Recent developments in artificial spider silk and functional gel fibers

It is highly desirable to develop fiber materials with high strength and toughness while increasing fiber strength always results in a decrease in toughness. Spider silk is a natural fiber material with an excellent combination of high strength and toughness, which is produced from the spinning dope solution by gelation and drawing spinning process. This encourages people to prepare artificial fibers by mimicking the material, structure, and spinning of natural spider silk. In this review, we first summarized the preparation of artificial spider silk prepared via such a gelation process from different types of materials, including nonrecombinant proteins, recombinant proteins, polypeptides, synthetic polymers, and polymer nanocomposites. In addition, different spinning approaches for spinning artificial spider silk are also summarized. In the third section, some novel application scenarios of the artificial spider silk were summarized, such as artificial muscles, sensing, and smart fibers.


| INTRODUCTION
Improving fiber's mechanical strength and toughness has become a long-term target in scientific research as well as in industrial applications.However, strength and toughness are mutually exclusive because the increase in fiber strength always accompanies a decrease in toughness.A variety of natural materials exhibit high strength and toughness, such as spider silks, bones, tendons, fish scales, wood, teeth, hairs, and so forth. 1 Especially the spider silk exhibits almost the highest combination of mechanical strength and toughness.For example, the Darwin bark spider silk exhibits a breaking strength of 1.6 GPa and a toughness of 350 MJ/m 3 . 2Therefore, the preparation of artificial fibers by mimicking the spider silk to achieve high strength and toughness has attracted great attention in recent decades.The spiders spin fiber from the spinning dope that contains the spidroin solution, which is subjected to a gelation process in which the fiber can be continuously drawn spun as the spidroin solution passes through an S-shaped spinning dope.0][11] The phrase "artificial spider silk" initially denotes the artificial fibers arising from the natural biological resources, especially spidroins, recombinant proteins, and polypeptides.Only in recent years, have alternative strategies employing synthetic polymers and polymer composites also developed to prepare such strong and tough fibers by mimicking the hierarchical structure and spinning process of spider silk.3][14] Because the preparation of such fibers also follows a solution-to-gelation transition process, this review would briefly describe only a few examples in this section.
In the second section, we summarized the preparation of artificial spider silk from hydrogel fibers by synthetic polymers and polymer nanocomposites.Here, the polymer composition, spinning strategyas well as the posttreatment are key issues affecting the gelation process and structural modulation to achieve high strength and toughness.We summarized different categories of spinning methods, including draw spinning, 3,15 wet-spinning, 6,16 microfluidic spinning, 17,18 post drawing, 19,20 and dynamic cross-linking. 21,22The advantage of employing such a gelation process is that the fiber's hierarchical structures can be delicately modulated during fiber drying, such as alignment, phase separation, self-assembly, post drawing, and twisting.This resulted in a variety of fiber materials with high strength and toughness.
In the third section, we summarized some novel applications of artificial spider silk, for example, for use as artificial spider silk, 23,24 sensors, 25,26 signal transmission, 27,28 thermal regulation, [29][30][31] and so forth.The natural spider silk exhibits super contraction behavior, where an elongated fiber would recover its initial length after exposure to moisture.This would enable the spider silk web to be distorted by the incoming prey to recover its initial shape when there is dew or rain.This process can also be employed to serve as artificial muscles to output work.By combing ion conduction or electron conduction, the hydrogel fibers can also serve as electrical conductors to transmit S C H E M E 1 Schematic of the spinning processes of tough hydrogel fiber-based materials, methods, and their applications in various technological and industrial sectors.Reproduced with permission: Copyright 2022, Wiley-VCH GmbH; 3 Copyright 2022, Elsevier; 6 Copyright 2020, American Chemical Society; 7 Copyright 2017, Elsevier. 8ignals, or be used as sensors to monitor the movement of humans.Except for hydrogel fibers, other types of fiber materials subject to a gelation process were also prepared.For example, porous fibers were prepared for use as thermal regulation, and multifunctional fibers were prepared to integrate sensing and actuation.Last but not the least, we discussed the future challenges and opportunities of artificial spider silk through such a gelation process.

