The Silk, Versatile Material for Biological, Optical, and 1 Electronic Fields: Review

Silk, seen as a material, is a fiber made from silkworm cocoons and spiders. They have 8 standard structural components and hierarchical structures. Different manufacturing 9 techniques allow obtaining silk in films, fibers, hydrogels, microspheres, and sponges. We can 10 tune the properties through the structure of secondary proteins. The paper explores the 11 application in biomedical, optics, and electronic fields by analyzing the technological trend. graft, graft, group rats, by using in the mucous between hard palate of right jaw and alveolar scaffold mixing an aqueous silk fibroin solution, refined, granular hydroxyapatite at 10: 1 509 sterilized by with gamma rays after freeze-drying three days. pretreated scaffold was to and grafted into the created The mucosa was sutured using Inspections were carried out every four weeks from the fourth to the to verify the state of growth of the new tissues. used different types of analysis, visual analysis, tissue analysis, and CT of the 513 bone defect; in the they used the Western Blot technique to verify the degree of bone generation. The found that mature osteoids appear at the eighth week and only at the twelfth week, observed through the bone tissue analysis, forming bone cells. Moreover, observed that in the samples in which the scaffolds were present, the generation was faster, and there was constant ossification in all parts of the defect, including the center. The new bone is generated via two processes, osteoinduction, and osteoconduction, and center of the bone defect. equipped with carbon nanotubes to provide further toughness and PEDOT: PSS electrically enhance it. Electro- 821 tendon subjected to tests for more than 40,000 flexion-elongation cycles, it turned out tough and durable. It 822 did not show variations in conductivity; mounted on a robot enabled the finger to handle different objects. This 823 tendon represents the most suitable solution for solving the need for a robotic finger to have the same fiber for both 824 the transmission of activation and detection signals. In the experiment reported, the researchers used biobased 825 carbons as a conductive filler to make SF biomaterial conductive [144]. They obtained this material called hydro 826 char [145] from the aqueous thermochemical process (HTP) that transforms the biomass into a carbonaceous solid 827 (biocarbon-HC). Then they converted it, by physical activation, into conductive biobased carbon. By acting on 828 the HTP parameters, it is possible to adjust their nanostructure and their chemical functionality. The bio-based 829 carbon can be rapidly doped with polar functionalities, adding oxygen and nitrogen, promoting dispersion in 830 silk fiber suspensions. They studied the effects produced by the variation of the dopant elements. Bio-based 831 carbons thus obtained dissolve in formic acid with CaCl2 silk fibers to produce thin films. The films are flexible 832 and stretchable at room temperature and humidity of 50%. The tests carried out showed that the mechanical 833 properties improve due to the presence of carbon nano materials. The resistivity of these films is lower than 834 those produced without resorting to the thermo chemical process. These materials show good cytocompatibility 835 due to the absence of toxic solvents. From the molecular dynamic simulations, a good conductivity has emerged 836 without causing significant changes in its secondary structure or the bonds with hydrogen. The results obtained 837 highlight the possibility of getting bio-based carbons with different morphologies and properties starting from 838 biomass with other biochemical parameters such as temperature, water biomass ratio, and reaction time. 839 The fields of application are different from biomedicine to electronics. 840 electrons from the electrolyte to conductive polymers. From 4th to 7th, sensitivity 943 remained unchanged; to 10th connections deteriorated, and it was no longer possible to detect its behavior. These 944 results suggest replacing transitional devices to monitor phenomena where a short observation period is required.

