable electronicskin and intelligent robotic systems. Hydrogels are idealmaterials for human–machine interfaces because of theirmechanical and chemical similarity with biological tissues. Arecent review reported by Yuk et al. provided a comprehensivediscussion of functional modes, design principles, and futureapplications of hydrogel interfaces for human–machine inte-gration.52 Kai, Yu, Huang, and co-workers also discussed thecorrelation between hydrogel properties and device perform-ances in their recent review.53 This is to provide a perspectiveon current challenges and future directions for the develop-ment of flexible electronics using environmentally responsivehydrogels.For example, properties such as stiffness, pore size, viscoe-lasticity, nano- and microarchitecture, degradability, ligandpresentation, and stimulus responsiveness can be widelymodulated in hydrogels. Therefore, applications in the bio-medical field are quite promising. The review by Cao, Zhang,and co-workers discussed the rational structural and func-tional design of hydrogels utilizing materials engineering toinfluence cell signaling cascades and fates.54 Cheng, Yue, andco-workers proposed an antibiotic-free strategy to combatimplant-related infections by using biodegradable and cyto-Review Nanoscale13232 | Nanoscale, 2024, 16, 13230–13246 This journal is © The Royal Society of Chemistry 2024compatible hydrogel coatings.55 Duan, Guo, and co-workersdeveloped a photo-crosslinked multifunctional antimicrobialadhesive hemostatic hydrogel dressing based on polyethyleneglycol monomethyl ether modified glycidyl methacrylate func-tionalized chitosan, methacrylamide dopamine, and zincions.56 This is intended to kill drug-resistant bacteria andpromote wound healing. Guo and co-workers developed a self-healing hydrogel based on quaternized chitosan, oxidizeddextran, tobramycin, and polydopamine-coated polypyrrolenanowires, with good electrical conductivity and antioxidantactivity.57 This is aimed at burn wound repairment. Qi, Shen,Hu, and co-workers developed a hydrogel with melanin nano-particles loaded on a polysaccharide matrix composed ofbiguanide chitosan and oxidized β-glucan for efficient healingof bacterially infected diabetic wounds.58 This wound dressingmaterial could be a new option for the treatment of diabeticwounds. Fu, Zhu, Fan, and co-workers developed a gel that isconducive to diabetic chronic wounds.59 They encapsulatedgelatin microspheres containing insulin and celecoxib. The gelwas prepared using phenylborate-grafted polyvinyl alcohol andchitosan. Showing dual-response temperature-sensitive shapeself-adaptation to glucose and matrix metalloproteinase-9,Zhao, Yang, and co-workers hybridized collagen-based naturalhydrogels with protocatechuic acid aldehyde for their ability toregulate macrophage heterogeneity.60 Useful for promotingangiogenesis and diabetic wound healing, He, Shen, and co-workers developed a novel glycyrrhizic acid-based hybridhydrogel dressing with intrinsic immunomodulatory pro-perties.61 This hybrid hydrogel, which also focuses on promot-ing rapid healing of diabetic wounds, is composed of an inter-penetrating polymer network with excellent injectability andmechanical strength. Zhu, Fan, and co-workers developed aninjectable hydrogel based on Ti3C2 MXene nanosheets coatedwith hyaluronic acid-grafted-dopamine and polydopamine.62This could be applied to diabetic wound healing in combi-nation with mild photothermal stimulation. Guo and co-workers designed a cross-linked multifunctional adhesivehydrogel based on sodium alginate, gelatin, and protocate-chuic aldehyde, with ferric ions added.63 The developed revers-ible adhesive hydrogel dressing can be served as a versatiletissue sealant.As described above, gels, especially hydrogels, have beenstudied in many fields. They can be used for various purposesbecause they can incorporate multiple components ofnanoarchitectonics. They have many advantages, such as theability to freely control their mechanical properties throughsolvent content and internal nano- and micro-structures. Ascan be seen from the examples, many efforts are being madefor practical applications in the biomedical field. Perhaps,hydrogels are promising as a model medium to realizenanoarchitectonics in biofunctional materials science. In thisreview, we will provide a more detailed overview of some of themore narrowly defined targets, especially for tissue engineer-ing, and look at the utility of hydrogel design and synthesis(nanoarchitectonics from molecules and polymers).Specifically, we will discuss (i) hydrogel bio-inks for 3D bio-printing, (ii) dynamic hydrogels as an artificial extracellularmatrix (ECM), and (iii) topographical hydrogels for tissueorganization. In detail, hydrogel bio-inks stand out for therheological properties of initial extrudability and printabilityas inks, as well as their self-supporting and shape mainten-ance abilities after being used to construct hydrogel scaffolds.Additionally, by regulating the printing formulation or pro-grams, hydrogel bio-inks loaded with cells or growth factors ofinterest can be readily customized to accomplish the spatio-temporal distribution which has great potential for artificial3D tissues or organs, etc. In dynamic hydrogels, the emphasisshifts to mechanical properties that dynamically respond toenvironmental stimuli such as pH, temperature, light, or bio-chemical signals. Dynamic hydrogels undergo reversiblechanges in stiffness or degradation rates to provide a suppor-tive matrix that can remodel and adapt to cell activity, facili-tating cell migration, proliferation, and differentiation.Topographical hydrogels rely on surface patterning and nano/micro-scale features to influence cell behaviors. They haveprecise spatial cues that mimic the native tissue microenvi-ronment and guide cell adhesion, alignment, and organiz-ation. Based on these backgrounds and conceptual evolutions,the construction strategies and functions of bio-gel nanoarchi-tectonics in medical applications and tissue engineering willbe discussed.2. Hydrogel bio-inks for 3Dbioprinting3D bioprinting technology is expected to achieve scalable bio-fabrication of structurally complex and functionally powerfultissue simulations for the study and amelioration of humandiseases. Bio-ink materials for 3D printing must present twomain roles: first, as raw materials, they can be used to manu-facture structured constructs and second, as downstream cellinduction niches, they can support cell growth, proliferation,and function. Hydrogels are ideal bio-ink materials that canmaintain high cell viability and can also combine with tra-ditional biological growth factors strategies to guide cell phe-notype and fate.Conventional hydrogels exhibit a homogeneous structure,which as bio-inks for 3D printing will restrict cell growth andmobility as well as impede the diffusion of oxygen and nutri-ents, thus hindering cell viability, infiltration, and prolifer-ation. Seymour et al. constructed microgel-based compositegranular 3D printing inks composed of UV-cross-linkablegelatin methacryloyl (GelMA) microgels and sacrificial gelatinmicrogels (Fig. 2A).64 After UV cross-linking and heat melting,crosslinked GelMA scaffolds remained, but gelatin wasremoved and left behind continuous void space. The void frac-tion could be readily controlled by the proportion of thegelatin microgel within total composite inks. Experiments ofthe rheological characteristics assessed that the total concen-tration of microgels impacted the printability and shapemaintenance, which were independent of the ratio ofNanoscale ReviewThis journal is © The Royal Society of Chemistry 2024 Nanoscale, 2024, 16, 13230–13246 | 13233GelMA : gelatin microgel inks, so the printability wasdecoupled from the void fraction. Furthermore, it also demon-strated that the interstitial void space of printed scaffolds wasbeneficial for human umbilical vein endothelial cell (HUVEC)growth and infiltration, which was