Electrostatic adhesion method, system and material

Abstract

Electroadhesion, or electric field-induced adhesion, occurs between non-adhesive cationic and anionic hydrogels. When the gel and tissue are placed under an electric field, the pair adheres strongly and then the adhesion persists indefinitely. Applying a direct current (DC) electric field of opposite polarity eliminates adhesion. Electroadhesion can be used to seal cuts or tears in tissue or model anionic gels. In one example, electroadhesion works on aorta, cornea, lung, and cartilage. In another example, an electroadhesive gel patch provides a robust seal over an opening in a bovine aorta, and a gel sleeve can rejoin severed pieces of gel tubing.

Description

[Technical field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims priority under 35 U.S.C. § 119 of U.S. Provisional Application No. 63 / 220,427, filed July 9, 2021, which is incorporated herein by reference in its entirety, including but not limited to the specification, claims, and abstract, and any drawings, tables, appendices, or figures thereof.

[0002] The present disclosure relates generally to sutureless tissue repair. Specifically, examples of the present disclosure describe at least materials and procedures for providing reversible electroadhesion in connection with sutureless repair of tissue. [Background technology]

[0003] The background discussion provided herein provides a context for the present disclosure. The work of the presently named inventors, and aspects of the description that may not otherwise be regarded as prior art at the time of filing, are not admitted, expressly or impliedly, to be prior art.

[0004] Electrostatic adhesion involves two oppositely charged polyelectrolyte hydrogels. Electrostatic adhesion was first observed and reported about 10 years ago. The starting point is to take two solid gels (slabs or strips), each formed by chemical cross-linking of monomers, one gel with a cationic backbone and the other with an anionic backbone. The two gels are brought into contact with each other along one face, and electrodes are placed along both sides.

[0005] A DC voltage is then applied in a specific orientation. Within a few seconds, the two gels adhere strongly together. The same gels would not adhere if they were brought into contact in the absence of an electric field. Hence the term "electrostatic adhesion", since the adhesion is induced by the electric field. If the polarity of the electric field is reversed, the gels may lose their adhesion and separate.

[0006] The mechanism of electroadhesion is still not fully understood, but is thought to involve molecular rearrangements of both polymer chains and counterions at the gel-gel interface. So far, there have been a few applications of electroadhesion, such as assembling gels into 3D structures. Overall, however, electroadhesion remains a strange phenomenon and has attracted little interest from the scientific community.

[0007] Thus, there is a need in the art for a device that utilizes electroadhesion to provide a robust seal over openings in cells, tissues (a collection of similar cells from the same origin and their extracellular matrix that together perform a specific function), and organs (a collection of tissues joined together in a structural unit to perform a common function). Summary of the Invention

[0008] Electrostatic adhesion can be induced between hydrogels and other kinds of soft matter. For example, gels can be electrostatically attached to animal (bovine) tissue. This result is surprising because some tissues can be soft and gel-like, but structurally very different from traditional polymer gels.

[0009] Gel-tissue electrostatic adhesion only works between certain types of gels and tissues, the reasons for which are disclosed herein. One particularly beneficial application for the gel is to use the gel as an adhesive to reseal damaged tissue. Currently, when tissue tears, sutures or staples are required to reattach the torn pieces, thereby allowing the tear to repair naturally over time. This suturing is a surgical operation that requires significant skill on the part of the surgeon, which often represents a difficult and expensive procedure.

[0010] Adhesives have been explored as an alternative to sutures during surgery. Several polymer adhesives are available for surgery, including those based on cyanoacrylates, fibrin, and polyethylene glycol (PEG) derivatives. Most of these materials are sticky in nature and form tight bonds when in contact with tissue. Such adhesives have many limitations, specifically, they usually do not have sufficient strength to hold two severed pieces of tissue together. As a result, adhesives usually cannot replace sutures, but are sometimes used in conjunction with sutures (e.g., instead of ten sutures, a combination of two sutures and adhesives may be used). Also, if the adhesive forms a solid film (either immediately after application or after a drying period), this may result in a physical barrier that prevents the delivery of nutrients to the underlying tissue. In comparison, adhesives in hydrogel form are preferred due to their soft nature and their permeability to moisture and nutrients. For a gel-adhesive to provide a viable alternative to sutures, it must adhere strongly to tissue.

[0011] An example of the use of electrostatically attached gel to seal a hole in a tubular animal tissue, i.e., a section of bovine aorta, is demonstrated herein. A strong adhesion is achieved between the gel and the tissue by applying a DC electric field of ten volts (10 V) for a brief period of ten to twenty seconds (10 to 20 s). This adhesion can later be reversed by reversing the polarity of the electric field. This disclosure demonstrates the potential utility of electrostatic adhesion in biomedical applications.

[0012] The following objects, features, advantages, aspects, and / or embodiments are not exhaustive and do not limit the overall disclosure. No single embodiment is required to provide every object, feature, or advantage. Any of the objects, features, advantages, aspects, and / or embodiments disclosed herein may be integrated with one another, either fully or partially.

[0013] It is a primary object, feature, and / or advantage of the present disclosure to improve or overcome the deficiencies in the art.

[0014] It is a further object, feature, and / or advantage of the present disclosure to use electroadhesion to enable an alternative surgical modality that eliminates the need for sutures. For example, a system of oppositely charged polymer gels, one in the form of a rectangular strip and the other in the form of a hollow tube, can be used. In an early case, a hole is made in the tube wall and a small gel strip is electrostatically attached over the hole. Water can flow through the patched tube at pressures above normal blood pressure (no leakage through the sealed hole). Then, in a more extreme case, the tube can be cut in two and the sections rejoined by attaching a sleeve of gel around the cut sections. To this end, long gel strips that are robust and flexible are fabricated and sutureless electroadhesion achieves a similar effect of sutures, i.e., joining the cut sections of the tube.

[0015] It is yet a further object, feature, and / or advantage of the present disclosure to expand the area of ​​materials that can be electrostatically attached, thereby expanding the usefulness of this electroadhesion.

[0016] It is yet a further object, feature, and / or advantage of the present disclosure to include the ability to achieve adhesion on command.

[0017] It is yet a further object, feature, and / or advantage of the present disclosure to revert electroadhesion in the event of an error. In other words, the gel patch can be easily detached from the tissue. The patch can then be reapplied on command.

[0018] It is yet a further object, feature, and / or advantage of the present disclosure to prophylactically maintain healthy cells and tissues using the methods described herein, i.e., prophylactically maintain healthy cells and tissues even in situations where the cells and tissues are not initially damaged.

[0019] Preferably, the sutureless method of tissue repair is safe, cost-effective, and reliable. For example, the hydrogels used herein can be biocompatible (do not cause adverse immune responses in the body), and electric fields can be applied to living animals as long as the voltage (e.g., 10V DC) is not too high. Furthermore, the electric field must only be on for a short, finite period of time (e.g., 20 seconds), a period short enough to avoid any adverse reactions.

[0020] The systems and methods disclosed herein may be used in a wide variety of applications. For example, electroadhesion may be useful in biomedical scenarios: Electroadhesion may allow surgical repairs to be performed in the future without the need for any sutures. Compared to current surgical adhesives, electroadhesive gel patches provide a very robust and durable seal that lasts indefinitely. Also, a unique feature of electroadhesion is that electroadhesion occurs on-command, upon application of an external stimulus. Furthermore, for many types of surgical repairs, the gels may be biodegraded into harmless products within a given number of days after surgery. Biocompatibility and biodegradability are tractable issues, as QDM could, in principle, be substituted for many other types of cationic gels.

[0021] Methods of using, manufacturing, and assembling materials may be practiced that facilitate tissue repair and thus help achieve some or all of the aforementioned objectives.

[0022] The materials described herein may be incorporated into systems and kits that accomplish some or all of the aforementioned objectives.

[0023] These and / or other objects, features, advantages, aspects, and / or embodiments will become apparent to those skilled in the art after reviewing the following brief and detailed description of the drawings. Moreover, the present disclosure encompasses aspects and / or embodiments not expressly disclosed, but which can be understood from a reading of the present disclosure, including at least (a) combinations of the disclosed aspects and / or embodiments, and / or (b) reasonable modifications not shown or described.