both recent progress in manufacturing processes and innovative applications. The objective of the manuscript is 23 to investigate both of these aspects, from the biological to the industrial one, considering the different process 24 methodologies applied to create a variety of structural forms. The approach is to analyze the nature of the fiber 25 and its potential applications. It starts with the structure and properties and continues with the innovative 26 preparation technologies and functionalization to modify its mechanical properties or give the silk the desired 27 functionality. Then the latest emerging applications are reported. In some sections, representing the experiences 28 carried out, we can see how the silk, among other things, can effectively contribute to the achievement of the 29 objectives of sustainable engineering. 30 Particular attention is paid to silkworms for their availability in large quantities from sericulture. The arachnid 31 species is difficult to raise due to their cannibal tendencies, but their silk has the best characteristics. The 32 biotechnological production of proteins (spindrois) makes it possible to overcome this obstacle. The availability 33 of recombinantly produced spider silk protein is essential for experimentation and their use in applications. Their 34 application was mainly in the biomedical field. Silk extracted is combined with other biomaterials to form 35 biopolymer compounds. The review analyzes applications that use worm and spider silk, although for the latter 36 to a limited extent due to the fewer testimonies in literature. If not clearly expressed, we refer to both types. Historically the silk used in the textile field is obtained by Bombyx mori silkworm ( Fig. ??a). 40 In nature, there are different types of silks produced by other animals, such as the Trichoptera, mites, and 41 spiders [1]. It is precisely the silk of spiders that becomes the subject of study by exceptional properties (Fig. 42 step, we remove the sericin by boiling the silk cocoons in solution with degumming agents. The obtained silk 126 fibers are then dissolved with appropriate solvents in an aqueous solution of purified fibroin by removing salts 127 by dialysis. We can activate the solution of water and fibroin by inserting different organic dopants (enzymes, 128 proteins) and inorganic (metal nanoparticles, quantum dots). We then deposit it on a particular substrate. The 129 crystallization process occurs through the self-assembly of the proteins stored in the air. Thus, we can create 130 different films or absorbable substrates for electronic or photon devices. 131 We report the steps of the manufacturing process in the following flowchart (Fig. 6). The degumming 132 represents the first step to the removal of sericin for biomedical applications. New methods based on microwaves, 133 ultrasounds, and CO2 supercritical fluid have been introduced [16]. Chemical dissolution of sericin is obtained 134 partly by hydrolysis and partly by dispersion, independent of the method. 135 Soapy degumming is a commonly used technique that determines a chemical bond between the alkalis, produced 136 by the hydrolysis of soap, with sericin making soda salts. The sericin is separated from the soap and dissolves in 137 the water [2]. Mixtures of soaps and alkalis improve the quality of the silk. The degumming phase is associated 138 with the bleaching phase obtained using hydrogen peroxide in alkaline conditions, acting on the PH through 139 ammonia [17]. 140 Silkworm degummed with citric acid treatment at 30% gave better results than treatment with soap and alkali, 141 obtaining the removal of the sericin at almost 100 %; the total weight loss resulted of 25.4% in the silk fibers.

142
Degumming with citric acid improves tensile strength and surface morphology [18]. 143 The use of chemical components causes environmental pollution; therefore, it is preferable to replace them 144 with natural enzymes extracted from papaya peel or pineapple peel that help improve the degumming process. 145 Enzymes act with a method of proteolytic degradation of sericin without affecting fibroin. In India, the 146 researchers tested unripened papaya as an enzyme. The proteolytic enzymes promote the hydrolysis process 147 of the peptide bonds produced by amino acids. The experimentation required careful tuning of some elements 148 such as degumming time, PH, process temperature, the percentage of the enzyme, and simultaneous selection of 149 mordanting and dyeing [19]. 150 Traditional degumming processes are expensive and harmful to the environment. They require a large quantity 151 of hot water to eliminate contaminants such as oil wax and natural pigments, producing high temperatures and 152 dispersing many chemicals into the environment. The new process has become more ecological and less expensive. 153 One of the most valuable techniques in removing sericin is supercritical fluid CO2, requiring less water and energy. 154 This process involves a pre-treatment with an organic acid which can be citric acid or tartaric acid. It involves 155 soaking the silk in purified water or deionized water for many hours and then transferring the silk from the bath 156 to containers of CO2 with a glycol-type non-ionic surfactant. With containers heated to temperatures around 12 a) Native silk fiber 223 Native silk fibers, derived from the Bombyx mori silkworm, represent the raw material used to produce regenerated 224 silk solutions. Native silk fibers are composed of fibroin, which provides high tensile strength. They are applied 225 initially in the medical field as sutures. Moreover, silk fibers also have the property of permeating water vapor and 226 oxygen and promoting skin fibroblasts and collagen formation. Subsequently, they have found wide applications 227 in the biomedical field [33]. 228 The filaments are suitable for constructing a porous nonwoven silk material for cell seeding, the fabrication of 229 the mesh structure, and scaffolds for ligament repair [34]. 230 Methylcellulose (MC) is also valid in tissue reconstruction for its resistance and anti-toxicity properties. 231 Recently, however, composites in silk fiber and methylcellulose (SF/MC) have been made to engineer bone. 232 The results obtained showed improved osseointegration between bone and composite and provided a reasonable Silk solution allows you to produce several different regenerated structures (Fig. 8) An increase in temperature or protein concentration and a decrease in ph can control the process. In these 264 conditions, with the change from random coil formation to ?-sheets formation, the solution will gel. Subsequently, 265 further aggregation can create gels with a three-dimensional network structure [46].