positively associated withthe void fraction (Fig. 2B). Therefore, this work could provide anew insights into bioprinting and tissue engineering appli-cations through fabricating microporous GelMA microgel inkswith advanced printability and shape maintenance.Therapeutic growth factors delivery often requires higherthan normal doses, which can cause unwanted side effects.Freeman et al. established a novel 3D printed compositescaffold with distinct spatiotemporally distributed growthfactors, which could be used as an implant for angiogenesisand bone defect healing.65 Two kinds of alginate/methyl-cellulose-based bioinks respectively containing vascular endo-thelial growth factor (VEGF) and bone morphogenetic protein-2 (BMP-2) were incorporated to fabricate the compositeprinted construct to achieve the above-mentioned tissue regen-eration (Fig. 3A). It had been demonstrated that the spatial dis-tribution of VEGF with decreasing load from the center to per-iphery within the implant was more conducive to vascularinfiltration than the implant loading with homogeneously dis-tributed VEGF, which could be credited to the cell migrationchemotactic effect. Moreover, peripherally distributed BMP-2with a slow-release profile, achieved by the addition of nano-particles LAPONITE® due to electrostatic attraction, wasassessed as more favorable for new bone formation thanBMP-2 with fast release in implants. Furthermore, the wholewas greater than the sum of the parts, and thereby the compo-site growth factor delivery system with both VEGF and BMP-2was also applied to bone defect healing. It had been provedthat the composite implant could not only enhance angio-genesis more significantly compared to the VEGF gradient-only loaded hydrogel but also promote bone regeneration andmaturation with little heterotopic bone formation (Fig. 3B),which was mainly attributed to appropriate growth factorrelease kinetics and non-supraphysiological dosages.Therefore, the composite growth factor loaded system dis-played in this work provides some new inspirations in bio-hydrogel designs and precisely controlled tissue regeneration,such as the spatiotemporal synergetic technique and con-trolled release strategies of multiple growth factors under theauxiliary of nanoparticles.In addition to the above examples, there are diverse appli-cations of hydrogels for 3D bioprinting. Properties such as bio-compatibility with shear viscosity reduction, adequate yieldstrength, and fast self-healing are desired in hydrogel inks for3D bioprinting. The searches of gel structures for this purposeare underway from various viewpoints. Zhang et al. developednovel self-healing pre-crosslinked hydrogel microparticles ofchitosan methacrylate/poly(vinyl alcohol) hybrid hydrogels.66Using this ink, they directly printed a series of biomimeticconstructs with very high aspect ratios and delicate microstruc-tures. It was possible to fabricate constructs easily and ver-satilely with excellent shape fidelity at organ-related scales,such as blood vessels, human ears, and rat femurs.Bioprinting by digital light processing (DLP) is advantageousfor the biofabrication of structurally complex tissues. Wanget al. used a method of selective enzymatic digestion of hyalur-Fig. 2 Schematic of the preparation process and cellular effect of a microgel-based composite granular 3D printing hydrogel with void space. (A)Schematic of preparing 3D printing scaffolds by using UV-crosslinkable gelatin methacryloyl (GelMA) microgels and sacrificial gelatin microgels. Thescaffold can create void spaces by melting the sacrificial gelatin microgel at 37 °C. (B) Cell infiltration was promoted with an increased void fractionof 3D-printed constructs, which was controlled by the proportion of sacrificial gelatin microgels.Review Nanoscale13234 | Nanoscale, 2024, 16, 13230–13246 This journal is © The Royal Society of Chemistry 2024onan methacrylate for DLP bioprinting.67 The molecular clea-vage approach provided a tissue-matched structure withoutloss of structural complexity and fidelity. With this method,stem cell-derived NGN2-accelerated progenitor cells (SNaPs)differentiated into neurons and astrocytes. They exhibitedstrong electrophysiological and other brain-like properties.With further optimization, the molecular cleavage strategy wasexpected to be applied to tissue engineering, which has beendifficult to realize.Kim et al. used bioink made from silk fibroin for DLP-3Dbioprinting in tissue engineering applications.68 Mechanicaland rheological properties could be adjusted by varying thecontent of the silk fibroin-based bioink. The bioink allowedthe construction of very complex organ structures such as theheart, blood vessels, brain, trachea, and ears with excellentstructural stability and reliable biocompatibility. It was particu-larly noteworthy that this approach only used naturally derivedpolymers. Recently, four-dimensional (4D) printing hasemerged as a next generation biofabrication technology. Kimet al. reported a 4D bioprinting system based on DLP and aphotocurable silk fibroin hydrogel, containing two or morecell types.69 Using this 4D bioprinting system, trachealmimetic tissues consisting of two types of cells were produced.When implanted into a damaged rabbit trachea, the implantspontaneously integrated with the host trachea. Both epi-thelium and cartilage formed at the predicted site. This raisedthe possibility of using this system for tissue engineering andbiomedical applications.The above illustrates the usefulness of hydrogels as bioinksfor 3D bioprinting. Their mechanical and biocompatibilityproperties are important parameters. The target organs andbiological tissues are diverse. The phenomena are intricateand complex, but the underlying polymer chemistry and physi-cal chemistry are based on prior knowledge. In other words,the design and synthesis of optimal hydrogels using suchknowledge leave a variety of grounds for the contribution ofnanoarchitectonics.3. Dynamic hydrogels as an artificialECMIn living organisms, cells constantly interact with the highlydynamic ECM and remodel it. This process promotes variouscell behaviors and fates, including growth, proliferation,migration, differentiation, and apoptosis. In addition to intrin-sic thermodynamic remodeling, the degradation of biologicalpolymers and the dissociation/recombination of force-inducedFig. 3 Schematic of the construction method and biological regeneration effect of 3D printing composite hydrogel scaffolds loaded with distinctspatiotemporally distributed growth factors. (A) The 3D printing hydrogels with spatial gradient distribution of BMP2 and VEGF based on the PCLframework as a support material were built and transplanted. (B) The spatial differential distribution of two kinds of growth factors within 3D printingconstructs proved more advantageous for promoting angiogenesis and bone regeneration.Nanoscale ReviewThis journal is © The Royal Society of Chemistry 2024 Nanoscale, 2024, 16, 13230–13246 | 13235physical crosslinks, which are two orthogonal external sources,also play roles in the dynamic characteristics of biologicalpolymer networks in the natural ECM. Hydrogels are widelyused as tunable biomimetic 3D cell culture matrices. Dynamichydrogels can change their structures and properties underenvironmental stimuli. The formation of these hydrogels isusually achieved through physical interaction or chemicalcross-linking, building a 3D network nanoarchitectonics thathas the capacity to swell in water and respond to external cues.Moreover, dynamic hydrogels comprise reversible bonds likehydrogen bonds, ionic interactions, or dynamic covalentbonds, so that the hydrogel can have reversible structuralchanges, which provides it the applications for self-healing,adaptation and responsiveness to environmental cues. Somehydrogels show fast responses to stimuli such as temperature,pH, light, and ionic strength. As a result, dynamic hydrogelscan be assembled from building blocks that adapt to