| ARTIFICIAL SPIDER SILK PREPARED FROM NONRECOMBINANT PROTEINS, RECOMBINANT PROTEINS, AND POLYPEPTIDES
Artificial recapitulation of the hierarchy of natural protein fibers may be crucial to develop advanced fibrous materials; however, it may be significantly challenging due to the complexity of the natural environment.Hence, insights into fiber formation can provide a new rationale for the design and preparation of fibers with programmed mechanical properties.Synthetic bioinspired fibers have exhibited impressive tensile properties, but the fiber formation process is still not well understood.Moreover, these systems are highly complex, and the formation process used for the process is expensive, 32 (Figure 1A).Spinning of artificial spider silk from protein and polypeptides is a typical, well-developed method in which fibers are produced from a solution and are subsequently converted first into a gel-like state either by wet spinning or dry spinning and finally to fibers.The extraordinary mechanical performance and functionality of spider silk and silkworm fibers have led to the wide exploration of their protein origins.These fibers exhibit several desirable characteristics; hence, they are interesting candidates for an array of applications, including drug delivery, sensors, wound healing, and biotechnological and tissue engineering (TE) applications. 33,34Protein fibers are typically realized by spinning technologies, including electrospinning, dry spinning, solution blow spinning, wet spinning, and draw spinning.These synthetic techniques may mimic the natural weaving process to afford nanofibers; however, these techniques are less robust, and the tuning of the fibers in terms of their diameter, length, and mechanical properties is difficult.During spinning, highly concentrated protein solutions are used for nanofiber production.After the fabrication of protein fibers, the physical solidification process cannot be avoided.Moreover, the synthesis of sustained functional protein fibers has not been reported thus far.Notably, the spinning behavior of silkworms and spiders can be regarded as a distinct microfluidic process.As an alternative, microfluidic artificial spinning has been exploited and reported to be easily tailorable for the controlled production of protein fibers.Unlike the newer methods, microfluidic spinning provides an easy platform for the controlled replication of a natural spinning mechanism.Yu et al. 35 employed a capillary microfluidic system to prepare bio-inspired helical microfibers with adjustable conformation, exhibiting multiple applications in biomedical engineering.Besides, the cost-effectiveness of microfluidics renders it a beneficial technique for the mass production of continuous microfibers.The application of microfluidics has been widened further in drug delivery and TE due to the use of biocompatible solvents for fiber spinning.Furthermore, microfluidics can easily produce bulk protein fibers of different shapes and consistent sizes.By carefully optimizing parameters of microfluidics, such as flow rate and drawing speed, mechanically robust protein fibers with tunable morphologies and characteristics can be obtained.In the following section, an overview of the use of microfluidics for fiber production is presented.
Despite extensive research on spider silk and silkworm protein-based fibers, cost-effective and robust approaches are not developed yet to prepare biological fibers, which are still challenging.A series of fibrous proteins, such as collagen and elastin as well as phage viruses, have been intensively investigated 10 ; however, their mechanical properties still remain unsatisfactory.The exceptional toughness of spider silk proteins originates from the combination of rigid and flexible areas.By employing microfluidic spinning, Liu et al. 9 produced high-performance fibers by using bovine serum albumin (BSA) and glutaraldehyde (GA) as the outer and inner channels of a microfluidic device, respectively.The cross-linking of the aldehyde and amino groups as well as stretching treatment rendered good mechanical properties to the fibers, resulting in a tensile strength of 300 MPa, a toughness of 50 MJ/m 3 , and Young's modulus of 4.4 GPa.Similarly, a wet-spinning-based approach was exploited to fabricate chimeric protein-based fibers with cationic elastin-like polypeptide sequences (ELP) and protein squid ring teeth (SRT), which were further crosslinked with GA.The in situ cross-linking was realized by the interaction of the lysine groups of ELP and amino groups of GA.After stretching, the synthetic spider silk exhibited extremely good mechanical properties, including a tensile strength of 630 MPa and a toughness of 130 MJ/m. 36ilk exhibits numerous biomedical and industrial applications.By adopting the natural process of biological spinning and replicating the hierarchical and molecular structures found naturally in silkworm and spider silks, silk fibers have been artificially spun by different techniques. 37Generally, artificial spinning systems can be divided into dry or wet spinning systems.Wet spinning involves the extrusion of a silk solution directly into a coagulation bath.On the other hand, in dry spinning, the solidification of fibers is delayed due to the evaporation of the solvent during spinning.The bioinspired spinning process mainly exploits three types of spinning dope: a natural liquid silk isolated from spider glands or a silkworm, a solution of regenerated silk, and a solution containing recombinant silk.Silk protein derived from natural silk fibers is referred to as regenerated silk.Previous studies have demonstrated that the pH of the spider silk gland reduces from 7.6 to 5.7.The specific conformational changes in the final spider silk protein domain, generating threads via locking and triggering processes, are induced by pH gradients.Bacteria and other genetically engineered species have been reported to exhibit effective expression of silk-inspired proteins or silk protein motifs. 38Several artificial spinning techniques have been developed to mimic the natural spinning system.Artificially produced silk can even exhibit mechanical properties greater than that of natural silk.Generally, spun fibers exhibit poor mechanical properties, which require fiber posttreatment.By exploiting gene engineering and biological fermentation, recombinant spider silk protein exhibiting a nonrepetitive domain at the N-terminus (NT), a repeatedly extensive region (Rep), and a nonrepetitive domain at the C-terminus (CT) was produced to mimic the structure of native spider silk protein and decipher the spinning mechanism of spider silk.Rising et al. created a biomimetic system that replicated the spinning process of spiders.By varying the shear force and pH gradients, a sophisticated artificial spinning device was created.A water-soluble Escherichia coli silk-like protein was expressed by this method, which comprised domains derived from the silks of two spider species: Euprosthenops australis and Araneus ventricosus.The concentrated recombinant silk protein solution was injected into an acidic bath, which replicated native conditions of native silk during its passage through the silk glands and channels of a spider.The self-assembly of the recombinant silk protein afforded micron-sized fibers with diameters ranging from 10 to 20 µm with physical properties similar to those of native silk fibers.Similarly, high-performance regenerated silk fibers were directly spun by a dry spinning method.The nematic silk microfibril solution was directly extruded into fibers in the air. 36The native silkworm silk-based fibers were partially dissolved into microfibrils, affording a nematic microfibril solution.Hence, natural silk fibers can maintain their hierarchical structures.The elastic modulus of as-spun regenerated silk fibers was 1164 GPa, which was greater than those of some of the naturally occurring spider silk.The natural spinning system was further reproduced using a microfluidic system.The rigid and flexible sections of spider dragline silk are composed of MaSp1 and MaSp2 proteins.Lewis et al. 39 combined the recombinant MaSp1 and MaSp2 proteins in an appropriate proportion to prepare fibers.Artificial spider silk was further subjected to an isopropanol/water mixture to further improve the mechanical properties of fibers, resulting in a yield strength of 221.7 MPa.Fan et al. 40 reported that as a minor component of spider egg case silk, tubuliform spidroin (TuSp2) not only accelerates self-assembly but remarkably promotes the molecular chain alignment of spidroins on physical shearing.The NMR structure of the repetitive domain of TuSp2 revealed that its dimeric structure with a unique charged surface serves as a platform to recruit different domains of the main egg case component TuSp1.Hu et al. 41 reported the biosynthesis and self-assembly of a mimic spidroin comprising amino-and carboxy-terminated domains bracketing 16 consensus repeats of the core region from the spider Trichonephila clavipes.The presence of both termini was essential for the selfassembly of the mimic spidroin into fibril-like nanostructures in a concentrated aqueous dope, affording an ordered alignment of these nanofibrils once extruded into an acidic coagulation bath.Finally, continuous macroscopic fibers were obtained with a tensile fracture toughness of 100.9 ± 13.2 MJ/m 3 , which was comparable to that of their natural counterparts.
F I G U R E 1 (A) Gradient map showing samples that easily formed stable fibers (green) and unstable fibers (yellow) and that did not form fibers (red).Reproduced with permission: Copyright 2022, Wiley-VCH GmbH. 32(B) Schematic of the fabrication of rTRM7 fiber by the drawing process.Reproduced with permission: Copyright 2022, Nature. 48(C) Photographs of the rTRM7 fiber during the drawing process.Reproduced with permission: Copyright 2022, Nature. 48(D) Schematic of biomimetic spinning: A concentrated solution of NT2RepCT was extruded through a glass capillary into a spinning bath containing an aqueous buffer, pH 5. The pH change and shear forces mimicked the conditions of native silk spinning and induced immediate fiber formation.The fibers were collected continuously on a collection wheel with a speed of 46 cm/s.Reproduced with permission: Copyright 2021, Elsevier. 49(E) Structural transition illustrations of the MRSF nanofibril under a humid environment, including two periods of initial contraction and periodic humidity actuation.Reproduced with permission: Copyright 2022, Elsevier. 53(F) Microbially synthesized polymeric amyloid fiber promoted β-nanocrystal formation and exhibited tensile strength in the gigapascal range.Reproduced with permission: Copyright 2021, American Chemical Society. 54(G) Schematic of the fabrication process of biomimicking sensing suture (BSS), including wet spinning for the fabrication of the protein core fiber and coating of the shells.Reproduced with permission: Copyright 2021, Wiley-VCH GmbH. 55(H) Schematic of the functionalization of the regenerated silk fibroin (RSF) fiber by polydopamine nanoparticles (PDA NPs).Reproduced with permission: Copyright 2022, Wiley-VCH GmbH. 56he silk-like polypeptide polymers demonstrate promise for industrial manufacturing due to their cost-effectiveness, robustness, and simplicity.Although considerable research has been conducted toward the development of synthetic silks by employing traditional chemical processes that simulate spider silks, numerous challenges that need to be considered still exist.A two-step chemical synthesis was employed to prepare a multi-block polypeptide that simulated the secondary structures of spider silk.In the first phase, chemo-enzymatic polymerization was employed to create two polypeptide fragments.Polyalanine was used to produce β-sheet threads of spider silk, which mimicked the crystal zone, while poly(glycinerandom-leucine) was produced as a flexible amorphous region.Next, these polypeptide fragments were ligated via the consumption of polyphosphoric acid as the reducing agent during the second stage. 42While it afforded an alternative route for mimicking the internal structure of spider silk, the molecular weight of the produced polypeptide chain was rather small, and its mechanical properties were also weak.The amine-terminated peptide, viz.poly(benzyl-1-glutamate) (PBLG), exhibiting a degree of polymerization greater than 18 resulted in the formation of an α-helix with a secondary structure, while it formed both α-helix and β-sheet crystal structures at a degree of polymerization less than 18. 43 Similarly, a chemical synthesis route was adopted to afford scalable super-tough fibers.The simultaneous introduction of β-sheet crystals and α-helical peptides into a pseudoprotein polymer led to a super toughness value of ~387 MJ/m 3 , which was comparable to that of the toughest spider silk, viz.aciniform silk of Argiope trifasciata, and almost two times greater than that of the common spider dragline silk. 44Furthermore, the pseudoprotein-polymer may offer the advantages of a convenient supply of raw materials and straightforward preparation, allowing for the mass production of fibers.Qiao et al. 45 employed a grafting-from approach to insert poly(valine) and poly(valine-γ-glycine) as β-sheets into an amorphous hydrophilic network via the ring-opening polymerization (ROP) of N-carboxy anhydride (NCA), which successfully mimicked the structures of the amorphous and crystalline regions of spider silk.Compared to the initial networks devoid of β-sheets, the β-sheet nanocrystal of artificial spider silk exhibited higher compressive strength and stiffness.NCA-based ROP is a cost-effective, economic, and easy method to synthesize different polypeptides, which may be subsequently used to prepare long-chain polypeptides.Fan et al. 46 designed natural silk-like hierarchical fibers by the self-assembly of crystallized silk fibroin (SF) droplets; the nanofibril bundles were aligned in their long-axis direction.These self-assembled SF fibers were formed by coalesced droplets, which underwent sprouting to form a branched fibrous network.Compared to natural SF fibers, hierarchical SF fibers significantly promoted the growth of human umbilical vein endothelial cells.