[0024] Certain embodiments in which the present disclosure may be practiced are illustrated and described in detail, wherein like reference characters represent like components throughout the several views. The drawings are presented for illustrative purposes and may not be drawn to scale unless otherwise indicated. [Brief description of the drawings]

[0025] [Figure 1A] Capture gels used in the inventors' electroadhesion studies. More specifically, anionic gels of alginate (Alg) cross-linked by divalent Ca2+ cations. The gels are fabricated in the form of hollow tubes. We show that the gels are elastic, stretchable, and flexible. A schematic of the gel structure is shown as an inset. [Figure 1B] Captures the gel used in the inventors' electrostatic adhesion studies. Shows cationic QDM gel strips made by polymerization of acrylamide derivatives. Shows that the gel is elastic, stretchable, and flexible. A schematic of the gel structure is shown as an inset. [Diagram 2]A-B capture the electrostatic attachment of the QDM gel-strip to the Alg tube. More specifically, A captures the gel and tube being contacted by graphite electrodes, with the positive electrode touching the cationic QDM gel and the negative electrode touching the anionic Alg tube. B shows that upon application of 10 volts (10 V) direct current (DC) for 10 seconds (10 s), the gel adheres tightly to the tube and conforms to the shape of the tube. When a puncture is made in the tube wall, the attachment of gel over the puncture location helps to patch the puncture, as seen in Figures 3A-3F. [Figure 3A] 1 illustrates and captures the electrostatic deposition of QDM gel used to patch a break in an Alg tube wall, and the change in pressure during that time. More specifically, a schematic of the test setup. An aqueous solution of 0.1 wt% FeCl3 is pumped through the lumen of an Alg tube that is immersed in a water bath of 0.1 wt% tannic acid. If FeCl3 leaks out of the tube, it reacts with the tannic acid and a black precipitate quickly forms in the bath. [Figure 3B] Electrostatic deposition of QDM gel used to patch a break in an Alg tube wall and the change in pressure during is illustrated and captured. If the tube is intact, there are no leaks and the bath is clear. [Figure 3C] This figure illustrates and captures the electrostatic deposition of QDM gel used to patch a break in an Alg tube wall, and the change in pressure during that time. The tube is shown to be punctured with a needle to create a 400 μm diameter hole. A black precipitate is seen in the bath as the fluid in the tube leaks out. [Figure 3D] This demonstrates and captures the electrostatic deposition of QDM gel used to patch a break in an Alg tube wall, and the change in pressure during that time. The tube is cut to a length of 7 mm with a blade. A black precipitate is seen in the bath as the fluid in the tube leaks out. [Figure 3E]Figure 3 illustrates and captures the electrostatic deposition of QDM gel used to patch a break in an Alg tube wall, and the change in pressure during. Shown is the tube from Figure 3D patched with QDM gel, and when resuming flow through the tube, no leaks are observed. [Figure 3F] We illustrate and capture the electrostatic deposition of QDM gel used to patch a break in an Alg tube wall, and the change in pressure during that time. Results from a pressure gauge placed upstream of the tube are shown in the figure, recording the pressure within the tube. When fluid leaks out and there is a break in the tube (similar to Figure 3D), the pressure drops to near zero. When the tube is patched (similar to Figure 3E), the pressure returns to its original value. [Figure 4A] Figure 1 shows the pressure change in the tube before and after applying a gel patch by electrostatic adhesion. More specifically, pressure measurements are shown before a puncture / cut is made in the wall of the alginate (Alg) tube and after the cut is sealed by electrostatic adhesion of a QDM gel patch. Data is shown for different cut sizes, and for each case, three bars are measurements of flow (i) before cutting (baseline), (ii) when the cut is made and not sealed, and (iii) after the cut is sealed. In all cases, the pressure drops as fluid leaks through the cut, but returns to baseline values ​​once the cut is sealed. [Figure 4B] Figure 4B shows the pressure change in the tube before and after applying a gel patch by electrostatic adhesion. Figure 4B shows data for different cut sizes for the burst pressure required to detach the QDM gel patch from the tube wall. In these examples, the baseline pressure is higher than in Figure 4A. Note that the burst pressure is much higher than the baseline pressure for the small cut size. [Figure 5A] 1 illustrates the electrical "stitching" of two severed pieces of tubing. A long QDM gel strip is used as a sleeve around the two pieces of Alg tubing. The orientation of the electrodes is as shown. A schematic of the process is shown. [Figure 5B]This illustrates the electrical "suture" of two severed pieces of tubing. A long QDM gel-strip is used as a sleeve around the two pieces of Alg tubing. The orientation of the electrodes is as shown. A photograph is shown in FIG. 5B. [Figure 5C] Illustrates the electrical "suture" of two severed sections of tubing. A long QDM gel-strip is used as a sleeve around the two pieces of Alg tubing. The orientation of the electrodes is as shown. Following this process, the sections of Alg tubing are shown to be "sutured" (joined) by the gel sleeve. [Figure 5D] This illustrates the electrical "suture" of the two severed pieces of tubing. A long QDM gel strip is used as a sleeve around the two pieces of Alg tubing. Finally, a steady flow is produced through the repaired tubing into a waste beaker as shown. [Figure 6] A-C show the electrostatic adhesion of QDM gel to bovine tissue. More specifically, A shows a strip of tissue (T-), specifically bovine aorta, with a strip of cationic QDM gel (G+) contacted in an E+G+TE- configuration, with the gel touching the positive electrode and the tissue touching the negative electrode. Ten volts (10V) of direct current (DC) is then applied for twenty seconds (20s). FIG. 6B shows that this causes the gel to strongly adhere to the tissue. As shown in FIG. 6C, when the gel-tissue pair is placed in an electric field of opposite polarity (E+T-G+E-), within ten seconds (10s), the adhesion is lost and the gel can be separated from the tissue. [Figure 7]All pairs were placed in a direct current (DC) electric field of 10 volts (10 V) applied for 20 seconds (20 s). For gel-gel, cationic QDM gel (G+) was contacted with anionic SA gel (G-). For gel-tissue, cationic QDM gel (G+) was contacted with various tissues. In all cases, the current I starts high and decreases with time. The maximum current recorded is used to calculate the current density j shown in the plot (note: j = I / contact area). The contact area ranged from 1.6 to 2.4 cm2 for the various tissues. No clear correlation is found between j and the occurrence of electroadhesion (see Table 1 in the main text). Data for gel-gel pairs in their native state (i.e., prepared in deionized water) or after immersion in PBS demonstrate that j depends primarily on the ionic strength of the fluid. [Figure 8A] The lap shear protocol is used to measure the adhesion strength. More specifically, FIG. 1 is a schematic of the lap shear example and a photograph of the example in progress. The sample is first attached onto the lap area and then secured to a glass slide on its backside using cyanoacrylate glue. Tension is then applied to the edge of the slide. [Figure 8B] The adhesion strength is measured using a lap shear protocol. Stress vs. strain curves from the lap shear examples for two sets of samples, gel-gel (QDM-Alg) and gel-tissue (QDM-Aorta), are plotted. Data is shown for electrostatic and contact adhesion (control) cases. The samples detach at the end of each curve, marked with an X. The stress at this point is a measure of the adhesion strength. [Figure 8C] The adhesion strength is measured using a lap shear protocol. The adhesion strength from the curves in FIG. 8B is graphed for the QDM-Alg and QDM-Aorta samples, and for the two cases of electrostatic and contact adhesion. In each category, at least three samples are analyzed and the average is plotted. Error bars correspond to the standard deviation. [Figure 9]Figure 1 shows adhesion between QDM gel and aortic strips measured after exposure to an electric field (10V DC) of different durations. A lap shear technique was used and adhesion strength was quantified using stress at break. The plot shows that electrostatic adhesion occurs within about ten seconds (~10s) of the electric field and adhesion strength saturates at about twenty seconds (20s). Data shown are averages (over at least three samples) and error bars correspond to standard deviations. The line through the data is a guide to the eye. [Figure 10A] Electrostatic adhesion of QDM gel to patch openings in the aorta is shown. More specifically, the anatomy of the aorta, a large artery, is shown and is shown on the left. A 15 cm long section from the descending thoracic region of the aorta is used for testing. The section is a hollow tube with holes on its surface that correspond to the arterioles (side branches), as shown in both the schematic and the photograph. [Figure 10B] Figure 1 shows the electrostatic adhesion of QDM gel to patch openings in the aorta. When an aqueous solution of 0.1 wt % FeCl3 is pumped through the aorta, fluid leaks out of the arterioles and falls into a bath containing tannic acid, thereby forming a black precipitate of ferric tannate. [Figure 10C] Electrostatic attachment of QDM gel to a patch opening in the aorta is shown.Two strips of QDM gel are electrostatically attached to the aorta to cover an arteriole. [Figure 10D] FIG. 1 shows electrostatic adhesion of QDM gel to the patch opening in the aorta. When FeCl3 solution is pumped through the patched aorta, no leakage is observed (the bath remains clear) and fluid flows steadily into the beaker on the right. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0026] Those skilled in the art need not view the nearly infinite number of different permutations of the features described in the following detailed description in an isolated drawing(s) to facilitate understanding of the present disclosure.