cellactivities when living cells are introduced. However, the naturalECM is very complex, and designing the physical and chemicalproperties of hydrogels to precisely manipulate their dynamicinteractions with cells remains challenging. Therefore, design-ing a 3D hydrogel matrix with adjustable dynamic character-istics to reproduce the spatiotemporal hierarchy of ECMdynamics is of great significance in comprehending therelationship between the natural ECM and cell behaviors.To explore the dynamic correlation between the naturalECM and cell behaviors, researchers are committed to develop-ing dynamic cell-adaptive hydrogels cross-linked by dynamicreversible bonds. Yang et al. investigated the indispensablerole played by the dynamic property of 3D hydrogels based onsupramolecular crosslinks in guiding cell behaviors and fates(Fig. 4).70 Hydrogels with similar reaction equilibrium con-stants but distinct kinetic constants were prepared throughhost–guest reversible interactions between the mono-acryloylβ-cyclodextrin (ac-β-CD) and hyaluronic acid chains (HA)equally grafted with adamantane (ADA) or cholic acid (CA)prior to photo-initiated polymerization, and were termedHA-ADA and HA-CA, respectively. Consistent with the higherdissociation kinetic constants of the HA-ADA hydrogel, it alsoexhibited faster stress relaxation than the HA-CA hydrogel asFig. 4 Schematic of the preparation principles and cell behavior of dynamic hydrogels with distinct stress-relaxation time. (A) The dynamic hydro-gels were prepared based on host–guest complexation, and different guest molecules were used to build dynamic hydrogels with different dis-sociation rate constants. A cell encapsulated in the dynamic hydrogel with a large dissociation rate constant was found more conducive to cellspreading and mechanosensing. (B) The importance of precise conjugated sites and robust binding strength of cell-adhesive ligands of RGD peptidesin cellular spreading and mechanosensing is emphasized.Review Nanoscale13236 | Nanoscale, 2024, 16, 13230–13246 This journal is © The Royal Society of Chemistry 2024verified through rheological experiments. In addition, humanMesenchymal Stem Cells (hMSCs) cultured within theHA-ADA-cRGD (RGD is the abbreviation for arginylglycylaspar-tic acid) hydrogel presented extensive stellate spreading andintensive cellular mechanotransduction and osteogenic differ-entiation, while hMSCs within the HA-CA-cRGD hydrogelexhibited a round morphology and weak mechanosensing andadipogenic differentiation (Fig. 4A). In addition, the preciseconjugated sites and robust binding strength of cell-adhesiveligands of RGD peptides also played a vital role in cellularspreading and mechanosensing (Fig. 4B). The above-mentioned cellular behaviors and multi-cell assemblyimpacted by the dynamics of hydrogels involved the concertedaction of cell–matrix interactions, cell-adhesive ligand β1 integ-rin, and cytoskeletal mechanotransduction. Altogether, higherdynamics of the ECM could provide the cell membrane morelocal space freedom to explore and recruit cell-adhesiveligands of the ECM, and activate intracellular downstreammechanical signaling pathways better.The collective behavior of cell and tissue patterns are alsocontrolled by the mechanical properties of the ECM, forexample, the viscosity, elasticity, viscoelasticity, fluidity, and soon. Among these features, how the viscoelasticity of the ECMaffects the collective cell’s organization from the spatial andtemporal aspects remains not very well studied. Elosegui-Artola et al. explored and illustrated the effects driven by thepassive viscoelasticity of the ECM on the spatiotemporal organ-ization of encapsulated collective cells using alginate hydrogels(Fig. 5).71 Through coordinating the formula of alginate poly-mers and calcium crosslinker concentration, hydrogels withvarying stress relaxation times were prepared, with indepen-dent control of the stiffness (Fig. 5A). Compared with elasticmatrices, epithelial cell spheroids cultured within viscoelastichydrogels were experimentally validated to show morphologi-cal instability (rapid growth, formation of finger-like protru-sions, and spherical symmetry breaking) (Fig. 5B), and highercellular mechanotransduction involved the activation of Rac1signaling pathways, and facilitation of epithelial-to-mesenchy-mal transitions (EMTs), which was recognized to promotetumor growth and metastasis (Fig. 5C). Moreover, a compu-tational simulation and prediction model was created. The cal-culation formulas of three variables of the matrix that could beused to recapitulate tissue organization within hydrogels wereconsidered in the model – the scaled fluidity and passivemechanical relaxation time and the scaled cell proliferativecapacity – and they were in concert to design a phase diagramto predict cell patterning. Based on formulations, the compu-tational model simulated that decreased viscosity of the ECMcould lead to tissue growth and instability, which wasvalidated by the above-mentioned experiments. Besides, themodel predicted cell motility, tissue proliferation, andincreased stiffness of the matrix independent of viscoelasticityor elasticity, and all these also could contribute to tissuegrowth and instability. Definitely, these predictions were sub-stantiated by related experiments. To prove the universal appli-cability of the model, the intestinal organoids culturing experi-ment was performed and indeed verified that the viscoelasti-city of ECM promoted tissue growth and morphologicalchanges.Natural fiber matrices are critical components of the ECM,and the effects of programmable and remodelable assembly ofa 3D fibrous hydrogel scaffold on cellular behavior have yet tobe investigated. Davidson et al. fabricated reassembled norbor-nene-modified hyaluronic acid (NorHA) fibrous hydrogelassemblies by photocrosslinking the resuspension solution offragments produced from mechanical disruption of the prepre-pared electrospun fiber (Fig. 6).72 The hydrogels were found topossess excellent physical properties of shear-thinning andself-healing before photocrosslinking, which is conducive tothe potential of application in extrusion printing constructs.Fig. 5 Schematic of a hydrogel with adjustable viscoelasticity and stiffness in spatiotemporally controlling the collective cell patterning. (A)Hydrogels with varying viscoelasticity and stiffness can be independently controlled by coordinating the formula of alginate molecular weight andcrosslinker concentration. (B) The viscoelasticity and elasticity of hydrogels synergistically drove organoid morphogenesis. (C) The molecular mecha-nism behind the symmetry breaking of organoids encapsulated in the viscoelastic hydrogel.Nanoscale ReviewThis journal is © The Royal Society of Chemistry 2024 Nanoscale, 2024, 16, 13230–13246 | 13237Moreover, the features of strain-stiffening and strain-inducedfiber alignment had been detected after photocrosslinking,and both features were dramatically demonstrated in the low-density (20%) fibrous assemblies compared to those ofmedian (50%) and high (75%) density hydrogels. After encap-sulating and culturing cells within varying fibre density hydro-gels, the low-density fibrous assemblies were found to exhibitmore extensive and more pericellular fiber recruitment, morereduction of volume, higher cell density, and compressivemoduli under the cellular mechanical forces than median andhigh-density hydrogels. Due to the spatial distribution ofmatrix fibers being converted from the initial isotropic orien-tation into an organized alignment consistent with a micro-scale hydrogel geometry under cell contraction, the cell-ladenfibrous assemblies were proposed to have the utility of micro-tissue fabrication. Furthermore, the hydrogel system couldalso be utilized to fabricate programmable biohydrogels viaprinting technology or photolithography methods, which wereenabled by the shear-thinning induced extrudability andphotocrosslinking of fibrous assemblies, respectively.As seen in the examples above, the physical and structuralcues of ECMs are diverse. Hydrogels are frequently used as syn-thetic ECMs for 3D cell culture. In addition to the examplesdescribed above, various other examples of studies have beenreported. Lou et al. reported an interpenetrating network (IPN)hydrogel system based on dynamically covalently cross-linkedHA and collagen I.73 The stress relaxation of IPN hydrogels canbe tuned by the component HA. The modulation was based onthe affinity of the HA cross-linker, the molecular weight, andthe concentration of HA. The resulting viscoelastic hyaluro-nan-collagen IPN hydrogels mimicked well the microenvi-ronment of the ECM, where mechanical cues in 3D cell cultureFig. 