266
The low PH and high temperature make the solution unstable. The concentration of the solution shapes the 267 mechanical properties and pore size of the hydrogel.

268
Currently, the hydrogel products are classified into physical or chemical gels depending on the cross linking 269 method used. The formation of hydrogels occurs through physical interactions such as hydrogen bonding, 270 hydrophobic interaction, electrostatic interaction, and ion interaction in the physical cross linking process.

271
The applied methods are self-assembly, ultrasonication, cutting, electric field, choice of appropriate values of 272 temperature and pH, use of organic solvents and surfactants, etc. The chemical crosslinking method favors the 273 creation of a spatial network structure through covalent bonds between the molecular chains of silk. Chemical 274 hydrogels are physically more stable and more resistant to traction than physical ones. The methods used are 275 essentially photopolymerization, irradiation, use of chemical and enzymatic agents [47].

276
The possibility of controlling the structural and functional characteristics of silk hydrogels and jet, it is possible to produce filaments of 2-5nm. The high fineness of the electrospun fibers allows the production 304 of materials with a very high surface/volume ratio and a high porosity. An electrospinning plant mainly consists 305 of an extruder that pushes the molten or solution polymer inside a capillary and a collector placed in front to 306 it ( Fig. ??). Electrostatic repulsion between the charges at the surface of the solution droplet produces the 307 fiber. The high voltage power supply is applied to the tip of the capillary tube. As the electric field strength 308 increases, the hemispherical surface of the fluid at the end of the capillary tube elongates to form a cone called 309 "Taylor cone," with further expansion, the charged fluid jet is expelled, and stretches becoming very long and      The methanol promotes the transition from random coil structure to ?-sheets.  The process requires adding polyethylene glycol so that preparation does not require other toxic chemicals and 338 solvents. The salt added to the solution makes the microspheres more homogeneous. 339 We can produce microspheres by adding lipid vesicles for the controlled application for drug delivery to a 340 targeted area of the body [69]. The removal of lipids occurs subsequently using methanol or sodium chloride, getting microspheres with ?-sheets structure. The transition rate from random coil structures to ?sheets depends 342 on methanol concentration. The microspheres treated with NaCl have a smoother surface compared to the 343 methanol treatment. Both types have a mixture of multilamellar and unilamellar structures. For the process 344 is used a lipid (e.g., 1, 2dioleoyl-sn-glycerol-3-phosphocholine) film to emulsify the solution [70]. Later, with 345 freezing/thawing cycles and lyophilization, water is removed. With centrifugation, the lipid is removed, getting 346 SF microspheres.

347
The application of polyvinyl alcohol (PVA) is another method for preparing silk microspheres [71]. This Silk is a textile fiber, also a biopolymer. Its extraordinary biological and functional properties have found wide 356 application from the biomedical field to microelectronics (Fig. 10).