The advent of mechanically strong and tough biological fibers by the incorporation of intermolecular linking networks is gaining importance.Wan et al. 47 fabricated protein-saccharide composite fibers via protein-initiated double-interacting networks.Three lysine-rich bioengineered proteins were introduced, and the multiple crosslinking interactions including electrostatic forces and covalent bonds remarkably improved the mechanical properties of composite fibers.The composite fibers exhibited a breaking strength of ~768 MPa, Young's modulus of ~24 GPa, and a toughness of ~69 MJ/m 3 .Zhang et al. 48employed recombinant scallop byssal proteins to prepare protein-based fibers, which exhibited excellent extensibility and self-recovery properties.The native byssal thread collected from scallop Chlamys farreri exhibited high extensibility (327% ± 32%), which outperformed most of the natural biological fibers.The most abundant scallop byssal protein type 5-2 (Sbp5-2) was used in the thread region.Besides, a recombinant protein consisting of seven tandem repeat motifs (rTRM7) of the Sbp5-2 protein was synthesized.The bio-inspired extensible rTRM7 fiber with high extensibility (234% ± 35%) and selfrecovery under wet conditions was produced by an organic solvent-enabled drawing process.The fabricated fibers recapitulated the hierarchical structure and mechanical properties of the native scallop byssal thread (Figure 1B,C).
The mechanical properties of artificial spider silks have already been optimized; however, the yield of recombinant silk proteins that can be used to produce fibers with good mechanical properties is typically extremely low, and several purification and spinning protocols still require the use of urea, hexafluoroisopropanol, and/or methanol.Thus, improved production and spinning methods with a minimal environmental impact are required.As a result, alternative approaches have been adopted to afford a miniature spider silk protein to improve its solubility in aqueous buffers as well as spinnability.Schmuck et al. 49 developed a production protocol that resulted in an expression level of >20 g target protein per liter in an E. coli fed-batch culture, and subsequent purification under native conditions yielded 14.5 g/L.This value corresponded to a nearly sixfold increase in expression levels, and a 10-fold increase in yield after purification compared with those reported for recombinant spider silk proteins.On the other hand, biomimetic spinning by using only aqueous buffers afforded fibers with a toughness modulus of 74 MJ/m 3 ; this value is the highest reported value for biomimetic as-spun artificial silk fibers (Figure 1D).Arndt et al. 50esigned spider silk proteins (minispidroins) and reported a clear increase in the β-sheet propensity and inter-β-sheet binding strength.Prokaryotic expression, protein purification, and biomimetic fiber spinning resulted in four fibers with significantly improved tensile strength in comparison with that of the original minispidroin.Hence, biomimetic fibers with toughness values matching those of native dragline silk fibers are successfully prepared.
Similarly, Cheng et al. 51 developed an artificial spider silk protein (spidroin) composite programmable woven textile (i-SPT) with high tensile properties, which exhibited biochemical sensing abilities as well as air permeability and motion monitoring capabilities for wound management.The recombinant spidroin solution was further mixed with polyurethane (PU), affording fibers with reversible pH responsiveness for wound healing applications.Jin et al. 52 conducted the metabolic engineering of Corynebacterium glutamicum, which efficiently secreted recombinant spidroins, by using a model spidroin MaSpI16, comprising 16 consensus repeats of the major ampullate (MA) spidroin 1 of spider T. clavipes.The high abundance (>65.8%) and titer (554.7 mg/L) of MaSpI16 in the culture medium facilitated facile, chromatography-free recovery of the spidroin with a purity of 93.0%.The high solubility of the purified spidroin permitted the preparation of highly concentrated aqueous dope (up to 66%), which was amenable for spinning into synthetic fibers with an appreciable toughness of 70.0 MJ/m 3 .Wu et al. 53 replicated the novel humidity actuation of natural spider silks by the regeneration of the abundant silkworm silk fibroin by microfluidic spinning technology.The alignment of the fibrils and diameter of the desired microfluidic-spun regenerated silk fibers (MRSFs) were optimized by the dehydration and shearing control of silk fibroins (SFs).These MRSFs exhibited a unique directional initial contraction property under exposure to humidity or organic solvents, which was attributed to the transition of the mesoscopic hierarchical structure of SF molecules between the hydrophilic and hydrophobic domains.The β-sheet transformation and mesoscopic reconstruction resulted in humidity-driven silk actuation (Figure 1E).
While the ability of amyloid proteins to form stable β-sheet nanofibrils may exhibit broad implications for biomaterials, the nanoscale characteristics of amyloid proteins rarely have been translated into their attractive macroscopic properties for mechanically demanding applications.Li et al. 54 fused amyloid peptides with flexible linkers from spidroin, affording polymeric amyloid proteins by using engineered microbes; these amyloid proteins were further subjected to wet spinning to afford macroscopic fibers.Three amyloid groups were fabricated into fibers.Structural analysis revealed the presence of β-nanocrystals that resembled the cross-β structure of amyloid nanofibrils.These polymeric amyloid fibers exhibited strong and molecular-weightdependent mechanical properties.Fibers comprising a protein polymer containing 128 repeats of the FGAILSS (representing an antiparallel-antifacial amyloid) sequence exhibited a tensile strength of 0.98 ± 0.08 GPa and a toughness of 161 ± 26 MJ/m 3 ; these fibers outperformed most of the recombinant protein fibers and some natural spider silk fibers (Figure 1F).
Surgical sutures play a key role across a wide range of medical treatments, and various sutures with different strengths, sizes, compositions, and performance exist.Recently, increasing attention has been focused on bioactive and electronic sutures composed of synthetic polymers due to their ability to reduce inflammation and medically and/or electronically facilitate wound healing.However, integrating sensing capabilities into bioactive sutures without adversely affecting their mechanical strength and biocompatibility, and/or bioactivity remains challenging.Liu et al. 55 designed a set of biomimicking, antibacterial, and sensing sutures based on regenerated silk fibroin (RSF).Inspired by the "core-shell" multilayered structure of natural spider silk fibers, these sensing sutures comprise hierarchical structures and heterogeneous functionalities to allow for the integration of multiple, clinically favorable functions into one suture device (Figure 1G).
Chen et al. 56 reported the polydopamine (PDA)induced functionalization of RSF fibers, which exhibited satisfactory photothermal conversion and flexibility.Based on multilevel engineering, an RSF solution containing PDA nanoparticles was subjected to wet spinning, affording PDA-incorporated RSF (PDA@RSF) fibers; these fibers were subsequently coated with PDA by the oxidative self-polymerization of dopamine to form PDA@RSF-PDA (PRP) fibers.During wet spinning, PDA was used to adjust the mechanical properties of RSF via the influence of its hierarchical structure.Meanwhile, the PDA coating rendered the extensive absorption ability of near-infrared light (NIR) and sunlight to the PRP fibers, which were subsequently fabricated into PRP fibrous membranes.The temperature of PRP fibrous membranes can be adjusted and increased for up to 50 °C within 360 s under 808-nm laser irradiation with a power density of 0.6 W/cm 2 .These PRP fibrous membranes exhibited good photothermal cytotoxicity both in vitro and in vivo (Figure 1H).
Water and humidity severely affect the material properties of spider MA silk, resulting in the plasticization, contraction, swelling, and torsion of the fiber.Several amino-acid residues have been proposed to be involved in this process, but the complex composition of the native fiber makes detailed investigations complicated.Greco et al. 57 observed super-contraction in biomimetically produced artificial spider silk fibers comprising defined proteins.The results revealed that the tyrosine residues, not the proline moieties, in the amorphous regions of the silk fiber are responsible for super-contraction.Furthermore, the response of artificial silk fibers to humidity can be tuned, which demonstrates the potential for the development of materials in wet environments (e.g., water-resistant fibers with maximum strain-at-break and toughness modulus).Generally, polymer hydrogels exhibit insufficient biomechanics, strong resistance to cell adhesion, and weak bioactivity, which in turn limits their applications in bone TE.Consequently, to overcome these limitations and develop scaffolds with good mechanical properties as well as osteogenesis and angiogenesis, DNA plasmid (pNF) was introduced into gelatin methacryloyl (GelMA) and thiolated chitosan (TCS) to afford a GelMA/TCS/pNF composite hydrogel with dual network structure. 58Chen et al. 59 fabricated silk composite fiber reinforced with telechelic-type polyalanine (TPA).When TPA was added in suitable ratios of 1 and 3 wt%, the mechanical properties of the composite fibers were significantly improved by ~42% and 51% in comparison with those of the fibers produced by using silk alone, exhibiting high tensile strength and toughness.As can be observed by atomic force microscopy, regularly packed and aligned granules within composite fibers were shown to enhance mechanical performance.Saric et al. 60 utilized MA spider silk to develop high-performance fibers, exhibiting high strength and elasticity.Two types of spidroins from Araneus diadematus were coproduced in E. coli to investigate possible dimerization and discern their effects on the mechanical properties of fibers.During the production of the two spidroins, a mixture of homoand hetero-dimers was formed, which was triggered by the carboxyl-terminated domains.Notably, homodimeric species of the individual spidroins were self-assembled in a manner different from that of the heterodimers, and stoichiometric mixtures of homodimers and heterodimers afforded spidroin networks upon assembly with a considerable impact on fiber mechanics upon spinning.