6 Schematic of the process of creating reassembled fibrous hydrogels by using fragments of electrospun fiber mats. The study demonstratedthat fibers in low-density fibrous assemblies, cells exerting contraction forces could recruit more fibers, leading to increased fiber alignment, greaterreduction in hydrogel volume, and higher cell density.Review Nanoscale13238 | Nanoscale, 2024, 16, 13230–13246 This journal is © The Royal Society of Chemistry 2024could direct the function and fate of stem cells. Bone marrow-derived hMSCs are promising cells for regenerative therapies,and ex vivo expansion is necessary to obtain clinically usefulcell numbers. Killaars et al. used hydrogels containing allylsulfide cross-linkers and radical-mediated addition–fragmenta-tion chain transfer processes at different time points.74Hydrogels containing hMSCs were softened in situ. The effectsof short- and long-term mechanical stimuli on epigeneticmodification of hMSCs were quantified. Epigenetic remodel-ing was persistent, suggesting that memory may be retained inneural progenitor cell (NPC) culture in 3D hydrogels. This wasan attractive strategy to increase the number of stem cellsneeded for therapeutic purposes. How the properties of the 3Dmaterial affect the maintenance of NPC stem cells in theabsence of differentiation factors has been less well explored.Madl et al. found that stem cell maintenance did not correlatewith initial hydrogel firmness in the range of physiologicallyappropriate firmness.75 Conversely, hydrogel degradation cor-related with and was necessary for the maintenance of NPCstemness. This finding suggested that matrix remodelingwithout cytoskeletal tension generation was one strategy tomaintain cellular stemness in 3D.Zhang et al. investigated the mechanosensing behavior ofhuman mesenchymal stem cells using a thermosensitive elec-trospun microfiber crosslinked hydrogel.76 The ability toswitch in situ from a rigid (37 °C) to a soft (25 °C) state in atemperature-induced manner for a number of cycles was inves-tigated. Cell proliferation, adhesion, mechanical threshold fornuclear migration of YAP signals, and osteogenic differen-tiation were enhanced compared to hMSCs grown undernormal culture conditions. This might be due to enhancedmechanical feedbacks via dynamic mechanical interactionsbetween cells and 3D fibrous constructs. The influence of earlyprotein deposition on cell behavior in hydrogels had not beenwell explored. Loebel et al. used biological orthogonal labelingtechniques to visualize early proteins within 1 day of culture ina variety of hydrogels.77 The role of nascent proteins in cellrecognition of engineered materials had been reaffirmed andhad implications for in vitro cell signaling studies and tissuerepairment applications. However, there is still room forfurther investigations in complex feedback mechanisms.Intracellular biomacromolecules were dynamically reorganizedin response to signals. This is dynamic nanoarchitectonics inliving systems. Freeman et al. prepared hydrogels based onpeptide amphiphiles, which can have DNA chains that degradein response to chemical triggers, and investigated their super-structural assembly behaviors.78 The hydrogels had the prop-erty of degrading upon the addition of molecules or changesin charge density and organizing into a superstructure ofentangled filaments. Experimental and simulation results indi-cated that reversible superstructures were formed when thelarge-scale dynamics of the supramolecular material was con-trolled by the formation of strong non-covalent bonds thatcould be broken from the outside. This dynamic supramolecu-lar system allowed us to consider how changes in the structuralfeatures of the hydrogel network modulate important phenoty-pic changes in astrocytes associated with brain and spinalcord injury and neurological diseases.The natural ECM has a decisive influence on cell behavior.Therefore, nanoarchitectonics of its artificial mimics is impor-tant for cellular tissue engineering and regenerative medicine.Hydrogels are very promising candidates, as seen in many ofthe examples above. The development of an artificial ECM ischallenging due to the need for responses to the interaction/feedback from cells. Therefore, it is necessary to analyze thedynamic cell behavior and synthesize corresponding materialsand structures. In such cases, the dynamic nanoarchitectonicsapproach is considered a powerful target.4. Topographical hydrogels for tissueorganizationTopographical scaffolding plays a crucial role in the develop-ment of epithelial organs and the solid vascular networks con-necting them. In tissue engineering, the scaffold used is oneof the most critical elements. Biocompatible hydrogel basedtopographical scaffold fabrications are expected to mimic fromthe microscale of the native ECM to macroscale of tissue topo-graphical structures.The mechanism of fluid transport by multivascular net-works and intravascular topographies has always been a verychallenging research topic as such complex 3D network chan-nels are difficult to construct. Grigoryan et al. constructed poly(ethylene glycol) diacrylate (PEGDA) hydrogels containing mul-tivascular networks based on 3D stereolithography throughbottom-up LBL photopolymerization under the assistance ofinnovative biocompatible photoabsorber additives, such as tar-trazine (yellow food coloring FD&C Yellow 5, E102), curcumin(from turmeric), or anthocyanin (from blueberries).79 3Dmonolithic hydrogels with the vessel wall integrated with afunctional bicuspid valve were fabricated, which could effec-tively spontaneously control the open-state of anterogradeflows and the close-state of retrograde flows. Besides, entangledvascular networks comprising two separated and non-intersectedchannels also were established. When one of the channels wasoxygen ventilation and another was perfused human red bloodcells, respectively, vascularized alveolar and lung-mimeticmodels were created and validated to extremely recapitulate thefunctional intervascular oxygen transportation between the circu-latory system and respiratory system. Furthermore, superiortherapeutic effects of the transplantation of compositive hydro-gel carriers containing vascular networks and encapsulated hep-atocytes in chronic liver injury were determined, so it wasrevealed that the system had clinical application value.The stem cell self-organization process that is fundamentalto organoid development has been difficult to control, whichleads to the lack of repeatability in most existing technologyfor organoid culturing. Gjorevski et al. developed an externalcontrol strategy based on photosensitive poly(ethylene glycol)(PEG) hydrogels to confine the geometry of intestinal orga-noids, and demonstrated the indispensable influence of a pre-Nanoscale ReviewThis journal is © The Royal Society of Chemistry 2024 Nanoscale, 2024, 16, 13230–13246 | 13239defined geometrical framework for the development of intesti-nal organoids (Fig. 7A).80 The crypt–villus axis of intestinalorganoids mostly occurred at the localized position of cellaccumulation within the shape-confined organoids, whichinvolved greater spatial distribution in the activation of YAPand Notch signaling pathways, thereby influencing the stemcell