357
18 Application in the biomedical field 358 One of the first silk applications was in the medical field due to its essential properties of:

359
? Biocompatibility, is not rejected by the immune system, does not favor the onset of thrombi; ?   The recognized natural silk has extraordinary properties that make it suitable to regenerate or improve the 373 functions of damaged tissues and organs. They are biocompatibility, biodegradability, anti-inflammatory, the 374 capacity of promoting the attachment, proliferation, and differentiation of many different cells type. For these 375 properties, it is also an essential structure for the adhesion of growth factors and to incorporate drugs [72]. In 376 addition to rebuilding damaged areas, silk matrices also provide bioactive molecules, genes, and cells.

377
The path for the preparation of tissue for reconstructive medicine consists of several steps ( fig. 11).

379
The skin protects the human body from dehydration, infectious agents, and, more generally, from environmental 380 conditions. Any damage produced by burns or wounds on the skin reduces its protective effect, so tissue 381 engineering interventions restore skin loss. Studies conducted in vitro and in vivo highlighted that the silkworm 382 or spider SF-based biomaterials favor cellular adhesion and fibroblast proliferation on skin wounds and improve 383 plasmatic imbibition capabilities to promote wound healing [73]. Thanks to its properties, this biomaterial is 384 applied alone or scaffolds for nanofibrous mats, hydrogels, sponges, or films tailored to tissue engineering. SF films 385 showed to have more cure potential than conventional hydrocolloids. Wounds treated with silk films have better  Studies showed that hydrogels incorporated into LP, compared to other composites, reduce the healing time [75].

392
The nanofibrous membranes have a high surface-to-volume ratio.  The last requirement is sufficient dimensional stability. Xenograft models find use in cancer research and 442 therapy. In addition to applications in regenerative medicine, xenograft models of human bone are also used as 443 experimental models of skeletal diseases, allowing for studying disease states in vivo, which would otherwise be 444 impossible on human subjects.

445
Stem cell-based (BTE) bone tissue engineering represents a clinically meaningful solution for bone repair. We 446 present a pure 3D silk fibroin (SF) scaffold used and fabricated by the freeze-drying method in the study. Human   Additionally, they must stimulate bone induction, resorbable and replaceable by bone, stable in varying 472 temperature and humidity.

473
The researchers analyzed many materials to make these synthetic grafts, including metals, ceramic materials, 474 polymers, and their composites. Choosing the most suitable material is essential as it must have the mechanical 475 properties suitable to support the expected loads depending on the type of application.

476
Metals such as titanium, nickel-titanium, and magnesium alloys are biocompatible, resistant, workable but 477 have a higher elastic modulus than bone which can cause stress-shielding. (This phenomenon consists in a loss 478 of density due to the reduced load on the natural bone compared to the metal fixation device, no stimulus for 479 continuous remodeling necessary to maintain bone mass).

480
Because of their fragility, ceramic materials are challenging to use as a scaffold for synthetic bone tissue. such as freeze-drying, electrospinning, gelation, and cold drying.

496
Researchers at Tufts University in Boston, led by Kaplan, were the first to study the efficacy of SF / HA old 497 scaffolds in bone regeneration. They found that hydroxyapatite is a substance with exceptional biocompatibility 498 and bioactivity and is substituted, after grafting, with the bone growing through the osteoinduction process.

499
Regeneration occurs via two methods, osteoconduction of the surrounding bone in the defect area and nucleation.

500
They noted that reconstruction in the presence of the hybrid composite was faster than regeneration by the 501 surrounding bone and that ossification was constant in all areas, including the center of the bone defect [94].