| Draw spinning inspired by the spinning of spiders
Polymeric fibers may offer a ubiquitous platform to realize good strength and toughness, which have attracted considerable research interest.Unlike the fabrication of synthetic fibers, which require high energy, spiders can easily produce silk fibers.Herein, different polymer-based hydrogel fibers, which can be drawn from hydrogels at an ambient temperature, have been used.Liu et al. 5 used synthetic vinyl-functionalized silica nanoparticles cross-linked with polyacrylic acid to mimic the primary structure of spider silk and afford a hierarchical core structure of artificial spider silk fibers via the controlled water-evaporation self-assembly.The rapid evaporation of water within 30 s afforded tough and stretchy threads, mimicking the morphology of synthetic spider silk.The doping of ions and insertion of twists further improved the mechanical properties of artificial spider silk fibers, which exhibited a toughness of 370 MJ/m 3 , a tensile strength of 895 MPa, and a damping capacity of 95%.
Synthetic spider silk exhibits a high energy dissipation capacity, which may be beneficial for kinematic energy shielding and jolt captivation.Ma et al. 4 synthesized core-shell-type composite fibers by using poly (methyl acrylate) (PMA) and a sodium polyacrylate hydrogel (PAH) as the core and shell, respectively.These synthetic silk fibers exhibited reversible transitions of amorphous and crystal-like domains and a tensile strength of 5.6 MPa, significant extensibility (tension at a disruption of 1200%), rapid self-healing (within 30 s) from high tension, good electrical conductivity (2 S/m), and excellent anti-freezing properties (at −35 °C, conductivity and stretchability of the composite fiber were preserved).Anderson et al. 62 also designed adjustable polymer fibers from bulk hydrogels.The tunable polymer filaments were drawn from boronic acids and 4-armed polyethylene glycol (PEG), which acted as a dynamic cross-linker for hyaluronic acid (HA).By manipulating the polymer assembly and precursor concentration, the mechanical properties of the polymer fibers were customized.The diameter of the polymer fiber ranged from 4 to 20 µm, with a maximum length of 10 m.The polymer fibers exhibited super-contraction in a humid environment, which was similar to the contraction behavior of spider dragline silk.The artificial spider silk with tunable mechanical properties possibly demonstrates a wide range of applications.Similarly, inspired by the spidroin structure and spider spinning process, He et al. 3 prepared a soluble and cross-linked nanogel.The cross-linked fibers manifesting spider-silk-like hierarchical structures, such as aligned nano-assemblies and sheath-core structures as well as cross-links, were spun.
The alignment and assembly of the polymer chains as well as the spiral architecture in the nanogel fiber were further tailored via the incorporation of nucleation seeds in the nanogel solution as well as pre-stretch application, which altogether improved the mechanical properties of fibers substantially.The breaking strength (1.27 GPa) and toughness (383 MJ/m 3 ) of the fibers approached those of the best dragline silk (Figure 2A,B).
Natural silk spinning is a strategy used by spiders and silkworms to construct their ultra-strong and tough silks; it can be considered an optimized meso-assembly processing engineering (MAPE) strategy that effectively coordinates molecular and supramolecular assembly and native spinning.Zhang et al. 63 employed a biomimetic MAPE strategy to fabricate biomaterials that mimic the structural and mechanical characteristics of biological tissues.Owing to its high failure strain (1200%), strength (5 ± 1 MPa), stiffness (18 ± 2 MPa), and toughness (6 ± 1 MJ/m 3 ), polyethylene oxide blend is considered as an ideal phasetransition system for mimicking native spinning  63 (D) "UC HYDROGEL" written by the hydrogel injected through a 19-gauge needle, a house-built spinner for the scalable production of hydrogel microfibers, microscopic image of the as-spun fibers with a nearly uniform diameter, and tensile stress-strain curve of a single-spun hydrogel fiber.Reproduced with permission: Copyright 2021, Wiley-VCH GmbH. 15Figure 2C).Scherman et al. 64 synthesized moisturepenetrating supramolecular fibers by using composite hydrogels, which comprised silica nanoparticles embedded into methyl viologen (P1), naphtholfunctionalized hydroxyethyl cellulose (HEC) (P2), and cucurbit [8]uril.P1 and P2 polymers were cross-linked using cucurbit [8]uril, affording a vigorous heteroternary multipart on both polymers with attached guest moieties.Double cross-links comprising dynamic bonds between P2 and P1 as well as UV-crosslinking-mediated covalent bonds within P2 afforded supramolecular fibers.With extraordinary dampness, this synthetic artificial silk absorbed up to 300% of its weight in water and shrank to half of its original length.These moisturesensitive supramolecular fibers can be exploited for artificial muscle-related applications.Spider silk is well known for its unique strength and toughness, while synthetic polymer-based fibers with similar properties exhibit significant technical challenges.Greiner et al. 65 fabricated a continuous yarn by using commercial polyacrylonitrile and bifunctional polyethylene glycol bisazide (PEG-BA).The yarn was strained at 160 °C in air and then toughened at various temperatures to improve mechanical properties.These fibers exhibited a tensile strength of 1236 ± 40 MPa, which was comparable to that of spider dragline silk.
Similarly, inspired by the hierarchical structure and repeating sequences of spider silk, Tang et al. 66 prepared hierarchical organic-inorganic structures, simultaneously exhibiting amorphous flexible domains and rigid crystal-like structures.Synthetic and natural polymers, as well as ceramics, were used to prepare these structures.Briefly, sodium alginate (Alg), calcium phosphate (CaP), polyvinyl alcohol (PVA), and hydroxyapatite (HAP) were used.The mechanical properties of these fibers (e.g., elongation-at-break, 80%, toughness, 296 J/g, and tensile strength, 950 MPa) were comparable to those of spider silk.PU, multiwalled carbon nanotubes (MWCNTs), and graphene oxide were spun by the wet-spinning method.Once exposed to water and humidity, these fibers shrunk up to 60%. 67The tensile strength of the fibers could be improved further via the modification of natural polymeric materials.For instance, light-weight ordinary bamboo exhibiting a toughness of 9.74 MJ/m 3 and a tensile strength of 1 GPa was densified by partially removing its hemicellulose and lignin content.As a result, in the dense bamboo structure, the long-oriented cellulose microfibrils improved hydrogen bonding and significantly overcame mechanical flaws, thereby contributing to their notable mechanical properties, including tensile strength, toughness, and bending strength. 68eorge et al. 69 exploited strained alkene and diphenyl tetrazine to produce cross-linked hydrogel microfibers.
The labile poly-(ethylene glycol-s-tetrazine) (PEG-bisTz) macromer enabled the production of novel cross-linked fibers with desirable mechanical and thermal properties, as well as degradation ability.When combined with PEG-bisTz3, cross-linked extracellular matrix-mimetic microfibers that supported cell culture and degraded over time were produced.The tunability of the bioorthogonal platform enabled the combinations of bisTz1, bisTz2, and bisTz3 macromers in the fiber backbone.Higherorder fiber assemblies, including tube and mesh structures, were constructed from multiple individual fibers.He et al. 15 used a novel hydrogel with impressive stretchability (>12,400%), long-term adhesion, strong antibacterial activity, and robust spinnability to prepare mechanically strong hydrogel fibers.The precursor solution containing Ag-lignin NPs, citric acid, acrylic acid, and poly (acrylamide-co-acrylic acid) (P(AAm-co-AA) was used to afford fibers.The interaction among the carboxylic (-COOH) and hydroxyl (-OH) groups enabled the hydrogen-bonding-mediated formation of interpenetrating networks, while electrostatic interaction between negatively charged hydroxyl ions (OH − ) and carboxylic ions (COO − ) and positively charged Ag-lignin NPs permitted energy dissipation under extensive deformation.Consequently, these multivalent interactions enabled ultrahigh stretchability and deformability of the hydrogel, which favored the subsequent spinning process.The hydrogel micro/nanofibers could be manufactured by a draw-spinning process using a house-built spinner or a commercial electrospinning machine.The as-generated hydrogel fiber with a micro-sized diameter (~50 µm) exhibited excellent mechanical properties (a tensile stress of 422.0 MPa, a strain of 86.5%, a Young's modulus of 8.7 GPa, and a toughness of 281.6 MJ/m 3 ) (Figure 2D) (Tables 1 and 2).