[0027] The present disclosure is not limited to what is described herein. Mechanical, electrical, chemical, procedural, and / or other changes may be made without departing from the spirit or scope of the present disclosure. Unless otherwise indicated, features shown or described are not necessary to enable the basic operation of the present disclosure. For example, where the present disclosure discusses adhesion between tissue and gel, it is understood that the same electrostatic adhesion can be applied to cells (a lower biological tissue level than tissue) and organs (a higher biological tissue level than tissue). In yet another example, where the present disclosure calls for the use of direct current (DC), it is understood that alternating current (AC) can be used instead, unless expressly stated otherwise.

[0028] Gel-gel electrostatic adhesion can be established with a combination of gels, one cationic and the other anionic. To mimic tubular tissue, an anionic gel can be provided in the form of a tube 100 with a diameter 102. As an example, the gel can be provided with divalent Ca 2+ It may include an anionic polysaccharide sodium alginate 104 cross-linked into a network by cations 106 .

[0029] An exemplary procedure for creating a tube 100 with an alginate (Alg) gel wall has been described by one of the inventors of the present application in Gargava et al., “Rapid electroformation of biopolymer gels in prescribed shapes and patterns: A simpler alternative to 3-D printing. ACS Appl. Mater. Interfaces 11, 37103-37111 (2019),” which is incorporated herein by reference in its entirety. More specifically, the use of an electric field to rapidly form a gel of biopolymer alginate (Alg) 104 in a specific three-dimensional (3-D) shape and pattern is described. For example, a gel of the biopolymer agarose, which is thermoresponsive and therefore can be molded into a specific shape. The agarose mold is then filled with Ca. 2+The beaker may be filled with cations 106 and placed into a beaker containing an Alg solution. The inside surface of the beaker is surrounded by aluminum foil (cathode 300+) and a copper wire (anode 300-) is attached to the agarose mold. These are connected to a direct current (DC) power source and when a potential of about ten volts (about 10 V) is applied, an Alg gel forms in a shape that replicates the mold. Gelling occurs when Ca 2+ ions 106 electrophoretically migrate away from the mould, whereby they cross-link Alg chains 104 adjacent to the mould. 2+ At (0.01 wt%), the Alg gel layer grows outward from the mold surface at a steady rate of about 0.8 mm / min and stops growing when the electric field is switched off. After a gel of the desired thickness is formed, the agarose mold can be melted leaving behind an Alg gel of a precise shape. The Alg gel 100 thus formed is transparent and robust. This process is particularly convenient for forming Alg gel 100 in the form of hollow tubes, including tubes with multiple concentric layers, each with a different payload. This technique is safe for encapsulation of biological species within a given Alg layer. Alg gel 100 can also be created in specific patterns by directing gel growth around selected areas. This technique allows for laboratory-scale fabrication of 3D alginate gels without the need for expensive 3D printers.

[0030] Throughout this procedure, all dimensions of the tube 100, including length, inner diameter 102, and wall thickness, are monitored. FIG. 1A shows a tube approximately ten centimeters (approximately 10 cm) long with an inner diameter of approximately one centimeter (approximately 1 cm) and a wall thickness of approximately one millimeter (approximately 1 mm). The inset shows the Ca 2+ Illustrated is the structure of the gel walls consisting of Alg chains 104 connected in zones by ions 106. The tubes have a pink color due to trace amounts of Rhodamine B (RB) dye added during the synthesis.

[0031] The counterpart to this tube 100 is a gel 200 made in the form of a rectangular strip. The gel 200 shown has a thickness 202 of about two millimeters (approximately 2 mm). The gel is synthesized by polymerizing a mixture 204 containing acrylamide (AAm, a non-ionic monomer), quaternized dimethylaminoethyl methacrylate (QDM, a cationic monomer), bis(acrylamide) (BIS, a non-ionic crosslinker), and Laponite (LAP) nanoparticles. The molar ratio of QDM to all monomers determines the charge level on the gel chains, which can be maintained at 16 mol %. The ratio of BIS to all monomers determines the stiffness of the gel, which can be maintained at 1.6 mol %. If the BIS content is too high, the gel becomes brittle. By adding 0.1 wt % LAP to the gelling mixture, the flexibility and stretchability of the final gel is greatly improved. The overall gel 200 is designated QDM200- to represent its cationic nature. 1B shows that the QDM gel strip 200- is flexible enough to be twisted or rolled up. The strip 200 can also stretch up to about 1.75 times its original length without bursting.

[0032] A cationic QDM gel-strip 200- can be electrostatically attached to an anionic Alg gel tube 100. Electrostatic attachment can involve two graphite electrodes 300 and a DC power supply. As shown in Figure 2A, the electrodes 300 must be placed in contact with the gel in a specific orientation, i.e., the strip 200 and tube 100 are in contact.

[0033] Many different types of electrodes 300+, 300- may function, including, but not limited to, the graphite electrodes mentioned above, silver electrodes, platinum electrodes, needle electrodes, ring electrodes, and / or any other suitable type of electrical conductor used to contact the non-metallic parts of the circuit (e.g., semiconductor, electrolyte, vacuum or air). The electrodes 300+, 300- may be applied from one side of the tissue, for example, both from the outside of the cylindrical container.

[0034] More specifically, the positive electrode (E +) 300+ Cationic Gel Strip (G + ) 200+, and the negative electrode (E - ) 300- in an anionic gel tube (G - ) 100. In other words, the cathode 300- (various shapes) contacts the gel 200-, the gel 200- contacts the tissue 100+, and the tissue 100+ contacts the anode 300+ (various shapes). The anode 300+ must not touch the gel 200-.

[0035] This orientation (hereafter referred to as E + G + G - E - In the electrostatic adhesion experiment (shown in FIG. 2B), a DC voltage of ten volts (10V) may be applied for about ten seconds (about 10s). When the voltage is switched off, the QDM strip 200- is found to be strongly attached to the alginate tube 100+ (FIG. 2B), and this attachment persists thereafter. If the reverse electrode orientation (E+G-G+E-) is used at the start, the two gels do not stick together. Conversely, if the electrostatically attached gel 200- is reconnected to the electric field in the reverse orientation described above and a ten volt (10V) electric field is applied for about ten seconds (about 10s), the gel 200- loses its attachment and can be easily separated. Thus, electrostatic adhesion between covalently crosslinked and physically crosslinked gels is demonstrated. In previous reports of electrostatic adhesion, all gels were covalently crosslinked.

[0036] The hydrogels used in the gel strip 200 are cross-linked hydrophilic polymers that are not soluble in water. Thus, they can form a three-dimensional network of hydrophilic polymers that retain water. They are highly absorbent and therefore maintain a well-defined structure. These properties underpin several applications, especially in the biomedical technology field. The type of hydrogel used can be synthetic or naturally derived.

[0037] The crosslinks that bind the polymers of hydrogels fall into two general categories: physical and chemical. Chemical hydrogels have covalent crosslinks, while physical hydrogels have non-covalent bonds. Chemical hydrogels result in strong, irreversible gels due to the covalent bonds, and they can also have deleterious properties that make them undesirable for medical applications. Chemical crosslinks consist of covalent bonds between the polymer chains. Hydrogels produced in this way are sometimes called "permanent" hydrogels.

[0038] Physical hydrogels, on the other hand, are highly biocompatible and non-toxic. The reversibility of physical hydrogels has been demonstrated by others only through the change of external stimuli such as pH or temperature. Physical crosslinks consist of (among others) hydrogen bonds, hydrophobic interactions, and chain entanglements.

[0039] Hydrogels are prepared using a wide variety of polymeric materials, which can be broadly divided into two categories, natural or synthetic polymers, depending on their origin. Natural polymers for hydrogel preparation include hyaluronic acid, chitosan, heparin, alginate, and fibrin. Common synthetic polymers include polyvinyl alcohol, polyethylene glycol, sodium polyacrylate, acrylate polymers, and their copolymers.