502
Researchers investigated bone regeneration using silk hydroxyapatite hybrid composite in a rat alveolar defect 503 model [95]. For testing, they were used thirty-six male Sprague-Dawley rats of 9 to 10 weeks of age and weighing 504 240-250g, divided into three groups of 12. The first group was sutured without a scaffold bone graft, the second 505 group was sutured with a silk scaffold graft, while the third group was grafted with a hybrid scaffold of silk 506 and hydroxyapatite. In rats, a 7 x 4 x 1.5 mm alveolar defect was created by incision using a power drill in 507 the mucous membrane between the hard palate of the right upper jaw and the alveolar bone. They produced 508 scaffold by mixing an aqueous silk fibroin solution, previously refined, with granular hydroxyapatite at a 10: 1 509 ratio and sterilized by irradiating with gamma rays after freeze-drying three days. The pretreated scaffold was 510 cut to the same size as the bone defect and grafted into the created cavity. The mucosa was then sutured using    results to treat small-caliber blood vessels [113]. The structure has a three-layer hybrid architecture, formed by 583 E.S. (electrospun) layers, one inside and outside, and in the middle TEX (textile) layer. The hybrid architecture 584 was engineered for the presurgical manipulation of the device and to improve the aggregation between the tissues 585 and the mechanical resistance. It is the TEX layer that gives the device a high mechanical resistance. It is 586 obtained, first electrospinning, during the manufacturing process, coating the TEX surface with the ionic liquid 587 to achieve complete adhesion between the three layers, ensuring the high mechanical resistance. After a series of 588 in vitro tests, the researchers implanted artifacts in large animals for in vivo tests. Experiments allowed to study 589 the type of interaction with fibroblasts and endothelial cells; cytokines and chemokines were analyzed to verify 590 the proliferative and anti-inflammatory capacities. The researchers also performed a blood component test. The   One of the sectors in which silk has found application, using its high refractive index, is that of the manufacture  Other integrated compounds are the metamaterials with silk proteins. Metamaterials are artificially structured 628 compounds whose properties arise from their structural composition rather than from materials. Silk represents 629 the substrate of the device in which plasmonic and metamaterials patterns are incorporated. Due to their excellent features, silk fibers also find application as optical fibers. Dragline spider silk acts as a sensor 646 to detect humidity, and more generally, as a chemical substance detector (ethanol, ammonia, etc.), representing 647 a better alternative to glass fibers that usually require coatings [125]. The physical principle underlying this 648 experience consists of the optical fiber's reaction in contact with the targeted chemical species. Under the action 649 of these substances, the fiber will change throughout its volume. Consequently, the parameters of the light 650 (intensity, phase, spectrum) that propagate along it will also vary. From the analysis of the light spectrum, it 651 is possible to trace the presence of the substance. The light is kept wholly confined to the fiber, and the effect 652 accumulates over its entire length. We produce Dragline silk extracted from spider glands and spinning with a 653 constant diameter and smooth surface as a chemical sensor for its sensitivity to different chemical substances.

654
Their presence affects the birefringence of the silk fibers [126]. Due to humidity, the phenomenon of infiltration 655 of water molecules occurs, which attacking the coil structures of silk fibers breaks the hydrogen bonds that hold 656 the protein threads together. This phenomenon will cause the silk to relax, causing it to contract. The sample 657 designed to measure the relative humidity of the environment is placed on a support and blocked at the two end 658 parts.

659
As the fiber is held back from resting, it tends to swell, producing a change in its geometry. The researchers 660 tested the sample using a set-up consisting of a laser to produce polarized light injected into the silk fiber  Another application is a thin silk paper created as a filter by adding two wt% silk micro fibr il suspensions 691 for the water treatment. At the end of the air drying, silk paper in A4 format was obtained, which was softer 692 and foldable in different shapes compared to the traditional cellulose-based paper. SEM showed a uniform 693 mesoporous structure. This mesostructure was used directly as a microfilter of water for bacteria and other 694 micro-sized contaminants. To remove organic solvents, it was necessary to reduce the pore diameter of the silk 695 paper using nanofibrils. SEM images confirmed the filtering effectiveness of these silk papers. The membranes 696 used for water treatment were produced from Bombyx mori silk nanofibrils [130]. Organic solvents dissolve them;

697
Antheraea pernyi silk nano fibrils were chosen because most solvents tolerate them. Therefore A. pernyi silk 698 nanofibrils were preferred as filters for organic solvent.

699
Scientists used silk paper as a conductive device by printing an electronic pattern such as a circuit board and 700 sensors loops. It can be chosen as electronic prototyping. They are suitable for modulating electrical signals but 701 being flexible can measure the deformation of objects subjected to stress. Devices subjected to several bending 702 cycles show no deformation when returning to the initial realignment position.