fate by regulating Paneth cell localization and differen-tiation (Fig. 7B), and ultimately mediating the formation ofcrypt and villu domains (Fig. 7C). This pre-setting of organoidgeometry could make the whole development process of orga-noids highly conservative, and there was no need to introduceexternal biochemical gradients. Furthermore, it was alsodemonstrated that the natural physiological structure of theintestinal epithelium in vivo could be further simulated whenintestinal organoids were cultivated within the shape-confinedhydrogel scaffolds.Similarly, in tissue engineering for muscle repair, scaffolddesign also plays a critical role. The topographical hydrogelscaffolds with conductivity that mimic the ECM are crucial forskeletal muscle repair. Xue et al. created an anisotropic andconductive hydrogel scaffold by using gelatin methacryloyl(GelMA) as the base hydrogel and silver nanowires (AgNW) asthe conductive dopant, employing a directional freezing tech-nique to achieve the desired topographical scaffold for muscledefect repair (Fig. 8).81 These topographical and mechanicalproperties closely resemble those of the native muscle ECM,enabling cell orientation through contact cues and electricalstimulation. When transplanted into rats with muscle defects,the electrically stimulated topographical hydrogel scaffoldshowed a marked improvement in muscle reconstruction,achieving muscle mass and strength restoration ratios of 95%and 99% of normal levels, respectively. This finding presentsthe potential of topographically optimized and conductivehydrogel scaffolds in advancing muscle repair applications.As seen in the above examples, cells and their tissues do nothave a uniform structure, and the corresponding gels requiretopographic structural control. Various attempts have beenmade, not limited to the above examples. Deshmukh et al.developed an acoustofluidic device that continuously patternedmammalian cells within hydrogel fibers.82 PhotopolymerizableFig. 7 Schematic of the geometry-driven deterministic organoid patterning of hydrogels. (A) Crypt formation of ISC colonies, which is indicated bythe occurrence of Paneth cells, could be artificially controlled precisely through embedding cells within the photopatterned hydrogel. (B) ISCsencapsulated in the geometry-defined hydrogel were found to exhibit symmetry-breaking and epithelial patterning, which may arise from the spatialdifferential distribution of YAP and Notch signaling. (C) Similar organoid patterning also occurred when ISCs were cultured on the hydrogels thatresemble the native intestinal mucosa.Review Nanoscale13240 | Nanoscale, 2024, 16, 13230–13246 This journal is © The Royal Society of Chemistry 2024hydrogels were externally induced to undergo gelatinization bylight when the cells were placed under the influence of anacoustic field. Muscle progenitor cells (myoblasts) could be pat-terned in parallel lines within the hydrogel, mimicking thestructure of skeletal muscle. There, increased formation of myo-tubes and spontaneous twitching of myotubes could beobserved. In addition, the anisotropy of natural tissues of othercell types, such as tendons, ligaments, and neurons, could bemimicked. Liu et al. reported a new technique called filamentoptical biofabrication.83 This technique allowed for the rapidfabrication of hydrogels consisting of a unidirectional networkof microfilaments with a diameter on the length scale of asingle cell. The formed microfilaments exhibit outstanding cellinduction properties in fibroblasts, tendon cells, endothelialcells, and myoblasts. It is also possible to form multidirectionalmicrofilaments within a single hydrogel construct. Potentialapplications of nanoarchitectonics in complex multicellulartissue engineering constructs would be considered more. Maet al. reported an approach for versatile tissue engineering fromtendon to bone, utilizing calcium silicate nanowires and algi-nate composite hydrogels as building blocks.84 3D printingtechnology and mechanical stretching post-processing wereintegrated to create structures with significantly enhancedmechanical properties ranging from nanoscale to submicronand microscale. The composite hydrogels significantlyenhanced tissue regeneration of bone-to-tendon, especiallyfibrocartilage transition tissue in vivo.As is the case with many mammalian tissues, organismshave specific cellular arrangements that allow for their uniquefunctions. Correspondingly, topographic controls such as thepatterning of hydrogels and their mixtures with the networkbecome important. Biological systems universally possess hier-archical and topographic structural properties. Therefore, arti-ficial structures such as hydrogels must have a topographicstructure. The nanoarchitectonics methodology, which hasadvantages in creating hierarchical structures, is expected tobe able to meet such demands.5. ConclusionsSome of the above examples are reviewed and summarized.These examples illustrate the utility of the concept ofnanoarchitectonics for research in the biological and medicalfields, especially in tissue engineering, using gels. For hydro-gels as bioinks for 3D bioprinting, mechanical and biocompa-tible properties are important parameters. The organs and bio-logical tissues to which they are applied are complex systems,but fundamentally they are controlled upon a combination ofknown phenomena of polymer chemistry and physical chem-istry. This is in common with the concept of nanoarchitec-tonics, which is based on the harmonization of fundamentalprocesses and phenomena. Also, it is useful for cellular tissueengineering and regenerative medicine to construct artificialmimics of ECMs with nanoarchitectonics of gels, as they play adecisive role in the behaviors of cells. During this process, theinteraction with cells is dynamic at the interfaces they come incontact with. Interfacial nanoarchitectonics emphasizingdynamic elements and nanoarchitectonics of soft materialssurfaces will be key. As shown in the last few examples, it isnot the cells themselves, but their specific arrangement andorganization that play a major role in the expression of func-tion. Patterning technology that corresponds to the hierarchi-cal structure of living organisms is required. A nanoarchitec-tonics technique that favors the formation of hierarchicalstructures can meet these requirements.Fig. 8 Schematic diagram of topographical scaffolds with conductivity for in vivo muscle repair under electrical stimulation. Reprinted with per-mission from ref. 46. Copyright 2024, Royal Society of Chemistry.Nanoscale ReviewThis journal is © The Royal Society of Chemistry 2024 Nanoscale, 2024, 16, 13230–13246 | 13241Cells that perform biofunctions, their tissue bodies, organs,and living organisms are structurally and functionally complexsystems. As a material that is compatible with these complexsystems, hydrogels are promising because of their ability tomanipulate various components, structures, and mechanicalproperties. It is necessary to assemble unit molecules, polymers,ions, etc. into macroscopic structures comparable to those ofcells and tissues. This is where the concept of nanoarchitec-tonics has many opportunities to demonstrate its power.Human beings have devised a variety of gels that can copewith such complex systems through accumulated experienceand scientific knowledge. However, a more rational approachrequires the introduction of data processing methodologies.The concepts of machine learning85 and materials informatics86are being used to select, design, and develop optimal materials.There are also proposals to combine nanoarchitectonics andmaterials informatics.87 A rational approach to large-scale pro-duction is also needed. The development of such method-ologies may also be achieved by supporting nanoarchitectonicswith artificial intelligence. The fabrication of optimal gel struc-tures from nanoscale structural elements by nanoarchitectonicswill be useful for the development of tissue