| Spinning of hydrogel fiber
For decades, researchers have focused on the green and scalable production of some fibrous materials with a high fracture energy.Although some progress has been made with respect to the research of materials with high fracture energy in recent years, inspired by the fiber structure of spider silk, it is still considerably challenging to produce artificial fibers with extremely high toughness using a simple and green process.Hydrogels are threedimensional (3D) networks synthesized by the chemical or physical cross-linking of hydrophilic natural or nonnatural polymers, which can swell in water and take up a significant amount of the solution.Hydrogels that can be used in several applications, including electrical conductivity, self-restoring capability, excessive stretchability, frost resistance, TE, luminescence, photomechanical hydrogels, wound healing, and sensitivity stimulation, are attractive for producing fibers with spider silk-like properties.On the other hand, typical hydrogels are mechanically weak and not appropriate under a majority of physiological load-bearing conditions.In this section, different strategies, which have been employed to design tough hydrogel fibers via the exploitation of noncovalent linkages, are discussed in subsequent sections.Hydrogels can be prepared in various shapes, including bulk, films, and threads, to suit various applications.

| Wet-spinning method
In wet spinning, the polymer solution is squeezed into a coagulation bath to form long fibers by a nonsolventinduced phase inversion process.First, the polymer is dissolved into an appropriate solvent; the nonsolvent for the polymer may lead to solvent removal and subsequently lead to polymer precipitation into consecutive fibers.The fiber diameter may vary in the range of a few nanometers to up to a few microns.On the laboratory scale, the wet spinning setup comprises an extruding spinneret coupled to a pump, which extrudes a polymer solution into a coagulation bath at an appropriate flow rate.Different synthetic polymers, such as polycaprolactone (PCL), poly(lactic-co-glycolic acid (PLGA), poly (lactide-co-caprolactone) (PLCL), and natural polymers, including collagen, chitosan, silk fibroin, and chitin as well as their combinations can be employed for wet spinning.In addition, the processing parameters during spinning may affect fiber performance, including the flow rate of the polymer solution, applied voltage, and air gap between the spinneret and coagulation bath.The processing of the fibers after spinning also may be crucial to further confirm their functionality. 70xtensive research has been conducted on the production of hydrogel fibers by using advanced spinning techniques.Core-sheath hydrogel fibers were synthesized in a continuous manner by integrated light-triggered dynamic wet spinning.A sodium alginate solution was used as the precursor to fabricate the sheath, and a poly (ethylene glycol) diacrylate (PEGDA) and acrylamide (AAm) solution was used to fabricate the core.A core-sheath spinning needle was used to extrude the spinning fluid into a calcium chloride (CaCl 2 ) coagulation bath, thereby forming calcium alginate via the ionic crosslinking of alginate with Ca 2+ .The UV light (wavelength of 360 nm) near the spinning nozzle was used to induce the free-radical polymerization of PEGDA and AAM, affording a gel network.Continuous core-sheath hydrogel optical filaments with modifiable fiber diameters may be prepared by wet spinning, exhibiting optical propagation and mechanical properties.This strategy also may be exploited for the fabrication of other functional core-sheath fibers. 71Wang et al. 72 also developed elastic, conductive, and self-healing hydrogel fibers using different concentrations of N-acryloylglycinamide (NAGA) and AAm by a continuous dry-wet spinning method.The thermally reversible sol-gel transition afforded a physically cross-linked hydrogel (NAGAco-AAm).These hydrogel filaments exhibited high stretchability (900%), tensile strength (2.27 MPa), self-recovery, and conductivity (0.69 S/m).The PNA/PMA core-sheath fibers further exhibited a poly(methyl acrylate) (PMA) elastomeric cover, rendering exceptionally high water evaporation and absorption resistance.Similarly, Wu et al. 73 prepared liquid-metal sheath-core microfibers by a coaxial wetspinning process, simultaneously exhibiting high conductivity (4.35 × 104 S/m) and exceptional stretchability (elongation-at-break, 1170% at 200% tension).Similarly, a microfluidic spinning technique along with in situ interfacial complexation was employed to prepare lignin-based carbon fibers.Chitosan was used as the cross-linker to realize a hierarchical assembly of highly oriented CNFs and lignin.Hence, highly oriented and compact lignin/CNF filaments are fabricated as suitable precursors of carbon fibers.After stabilization and carbonization, bio-based carbon fibers comprising fine graphite microcrystals and a carbon lattice were obtained, exhibiting excellent mechanical performance and electrical conductivity.At a lignin content of 75 wt%, the tensile strength and electrical conductivity of carbon fibers reached 1648 MPa and 185.33 S/cm, respectively. 18urrently, optical fibers are conventionally selected for fast and high-capacity communication networks due to their lightweight structures, flexibility, and immunity to electromagnetic interference.Polymer optical fibers (POFs) are used in numerous short-distance applications.Notably, the incorporation of luminescent nanomaterials in POFs offers optical amplification and sensing for advanced nanophotonics.Owing to the limitation of the presence of non-sustainable components and processes of POFs, as well as other potential risks from luminescent nanomaterials, photobleaching, oxidation, and cytotoxicity, biopolymer-based optical fibers containing nontoxic luminescent nanomaterials serve as a good platform.Strong, yet ductile, composite fibers were obtained using methylcellulose (MC)-containing gold nanoclusters.These fibers functioned as short-distance optical fibers with a low propagation loss of 1.47 dB/cm.Similarly, owing to their excellent mechanical properties (viz.elastic modulus and maximum strain values of up to 8.4 GPa and 52%, respectively), low attenuation coefficient, and high photostability, these MC-based composite fibers are excellent candidates for multifunctional optical fibers and sensors. 74i et al. 75 used stiff TEMPO oxide cellulose nanofibers (TOCNF) and soft waterborne PU (WPU) macromolecules (30-50 nm) to design homogeneous and hierarchical compact structures by a tunable wetdrawing and ionic cross-linking method.Qu et al. 76 prepared thermally-electrically responsive shape memory fibers composed of PCL and thermoplastic PU (TPU) with electric heating and strain sensing properties by the wet spinning and dip coating of MWCNTs on the fiber surface.The fibers exhibited strain ranging from 100% to 400%.The melting and crystallization of PCL represented switches of the shape memory function.After 9 dipcoating cycles of MWCNTs, the steady-state maximum temperature (T max ) of the as-spun PCL-TPU/9WMCNT fiber and the fiber stretched to a strain of 50% reached 59.7 °C and 54.4 °C, respectively.The PCL-TPU/ 9WMCNT fiber exhibited a high gauge factor (21.11), a fast response speed (187 ms), and excellent cycling stability (2000 cycles) at a strain of 20%.Liu et al. 77 reported a robust spider-silk-inspired wet adhesive (SA) comprising core-sheath nanostructured fibers with a polyvinylpyrrolidone (PVP) nano-sheath as the hygroscopic adhesive and a PU nanocore as the support.The wet adhesion of SA was achieved by the unique dissolving-wetting-adhering process of core-sheath nanostructured fibers.Furthermore, the SA maintained reliable adhesion on wet and cold substrates from 4 to −196 °C and even tolerated splashing, violent shaking, and weight loading in liquid nitrogen (−196 °C), demonstrating promise in cryogenic (Figure 3A).Similarly, Guimaraes et al. 78 employed wet spinning for the ionic cross-linking of natural polysaccharides to develop an optical hydrogel.Multilayer hydrogel optical fibers were obtained by highly dynamic ionic cross-linking of polysaccharides.The unique permeability of the asprepared hydrogels is also integrated with plasmonic nanoparticles for the molecular detection of SARS-CoV-2 in fiber-coupled biomedical swabs (Figure 3B).Similarly, Chen et al. 6 fabricated a tough, strong fiber with an asymmetric structure by wet-spinning, stretching, and water-inducing methods using TEMPO-oxidized nanocellulose (TOCN)/alginate/borax/PVA. The hybrid fiber exhibited a tensile strength of ~534.1 MPa and a toughness of ~142.8MJ/m 3 , as well as responsiveness to humidity changes (water-driven ability) due to its asymmetric structure (Figure 3C).Su et al. 16 proposed a fabrication strategy for robust fibers using a recombinant unfolded protein comprising resilin and supercharged polypeptide by a wet-spinning approach.The existing fibers with highly ordered structures induced by supramolecular complexation exhibited excellent mechanical performance (strength of ~550 MPa and toughness of ~250 MJ/m 3 ), which surpassed the mechanical properties of various polymers and artificial protein fibers.Biocompatibility and superior mechanical properties permitted the application of fiber patches for the efficient repair of abdominal hernia in rats (Figure 3D).Chen et al. 79 developed a wet-spinning strategy to fabricate superstrong, super-stiff chitosan filaments from an aqueous KOH/urea solution by a two-step drawing process.The highly ordered hierarchical structure of the resulting filaments contributed to their excellent mechanical properties.The tensile strength and elastic modulus of the chitosan filaments were 878 ± 123 MPa and 44.7 ± 12.3 GPa, respectively; these values were comparable to those of spider silk and bacterial cellulose (Figure 3E).
Recently, conducting polymer-based thermoelectric (TE) fibers has attracted extensive attention.However, intrinsically stretchable TE fibers that simultaneously exhibit good TE performance and stability under cyclic loading are still not reported much.Wen et al. successfully produced high-performance stretchable TE-fibers comprising poly (3,4-ethylenedioxythiophene): poly (styrenesulfonic acid) (PEDOT:PSS) and WPU by a simple one-step wet-spinning approach. 80Wu et al. 81 exploited entropy-mediated polymer-mineral cluster interactions to prepare thermal stiffening hydrogels with a record-high storage modulus enhancement of 13,000 times, covering a superwide region from 1.3 kPa to 17 MPa.Such a dramatic thermal stiffening effect was attributed to the transition from liquid-liquid to solid-liquid phase separation, which was governed by the enhanced polymer-cluster interactions on the molecular level.The hydrogel was subsequently processed into sheath-core fibers and smart fabrics, exhibiting self-strengthening and self-powered sensing properties by coweaving another liquid metal fiber as the joule heater and triboelectric layer (Figure 3F).