[0040] Two mechanisms have been suggested behind physical hydrogel formation. The first is the gelation of nanofibrous peptide assemblies, which is usually observed for oligopeptide precursors. The precursors self-assemble into fibers, tapes, tubes, or ribbons that intertwine to form non-covalent crosslinks. The second mechanism involves non-covalent interactions of crosslinked domains separated by water-soluble linkers, which is usually observed in longer multi-domain structures. Supramolecular interactions can also be tailored to generate self-supporting networks that do not precipitate and to lock down the water that is essential for gel formation.

[0041] It should be understood that electroadhesion can also be induced between two physical gels of opposite charge, or between a physical gel and a chemical gel. Specifically, millimeter-scale spherical capsules made from biopolymers (alginate, chitosan) by ionic crosslinking can be strongly attached despite the small contact area. In such cases, electroadhesion can be induced rapidly (in 10-60 seconds) by low voltages (3-25 V DC) and is fully reversible. For example, adhesion can be achieved with voltages as low as 3 V if the gel-tissue or gel-gel time in the electric field is extended. The adhesion is strong enough to allow the capsules / gels to assemble into robust structures in three dimensions (3D). Such 3D structures can include capsule-capsule chains, capsule arrays on a base gel, and 3D cubes. Electroadhesion-based assembly of spherical building blocks can be performed faster and easier than any alternative technique. Electroadhesion can also be used for the selective sorting of charged soft matter: for example, a "finger robot" can selectively "pick up" capsules of opposite charge by electroadhesion and then "drop" these structures by reversing the polarity. Overall, electric fields can be used to conveniently manipulate a diverse range of soft matter. EXAMPLES

[0042] The embodiments of the present invention are further defined by the following non-limiting examples. These examples, while showing certain embodiments of the present invention, should be understood to be given by way of illustration only. From the above discussion and these examples, those skilled in the art can ascertain the essential characteristics of the present invention, and can make various changes and modifications of the embodiments of the present invention to adapt them to various applications and conditions without departing from the spirit and scope thereof. Thus, in addition to those shown and described herein, various modifications of the embodiments of the present invention will be apparent to those skilled in the art from the foregoing description. Such modifications are also intended to fall within the scope of the appended claims.

[0043] Gel-Gel Electroadhesion Electroadhesion was used to repair a puncture 108, cut 112, or broken gel tube 100. A cut 112 in the wall of an alginate tube 100 may be repaired by placing a QDM gel 200+ over the cut. For purposes of example, the cut 112 may be made with a needle or razor blade and may vary in size. A rectangular patch of QDM gel 200+ (e.g., 15 mm long, 8 mm wide, 2 mm thick) may be used in the electroadhesion procedure described above. The QDM gel patch 200+ was secured over the cut 112 in the tube wall. Note that the patch adheres securely to the tube 100 and conforms to the curvature of the tube, as shown in FIG. 2B.

[0044] To test the strength of the patch-tube attachment, a fluid flow 400 was introduced through the patched tube 100. If the patch 200 was not secured, the fluid would leak out of the break 112 in the tube 100. The test determined whether the patch could completely seal the leak and whether it could withstand the pressure exerted by the fluid. As shown in Figures 3A-3B, the protocol for the leak test involves immersing the Alg tube 100 in a water bath 110 containing 0.1% tannic acid. A 0.1 wt% solution of ferric chloride (FeCl3) in water is then flowed through the lumen of the tube using a peristaltic pump. When FeCl3 comes into contact with the tannic acid, a black precipitate of ferric tannate 114 is instantly formed. Even though a small puncture 108 (400 μm) is made in the tube wall using a needle, the leakage of fluid from the puncture can be easily detected by eye due to the formation of a black precipitate 114 (Figure 3C). This leakage is much greater when a large cut 112 (7 mm long) is made in the tube wall with a blade (FIG. 3D). FIG. 3E shows an alginate tube 100 with said large cut patched with QDM gel 200 using electroadhesion. In this case, there is a steady flow 400 of fluid through the tube 100 and no leakage whatsoever.

[0045] To quantify the above example, a pressure gauge was placed upstream of the puncture site in the tube. It measures the pressure P exerted by the fluid flow on the tube wall. When some of the fluid leaks through the break 112, P drops relative to its initial value (corresponding to a steady flow with no leakage). If there is significant leakage, P drops to near zero. For example, the bar graph in FIG. 3F shows that when fluid flows through the tube 100 at a flow rate of 5 mL / min, the initial P is 40.1 mm-Hg. When a 7 mm long break is made in the tube wall and flow is resumed at the above flow rate, P drops to 0.7 mm-Hg. If the break is then patched with QDM gel using electrostatic adhesion and the example is repeated, P then increases to 39.8 mm-Hg, nearly the same as the initial pressure. The data shows that the electrostatically attached patch tolerates the above flow conditions well.

[0046] The above pressure measurements depend on both the flow conditions in the tube 100 and the size of the break 112. If the flow rate increases beyond a critical value, the pressure exerted by the fluid can detach the electrostatically attached patch, which then leaks into the surrounding bath 110. The pressure at this failure point is defined as the burst pressure, "Pburst." Pburst represents the limit of the conditions tested.

[0047] Figures 4A-4B show pressure measurements for various puncture / cut sizes. P-burst is 252 mm-Hg for a small (0.4 mm) puncture, 216 mm-Hg for a medium (1.4 mm) puncture, and 82 mm-Hg for a large (7 mm) cut. These P-burst values ​​indicate a robust sealing capability under typical blood flow conditions (normal systolic blood pressure is 120 mm-Hg in healthy humans). Note that the P-burst can be easily increased by using a larger gel patch around the cut or by introducing a second gel patch over the first in a crossing geometry.

[0048] Electrostatic adhesion can repair much more extreme "damage" compared to cuts in the tube wall. In this case, we attempted to cut an alginate tube 100 in half and use a QDM gel-strip 200 to join the two pieces. First, a long, flexible gel-strip 200 (15 mm long, 8 mm wide, 2.5 mm thick) was made. The two pieces of the tube were brought into contact laterally and the QDM gel-strip was wrapped around the tube section, as shown in FIG. 5A. During electrostatic adhesion, the negative electrode 300- remained in contact with the tube 100- at all times while the positive electrode 300+ rotated along the exterior of the gel-strip 200+, as shown in FIG. 5B.

[0049] The end result is that the QDM gel acts as a sleeve that wraps around the cut fragment, as shown in Figure 5C. Note that the length of the gel strip 200 was chosen to match the circumference of the sleeve so that there are no gaps between the ends of the strip 200. Thus, the patched tubes 100 and 200 behave like a single entity. Fluid can then flow 400 through the patched tube without leakage, as shown in Figure 5D.

[0050] Gel-tissue electrostatic adhesion Furthermore, electroadhesion of the gel 200 can be extended to soft materials other than gels. There are many soft materials naturally occurring in nature. These include tissues of various organisms including mammals, birds, worms, aquatic organisms, and plant materials and foods. For example, the gel 200 can be electroadhered to animal tissue 500 forming an animal organ. Electroadhesion can be applied to a wide range of organisms and tissues including, but not limited to, bovine (e.g., cows), porcine (e.g., pigs), murine (e.g., rodents such as mice), avian (e.g., birds such as chickens), fish (e.g., fish such as salmon), crustaceans (e.g., shrimp, crabs, etc.), and plants (e.g., strawberries, carrots, lettuce, etc.). Exemplary organs that can be electroadhered include, but are not limited to, aorta, cornea, intestine, lungs, muscle, tendon, cartilage, fascia, and dermis.

[0051] Bovine tissue from the bovine aorta was cleaned and prepared for this example. Bovine tissue samples 500 were then tested along with the same QDM gel 200 as above, as shown in Figures 6A-6C. A section of the bovine aorta, one of the largest arteries in animals, was tested first. A rectangular strip 200 of aorta (1.5 x 2.5 cm) was cut and sewn onto a piece of paper. 2 ) was used along with a similar strip of QDM gel. As shown in FIG. 5A, the gel and tissue were aligned in the same orientation (E + G + T - E - ) in contact with the electrode 300 and the cationic QDM gel (G + ) is connected to the positive electrode and the tissue (T) is connected to the negative electrode. A direct current DC voltage of 10 volts (10V) is then applied for about 20 seconds (about 20s), which causes the gel to strongly adhere to the tissue (FIG. 5B). This suggests that the tissue behaves like an anionic gel, and therefore the notation T - It becomes.

[0052] Reverse orientation (E + T - G + E - ), no attachment is observed. Also, as shown in Figure 5C, if the electrostatically attached gel-tissue pair is placed in the reverse orientation and an electric field is applied, the gel-tissue attachment reverses and the two can easily separate as in the gel-gel case. Thus, QDM gels can be reversibly electrostatically attached to the aorta.

[0053] Regarding the strength of electrostatic adhesion between the gel and the tissue, it should be understood that when the QDM gel contacts the aorta in the absence of an electric field, a weak adhesion is found, referred to as "contact adhesion." The contact adhesion is weak enough that the gel can be peeled intact from the tissue by hand without applying much force. In contrast, when the gel is electrostatically attached to the aorta, it cannot be peeled intact by hand or removed from the aorta using a scalpel. Thus, a strong adhesion of the gel to the tissue is induced by the electric field, and this adhesion is much stronger than the contact adhesion between the two.

[0054] Once electrostatic adhesion of QDM gel to the aorta was confirmed, the same phenomenon could be observed with other types of bovine tissue. In all cases, a strip of tissue was cut similar to that in Figures 6A-6C and tested against a similar strip of QDM gel. First, it was determined whether there was "contact adhesion" when the gel and tissue strips were pressed together without an electric field. The degree of adhesion (or lack thereof) was assessed using a subjective scale of adhesion strength, as seen in Table 1. To this end, an attempt was made to separate the gel from the tissue, and it was found to be easy to do this.

[0055] The results were then classified as follows: 0 = negligible, 1 = weak, 2 = moderate, 3 = strong, and 4 = very strong adhesion. For a given gel-tissue pair, the "contact adhesion" results provided a baseline. Electrostatic adhesion was then induced from the same gel-tissue pair using the same protocol as in Figures 6A-6C (i.e., using 10 V DC applied for 20 seconds). After switching off the electric field, adhesion strength was assessed using the 0-4 scale described above, and the results were compared to the baseline. Results for all tissue types are presented in Table 1. [Table 1]

[0056] The left half of Table 1 lists several tissues where the strength of electrostatic adhesion is much higher than the baseline case of contact adhesion. The largest contrast is with the cornea from the eye, where the QDM gel shows very little contact adhesion (0 on the scale), but very strong electrostatic adhesion (about 4 on the scale). Other tissues where electrostatic adhesion is clearly stronger and distinct from the baseline include lung, cartilage, and certain types of skeletal muscle. In the case of the aorta shown above in Figures 6A-6C, contact adhesion is not zero, but electrostatic adhesion is clearly much stronger. Conversely, the right half of Table 1 lists tissues where electrostatic adhesion is not significant under the conditions tested. In the cases of heart, brain, spleen, and adipose tissue, there is no significant adhesion at contact or due to the electric field. In the case of the thymus, weak adhesion is observed due to the electric field, but this is not well distinguished from contact adhesion. Tissues can be structurally complex, and that complexity is particularly evident in the inventors' tests of tendons and skeletal muscles (the bottom three entries in Table 1). When these tissues are cut in longitudinal sections, the samples do not exhibit significant electrostatic adhesion, however, when the same tissues are cut in transverse sections, electrostatic adhesion is evident. Thus, there is significant anisotropy in the tissue structure, which also influences the results here. Overall, it can be concluded from Table 1 that cationic QDM gels can be electrostatically attached to several types of animal tissues.

[0057] Concomitantly, with regard to voltage, electrostatic adhesion of gel to tissues can be achieved even with voltages as low as 3 V, but applied for longer durations (approximately 60-120 s). For both the gel-tissue and gel-gel systems, no adhesion was observed for voltages below 3 V, which was generally consistent with previous testing. Conversely, for some of the tissues in Table 1 for which electrostatic adhesion was not successful with the current protocol (10 V for 20 s), it is longer. It should be appreciated that increasing the application time (e.g., 60 s) could potentially enable stronger electrostatic adhesion with more of the tissue types listed in Table 1.

[0058] Electrostatic adhesion works for some types of tissues and not others. An anionic counterpart to the QDM gel 200 was made by copolymerizing AAm with an anionic monomer such as sodium acrylate (SA). However, this gel could not be electrostatically attached to any tissue. Thus, in all successful cases of electrostatic adhesion, the gel 200 is cationic (i.e., QDM), which means that the tissue 500 must be anionic. Animal tissue 500 is expected to have a microstructure consisting of cells (either discrete or densely packed in clusters) embedded in a network of polymer chains, i.e., extracellular matrix (ECM). The ECM tends to have different compositions in different tissues. The two major proteins of the ECM are collagen and elastin. The percentage of each of these proteins in the tissue, where found, is given below.

[0059] These values ​​are shown in Table 2, divided into two halves similar to Table 1, with tissues on the left exhibiting electrostatic adhesion and tissues on the right not exhibiting electrostatic adhesion. In addition to protein, the water content in each tissue is also shown. [Table 2]

[0060] Note: Aorta: Collagen and elastin composition of the aorta, water content. b. Cornea: Collagen composition, percentage of elastin not stated, water content. c. Lung: Collagen and elastin composition, water content of rat lung d. Cartilage: Collagen composition of human cartilage, percentage elastin not stated, water content. e. Tendons: collagen and elastin composition of tendons, water content. f. Skeletal muscle: Collagen and elastin composition, water content of skeletal muscle. g. Heart: Collagen and elastin composition of the heart, water content. h. Brain: Collagen and elastin composition, water content of rat brain. i. Spleen: Spleen collagen and elastin composition, water content. j. Fat: Unspecified collagen percentage, elastin composition, and water content of human adipose (fat) tissue. k. Thymus: percentage of collagen not given, data on elastin and water content not available in literature.

[0061] One observation from Table 2 is that many (but not all) tissues in the left half have high collagen content. Collagen itself is a protein with a net neutral charge at ambient pH and does not by itself confer anionic properties to the tissue. However, collagen-rich tissues are often associated with protein-sugar hybrid polymers called glycosaminoglycans (GAGs), which are known to be strongly anionic. GAGs anchor cells to the ECM by simultaneously attaching to collagen fibers in the ECM as well as proteins on the cell surface. GAGs, such as heparan sulfate, have a high affinity for collagen types I and III, the main types of collagen in the aorta. Another observation from Table 2 is that ECMs rich in some types of collagen also have high concentrations of elastin. Elastin has been reported to be cationic at ambient pH, which allows it to bind to GAGs via electrostatic interactions. Taken together, in tissues containing collagen, GAGs, elastin, and other polymers, the overall composition of charged polymers dictates the net charge of the tissue. Tissues with net anionic properties tend to undergo electrostatic adhesion (to cationic gels such as QDM). If the water content in the tissue is too low (such as in the case of adipose or brain tissue), the tissue may not exhibit electrostatic adhesion.

[0062] An additional factor to consider is the ionic strength of the tissue (the fluid in the tissue). The interaction between cationic and anionic polymers is affected by ionic strength. In this regard, therefore, the QDM gel and a representative tissue (aorta) can be immersed in different biologically relevant fluids and then examined for adhesion. These fluids are expected to have an ionic strength of about 0.15M. When immersed in whole blood (bovine), the gel and tissue electrostatically adhere similarly to their native state. When immersed in plasma (bovine) or phosphate buffered saline (PBS), the gel-tissue adhesion was initially weak but then increased. By increasing the time of application of the electric field from 20 to 60 seconds, significant adhesion between the gel and the tissue was obtained in all cases.

[0063] The current I during electroadhesion examples reported for various pairs was recorded in FIG. 7. The data in FIG. 7 are plotted in terms of current density j (i.e., I / contact area). j appears to be primarily dependent on the ionic strength of the gel and tissue, e.g., for the two gels (G + and G - ) are electrostatically attached in their native state (i.e., after preparation in deionized water), j is 52 mA / cm 2 However, when the same gel is immersed in PBS, it is 126 mA / cm 2 Gels of the same charge (e.g., two G + Similar currents are observed when the gel is in contact with the tissue, but in the absence of adhesion. For gel-tissue examples, j for various tissues is shown in Figure 7. For electrostatically attached tissues, j is as low as 17 mA / cm for lungs. 2 from the aorta and cornea to approximately 80 mA / cm 2 For non-electrostatically attached tissues, j varies from nearly zero in adipose tissue to 42 mA / cm in cardiac tissue. 2 From these values, no clear relationship between j and adhesion (or lack thereof) can be discerned. It should be noted that the reported j values ​​correspond to the highest currents reported near the beginning of the examples. Over time, the currents drop to a steady state of 20-30% of the values ​​shown above.

[0064] The gel-tissue adhesion strength was measured and compared to that of the gel-gel case. Measurements were performed using a lap shear test protocol, which is described in more detail in the methods section below. In this test, two rectangular specimens are attached to each other over a portion of their area, called the "lap", as shown in Figure 8A. The outer surfaces of the two specimens are then affixed to a glass slide 600 using cyanoacrylate glue. The setup is then placed in a test fixture, and each glass slide is gripped at its end by the jaws of the fixture. A tensile strain is then applied until failure occurs, and the magnitude of the stress at break is a measure of the adhesion strength. Stress vs. strain curves for two sets of specimens, a QDM gel attached to an Alg gel, and the same QDM gel attached to a bovine aorta, are presented in Figure 8B. In both cases, the test is first performed under "contact attachment", where the specimens are pressed together without an electric field. The two specimens are then electrostatically attached and the test is repeated. For both gel-gel and gel-tissue, the stress-strain curves for electrostatic adhesion extend to much higher stresses compared to contact adhesion (FIG. 8B), indicating the strong adhesion imparted by the electric field.

[0065] The adhesion strengths determined from the above curves are plotted in FIG. 8C. The strength of the gel-gel (QDM-Alg) electrostatic adhesion is found to be about 25 kilopascals (about 25 kPa). For comparison, previous attempts have measured adhesion strengths for cationic and anionic acrylamide-based gel pairs (using the same lap shear technique) and reported values ​​of only about 10 kilopascals (10 kPa). For the electrostatically attached gel-tissue pair (QDM aorta), the adhesion strength is about 20 kilopascals (20 kPa), comparable to the gel-gel case. In both cases, the strength of the contact adhesion is much lower (about 5 kPa). These measurements confirm that electrostatic adhesion is substantially stronger in both the gel-gel and gel-tissue cases.

[0066] In the gel-gel case, when failure occurred, it was generally a cohesive failure, i.e., pieces of each gel were found to remain on top of the other gel. In the gel-tissue case, failure was also generally cohesive. Some gel remained attached to the tissue, whereas the tissue never remained attached to the gel. This difference may be because the tissue tested (aorta) was generally much stiffer than the QDM and Alg gels.

[0067] The adhesion strength is a function of time under the electric field, and the corresponding data is shown in Figure 9. These data are for QDM gels crosslinked with BIS (containing no LAP nanoparticles) in contact with bovine aorta. Using the same lap shear protocol as in Figures 8A-8C, and using the stress at break as a measure of adhesion strength, gel-tissue pairs were placed in an electric field generated by ten volts direct current (10 V DC) for different times. The data reveal that sufficient (i.e., much higher than contact adhesion) electrostatic adhesion occurs within ten seconds (10 s) in the electric field.

[0068] Subsequently, the adhesion strength gradually decreases to a constant value by about twenty seconds (20 s), and similar values ​​are obtained with longer contact times (e.g., 40 s). Thus, twenty seconds (20 s) of time in the electric field appears to be more than sufficient to induce significant electrostatic adhesion between the gel and tissue. Similar data on adhesion strength as a function of contact time have been reported previously for gel-gel adhesion.

[0069] Electroadhesion to repair severed or damaged tissue The electrostatically attached gel patch can seal a cut on tissue, effectively mimicking a surgical repair. These examples are similar to those previously demonstrated with the anionic gel tubes of Figures 3A-F and 5A-5D above, where the cut 112 was sealed by a QDM gel patch 200. The example associated with Figure 9 again used a cationic QDM gel 200, but this time involved a section from a bovine descending thoracic aorta 700, approximately 15 cm in length and 2-2.5 cm in diameter (Figure 10A). The aorta 700 has paired holes along its length that correspond to arterioles 702. The arterioles 702 are small branches from the aorta 700 that transport blood to various organs. When the aorta is used as a tube, fluid leaks through the arterioles. This is illustrated by Figure 10B, which used a testing protocol similar to that of Figures 3A-F. A solution of 0.1% FeCl3 is pumped through the lumen of the aorta 700. The fluid leaks out through the arteriole 702 and drips into the bath 110 containing 0.1% tannic acid, which immediately forms a black precipitate of ferric tannate 114. Note that the aorta 700 was not immersed in the bath to avoid any reaction of the tissue with the tannic acid.

[0070] Next, two rectangular patches of QDM gel 200 were made for two pairs of arterioles 702 in the aorta 700. The gel patch 200 was fixed over the arteriole 702 (one patch covering two adjacent arterioles) using electrostatic adhesion (10V, 20s). The gel firmly attached to the tissue, as seen in FIG. 10C. The flow of FeCl3 solution through the aorta was then resumed. FIG. 10D shows that there is no leakage through the arteriole 702, i.e., the hole remains sealed, allowing fluid to flow right through the aorta 700. The output fluid 402 was collected in a beaker containing 0.1% tannic acid at the end of the aorta 700. A black precipitate 114 of ferric tannate is seen in the beaker but not in the water bath 110, thus confirming that there is no leakage through the tissue during the flow process.

[0071] method Materials. Chemicals: monomers acrylamide (AAm) and N,N'-methylenebis(acrylamide) (BIS), initiator ammonium persulfate (APS), calcium chloride dihydrate (CaCl2) salt, tannic acid, sodium hydroxide, phosphate buffered saline (PBS) tablets, and dye rhodamine B were from Sigma-Aldrich. Accelerator N,N,N',N'-tetramethylethylene-diamine (TEMED) was from TCI America. Monomer N,N'-dimethylaminoethyl methacrylate, quaternary ammonium salt (QDM) was from MPD Chemicals. Two biopolymers, alginate (Alg) (from brown algae, medium viscosity) and agarose (1-A type, low EEO, melting temperature approx. 88 °C), were purchased from Sigma-Aldrich. Laponite XLG nanoparticles (LAP) were a gift from Southern Clay Products. Cyanoacrylate glues (Gorilla Glue gel and Krazy Glue) and Rust-Oleum hydrophobic coating were purchased from The Home Depot. Deionized (DI) water was used in the examples described herein.

[0072] Synthesis of alginate tubes. First, alginate tubes were prepared using a cylindrical agarose gel mold containing Ca2+2 ions. For this, 2.5 wt% agarose and 5 wt% CaCl2 were added to DI water and heated above 80°C until the agarose was completely dissolved. The hot solution was then poured into a tube capped at one end. Upon cooling to room temperature, a solid (gel) cylinder of agarose was obtained. This cylinder was then placed in a solution of 2 wt% Alg for 12 minutes. During this time, the Ca 2+The ions diffuse out of the agarose resulting in an Alg gel around the cylindrical core. The final step was to soak the material in 3 wt% CaCl2 solution for 20 minutes and then cut the edges. The Alg tube can then be slid out of the agarose core. Alg tubes can be prepared across a range of dimensions using this method. Tubes were prepared in two typical dimensions using agarose cores of different diameters and lengths: (a) 1 cm diameter and 10 cm length, and (b) 2 mm diameter and 60 cm length. The tubes were stored in 1 wt% CaCl2 solution and stained with 0.1 mM rhodamine B for contrast purposes. Typically, the tubes were used within 24 hours of preparation.

[0073] Synthesis of QDM gels. Cationic QDM gels were prepared using the following protocol. First, DI water was degassed by bubbling nitrogen gas for 30 minutes. To aid in easy removal of the gel, the Petri dish used for gel preparation was coated with a spray of Rust-Oleum hydrophobic coating and then left to stand for 10 minutes before being wiped dry. Two variants of QDM gels were prepared: with LAP and without LAP. For the synthesis of QDM gels without LAP, 1 M (1.4 g) Aam, 0.16 M (809 μL) QDM solution, 0.019 M (0.06 g) BIS, 0.0088 M (0.04 g) APS, and 0.01 M (30 μL) TEMED were combined in 20 mL of degassed DI water. The above monomer mixture was then poured into the pre-coated Petri dish and kept in a nitrogen environment for 3 hours, at which point the gel was fully polymerized. For the synthesis of QDM gels containing LAP, the first step was to add 1 wt % (0.2 g) of LAP particles to 20 mL of degassed water and stir until the particles were well suspended (confirmed by a sample appearing clear and homogenous).

[0074] The pH of the solution was then lowered to 4.5 using 1M HCl. 0.16M (809 μL) QDM was then added dropwise to the LAP mixture, followed by 1M (1.4 g) AAam, 0.0095M (0.03 g) BIS, 0.0088M (0.04 g) APS, and 0.01M (30 μL) TEMED. When the pH was below 5, the QDM was able to dissolve in the LAP suspension (no agglomerates). The TEMED raised the pH again to about 8.5. The above solution was placed into a pre-coated Petri dish and polymerized as described above. After polymerization, the gel was stored in a refrigerator and typically used within 24 hours of preparation.

[0075] Synthesis of SA gels. Anionic SA gels were prepared by a procedure similar to that described above for QDM gels. In this case, the monomer solution contained 1.4 M (2 g) AAm, 0.11 M (0.2 g) SA, 0.019 M (0.06 g) BIS, 0.0088 M (0.04 g) APS, and 0.01 M (30 μL) TEMED in 20 mL of degassed DI water. The solution was poured into a pre-coated Petri dish and kept in a nitrogen environment for 2 hours. After polymerization, the gels were stored in a refrigerator and typically used within 24 hours of preparation.

[0076] Tissue preparation protocol. All tissues were ethically obtained immediately after slaughter from a local butcher. All experiments on tissues were performed within 24 hours of tissue collection. When tissues were initially received, organs were typically encased in fat and other matrix materials. For example, the aorta was surrounded by fat and connected to sections of the heart and lungs. Therefore, for experiments with the aorta, the aorta had to be harvested from its surrounding sections and cleaned. The harvested aorta was then sectioned into even smaller pieces for electroadhesion experiments, as shown in the figure above. For most experiments, tissue sections were sliced ​​to a thickness of 0.3 ± 0.1 mm. Exceptions were made for naturally thin tissues such as the cornea.

[0077] Adhesion experiments. A DC power supply (Agilent, model E3612A) with a range of 0-60 V, 0-0.5 A was used for electrostatic adhesion experiments. The voltage was set at 10 V for most experiments. Graphite electrodes (from Saturn Industries) were cut to a size of 2 × 3 × 0.15 cm and connected to the DC power supply using alligator clips. Electrodes were placed on either side of the gel-gel or gel-tissue pairs, as shown in Figures 2A-B and 6A-6C. Gel strips were generally 2 mm thick, while tissue strips were 2-5 mm thick. Thus, the electric field strength across the gel-tissue sandwich was 1.4-2.5 V / mm. For the gel-tissue experiments reported in Table 1, the following procedure was used: Tissue of interest was taken from a given batch obtained from the butcher, and for a given tissue type, at least three tissue samples were prepared as described above. Three QDM gel strips were then prepared. Gel-tissue contact adhesion was measured first, followed by their electrostatic adhesion. Two observers independently ranked the adhesion strength in each experiment on a scale of 0 to 4, where 0 = negligible, 1 = weak, 2 = moderate, 3 = strong, and 4 = very strong adhesion (this scale is also shown at the bottom of Table 1). The average of both observers' rankings was recorded for that experiment. Whenever there was a problem, the second observer was blinded to the sample type to avoid biasing the two evaluations. After three such trials with tissue, the average of the measurements was determined and is shown in Table 1.

[0078] Pressure Test. The test setup is shown diagrammatically in Figure 6A. A peristaltic pump (Pharmacia-LKB-Pump P-1) was used to pump 0.1% FeCl3 solution through the Alg tube at a flow rate of 5 mL / min. The tube was placed in a basin 15 cm long, 5 cm wide, and 5 cm high. Openings were made on both sides to allow the passage of the tube. The basin was filled with 0.1% tannic acid solution to a height of 2 cm, and the Alg tube (60 cm long) was positioned so that its mid-section was immersed in this solution (see Figure 6A). A clamp was fixed to the bottom of the basin to control the path and position of the Alg tube within the basin. A pressure gauge (PRTemp 1000, Madge Tech) was placed upstream of the Alg tube, and pressure was recorded in real time (every 2 seconds) on a computer using Madge Tech software. Pressure measurements were taken during flow in the tube before puncture, during puncture, and after puncture repair by electrostatic adhesion of a QDM gel patch. Burst pressure (for patched tubing) was determined by clamping the distal end of the Alg tubing and continuing flow into the tubing, increasing pressure within the tubing. The highest pressure recorded before the patch was removed was designated as the burst pressure. All measurements correspond to individual trials.

[0079] Lap shear testing. Lap shear testing was performed using an Instron Model 5565 instrument. Testing was performed following the protocol recommended by the American Society for Testing and Materials (ASTM) used in previous studies. 33–35 gels and tissues were cut into rectangular sections with dimensions of 1.5 × 4 cm. QDM gel sections were 3 mm thick, Alg sections were 1 mm thick, and tissue sections were 2.5 ± 1 mm thick. Gel-gel and gel-tissue samples were electrostatically attached over a lap height of approximately 1.5 cm (see Figure 8A). After electrostatic attachment, the dangling ends of the gel and tissue were firmly attached to a glass slide using cyanoacrylate glue. Krazy Glue was found to be the best for fixing the QDM and Alg gels to the glass slides, and a cure time of 1 hour was used. To fix the tissue to the same slide, Gorilla Glue was best and a 2 hour curing time was used (the tissue surface exposed to air was covered with a piece of gauze soaked in PBS solution during this time). The glass slide provided a stiff, inelastic scaffold for the Instron to grip and ensured that shear was only applied to the lapped area. The Instron was then used to stretch the specimen at a rate of 10 mm / min and the force was recorded during this process. At least three specimens for each of the categories in Figure 8C were tested and statistics were analyzed using a Student's T-test.

[0080] From the foregoing, it can be seen that the present disclosure achieves at least all of the stated objectives. For example, it has been demonstrated that electroadhesion can be applied to new materials and geometries. Cationic (QDM) gels and animal (bovine) tissue can be utilized for such electroadhesion. The gels and tissues can be attached to each other and to E + G + T - E - The gel was placed in contact with an electrode of the cationic gel G + is positive electrode E + Touching the organization T - is the negative electrode E -(The tissue was in contact with the QDM gel. A DC voltage of 10 V was then applied for 20 seconds, causing the gel to strongly adhere to the tissue, and the adhesion persisted after the electric field was turned off. The strength of adhesion between the QDM gel and bovine aorta, measured by lap shear testing, was approximately 20 kPa. In addition to aorta, electrostatic adhesion also worked on cornea, lung, cartilage, and certain types of skeletal muscle and tendon. Cationic gels electrostatically adhere to tissue, meaning that the tissue has anionic properties. Placing the electrostatically attached gel-tissue pair in an electric field of opposite polarity can result in loss of adhesion and separation of the two.

[0081] Furthermore, electroadhesion may seal cuts or tears in the tube. Initial experiments in this regard were performed using a tube of anionic Alg gel as a model system. In an extreme case, two severed pieces of Alg tubing were joined using electrostatically attached QDM gel strips that were flexible enough to span the cut sections and encircle the tube. Similarly, in the case of bovine aorta, QDM gel was electrostatically attached over an opening in the tissue (corresponding to an arteriole). In both cases, the electrostatically attached patch provided a robust and durable seal, allowing fluid to flow through the lumen of the tube. This disclosure enhances the possibility of using electroadhesion to perform surgical repairs in the future. The use of strongly attached gel patches could eliminate the need for sutures or staples in many surgical procedures. The ability to achieve adhesion on command using electric fields, and also the ability to reverse adhesion in the event of an error, allows surgery to be performed in a more rapid, durable, and precise manner.

[0082] List of reference characters The following list of reference letters and descriptors is neither exhaustive nor limiting, and includes reasonable equivalents. Where possible, elements identified by the following reference letters, and / or those elements that are more or less ubiquitous within the art, may replace or supplement any element identified by another reference letter. [Table 3]

[0083] Glossary Unless otherwise defined, all technical and scientific terms used above have the same meaning as commonly understood by one of ordinary skill in the art to which the embodiments of the present disclosure pertain.

[0084] The terms "a," "an," and "the" include both singular and plural referents.

[0085] The term "or" is equivalent to "and / or" and means any one member or combination of members of a particular list.

[0086] As used herein, the word "exemplary" refers to an example, instance, or illustration, and does not refer to a most preferred embodiment, unless specifically stated otherwise.

[0087] The term "about" as used herein refers to slight variations in a quantity for any quantifiable variable. Unintentional errors may occur, for example, from the use of typical measuring techniques or equipment, or from differences in manufacture, source, or purity of the components.

[0088] The term "substantially" refers to a large or significant degree. Thus, given the appropriate context, "substantially" can refer to a plurality, a majority, and / or a vast majority of the quantifiable variables in question.

[0089] The term "generally" encompasses both "about" and "substantially."

[0090] The term "configured" describes a structure that is capable of performing a task or adopting a particular configuration. The term "configured" may be used interchangeably with other similar phrases such as built, arranged, adapted, manufactured, etc.

[0091] Terms characterizing order, position, and / or orientation are not limiting and are merely referenced according to the figures presented.

[0092] "The present invention" is not intended to refer to any single embodiment of a particular invention, but rather encompasses all possible embodiments described in the specification and claims. The "scope" of the present disclosure is defined by the appended claims, along with the full scope of equivalents to which such claims are entitled. The scope of the present disclosure is further limited as including any possible modifications to any of the aspects and / or embodiments disclosed herein that result in other embodiments, combinations, subcombinations, etc. that will be apparent to those skilled in the art.

[0093] The disclosure is further defined by the following numbered paragraphs:

[0094] 1. A method comprising electrostatically attaching a cationic hydrogel to anionic cells.

[0095] 2. The method of paragraph 1, further comprising contacting a tissue comprised of said anionic cells with a negative electrode, contacting a cationic hydrogel with a positive electrode, contacting the cationic hydrogel and tissue for a finite period of time within an electric field powered by a direct current (DC) or an alternating current (AC), and electrostatically attaching the cationic hydrogel to the tissue.

[0096] 3. The method of paragraph 2, further comprising maintaining attachment after a finite time has elapsed and no direct current (DC) or alternating current (AC) is applied to either the positive or negative electrode.

[0097] 4. The method of paragraphs 2 or 3, further comprising conjugating the two anionic cell populations with a cationic hydrogel.

[0098] 5. The method of any one of paragraphs 2-4, further comprising removing adhesion between the anionic cells and the cationic hydrogel by applying an electric field of reverse polarity for an additional finite period of time.

[0099] 6. The method of any one of paragraphs 2-5, wherein the anionic cell population comprises collagen and elastin.

[0100] 7. The method of any one of paragraphs 2-6, further comprising patching the puncture or cut in the tissue.

[0101] 8. The method according to any one of paragraphs 2 to 7, wherein the electrostatic adhesion between the cationic hydrogel and the tissue is of a chemical type and comprises: a. an s-IPN having a cationic charge; or b. a monomer or comonomer having a cationic charge.

[0102] 9. The method of any one of paragraphs 2 to 8, wherein the electrostatic adhesion between the cationic hydrogel and the tissue is of a physical type.

[0103] 10. The method of any one of paragraphs 2 to 9, wherein the electrostatic adhesion between the cationic hydrogels occurs in a double network, where one or both networks carry a cationic charge.

[0104] 11. Flowing a ferric chloride solution through an anionic cell; 11. The method of any one of paragraphs 2-10, further comprising immersing the anionic cell in a water bath containing 0.1% tannic acid to determine whether the anionic cell has any leakage.

[0105] 12. The method of any one of paragraphs 2-11, further comprising sealing the arterioles using an electrostatically attached cationic hydrogel.

[0106] 13. The method of any one of paragraphs 2 to 12, further comprising measuring the gel-tissue attachment strength between the anionic hydrogel and / or the anionic cell group and the cationic hydrogel by adhering the sample onto a glass slide using cyanoacrylate glue.

[0107] 14. A system for achieving sutureless tissue repair, comprising: a cationic hydrogel; anionic cells; and electrodes adapted to (1) receive power from a direct current (DC) power source and (2) contact the cationic hydrogel with the anionic cells.

[0108] 15. The system of paragraph 14, wherein the anionic hydrogel is formed into a cylindrical tube.

[0109] 16. The system of paragraphs 14 or 15, wherein the cationic hydrogel is formed into a strip.

[0110] 17. An electrostatically attached material comprising a covalently crosslinked gel electrostatically attached to a physically crosslinked gel.

[0111] 18. Covalently crosslinked gels can be used to bind divalent Ca 2+ 18. The electrostatically attached material of paragraph 17 comprising a cationically crosslinked alginate.

[0112] 19. The electrostatically attached material of paragraphs 17 or 18, wherein the physically crosslinked gel comprises a mixture comprising a nonionic monomer, a cationic monomer, a nonionic crosslinker, and crystalline nanoparticles having high ionic surface area.

[0113] 20. The electrostatically attached material of paragraph 19, wherein the nonionic monomer comprises acrylamide.

[0114] 21. The electrostatically attached material of paragraphs 19 or 20, wherein the cationic monomer comprises quaternized dimethylaminoethyl methacrylate.

[0115] 22. The electrostatically attached material of any one of paragraphs 19-21, wherein the non-ionic crosslinker comprises bis(acrylamide).

[0116] 23. The electrostatically attached material of any one of paragraphs 19-22, wherein the crystalline nanoparticles having ionic surface area comprise Laponite nanoparticles.

Claims

1. A method comprising electrostatically attaching a cationic hydrogel to anionic cells.

2. Contacting a tissue composed of the anionic cells with a negative electrode, contacting the cationic hydrogel with a positive electrode, contacting the cationic hydrogel and the tissue for a finite time within an electric field powered by direct current (DC) or alternating current (AC), and electrostatically attaching the cationic hydrogel to the tissue, the method according to claim 1.

3. The method according to claim 2, further comprising maintaining the attachment after the finite time has elapsed and the direct current (DC) or alternating current (AC) is no longer applied to either the positive or negative electrode.

4. The method according to claim 2, further comprising joining two groups of anionic cells to the cationic hydrogel.

5. The method according to claim 2, further comprising removing the attachment between the anionic cells and the cationic hydrogel by applying an electric field of opposite polarity for an additional finite time.

6. The method according to claim 2, wherein the group of anionic cells contains collagen and elastin.

7. The method according to claim 2, further comprising patching a puncture or cut in the tissue.

8. The electrostatic attachment between the cationic hydrogel and the tissue is of a chemical type, a. an s-IPN having a cationic charge, or b. a monomer or comonomer having a cationic charge, the method according to claim 2.

9. The method according to claim 2, wherein the electrostatic attachment between the cationic hydrogel and the tissue is of a physical type.

10. The method according to claim 2, wherein the electrostatic attachment between the cationic hydrogels occurs in a double network in which one or both networks have a cationic charge.

11. Flowing an iron chloride solution through the anionic cells, immersing the anionic cells in a water bath containing 0.1% tannic acid to determine whether there is any leakage from the anionic cells, the method according to claim 2.

12. The method according to claim 2, further comprising using the electrostatically attached cationic hydrogel to seal arterioles.

13. The method according to claim 2, further comprising measuring the gel-tissue adhesion strength between the anionic hydrogel and / or anionic cell population and the cationic hydrogel by fixing a sample on a slide glass using a cyanoacrylate group.

14. A system for achieving seamless tissue repair, comprising: a cationic hydrogel; anionic cells; an electrode that (1) receives power from a direct current (DC) power source and (2) is adapted to bring the cationic hydrogel into contact with the anionic cells.

15. The system according to claim 14, wherein the anionic hydrogel is formed in a cylindrical tube.

16. The system according to claim 14, wherein the cationic hydrogel is formed in a strip.

17. An electrostatically adhered material, comprising: a covalently crosslinked gel electrostatically adhered to a physically crosslinked gel.

18. The covalently crosslinked gel contains divalent Ca ２＋ The electrostatically adhered material according to claim 17, comprising an alginate crosslinked by a cation.

19. The electrostatically adhered material according to claim 17, wherein the physically crosslinked gel comprises a mixture containing a nonionic monomer, a cationic monomer, a nonionic crosslinking agent, and crystalline nanoparticles having a high ionic surface area.

20. The electrostatically adhered material according to claim 19, wherein the nonionic monomer comprises acrylamide.

21. The electrostatically adhered material according to claim 19, wherein the cationic monomer comprises quaternized dimethylaminoethyl methacrylate.

22. The electrostatically adhered material according to claim 19, wherein the nonionic crosslinking agent comprises bis(acrylamide).

23. The electrostatically adhered material according to claim 19, wherein the crystalline nanoparticles having an ionic surface area comprise laponite nanoparticles.

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