engineering bio-medical materials at the practical level. The participation of newtechnologies such as machine learning will also promote it.Author contributionsJingwen Song: conceptualization, writing – original draft, andwriting – review & editing. Wenyan Lyu: writing – originaldraft. Kohsaku Kawakami: project administration, review &editing, and funding acquisition. Katsuhiko Ariga: conceptual-ization, writing – original draft, writing – review & editing, andfunding acquisition.Data availabilityThis is a review article and does not include any original data.Conflicts of interestThere are no conflicts to declare.AcknowledgementsThis study was partially supported by Japan Society for thePromotion of Science KAKENHI (Grant Numbers JP20H00392and JP23H05459).References1 (a) D. Guo, R. Shibuya, C. Akiba, S. Saji, T. Kondo andJ. Nakamura, Science, 2016, 351, 361–365; (b) E. Zhang,Q. Zhu, J. Huang, J. Liu, G. Tan, C. Sun, T. Li, S. Liu, Y. Li,H. Wang, Xi. Wan, Z. Wen, F. Fan, J. Zhang and K. Ariga,Appl. Catal., B, 2021, 293, 120213; (c) K. Maeda, F. Takeiri,G. Kobayashi, S. Matsuishi, H. Ogino, S. Ida, T. Mori,Y. Uchimoto, S. Tanabe, T. Hasegawa, N. Imanaka andH. Kageyama, Bull. Chem. Soc. Jpn., 2022, 95, 26–37;(d) G. Chen, S. K. Singh, K. Takeyasu, J. P. Hill,J. Nakamura and K. Ariga, Sci. Technol. Adv. Mater., 2023,23, 413–423; (e) H. Imahori, Bull. Chem. Soc. Jpn., 2023, 96,339–352.2 (a) A. H. Khan, S. Ghosh, B. Pradhan, A. Dalui,L. K. Shrestha, S. Acharya and K. Ariga, Bull. Chem. Soc.Jpn., 2017, 90, 627–648; (b) Md. S. Islam, Y. Shudo andS. Hayami, Bull. Chem. Soc. Jpn., 2022, 95, 1–25;(c) A. Yoshino, Bull. Chem. Soc. Jpn., 2022, 95, 195;(d) T. Hosaka and S. Komaba, Bull. Chem. Soc. Jpn., 2022,95, 569–581; (e) P. A. Shinde, Q. Abbas, N. R. Chodankar,K. Ariga, M. A. Abdelkareem and A. G. Olabi, J. EnergyChem., 2023, 79, 611–638.3 (a) S. Ishihara, J. Labuta, W. V. Rossom, D. Ishikawa,K. Minami, J. P. Hill and K. Ariga, Phys. Chem. Chem. Phys.,2014, 16, 9713–9746; (b) A. Muranaka, H. Ban, M. Naito,S. Miyagawa, M. Ueda, S. Yamamoto, M. Harada,H. Takaya, M. Kimura, N. Kobayashi, M. Uchiyama andY. Tokunaga, Bull. Chem. Soc. Jpn., 2022, 95, 1428–1437;(c) T. Murata, K. Minami, T. Yamazaki, T. Sato,H. Koinuma, K. Ariga and N. Matsuki, Bull. Chem. Soc. Jpn.,2023, 96, 29–34; (d) S. d. K. Sundaram, Md. M. Hossain,M. Rezki, K. Ariga and S. Tsujimura, Biosensors, 2023, 13,1018; (e) Y. Sasaki and T. Minami, ChemNanoMat, 2024, 10,e202300335.4 (a) M. Wen, G. Li, H. Liu, J. Chen, T. An and H. Yamashita,Environ. Sci.: Nano, 2019, 6, 1006–1025; (b) X. Han,S. Wang, M. Liu and L. Liu, Bull. Chem. Soc. Jpn., 2022, 95,1445–1452; (c) R. Li, D. Huang, S. Chen, L. Lei, Y. Chen,J. Tao, W. Zhouab and G. Wang, Nanoscale, 2022, 14,10299–10320; (d) J. Wang, F. Matsuzawa, N. Sato, Y. Amanoand M. Machida, Bull. Chem. Soc. Jpn., 2023, 96, 1088–1098; (e) J. Yang, L. Huang, J. You and Y. Yamauchi, Small,2023, 19, 2301044.5 (a) R. Zhang and T. Hanaoka, Nat. Commun., 2022, 13,3629; (b) A. Chapman, E. Ertekin, M. Kubota, A. Nagao,K. Bertsch, A. Macadre, T. Tsuchiyama, T. Masamura,S. Takaki, R. Komoda, M. Dadfarnia, B. Somerday,A. T. Staykov, J. Sugimura, Y. Sawae, T. Morita, H. Tanaka,K. Yagi, V. Niste, P. Saravanan, S. Onitsuka, K.-S. Yoon,S. Ogo, T. Matsushima, G. Tumen-Ulzii, D. Klotz,D. H. Nguyen, G. Harrington, C. Adachi, H. Matsumoto,L. Kwati, Y. Takahashi, N. Kosem, T. Ishihara,M. Yamauchi, B. B. Saha, M. A. Islam, J. Miyawaki,H. Sivasankaran, M. Kohno, S. Fujikawa, R. Selyanchyn,T. Tsuji, Y. Higashi, R. Kirchheim and P. Sofronis, Bull.Chem. Soc. Jpn., 2022, 95, 73; (c) S. Chen, J. Liu, Q. Zhang,F. Teng and B. C. McLellan, Renewable Sustainable EnergyRev., 2022, 167, 112537; (d) N. Tsubaki, Y. Wang, G. Yanand Y. He, Bull. Chem. Soc. Jpn., 2023, 96, 291–302;Review Nanoscale13242 | Nanoscale, 2024, 16, 13230–13246 This journal is © The Royal Society of Chemistry 2024(e) T. Fukushima, M. Higashi and M. Yamauchi, Bull.Chem. Soc. Jpn., 2023, 96, 1209–1215.6 (a) T. Tsuchiya, T. Nakayama and K. Ariga, Appl. Phys.Express, 2022, 15, 100101; (b) Y. Saito, H. Sasabe,H. Tsuneyama, S. Abe, M. Matsuya, T. Kawano, Y. Kori,T. Hanayama and J. Kido, Bull. Chem. Soc. Jpn., 2023, 96,24–28; (c) M. Ishii, Y. Yamashita, S. Watanabe, K. Ariga andJ. Takeya, Nature, 2023, 622, 285–291; (d) M. Matsuya,H. Sasabe, S. Sumikoshi, K. Hoshi, K. Nakao, K. Kumada,R. Sugiyama, R. Sato and J. Kido, Bull. Chem. Soc. Jpn.,2023, 96, 183–189; (e) Y. Yamamoto, H. Yano,S. Karashima, R. Uenishi, N. Orimo, J. Nishitani andT. Suzuki, Bull. Chem. Soc. Jpn., 2023, 96, 938–942;(f ) K. Ariga, S. Akakabe, R. Sekiguchi, M. L. Thomas,Y. Takeoka, M. Rikukawa and M. Yoshizawa-Fujita, ACSOmega, 2024, 9, 22203–22212.7 (a) S. Quader, K. Kataoka and H. Cabral, Adv. Drug DeliveryRev., 2022, 182, 114115; (b) Y. Ju, H. Liao, J. J. Richardson,J. Guo and F. Caruso, Chem. Soc. Rev., 2022, 51, 4287–4336;(c) Y. Han, P. Wen, J. Li and K. Kataoka, J. ControlledRelease, 2022, 345, 709–720; (d) L. T. B. Nguyen and M. Abe,Bull. Chem. Soc. Jpn., 2023, 96, 899–906; (e) S. Mohanan,C. I. Sathish, T. J. Adams, S. Kan, M. Liang and A. Vinu,Bull. Chem. Soc. Jpn., 2023, 96, 1188–1195.8 (a) H. Sekine, T. Shimizu, K. Sakaguchi, I. Dobashi,M. Wada, M. Yamato, E. Kobayashi, M. Umezu andT. Okano, Nat. Commun., 2013, 4, 1399; (b) L. Moroni,J. A. Burdick, C. Highley, S. J. Lee, Y. Morimoto,S. Takeuchi and J. J. Yoo, Nat. Rev. Mater., 2018, 3, 21–37;(c) X. Fu, G. Liu, A. Halim, Y. Ju, Q. Luo and G. Song, Cells,2019, 8, 784; (d) Y. Shang, J. Zeng, Z. Xie, N. Sasaki andM. Matsusaki, Bull. Chem. Soc. Jpn., 2022, 95, 1163–1168;(e) R. Hama, A. Ulziibayar, J. W. Reinhardt, T. Watanabe,I. Kelly and T. Shinoka, Biomolecules, 2023, 13, 280.9 (a) Y. Hashimoto, T. Suzuki and K. Hashimoto, Mol.Psychiatry, 2022, 27, 1898–1907; (b) M. Komiyama, Bull.Chem. Soc. Jpn., 2022, 95, 1308–1317; (c) Y. Cui, A. Taguchi,H. Shida, S. Konno, K. Takayama, A. Taniguchi andY. Hayashi, Bull. Chem. Soc. Jpn., 2022, 95, 1156–1162;(d) A. Watanabe, M. Iwagami, J. Yasuhara, H. Takagi andT. Kuno, Vaccine, 2023, 41, 1783–1790; (e) S. Sugita,H. Ishitani and S. Kobayashi, Bull. Chem. Soc. Jpn., 2023,96, 744–751.10 (a) A. Bieniek, A. P. Terzyk, M. Wiśniewski, K. Roszek,P. Kowalczyk, L. Sarkisov, S. Keskin and K. Kaneko, Prog.Mater. Sci., 2021, 117, 100743; (b) A. R. Pradipta,H. Michiba, A. Kubo, M. Fujii, T. Tanei, K. Morimoto,K. Shimazu and K. Tanaka, Bull. Chem. Soc. Jpn., 2022, 95,421–426; (c) V. J. Sahayasheela, Z. Yu, Y. Hirose,G. N. Pandian, T. Bando and H. Sugiyama, Bull. Chem. Soc.Jpn., 2022, 95, 693–699; (d) L. Sutrisno and K. Ariga, NPGAsia Mater., 2023, 15, 21; (e) C. Tay, A. Tanaka andS. Sakaguchi, Cancer Cell, 2023, 41, 450–465.11 (a) Y. Sugimoto, P. Pou, M. Abe, P. Jelinek, R. Pérez,S. Morita and Ó. Custance, Nature, 2007, 446, 64–67;(b) A. Shiotari and Y. Sugimoto, Nat. Commun., 2017, 8,14313; (c) K. Kimura, K. Miwa, H. Imada, M. Imai-Imada,S. Kawahara, J. Takeya, M. Kawai, M. Galperin and Y. Kim,Nature, 2019, 570, 210–213; (d) K. Tada, Y. Hinuma,S. Ichikawa and S. Tanaka, Bull. Chem. Soc. Jpn., 2023, 96,373–380; (e) H. Hoelzel, S. Lee, K. Y. Amsharov, N. Jux,K. Harano, E. Nakamura and D. Lungerich, Nat. Chem.,2023, 15, 1444–1451.12 (a) Y. Okawa and M. Aono, Nature, 2001, 409, 683–684;(b) P. Mishra, J. P. Hill, S. Vijayaraghavan, W. Van Rossom,S. Yoshizawa, M. Grisolia, J. Echeverria, T. Ono, K. Ariga,T. Nakayama, C. Joachim and T. Uchihashi, Nano Lett.,2015, 15, 4793–4798; (c) G. J. Simpson, V. García-López,P. Petermeier, L. Grill and J. M. Tour, Nat. Nanotechnol.,2017, 12, 604–606; (d) S. Kawai, O. Krejčí, T. Nishiuchi,K. Sahara, T. Kodama, R. Pawlak, E. Meyer, T. Kubo andA. S. Foster, Sci. Adv., 2020, 6, eaay8913; (e) W.