| Postdrawing method
Fabrication of gel fibers with mechanical characteristics and anisotropy comparable to those of biological fibrous tissues has been a perpetuating challenge.By employing a phase-sensitive spinning process and using a monomer/nanoparticle hybrid precursor, nanocomposite gel fibers with remarkable anisotropy were obtained.This procedure consisted of in situ reactive spinning and a subsequent postdrawing procedure.The pre-gel phase existed between precursors and cross-linked hydrogels, which was monitored by rheological technology.The pre-gel was prepared by the extrusion of a precursor solution comprising oligo(ethylene glycol) methacrylate (OEGMA), clay, and N,N-dimethyl acrylamide (DMAA), as well as an accelerator and an initiator, by a syringe into a polytetrafluoroethylene (PTFE) tube.Highly oriented hydrogel fibers were synthesized by the poststretching of a pre-gel after free-radical polymerization.Post-stretching of the pre-gel hydrogel fibers rendered a highly anisotropic microstructure and outstanding mechanical characteristics.Owing to the structural alignment resulting from the postdrawing process, the gel fibers exhibited remarkably high toughness (fracture energy of 79.9 kJ/m 2 ) and excellent elastic modulus (16.14 MPa). 19This spinning method might be employed potentially to afford hydrogel fibers using different monomers.DMMA was further replaced by AAm.The post-stretching of fibers afforded symmetrical polymer clay microdomains as well as improved mechanical properties.By replacing the AAm monomer with DMMA, a tensile strength of ∼9.76 MPa, an elongation-at-break of ∼190%, a toughness of ~103.7 kJ/m 2 , and an optical propagation of ~0.26 dB/cm were obtained. 7iber-based flexible TE generators are highly desirable due to their capability of converting thermal energy into electricity as well as their potential applications in wearable and portable electron devices.The unfolded protein RS-GA fiber was produced by squeezing an RS protein solution into a coagulation bath containing GA, followed by collection using a motor.Reproduced with permission: Copyright 2022, Wiley-VCH GmbH. 16(E) Fabrication and hierarchical structure of chitosan filaments by wet spinning via a two-step drawing process.Reproduced with permission: Copyright 2021, Wiley-VCH GmbH. 79F) Schematic design of a mineral hydrogel-based mechanoadaptive smart fabric.Hybridizing a mineral hydrogel with a PAAm hydrogel having a bicontinuous structure affords a thermal stiffening elastic hydrogel and corresponding sheath-core fibers.By the subsequent coweaving of another liquid metal fiber, a smart fabric with mechanoadaptive and self-powered sensing properties is finally prepared.Reproduced with permission: Copyright 2022, Wiley-VCH GmbH. 81GA, glutaraldehyde; SA, spider-silk-inspired wet adhesive.
Liu et al. 20 successfully prepared PEDOT:PSS/Te NW (tellurium nanowire) hybrid fibers.Te NWs of different contents were incorporated into fibers by the gelation of PEDOT:PSS.The TE performance of these hybrid fibers was greater than that of an individual PEDOT:PSS fiber, which was ascribed to the high electrical conductivity of Te NWs.The posttreatment of fibers further improved the TE performance (Figure 4A).Similarly, Li et al. 82 prepared a pure Ti 3 C 2 T x Mxene aerogel fiber by dynamic sol-gel spinning and subsequent drying using supercritical CO 2 .The aerogel fibers exhibited a mesoporous structure with tunable porosity (96.5%-99.3%),an ultrahigh electrical conductivity (104 S/m), and electrothermal/photothermal dual responsiveness.Similarly, Xie et al. 83 fabricated perusable hydrogel microtubes by microfluidics.The hydrogel microtubes were continuously generated from microfluidic devices, which were realized by the cross-linking of alginate by Ca 2+ in the coaxial flows and collecting bath.Notably, cells were directly printed along with the alginate prepolymer, affording cell-laden hydrogel microtubes.The composable microfluidic devices and platforms were further exploited for the facile generation of six biomimetic perfusable microtubes.

| Dynamic cross-linking method
To further afford hydrogel microfibers, the dynamic cross-linking method (DCS) is employed, which is suitable for the large-scale production of fibers while simultaneously avoiding the use of microfluidics.Zhu et al. employed DCS to afford continuous hydrogel fibers.A fiber-shaped aggregate was formed by squeezing a PEGDA solution into a water bath, followed by UVmediated polymerization to afford a stable 3D networklike structure.The hydrogel fiber diameter could be judicially controlled; the resulting fibers could absorb water efficiently due to their high specific surface area. 21he addition of cellulose nanocrystals (CNC) into the PEGDA solution further improved the mechanical properties of hydrogel fibers (Figure 4B). 8,84rtificially encoded microfibers inspired by biosynthetic fibrous microstructures are drawing considerable research attention, while their practical applications are hindered by multiple limitations.Zhang et al. 85 proposed a programmable dynamic interfacial spinning (DIS) process for producing volume-encoded microfibers with a superior encoding capacity and reliability.The produced microfibers comprised a sheath of the deformed hydrogel encapsulating sequentially aligned droplets, and their morphologies were controlled by adjusting the flow rates of the corresponding fluids and vibration parameters of the spinning nozzle.Liu et al. 86 introduced an aqueous two-phase system for fabricating stable and hollow spindle-knotted microfibers.These bioinspired spindle-knotted microfibers with continuous hollow channels were fabricated by a simple and flexible multiphase-laminar-flow microfluidic method.The maximum droplet volume was almost 1663 times that of the microfiber knot.Similarly, Zhang et al. 87 reported a DIS process to fabricate fog-harvesting microfibers that exhibited multiple biomimetic structures.Specifically, the DIS process utilizes the tunable vibration of the spinning nozzle at the air-liquid interface to facilitate the facile and controllable generation of spider-silk-like microfibers comprising periodic spindle knots and slender joints.The fibers exhibited a 405 times higher water transport velocity than that of natural spider silk and a 4.7 times higher water hanging ability than that of the previously reported knotted fibers (Figure 4C,D).

| Hydrogel fibers for artificial muscles, sensing, and smart fibers
Hydrogel-based artificial muscles, sensing, and smart fibers have been a hot research topic due to their several advantages.Soft and compliant materials are preferred over traditional metal-based materials for biomedical applications.Owing to their excellent flexibility, hydrogel artificial muscles exhibit a higher degree of freedom in their movements, which is crucial for managing fragile tissues or biomaterials with complex geometry.In addition, hydrogels also exhibit good biocompatibility due to their high water levels.On the other hand, hydrogels must be sufficiently tough to withstand repeated deformation during cyclic actuation and movement.In this section, artificial muscles and strain sensing based on hydrogel fibers are examined.

| Hydrogel-based artificial muscles
Artificial muscles demonstrate immense promise as intelligent materials that can replicate the motion of living organisms without using conventional power systems.As artificial muscles, hydrogels exhibit several advantages in comparison to other building materials, including a wide range of stimuli-responsiveness, sensitivity, and large-volume deformation. 88Hydrogels with a high water content are similar to biological muscles.The use of hydrogels as artificial muscles is difficult due to their weak work capabilities and limited mechanical properties.To develop artificial muscles that can respond to glucose, Kim et al. 23 designed self-helical-type hydrogel fibers.The hydrogel was originally placed over twisted nylon to create self-helical fibers.In an aqueous environment, during the swelling state, the sheath-core fiber spontaneously changed into a helical configuration via the balance of the forces between the cores comprising twisted nylon fibers and the sheath comprising hydrogels, thereby regaining energy.In addition, by exploiting the reversible interaction between glucose and phenylboronic acid, controlled actuation was rendered to these fibers.Fibers with a work density of 130 kJ/m 3 were prepared.Chang et al. 24 employed a sequential shaping approach to fabricate tendon-inspired hydrogel artificial muscles.To strengthen the hydrogel, tunicate cellulose nanocrystals (TCNCs) were integrated into polymeric linkages via host-guest interactions.By mimicking the tendril hydrogels, the formed structure afforded electrostatic interactions between Fe 3+ and COO− with the hydrogels reinforced with TCNC via successive stretching, twisting, and coiling processes.Once exposed to the solvents, the hydrogel muscles exhibited a large actuation degree, substantial shape memory, and actuation strain.Furthermore, by exploiting the self-lubricated spinning (SLS) strategy, Duan et al. 89 developed hydrogel fibers that continuously responded to electrical signals.The polyelectrolyte component of these hydrogel fibers rendered a rapid electro-response property, which was significantly greater than that of previously reported hydrogel fiber-based actuators.With the addition of triethylene glycol (TEG), the strength of the fibers was improved from 114 kPa to 5.6 MPa.
Lang et al. 90 prepared hydrogel fiber actuators by the combination of solution-phase block copolymer self-assembly and strain-programmed crystallization.The actuators comprised highly aligned nanoscale structures with alternating crystalline and amorphous domains, resembling the ordered and striated pattern of mammalian skeletal muscles.The reported nanostructured block copolymer muscles exhibited excellent efficiency (~75.5%),actuation strain (~80%), and mechanical properties (elongation-at-break, ~900%, and toughness, ~121.2MJ/m 3 ).In addition, the hydrogel fibers exhibited on/off rotary actuation with a peak rotational speed of 450 r/min.Wang et al. 91 designed a versatile ionic hydrogel with a rapid self-healing ability, ultrastretchability, and stable conductivity, even at −80 °C.The hydrogels with hydrogen-bonded-network nanostructures exhibited self-healing characteristics, a large deformation tolerance of over 7000%, a superior conductivity of 11.76 S/cm, and an antifreezing ability.These hydrogels may be exploited for artificial electronic devices for use in harsh environments.As a proof-ofprinciple, artificial nerve fibers were designed, which replicated the structural and morphological features of myelinated axons and exhibited rapid and potentialgated signal transmission.These artificial nerve fibers were integrated into a robot, which exhibited real-time high-fidelity and high-throughput information interaction under high deformation and cryogenic temperatures (Figure 5A,B).