703
The excessive use of pesticides and fertilizers in agriculture has created significant environmental problems such 704 as soil foul-up from antibiotics and acidification and pollution of the aquatic environment due to excess nitrates 705 and phosphates. As a result, nano fertilizers have developed in recent years and controlled release pesticides.

706
The goal is to create products absorbed by the cultures without interaction with the external environment 707 [131]. For this purpose, researchers tested whether the use of A. pernyi silk nanoparticles of 11 ± 4 nm can 708 provide fertilizers. Bulbs of Narcissus pseudonarcissus (N. pseudonarcissus) incubated in a culture medium were 709 grown, using homogeneous dispersion of silk and rhodamine B (RhB) nanoparticles to deliver small molecules for  processing. To evaluate their applicability as waveguides, we can characterize them optically using two methods: 723 the cutback method commonly used to determine losses in waveguides as is usually done in telecommunications 724 for optical fibers.

725
The technique uses the Beer-Lambert law of attenuation, which considers that the propagation losses along the 726 fiber length are prolonged. The other method used is Image-based Analysis, according to which the performance 727 of the fibers is evaluated directly from the microscope images. This method is based on the scattered light at a 728 certain point of the fiber that is proportional to the radiation of the wave that propagates within it. Therefore, 729 the measure of wave attenuation inside can be deduced from scattered light as a function of position along with 730 it. The researchers experimented that when a large amount of light is highlighted in a certain point of the fiber, 731 it means that point is the localized scattering center of the light wave that travels in it. From that point on, the 732 optical power gradually decreases along with it. The optical wave continues to propagate with a lower intensity.

733
The loss coefficient obtained depends on many factors, such as the effects produced by the localized scatterers, 734 the structural characteristics of fiber and waveguide. From the images acquired by a non-linear microscope, the 735 second and third harmonic presence was noted in the signal, with the third harmonic present along with the 736 entire fiber. In contrast, the second was more relevant in the center where the center-symmetry breaks due to 737 twisting of the fiber around this point.

738
A further experience gained in the field of optoelectronics was the design of waveguides with the use of direct  The same behavior occurs for both linear and curved guides. From research emerged that propagation losses 751 were (5.8 ± 1.0) dB / cm and (6.8 ± 1.0) dB / cm at 632.8 nm for linear and curved waveguides. The propagation 752 losses in these guides are more significant than those obtained by direct ink writing. This greater loss is probably 753 attributable to surface roughness in the thickening areas of the material. Although the losses are high, they 754 are comparable with those found in unprocessed silk fibers (10.5±4) dB/cm, in the range of 800-850 nm [136].

755
The results obtained through simulation and experimentally showed an almost symmetrical mode in which the 756 light confines to the waveguide edges. The radiation produces deformation on the edges of the irradiated area 757 by varying the refractive index, which is lower in the central region than the edges with a value equal to Î?"n 758~1 × 10-3. A He-Ne laser with 632.8 nm light produced the characterization of the waveguides. We obtain the  The latter is preferred not only for its specific properties but also for its simplicity and favorable cost. In recent 849 years, manufacturing oriented on devices in which SF, in the form of silk films, silk hydrogels, and silk fibers,  Compared to traditional electronic systems, possessing the same mechanical characteristics as human organs, 859 they can ensure accurate signals even during movement [150]. The silk film is preferred as it is more suitable for 860 the preparation of functional substrates. However, its use is limited in cases where good elasticity is required, 861 such as producing electronic devices conformable to the epidermis.

862
In the experience proposed, the authors overcame this problem by manufacturing a plasticized silk film [151].

863
Silk proteins represent the base layer on which to manufacture soft and elastic electrodes on the skin. The  The electrodes must also be transparent as well as flexible, biocompatible, and biodegradable. In recent years, 873 efforts have focused on fabricating different types of transparent materials for SnIn2O3 doped electrodes. But 874 ITO film on flexible substrates with polyethylene (PET) and polyimide is unsuitable for wearable devices, making 875 it not biocompatible with the human body. Compared to ITO film, the researchers found that the use of silver 876 nanowires embedded in a silk fiber substrate fully satisfies the requirements of flexible electronics.

877
In recent research, the authors created a highly extensible, transparent, flexible SF-based film with a low 878 modulus of elasticity, perfectly adherent to the skin. The film integrated with silver nanofibers (AgNFs) / SF 879 synthesized through a water-free procedure showed low extensibility. After numerous bending cycles, it is offered 880 excellent stability. We can identify it as an electrode for the manufacture of intelligent touch sensors [152].

881
The sensor was sensitive to pressure and deformation, showing permeability to water and air and not producing 882 37 D) FLEXIBLE ELECTRONICS inflammation; it was implanted directly on human skin. The experiment was done by gluing it on the arm at the 883 elbow and on the larynx. Positioning on the larynx enabled the trachea and esophagus vibrations to be detected 884 in real-time, thereby monitoring swallowing, drinking, and pronunciation. Abnormal pressure values are related 885 to the onset of diseases of the laryngeal organs. Positioning on the arm allows monitoring finger/arm movement 886 and muscle contraction. The functional element of the pressure-strain sensor is given by the sandwich structure in 887 which the authors placed an Eco-flex layer acting as a dielectric between the two AgNF / SF electrodes (Fig. 15).

888
The results obtained in the absence of inflammation confirm the feasibility of this technology in the manufacture 889 of wearable electrodes.

890
The electronic skin can simulate the human skin and implement tactile sensation made by thin, soft, and 891 elastic devices, suitably functionalized to realize these functions. Research is developing new solutions to improve 892 flexibility and elasticity and make the various electronic skin adaptable to human skin. Silk films are an ideal 893 material to make electronic skins.

894
Below is an experience based on SF (SFCM) composite membrane with polyurethane that acts as a substrate was chosen, which in addition to being biocompatible and economical, is also physically / chemically stable.

910
[155]. As an artificial PZ energy-generating skin (EG-skin), the structure, adhesive to human skin, incorporates 911 ZnO nanotubes (ZnONR), capable of collecting biomechanical energy and detecting movements. The presence 912 of ZnONR improves the piezoelectricity eight times compared to native silk hydrogels. The PZ response can 913 be further enhanced when the EG-skin is encapsulated within two thin silk membranes. Tests carried out on 914 biodegradability, and adhesive properties on the skin showed that these EG-skin devices constitute a perfect 915 interface between the artificially generated skin and natural tissues. To verify the energy generation capacity 916 of the EG-skin, the device was placed on the forearm to measure the muscular effort when we apply a force to 917 the hand: the action induces a power of 6.2 ?W / cm2. The device was also positioned on the elbow to collect 918 the energy produced by the flexion-release of the elbow: the power had 0.2 ?W / cm2. In light of the results 919 obtained, the hybrid skin made of engineered silk protein hydrogel can be a versatile platform for wearable and 920 implantable devices.

921
Due to its biodegradability and programmable water solubility properties, researchers used SF as a component 922 of implantable devices both with different shapes (silk film, silk sponges, and silk hydrogels) and for various 923 applications (wireless thermal therapy, drug release, bone repair). Programmable water solubility is achieved 924 through a post-treatment process to change the crystal structure. The possibility of controlling some of its 925 specific properties made SF a suitable biomaterial for biological transfer, allowing for a perfect integration 926 between biological tissue and electronic devices. The use of SF to manufacture implantable and degradable 927 biosensors allowed us to overcome the problems connected with mechanically flexible and implantable sensors.

928
For their removal, it is necessary to proceed with an extraction surgery.

929
The experience made by some researchers, in realizing an organic biosensor, shows a structure in which only 930 conductive silk ink is used plus a flexible silk substrate without any metallic component [156]. The structure 931 consists of an integrated three-electrode configuration. The organic electrode as a working electrode, Ag / AgCl 932 as the standard reference electrode, and Pt as the counter electrode are manufactured by an organic conducting 933 ink. The conductive silk sericin ink is micro-patterned on a layer of fibroin with a photolithographic process.

934
The designers realized the electrical connections using a conductive polymeric wire coated with silk fibroin. This 935 entirely organic device can allow the biomonitoring of analytes in the human body or the environment for a 936 controlled period followed by a degradation phase [157]. The researchers tested the device to verify performance 937 as a biosensor; they chose ascorbic acid (AA) as a target. It is essential for the human organism as it is decisive 938 in collagen formation to develop bones, muscles, and blood vessels. The rapid response time of the sensor was on 939 the order of few seconds, showing a high sensitivity. They also extended the test to the proteolytic degradation 940 phase. The researchers found operating stability during the first four days, followed by an improvement in 941 sensitivity, presumably due to the biodegradation of the silk matrix, which exposed PEDOT: PSS led to an 942 improvement in the transfer of electrons from the electrolyte to conductive polymers. From 4th to 7th, sensitivity 943 remained unchanged; to 10th connections deteriorated, and it was no longer possible to detect its behavior. These 944 results suggest replacing transitional devices to monitor phenomena where a short observation period is required.

945
They verified the performance of the biosensor against biofouling. In vivo monitoring of metabolites can lead to 946 contamination of biosensors with a consequent reduction in performance [158]. Nonspecific adsorption of proteins 947 or cells can lead to biosensor occlusion. The presence of a membrane layer of organic material can reduce the 948 biofouling phenomenon. The biosensor having an organic structure has shown a natural resistance to biofouling. 949 Therefore, the fully organic silk biosensor with core-sketch PEDOT: PSS silk fibroin conductive wires can permit 950 real-time, continuous monitoring of health parameters without compatibility problems, with perfect adherence 951 to the epidermis. In addition to AA, we can investigate a wide variety of target metabolites. It is possible to 952 immobilize enzymes and antibodies in the conducting ink.

953
For the performance shown, the device can be a transient biosensor for monitoring metabolites in cases where 954 a long period of operation is not required.

955
Energy harvesting technology is a cutting-edge topic for application in wearable technology and the energy 956 stored connected with motion tracking. The availability of intelligent clothing has been beneficial for monitoring 957 human health conditions by preventing harmful events and favoring health improvement conditions. These there is a transfer of charges between them due to their difference in polarity; consequently, a current is generated.

965
The integration of polymeric fibers/tissues with nanomaterial allows manufacturing fabrics to collect energy with 966 TENG technology [160]. The mechanical robustness and structural stability of these devices are not able to 967 provide high functional performance. SF is selected in the manufacture of TENGs because it has the necessary 968 prerequisites.

969
Moreover, SF has a solid ability to lose electrons; therefore, pairing it with those materials that quickly gain 970 electrons can ensure high performance. In the application we propose [161], the authors with 3D printing made 971 a TENG device with a coaxial composite fiber of carbon nanotubes and SF, where CNT acted as a conductive 972 core and SF acted a dielectric sheath. The dielectric material, another component of the triboelectric pair, was 973 polyethylene terephthalate (PET).

974
The tests showed that this configuration resulted in a maximum power density of 18 mW/m2. This structure 975 has the advantage of having a high integration of functional and electrode materials and simple fabrication for 976 the 3D printing technology used.

977
The following table highlights the field of applications of silk.

980
For future developments, silk, with its specific properties, is the solution to meet the need to have multifunctional, 981 non-polluting, and economical devices.

982
It can be subject to different processes modifying its original structure with different shapes and chemical 983 and mechanical properties for tissue engineering application. Recent work shows the possibility of using silk for 984 peripheral nerve regeneration and intervertebral discs. The particular characteristics of the material, from the 985 structure to the process, the flexibility of modification of the properties, and the availability of functionalization 986 techniques, have made silk ideal as a technological platform. It is suitable for creating sustainable, implantable, 987 and bioabsorbable optical and electronic systems to replace traditional materials.

988
The Sustainable Development Goals (SDGs) require a drastic reduction of electronic waste. Current technology 989 in electronic and photonic devices applies processes that use chemicals that generate equally hazardous waste 990 once their lifespan has expired. 991 Therefore, we must orient technological efforts towards applying materials of biological origin to cope with the 992 depletion of oil and the reduction of toxic byproducts.

993
The silk can provide a substantial contribution to solving the problem.