-H. Soe,M. Kleinwächter, C. Kammerer, G. Rapenne andC. Joachim, J. Phys. Chem. C, 2020, 124, 22625–22630.13 (a) K. Ariga, Q. Ji, W. Nakanishi, J. P. Hill and M. Aono,Mater. Horiz., 2015, 2, 406–413; (b) L. Cao, Y. Huang,B. Parakhonskiy and A. G. Skirtach, Nanoscale, 2022, 14,15964–16002.14 K. Ariga, Nanoscale Horiz., 2021, 6, 364–378.15 K. Ariga and Y. Yamauchi, Chem. - Asian J., 2020, 15, 718–728.16 (a) R. P. Feynman, Eng. Sci., 1960, 23, 32–36; (b) M. Roukes,Sci. Am., 2001, 285, 48–51.17 K. Ariga, K. Minami, M. Ebara and J. Nakanishi, Polym. J.,2016, 48, 371–389.18 (a) K. Ariga, Curr. Opin. Colloid Interface Sci., 2023, 63,101656; (b) O. Azzaroni, E. Piccinini, G. Fenoy,W. Marmisollé and K. Ariga, Nanotechnology, 2023, 34,472001.19 K. Ariga, J. Li, J. Fei, Q. Ji and J. P. Hill, Adv. Mater., 2016,28, 1251–1286.20 (a) K. Ariga, M. Nishikawa, T. Mori, J. Takeya,L. K. Shrestha and J. P. Hill, Sci. Technol. Adv. Mater., 2020,20, 51–95; (b) E. Mieda, Y. Morishima, T. Watanabe,H. Miyake and S. Shinoda, Bull. Chem. Soc. Jpn., 2023, 96,538–544; (c) K. Saito and Y. Yamamura, Bull. Chem. Soc.Jpn., 2023, 96, 607–613.21 (a) K. Ariga, X. Jia, J. Song, J. P. Hill, D. T. Leong, Y. Jia andJ. Li, Angew. Chem., Int. Ed., 2020, 59, 15424–15446;(b) K. Ariga, J. Song and K. Kawakami, Chem. Commun.,2024, 60, 2152–2167.22 M. Aono and K. Ariga, Adv. Mater., 2016, 28, 989–992.23 (a) M. Komiyama, K. Yoshimoto, M. Sisido and K. Ariga,Bull. Chem. Soc. Jpn., 2017, 90, 967–1004; (b) K. Ariga,Int. J. Mol. Sci., 2022, 23, 3577.24 R. B. Laughlin and D. Pines, Proc. Natl. Acad. Sci., 2000, 97,28–31.25 (a) K. Ariga and R. Fakhrullin, Bull. Chem. Soc. Jpn., 2022,95, 774–795; (b) K. Ariga, Bull. Chem. Soc. Jpn., 2024, 97,uoad001.26 (a) T. Govindaraju and M. B. Avinash, Nanoscale, 2012, 4,6102–6117; (b) W. Nakanishi, K. Minami, L. K. Shrestha,Nanoscale ReviewThis journal is © The Royal Society of Chemistry 2024 Nanoscale, 2024, 16, 13230–13246 | 13243Q. Ji, J. P. Hill and K. Ariga, Nano Today, 2014, 9, 378–394;(c) K. Ariga and M. Shionoya, Bull. Chem. Soc. Jpn., 2021,94, 839–859; (d) G. Chen, F. Sciortino, K. Takeyasu,J. Nakamura, J. P. Hill, L. K. Shrestha and K. Ariga, Chem. –Asian J., 2022, 17, e202200756; (e) P. A. Shinde,N. R. Chodankar, H.-J. Kim, M. A. Abdelkareem,A. A. Ghaferi, Y.-K. Han, A. G. Olabi and K. Ariga, ACSEnergy Lett., 2023, 8(10), 4474–4487; (f ) E. Ruiz-Hitzky andC. Ruiz-Garcia, Nanoscale, 2023, 15, 18959–18979.27 (a) M. Ramanathan, L. K. Shrestha, T. Mori, Q. Ji, J. P. Hilland K. Ariga, Phys. Chem. Chem. Phys., 2013, 15, 10580–10611; (b) J. Kim, J. H. Kim and K. Ariga, Joule, 2017, 1,739–768; (c) A. Nayak, S. Unayama, S. Tai, T. Tsuruoka,R. Waser, M. Aono, I. Valov and T. Hasegawa, Adv. Mater.,2018, 30, 1703261; (d) M. Eguchi, A. S. Nugraha,A. E. Rowan, J. Shapter and Y. Yamauchi, Adv. Sci., 2021, 8,2100539; (e) K. Lee, M. Han, G. Kwon, Y. Jeon, J. Kim andJ. You, Appl. Surf. Sci., 2023, 613, 155955.28 (a) K. Ariga, Q. Ji, T. Mori, M. Naito, Y. Yamauchi, H. Abeand J. P. Hill, Chem. Soc. Rev., 2013, 42, 6322–6345;(b) R. Chang, L. Zhao, R. Xing, J. Li and X. Yan, Chem. Soc.Rev., 2023, 52, 2688–2712; (c) Q. Liu, H. Li, B. Yu, Z. Meng,X. Zhang, J. Li and L. Zheng, Adv. Funct. Mater., 2022, 32,2201196; (d) Z. Li, F. Yu, X. Xu, T. Wang, J. Fei, J. Hao andJ. Li, J. Am. Chem. Soc., 2023, 145, 20907–20912.29 (a) K. Ariga, Small Struct., 2021, 2, 2100006; (b) Y. Jia,X. Yan and J. Li, Angew. Chem., Int. Ed., 2022, 61,e202207752; (c) D. Parbat, N. Jana, M. Dhar and U. Manna,ACS Appl. Mater. Interfaces, 2023, 15, 25232–25247;(d) X. Shen, J. Song, C. Sevencan and D. T. Leong, Sci.Technol. Adv. Mater., 2023, 23, 199–224.30 (a) A. Juste-Dolz, M. Delgado-Pinar, M. Avella-Oliver,E. Fernández, J. L. Cruz, M. V. Andrés and Á. Maquieira,ACS Appl. Mater. Interfaces, 2022, 14, 41640–41648;(b) J. Liu, R. Wang, H. Zhou, M. Mathesh, M. Dubey,W. Zhang, B. Wang and W. Yang, Nanoscale, 2022, 14,10286–10298; (c) S. Kim, S. Baek, R. Sluyter,K. Konstantinov, J. H. Kim, S. Kim and Y. H. Kim, EcoMat,2023, 5, e12356; (d) J. V. Vaghasiya, C. C. Mayorga-Martinezand M. Pumera, npj Flexible Electron., 2023, 7, 26;(e) H.-M. Deng, M.-J. Xiao, Y.-L. Yuan, R. Yuan andY.-Q. Chai, Sens. Actuators, B, 2024, 398, 134715.31 (a) A. R. Ferhan, S. Park, H. Park, H. Tae, J. A. Jackman andN.-J. Cho, Adv. Funct. Mater., 2022, 32, 2203669;(b) M. Komiyama, Beilstein J. Nanotechnol., 2023, 14, 218–232; (c) Y. N. Reddy, A. De, S. Paul, A. K. Pujari andJ. Bhaumik, Biomacromolecules, 2023, 24, 1717–1730;(d) S. Mohanan, X. Guan, M. Liang, A. Karakoti andA. Vinu, Small, 2023, 2301113; (e) W. Tian, C. Wang, R. Chu,H. Ge, X. Sun and M. Li, Biomater. Res., 2023, 27, 100.32 (a) E. Psarra, U. König, Y. Ueda, C. Bellmann, A. Janke,E. Bittrich, K.-J. Eichhorn and P. Uhlmann, ACS Appl.Mater. Interfaces, 2015, 7, 12516–12529; (b) B. Tian, J. Liu,S. Guo, A. Li and J.-B. Wan, Int. J. Biol. Macromol., 2023,243, 125161; (c) X. Jia, J. Chen, W. Lv, H. Li and K. Ariga,Int. J. Biol. Macromol., 2023, 4, 101251; (d) W. Hu, J. Shi,W. Lv, X. Jia and K. Ariga, Sci. Technol. Adv. Mater., 2023,23, 393–412; (e) Z. Hajikhani, I. Haririan, M. Akrami andS. Hajikhani, Nanomedicine, 2023, 18, 1441–1458.33 (a) Q. Ren, N. Yu, L. Wang, M. Wen, P. Geng, Q. Jiang,M. Li and Z. Chen, J. Colloid Interface Sci., 2022, 614, 147–159; (b) H. Duan, F. Wang, W. Xu, G. Sheng, Z. Sun andH. Chu, Dalton Trans., 2023, 52, 16085–16102; (c) Y. Liu,J. Zhao, X. Xu, Y. Xu, W. Cui, Y. Yang and J. Li, Angew.Chem., Int. Ed., 2023, 62, e202308019; (d) P. Jayachandran,S. Ilango, V. Suseela, R. Nirmaladevi, M. R. Shaik, M. Khan,M. Khan and B. Shaik, Biomedicines, 2023, 11, 217;(e) N. Yang, X. Pan, X. Zhou, Z. Liu, J. Yang, J. Zhang, Z. Jiaand Q. Shen, Adv. Healthcare Mater., 2023, 2302752.34 (a) K. Ariga, Nanoscale, 2022, 14, 10610–11062; (b) K. Ariga,Chem. Mater., 2023, 35, 5233–5254.35 (a) I. R. Vetter and A. Wittinghofer, Science, 2001, 294,1299–1304; (b) K. N. Ferreira, T. M. Iverson, K. Maghlaoui,J. Barber and S. Iwata, Science, 2004, 303, 1831–1838;(c) D. A. Bryant and D. P. Canniffe, J. Phys. B: At., Mol. Opt.Phys., 2018, 51, 033001.36 (a) K. Ariga, Y. Yamauchi, T. Mori and J. P. Hill, Adv. Mater.,2013, 25, 6477–6512; (b) K. Ariga, Langmuir, 2020, 36, 7158–7180; (c) S. Negi, M. Hamori, H. Kitagishi and K. Kano,Bull. Chem. Soc. Jpn., 2022, 95, 1537–1545; (d) S. Negi,M. Hamori, Y. Kubo, H. Kitagishi and K. Kano, Bull. Chem.Soc. Jpn., 2023, 96, 48–56; (e) O. N. Oliveira Jr., L. Caseliand K. Ariga, Chem. Rev., 2022, 122, 6459–6513;(f ) J. Adachi, M. Naito, S. Sugiura, N. H.-T. Le,S. Nishimura, S. Huang, S. Suzuki, S. Kawamorita,N. Komiya, J. P. Hill, K. Ariga, T. Naota and T. Mori, Bull.Chem. Soc. Jpn., 2022, 95, 889–897.37 (a) G. Decher, Science, 1997, 277, 1232–1237; (b) K. Ariga,J. P. Hill and Q. Ji, Phys. Chem. Chem. Phys., 2007, 9, 2319–2340; (c) G. Rydzek, Q. Ji, M. Li, P. Schaaf, J. P. Hill,F. Boulmedais and K. Ariga, Nano Today, 2015, 10, 138–167;(d) Z. Zhang, J. Zeng, J. Groll and M. Matsusaki, Biomater.Sci., 2022, 10, 4077–4094; (e) K. Ariga, Y. Lvov andG. Decher, Phys. Chem. Chem. Phys., 2022, 24, 4097–4115;(f ) J. Borges, J. Zeng, X. Q. Liu, H. Chang, C. Monge,C. Garot, K. Ren, P. Machillot, N. E. Vrana, P. Lavalle,T. Akagi, M. Matsusaki, J. Ji, M. Akashi, J. F. Mano,V. Gribova and C. Picart, Adv. Healthcare Mater., 2024,2302713.38 (a) Y. Shan, G. Zhang, W. Yin, H. Pang and Q. Xu, Bull.Chem. Soc. Jpn., 2022, 95, 230–260; (b) M. Daniel,G. Mathew, M. Anpo and B. Neppolian, Coord. Chem. Rev.,2022, 468, 214627; (c) L. Larasati, W. W. Lestari andM. Firdaus, Bull. Chem. Soc. Jpn., 2022, 95, 1561–1577;(d) T. Ohata, K. Tachimoto, K. J. Takeno, A. Nomoto,T. Watanabe, I. Hirosawa and R. Makiura, Bull. Chem. Soc.Jpn., 2023, 96, 274–282; (e) Q. Yao, X. Zhang, Z.-H. Lu andQ. Xu, Coord. Chem. Rev., 2023, 493, 215302.39 (a) Y. Hara and K. Sakaushi, Nanoscale, 2021, 13, 6341–6356; (b) Y. Charles-Blin, T. Kondo, Y. Wu, S. Bandow andK. Awaga, Bull. Chem. Soc. Jpn., 2022, 95, 972–977;(c) L. Huang, J. Yang, Y. Asakura, Q. Shuai andReview Nanoscale13244 | Nanoscale, 2024, 16, 13230–13246 This journal is © The Royal Society of Chemistry 2024Y. Yamauchi, ACS Nano, 2023, 17, 8918–8934; (d) S. Zhang,L. Lombardo, M. Tsujimoto, Z. Fan, E. K. Berdichevsky,Y.