| Hydrogel fibers for sensing
Hydrogels fibers that are both highly conductive and mechanically robust have demonstrated immense potential in various applications ranging from healthcare to soft robotics.However, the creation of such materials remains an enormous challenge.Lu et al. 92 developed bioinspired chemically integrated silica-nanofiberreinforced hydrogels (SFRHs) with robust mechanical and electronic performance.Acrylamide monomers were exploited in the presence of well-dispersed silica nanofibers and vinyltriethoxysilane, affording homogenous SFRHs with interfacial chemical bonding.The resultant SFRHs exhibited excellent mechanical properties, including a tensile strength of 0.3 MPa at a fracture strain of 1400%, a high elastic modulus of 0.11 MPa (comparable to that of human skin), and super-elasticity over 1000 tensile cycles without plastic deformation while maintaining high transmittance (≥83%).Wang et al. 93 reported a simple photopolymerization approach for the rapid preparation of a polymerizable deep eutectic solvent (PDES) fiber, which exhibited excellent stability at high and low temperatures, in organic solvents, and in dry environments, which may overcome the volatility and freezability of conventional gel materials.These poly (PDES) fibers exhibited outstanding mechanical F I G U R E 5 (A) Ultra-stretchable and self-healing artificial nerve fiber (SSANF) is expected to work as a communication unit of biomimetic intelligent robots.The information interaction of SSANF helps in the transfer of energy and message to the next part.Reproduced with permission: Copyright 2022, Wiley-VCH GmbH. 90,91(B) In addition to increase in the LiCl concentration, the conductivity of SSIH increases.Reproduced with permission: Copyright 2022, Wiley-VCH GmbH. 90,91(C) Schematic of the fabrication and excellent properties of poly(PDES) fibers, including tolerance in harsh environments, transparency, stretchability, and knittability.Reproduced with permission: Copyright 2021, American Chemical Society. 92(D) Biodegradable, super-strong, and conductive cellulose macrofibers for a fabric-based triboelectric nanogenerator.Reproduced with permission: Copyright 2022, Springer. 100nd sensing properties, including negligible hysteresis and creep, rapid resilience after long stretching (10 min), and signal stability during high-frequency cyclic stretching (Figure 5C).Wu et al. 28 replicated the spider web capture-like phenomenon and perceptive capacity in the developed hydrogel fiber web.The resulting multifunctional hydrogel fiber exhibited freeze tolerance, conductivity, weight retention, strain sensing, and spider silk-like reversible adhesiveness.The fibers were fabricated by the UV curing of polyacrylamide-poly (ethyleneimine)-glycerol-salt followed by a poststretching process.In strain resistance testing, the hydrogel fibers were found to sense force in the range of 0.5%-34.5%.
Besides, ion-conductive hydrogel microfibers that exhibit softness, stretchability, and transparency have gathered considerable research attention.The applicability of hydrogel fibers for a wide range of applications is limited owing to repeated freezing and drying, while organic hydrogel fibers can be alternative options.Hydrogel fibers are continuously subjected to wet spinning using a newly developed hybrid cross-linking technique.By simply replacing the solvent, these fibers are converted into organo-hydrogel fibers.Organo-hydrogel fiber strain sensors achieving high-frequency motion (4 Hz) and highspeed motion (24 cm/s) with accuracy have been reported to be powerful for the detection of rapid cyclic motions. 94u et al. 95 synthesized hydrogel microfibers with good spinnability, conductivity, and mechanical strength, which were devoid of coatings but retained water.In the continuous draw spinning process, the Fe-citrate complex redox chemistry was employed.Poly(acrylamide-co-sodium acrylate)-based microfibers exhibiting ionic conductivity, extreme stretchability, and homogeneity with programmable diameters were prepared.Zhang et al. 17 employed ionic polyimide-based hydrogel filaments by a wet-spinning process.The resulting hydrogel filaments based on ionic polyimide exhibited an exceptional conductivity of ∼21 mS/ cm and good mechanical properties.Consequently, strain sensors prepared from hydrogel polyimide filaments exhibited a direct response, good cycling stability, and higher sensitivity.
Wang et al. 96 reported a simple one-step method to prepare ultra-tough and stretchable ionogels by the random copolymerization of two common monomers with distinct solubilities of the corresponding polymers in an ionic liquid (IL).Tang et al. 97 proposed a general, protein unfoldingchemical coupling strategy to fabricate pure protein BSA hydrogels by avoiding the use of additional additives to achieve high mechanical strength and excellent cytocompatibility.The thermal-induced protein unfolding/gelation afforded a physically cross-linked network, while the amide linkage afforded a chemically cross-linked network.Fiberbased TE materials have attracted considerable attention in wearable electronic devices due to their 3D deformation, lightweight nature, and excellent electron transfer properties.Yang et al. 98 prepared ternary TE fibers using PEDOT:PSS, Te-NWs, and PVA.The incorporation of PVA improved the mechanical performance of PEDOT:PSS, and a PVA content of less than 10 wt% positively affected the electrical conductivity (σ) of the as-prepared ternary fibers (PEDOT:PSS/PVA/Te-NWs).Wang et al. 99 added temperature-sensitive particles with different reversible colors that change with temperature, and the resultant hydrogel is injected and extruded to prepare high-strength, high-conductivity, and temperature-sensitive woven organic hydrogel fibers for monitoring human-machine movement and temperature.HEC was incorporated into a PVA hydrogel to form large pores to promote ion adsorption.The hydrogel immersed in a sodium chloride solution exhibited a conductivity of 5.77 S/m, while the tensile strength and elongation-at-break were 2.86 MPa and 400%, respectively.It is imperative to integrate high wearing comfort, excellent conductivity, and superior stretchability in wearable strain sensors.Xu et al. 100 reported a wet-spun encapsulation strategy for the preparation of a highly stretchable and fatigue-resistant ionic conductive fiber with a unique coaxial structure of an IL core and a thermoplastic elastomer sheath (IL@TPE).Hu et al. 101 incorporated CNTs and polypyrrole (PPy) into bacterial cellulose hydrogels by wet stretching, affording superstrong, biodegradable, and washable conductive macro-fibers.These fibers exhibited high tensile strength (~449 MPa), good electrical conductivity (~5.32 S/cm), and excellent stability.The tensile strength and conductivity were only decreased by 6.7% and 8.1%, respectively, after immersion in water for up to day 1 (Figure 5D).Similarly, Gao et al. 23 developed ultra-robust (~17.6 MPa) and stretchable (~700%) conducting microfibers by the incorporation of CNTs into PU fibers, which may be exploited for the fabrication of fibrous mechanical sensors.The resultant mechanical sensor exhibited high sensitivity for strain detection as well as a high strain resolution and a large detection range (0.0075%-400%) (Figure 6A).
Park et al. 102 developed brain tissue-mimicking multifunctional sensing and actuation platforms by the integration of multimaterial fibers within a soft hydrogel matrix.These hybrid devices exhibited adaptive bending stiffness as confirmed by the hydration state of the hydrogel matrix, which may enable the direct insertion of these biomaterials into the deep brain regions while minimizing the tissue damage associated with the brain micromotion after implantation (Figure 6B).Feng et al. 103 developed metallogels (MOGs) with a rapidly reversible forcestimulated sol-gel transition and encapsulated them into a hollow thermoplastic elastomer (TPE) microfiber by simple coaxial spinning.The resultant MOG@TPE coaxial fiber exhibited high stretchability (>100%) in a broad temperature range (−50 °C-50 °C).The MOG@TPE fibrous strain sensor exhibited a high-yet-linear working curve, rapid response time (<100 ms), highly stable conductivity under large deformation, and excellent cycling stability (>3000 cycles).Similarly, Ding et al. 26 developed a transparent, stretchable, resilient, and high-performance hydrogel fiber-based bimodal sensor by using a polyacrylamide-Alg double network hydrogel.These sensors exhibited high sensitivity (3.17%/cm), a wide working range (18 cm), rapid response/ recovery speeds (90/90 ms), good stability in case of proximity sensing and impressive pressure sensing performance, including high sensitivity (0.91 kPa −1 ), a short response/recovery time (40/40 ms), a low detection limit (63 Pa), and good linearity.

| Fibers for signal transmission thermal regulation, and multifunctional applications
Smart fibers play key roles in the development and dayto-day activities of human society. 104,105Innovations related to flexible electronics smart fibers with sensing, thermal regulation, and energy management capabilities have attracted immense interest from academic and industrial communities. 106,107Smart fibers are anticipated to revolutionize personal health management due to their manifold characteristics, providing the foundation for several intelligent wearables. 72In this review, a brief overview of the design and fabrication of smart fibers for health management applications is provided.Chen et al. 108 reported the fabrication of an electrically and mechanically biocompatible alginate hydrogel ionotronic fiber (AHIF), which is prepared by the combination of ionic chelation-assisted wet spinning and mechanical training.These favorable structural features render AHIF with tissue-mimicking mechanical characteristics, such as self-stiffening and soft tissue-like mechanical properties.In addition, tissue-like chemical components, that is, biomacromolecules, Ca 2+ , and water, render biocompatibility and tissue-matching conductivity to AHIF.Alginate-based fibers with good biocompatibility and non-immunogenicity demonstrate wide applications in biomedical materials.Xu et al. 109 reported an alginate ester/Antarctic krill protein (AE/AKP) composite fiber with a covalent cross-linked and hydrogen-bonded structure was synthesized on the basis of the acid-catalyzed phase separation reaction spinning.By using sodium alginate as the matrix, cytotoxicity test results revealed that the fiber exhibits nontoxicity.The prepared dual-release pharmaceutical microfibers serve as an ideal material for new biomedical applications.Huang et al. 17 reported a microfluidic spinning method for engineering heterotypic bead onstring fibers that can carry dual cargos and deliver on demand.The core of this technology involves the combination of microfluidic spinning and biomaterial preparation, in which hydrophobic and hydrophilic cargos can be integrated into a bead-on-string microfiber structure.The heterotypic bead-on-string fibers exhibited biocompatibility and in vivo hemostatic ability.These heterotypic bead-on-string fibers were subsequently woven as a skin scaffold and promoted wound healing via the loading of antibacterial and anti-inflammatory cargos.Similarly, graphene and CNT-based conductive fibers with superior mechanical and electrical performance are highly desirable due to their immense application potential in wearable electronic devices.However, the uniform dispersion of graphene in a polymer matrix is still challenging, especially under aqueous system conditions.Pan et al. 110 proposed an inorganic basemediated strategy to disperse graphene in an aqueous cellulose solution by simple mechanical stirring without any surfactants, affording stable cellulose/graphene aqueous inks.In addition, Pan demonstrated that the inorganic metal ions adsorbed on the graphene surface as well as the steric hindrance effect of cellulose chains could effectively prevent the p-p stacking of nanosheets.
Owing to their low density, high porosity, and large surface area, aerogels are promising for the next generation of high-performance thermal insulation fibers and textiles.However, aerogel fibers are limited due to their weak mechanical properties or complex fabrication processes.Liu et al. 111 proposed a wet-spinning approach for fabricating nanofibrous Kevlar (KNF) aerogel threads (i.e., aerogel fibers) with high thermal insulation under extreme environments.The flexible, strong KNF aerogel fibers were woven into textiles to reveal their excellent thermal insulation property under extreme temperatures (−196 °C or +300 °C) and at room temperature (Figure 6C). 29Stretchable ionic conductors are appealing for tissue-like soft electronics; however, these conductors exhibit a tardy mechano-electric response due to their poor modulation of ionic conduction arising from the intrinsic homogeneous soft chain network.Yao et al. 27 designed a highly robust ionotronic fiber by integrating an IL and a liquid crystal elastomer with alternate rigid mesogenic units and soft chain spacers, exhibiting an unprecedented enhancement in the strain-induced ionic conductivity (~103 times enhancement with stretching to 2000% strain).Moreover, the fiber retained thermal actuation properties with a maximum of 70% strain changes upon heating and enabled integrated selfperception and actuation (Figure 6D).Physical eutectogels are appealing materials for technological devices due to their superior ionic conductivity, thermal and electrochemical stability, non-volatility, and cost-effectiveness.Zhang et al. 112 proposed a simple and universal solventreplacement approach to regulate the spatiotemporal expression of intra/interpolymer interactions to prepare strong, tough physical eutectogels.The exchange of DES with water can restrengthen the weakened interactions between PVA chains in water, enabling the crystallization of PVA to afford a uniform and robust polymer network.Consequently, the resultant PVA eutectogel exhibited record-high strength (20.2 MPa), toughness (62.7 MJ/m 3 ), and tear resistance (tearing energy of Σ42.4 kJ/m 2 ), while exhibiting excellent stretchability (Σ550% strain), repairability, and adhesive performance.

| CONCLUSION AND FUTURE OUTLOOK
In the last few years, significant progress has been made toward the fabrication of nonnatural spider silk mimics.These man-made materials with extraordinary toughness and a strength ratio are not common, and they exhibit a significant technological challenge.A series of approaches involving the use of metal and glass, cellulose crystals, and carbon-based materials have been employed for the fabrication of nonnatural silk-like fibers.Electrospinning affords nonnatural silk-like fibers; nevertheless, the poor mechanical properties of such electrospun hydrogel nanofibers limit their applications.Currently, most of the reported biomimetic spider silk-like fibers and smart fibers are fabricated on the laboratory scale, and several challenges exist with respect to their industrial-scale production.Consequently, it is imperative to conduct advanced research to further improve methodological aspects for the production of biomimetic spider silk-based structures.However, natural fibers based on recombinant spider silk and dragline spider silks are limited due to the lack of these proteins and their high cost.
Spiders are utilized as fascinating models as amazing silk threads can be prepared using water as the solvent at room temperature.For more than hundreds of millions of years, spiders have perfected this approach; however, it has not been accurately bio-mimicked thus far.The tedious production of spider silks hampers their mass production and commercialization.Synthetic spider silk has been mimicked in vitro.However, the mechanical capabilities of synthetic spider silk prepared by these technologies, as well as the secondary structure of the spider silk protein, still lag far behind those of native spider silk.Synthetic spider silk technology developed in a short time does not compare well to the spider spinning technology that has progressed for hundreds of millions of years.Nevertheless, alternative materials, such as polymer materials, polypeptides, recombinant or nonrecombinant spider protein, and carbon nanotube yarns, have been designed to realize the high strength and toughness of natural spider silk.
New research directions aimed at the production of high-performance spider silk need further attention.Artificial spider silk composed of polymer materials also raises some concerns that need to be addressed, such as the water retention property, mechanical stability, contact comfort with the human body, and cost, which are key factors in promoting its industrial applications.Synthetic spider silk composed of polymer materials is being used in industry, which opens up new avenues in the fields of polymers.One day, synthetic silk fibers could be used to replace various natural and man-made fibers in manufacturing and medical research.
Schematic of the spinning of the nanogel fiber.Reproduced with permission: Copyright 2022, Wiley-VCH GmbH. 3 (B) Comparison of the stress-at-break and toughness of the nanogel fibers in this study with those of other typically strong and tough fiber materials in literature.Reproduced with permission: Copyright 2022, Wiley-VCH GmbH. 3 (C) Meso-structural changes of biomimetic mesoassembling film (BMAF) during mechanical training.Reproduced with permission: Copyright 2022, Wiley-VCH GmbH.

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Mechanical properties of biomimetic tough hydrogel fibers obtained by draw spinning.

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I G U R E 3 (A) Schematic of the SA fabricated by a coaxial electrospinning process, where the inner fluid and outer fluid form the nanocore support and hygroscopic adhesive nanosheet, respectively.Optical image of single hygroscopic spider silk under humid conditions.White dotted lines indicate the boundary of the hygroscopic adhesive coat.Reproduced with permission: Copyright 2021, Wiley-VCH GmbH. 77(B) Photograph of an asfabricated optical core-clad hydrogel fiber.Schematic of the optical fiber input-output setup for light guiding and collection (top) and the actual experimental setup (bottom) for acquiring optical data under semi-dry conditions (wet fiber, out of the liquid environment).Reproduced with permission: Copyright 2021, Wiley-VCH GmbH. 78(C) Schematic of the fiber preparation and water-inducing process.Photograph of the spinning equipment and fibers.Reproduced with permission: Copyright 2022, Elsevier. 6(D) Schematic of the fabrication of unfolded protein RS-GA fibers by a wet-spinning technique.

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I G U R E 4 (A) Preparation of organic/inorganic hybrid fibers by gelation with facile posttreatment and subsequently use for the assembly of a fiber TE generator for energy conversion.Reproduced with permission: Copyright 2021, Elsevier. 20(B) Schematic illustration of the dynamic-crosslinking-spinning.Enlarged schematic shows the polymerization process underdrawing force.Reproduced with permission: Copyright 2017, Elsevier. 8(C) Controllable generation of deformed hydrogel microfibers by the DIS method.Schematic of the formation of a knotted hydrogel microfiber.Reproduced with permission: Copyright 2022, Elsevier. 86,87(D) Formation of biomimetic microgrooves and microgroove-assisted water transport on multiaxial combinational biomimetic fiber.Reproduced with permission: Copyright 2022, Elsevier. 86,87DIS, dynamic interfacial spinning; TE, thermoelectric.

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I G U R E 6 (A) Schematic of the fibrous strain sensor, including PU foundation, an Eco/CNT conductive layer, an Ecoflex encapsulation layer, and a photograph of a respiratory monitoring system.Reproduced with permission: Copyright 2022, Wiley-VCH GmbH.25 (B) Conceptual illustration of the designed hydrogel hybrid probe and its application to minimize the impact on the brain tissue.Reproduced with permission: Copyright 2021, Nature.101(C) Schematic of the nanofibrous Kevlar aerogel threads for thermal insulation in harsh environments.Reproduced with permission: Copyright 2019, American Chemical Society.110(D) Swimming lane-inspired working mechanism of a highly robust ionotronic fiber with the unprecedented mechanomodulation of ionic conduction.Reproduced with permission: Copyright 2021, Wiley-VCH GmbH.27CNT, carbon nanotube; PU, polyurethane.
Mechanical properties of the biomimetic wet-spun tough hydrogel fibers.
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