-S. Wei, K. Kageyama, Y. Nishiyama and S. Horike, Angew.Chem., Int. Ed., 2023, 62, e202312095; (e) Y. Zhao, T. Irie,J. Sakai, H. Mabuchi, S. Biswas, T. Sekine, S. Das, T. Benand Y. Negishi, ACS Appl. Nano Mater., 2023, 6, 19210–19217.40 (a) N. Ma and S. Horike, Chem. Rev., 2022, 122, 4163–4203;(b) S. Horike, Bull. Chem. Soc. Jpn., 2023, 96, 887–898.41 (a) C. Creton, Macromolecules, 2017, 50, 8297–8316;(b) R. Yoshida, Polym. J., 2022, 54, 827–849;(c) M. Z. I. Nizami, B. D. L. Campéon, A. Satoh andY. Nishina, Bull. Chem. Soc. Jpn., 2022, 95, 713–720;(d) H. Jia and T. Michinobu, ChemNanoMat, 2023, 9,e202300020; (e) R. Tamate and T. Ueki, Chem. Rec., 2023,23, e202300043.42 R. Chang, C. Yuan, P. Zhou, R. Xing and X. Yan, Acc. Chem.Res., 2024, 57, 289–301.43 (a) Y. Noda, Y. Hayashi and K. Ito, J. Appl. Polym. Sci., 2014,131, 40509; (b) A. B. Imran, K. Esaki, H. Gotoh, T. Seki,K. Ito, Y. Sakai and Y. Takeoka, Nat. Commun., 2014, 5,5124; (c) K. Mayumi, C. Liu, Y. Yasuda and K. Ito, Gels,2021, 7, 91.44 C. Liu, N. Morimoto, L. Jiang, S. Kawahara, T. Noritomi,H. Yokoyama, K. Mayumi and K. Ito, Science, 2021, 372,1078–1081.45 Y. Sekine and T. Nankawa, Bull. Chem. Soc. Jpn., 2023, 96,1150–1155.46 R. Kubota, Bull. Chem. Soc. Jpn., 2023, 96, 802–812.47 Y. Aoyama, N. Sato, A. Toyotama, T. Okuzono andJ. Yamanaka, Bull. Chem. Soc. Jpn., 2022, 95, 314–324.48 R. Xing, C. Yuan, W. Fan, X. Ren and X. Yan, Sci. Adv.,2023, 9, eadd8105.49 X. Pan, J. Li, N. Ma, X. Ma and M. Gao, Chem. Eng. J., 2023,461, 142062.50 B. Salahuddin, M. K. Masud, S. Aziz, C.-H. Liu,N. Amiralian, A. Ashok, S. M. A. Hossain, H. Park,M. A. Wahab, M. A. Amin, M. A. Chari, A. E. Rowan,Y. Yamauchi, M. S. A. Hossain and Y. V. Kaneti, Bull. Chem.Soc. Jpn., 2022, 95, 198–207.51 Z. Shen, Z. Zhang, N. Zhang, J. Li, P. Zhou, F. Hu, Y. Rong,B. Lu and G. Gu, Adv. Mater., 2022, 34, 2203650.52 H. Yuk, J. Wu and X. Zhao, Nat. Rev. Mater., 2022, 7, 935–952.53 L. Hu, P. L. Chee, S. Sugiarto, Y. Yu, C. Shi, R. Yan, Z. Yao,X. Shi, J. Zhi, D. Kai, H.-D. Yu and W. Huang, Adv. Mater.,2023, 35, 2205326.54 H. Cao, L. Duan, Y. Zhang, J. Cao and K. Zhang, SignalTransduction Targeted Ther., 2021, 6, 426.55 Y. Liu, T. Dong, Y. Chen, N. Sun, Q. Liu, Z. Huang, Y. Yang,H. Cheng and K. Yue, ACS Appl. Mater. Interfaces, 2023, 15,11507–11519.56 Y. Yang, Y. Liang, J. Chen, X. Duan and B. Guo, Bioact.Mater., 2022, 8, 341–354.57 Y. Huang, L. Mu, X. Zhao, Y. Han and B. Guo, ACS Nano,2022, 16, 13022–13036.58 Y. Xiang, X. Qi, E. Cai, C. Zhang, J. Wang, Y. Lan, H. Deng,J. Shen and R. Hu, Chem. Eng. J., 2023, 460, 141852.59 W. Zhou, Z. Duan, J. Zhao, R. Fu, C. Zhu and D. Fan,Bioact. Mater., 2022, 17, 1–17.60 Y.-J. Fu, Y.-F. Shi, L.-Y. Wang, Y.-F. Zhao, R.-K. Wang, K. Li,S.-T. Zhang, X.-J. Zha, W. Wang, X. Zhao and W. Yang, Adv.Sci., 2023, 10, 2206771.61 Y. Qian, Y. Zheng, J. Jin, X. Wu, K. Xu, M. Dai, Q. Niu,H. Zheng, X. He and J. Shen, Adv. Mater., 2022, 34,2200521.62 Y. Li, R. Fu, Z. Duan, C. Zhu and D. Fan, ACS Nano, 2022,16, 7486–7502.63 Y. Liang, H. Xu, Z. Li, A. Zhangji and B. Guo, Nano-MicroLett., 2022, 14, 185.64 A. J. Seymour, S. Shin and S. C. Heilshorn, Adv. HealthcareMater., 2021, 10, 2100644.65 F. E. Freeman, P. Pitacco, L. H. A. van Dommelen, J. Nulty,D. C. Browe, J.-Y. Shin, E. Alsberg and D. J. Kelly, Sci. Adv.,2020, 6, eabb5093.66 H. Zhang, Y. Cong, A. R. Osi, Y. Zhou, F. Huang,R. P. Zaccaria, J. Chen, R. Wang and J. Fu, Adv. Funct.Mater., 2020, 30, 1910573.67 M. Wang, W. Li, J. Hao, A. Gonzales III, Z. Zhao,R. S. Flores, X. Kuang, X. Mu, T. Ching, G. Tang, Z. Luo,C. E. Garciamendez-Mijares, J. K. Sahoo, M. F. Wells,G. Niu, P. Agrawal, A. Q. Hinojosa, K. Eggan andY. S. Zhang, Nat. Commun., 2022, 13, 3317.68 S. H. Kim, Y. K. Yeon, J. M. Lee, J. R. Chao, Y. J. Lee,Y. B. Seo, Md. T. Sultan, O. J. Lee, J. S. Lee, S.-i. Yoon,I.-S. Hong, G. Khang, S. J. Lee, J. J. Yoo and C. H. Park, Nat.Commun., 2018, 9, 1620.69 S. H. Kim, Y. B. Seo, Y. K. Yeon, Y. J. Lee, H. S. Park,Md. T. Sultan, J. M. Lee, J. S. Lee, O. J. Lee, H. Hong,H. Lee, O. Ajiteru, Y. J. Suh, S.-H. Song, K.-H. Lee andC. H. Park, Biomaterials, 2020, 260, 120281.70 B. Yang, K. Wei, C. Loebel, K. Zhang, Q. Feng, R. Li,S. H. D. Wong, X. Xu, C. Lau, X. Chen, P. Zhao, C. Yin,J. A. Burdick, Y. Wang and L. Bian, Nat. Commun., 2021, 12,3514.71 A. Elosegui-Artola, A. Gupta, A. J. Najibi, B. R. Seo,R. Garry, C. M. Tringides, I. de Lázaro, M. Darnell, W. Gu,Q. Zhou, D. A. Weitz, L. Mahadevan and D. J. Mooney, Nat.Mater., 2023, 22, 117–127.72 M. D. Davidson, M. E. Prendergast, E. Ban, K. L. Xu,G. Mickel, P. Mensah, A. Dhand, P. A. Janmey, V. B. Shenoyand J. A. Burdick, Sci. Adv., 2021, 7, eabi8157.73 J. Lou, R. Stowers, S. Nam, Y. Xia and O. Chaudhuri,Biomaterials, 2018, 154, 213–222.74 A. R. Killaars, J. C. Grim, C. J. Walker, E. A. Hushka,T. E. Brown and K. S. Anseth, Adv. Sci., 2019, 6, 1801483.75 C. M. Madl, B. L. LeSavage, R. E. Dewi, C. B. Dinh,R. S. Stowers, M. Khariton, K. J. Lampe, D. Nguyen,O. Chaudhuri, A. Enejder and S. C. Heilshorn, Nat. Mater.,2017, 16, 1233–1242.76 J. G. Zhang, C. Cheng, J. L. Cuellar-Camacho, M. Li, Y. Xia,W. Li and R. Haag, Adv. Funct. Mater., 2018, 28, 1804773.Nanoscale ReviewThis journal is © The Royal Society of Chemistry 2024 Nanoscale, 2024, 16, 13230–13246 | 1324577 C. Loebel, R. L. Mauck and J. A. Burdick, Nat. Mater., 2019,18, 883–891.78 R. Freeman, M. Han, Z. Álvarez, J. A. Lewis, J. R. Wester,N. Stephanopoulos, M. T. McClendon, C. Lynsky,J. M. Godbe, H. Sangji, E. Luijten and S. I. Stupp, Science,2018, 362, 808–813.79 B. Grigoryan, S. J. Paulsen, D. C. Corbett, D. W. Sazer,C. L. Fortin, A. J. Zaita, P. T. Greenfield, N. J. Calafat,J. P. Gounley, A. H. Ta, F. Johansson, A. Randles,J. E. Rosenkrantz, J. D. Louis-Rosenberg, P. A. Galie,K. R. Stevens and J. S. Miller, Science, 2019, 364, 458–464.80 (a) N. Gjorevski, M. Nikolaev, T. E. Brown, O. Mitrofanova,N. Brandenberg, F. W. DelRio, F. M. Yavitt, P. Liberali,K. S. Anseth and M. P. Lutolf, Science, 2022, 375, eaaw9021;(b) T. R. Huycke and Z. J. Gartner, Science, 2022, 375, 26–27.81 Y. Xue, J. Li, T. Jiang, Q. Han, Y. Jing, S. Bai and X. Yan,Adv. Healthcare Mater., 2024, 13, 2302180.82 D. V. Deshmukh, P. Reichert, J. Zvick, C. Labouesse,V. Künzli, O. Dudaryeva, O. Bar-Nur, M. W. Tibbitt andJ. Dual, Adv. Funct. Mater., 2022, 32, 2113038.83 H. Liu, P. Chansoria, P. Delrot, E. Angelidakis, R. Rizzo,D. Rütsche, L. A. Applegate, D. Loterie and M. Zenobi-Wong, Adv. Mater., 2022, 34, 2204301.84 H. Ma, C. Yang, Z. Ma, X. Wei, M. R. Younis, H. Wang,W. Li, Z. Wang, W. Wang, Y. Luo, P. Huang and J. Wang,Adv. Healthcare Mater., 2022, 11, 2102837.85 (a) Y. Takagiwa, Z. Hou, K. Tsuda, T. Ikeda and H. Kojima,ACS Appl. Mater. Interfaces, 2021, 13, 53346–53354;(b) Y. Liang, C. Jiao, P. Zhou, W. Li, Y. Zang, Y. Liu,G. Yang, L. Liu, J. Cheng, G. Liang, J. Wang, Z. Zhong andW. Yan, Bull. Chem. Soc. Jpn., 2023, 96, 148–155;(c) Y. Komoto, J. Ryu and M. Taniguchi, Chem. Commun.,2023, 59, 6796–6810; (d) N. Saito, A. Nawachi, Y. Kondo,J. Choi, H. Morimoto and T. Ohshima, Bull. Chem. Soc.Jpn., 2023, 96, 465–474; (e) K. Nakaguro, Y. Mitsuta,S. Koseki, T. Oshiyama and T. Asada, Bull. Chem. Soc. Jpn.,2023, 96, 1099–1107.86 (a) S. Ju, T. Shiga, L. Feng, Z. Hou, K. Tsuda and J. Shiomi,Phys. Rev. X, 2017, 7, 021024; (b) L. Himanen, A. Geurts,A. S. Foster and P. Rinke, Adv. Sci., 2019, 6, 1900808;(c) S. Hashimura, Y. Yamaguchi, H. Takeda, N. Tanibata,M. Nakayama, N. Niizeki and T. Nakaya, J. Phys. Chem. C,2023, 127, 21665–21674; (d) K. Hatakeyama-Sato, Polym. J.,2023, 55, 117–131; (e) X. Zheng, X. Zhang, T.-T. Chen andI. Watanabe, Adv. Mater., 2023, 35, 2302530;(f ) S. Hashimura, Y. Yamaguchi, H. Takeda, N. Tanibata,M. Nakayama, N. Niizeki and T. Nakaya, J. Phys. Chem. C,2023, 127, 21665–21674.87 (a) W. Chaikittisilp, Y. Yamauchi and K. Ariga, Adv. Mater.,2022, 34, 2107212; (b) R. Hikichi, Y. Tokura, Y. Igarashi,H. Imai and Y. Oaki, Bull. Chem. Soc. Jpn., 2023, 96, 766–774.Review Nanoscale13246 | Nanoscale, 2024, 16, 13230–13246 This journal is © The Royal Society of Chemistry 2024 Button 1: