Dry double-sided material for adhering wet tissue and devices

Abstract

Improved tissue adhesives The present invention provides a dry adhesive material, particularly in the form of a film or tape, for adhering one or more wet surfaces, comprising: (i) one or more hydrophilic polymers, (ii) one or more amine coupling groups, and (iii) one or more crosslinking agents. When placed in contact with the one or more wet surfaces, the dry adhesive material absorbs liquid from the one or more wet surfaces, swells to form temporary crosslinks with the wet surfaces, and forms covalent crosslinks with the one or more wet surfaces.

Description

[Technical Field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims the benefit of U.S. Provisional Application No. 62 / 845,976, filed May 10, 2019. All teachings of the above application are incorporated herein by reference.

[0002] Government support statement This invention was made with government support under Grant No. CMMI-1661627 awarded by the National Science Foundation (NSF). The government has certain rights in this invention.

[0003] The present invention relates generally to materials and methods for adhering tissue, and more particularly to dry-sided materials and methods for adhering wet tissue, particularly in the form of flexible double-sided tapes or films. According to preferred embodiments, the dry-sided materials include a combination of one or more hydrophilic polymers, one or more amine coupling groups, and one or more crosslinking agents. [Background technology]

[0004] It is generally understood that two dry surfaces can bond instantaneously when they come into contact with each other through intermolecular forces such as hydrogen bonding, electrostatic interactions, van der Waals interactions, etc. However, it is very difficult to form such instantaneous adhesion between wet surfaces, such as biological tissues, because water separates the molecules from the two surfaces, forming instantaneous interactions that prevent adhesion between the surfaces.

[0005] Gluing together wet surfaces, such as damaged tissue, or attaching devices to wet surfaces offers advantages over suturing or stapling. Existing tissue adhesives, primarily in the form of liquid or wet hydrogels, face many limitations, including weak bonding, poor biocompatibility, poor mechanical compatibility with tissue, and slow adhesion formation. In particular, as shown in Figures 1A-1B, such existing tissue adhesives rely on the diffusion of their molecules (e.g., monomers / macromers or polymers) into the polymer network of the tissue for bonding, which can take a significant amount of time and result in weak adhesion. The adhesion process is further hindered by the presence of interfacial liquid between the adhesive and the tissue.

[0006] For example, commercially available adhesives (e.g., fibrin glue, albumin-based adhesives, polyethylene glycol-based adhesives), nanoparticle solutions, and mussel-inspired adhesives exhibit slow adhesion formation (>1 min) and weak adhesion (20 J m) on wet surfaces. -2(See Vakalopoulos, K.A. et al. Mechanical strength and rheological properties of tissue adhesives with regard to colorectal anastomosis: an ex vivo study. Annals of Surgery 261, 323-331 (2015); Rose, S. et al. Nanoparticle solutions as adhesives for gels and biological tissues. Nature 505, 382-385 (2014); Lee, B.P., Messersmith, P.B., Israelachvili, J.N. & Waite, J.H. Mussel-inspired adhesives and coatings. Annual Review of Materials Research 41, 99-132 (2011)). Cyanoacrylate adhesives have been found to further suffer from high cytotoxicity and inflexibility after curing (see Annabi, N., Yue, K., Tamayol, A. & Khademhosseini, A. Elastic sealants for surgical applications. European Journal of Pharmaceutics and Biopharmaceutics 95, 27-39 (2015); Karp, J.M.A. Slick and Stretchable Surgical Adhesive. New England Journal of Medicine 377, 2092-2094 (2017)). -2Although adhesion of bulk hydrogels to tissues with interfacial toughness on the order of 100 μm has been reported, such hydrogels require prolonged pressure application, at least 10 to 30 minutes, to form an adhesion (see Li, J. et al., Tough adhesives for diverse wet surfaces. Science 357, 378-381 (2017)). Furthermore, such bulk hydrogel adhesives can only hold tissues together (see Figure 1B) and cannot achieve adhesion directly between tissue surfaces. In other words, the bulk hydrogel must be present between two tissue surfaces to hold them together. Therefore, removing the hydrogel results in separation of the tissue surfaces.

[0007] Thus, the diffusion-based mechanisms and resulting limitations of existing tissue adhesives have significantly hindered their success and range of applications. Given the great potential of tissue adhesives, improvements are greatly needed. Summary of the Invention

[0008] According to one aspect, the present invention provides a dry adhesive material for adhering one or more wet surfaces, the dry adhesive material comprising: (i) one or more hydrophilic polymers; (ii) one or more amine coupling groups; and (iii) one or more crosslinkers. The dry adhesive material is in the form of a film or tape having an upper surface and a lower surface. The dry adhesive material has a liquid content such that, upon placing one or more of the upper and / or lower surfaces of the dry adhesive material in contact with one or more wet surfaces, the dry adhesive material absorbs liquid from the one or more wet surfaces, swells, and forms temporary crosslinks between the dry adhesive material and the wet surfaces, and forms covalent crosslinks between the one or more amine coupling groups and the one or more wet surfaces.

[0009] Embodiments according to this aspect may include one or more of the following features: (i) the one or more hydrophilic polymers may be selected from polyacrylic acid, polyacrylamide, polyvinyl alcohol, polyhydroxyethyl methacrylate, polyethylene glycol, polyvinylpyrrolidone, polystyrene sulfonate, casein, albumin, gelatin, collagen, chitosan, hyaluronic acid, alginic acid, oxidized alginate, pectin, and combinations thereof; (ii) the one or more amine coupling groups may be selected from N-hydroxysuccinimide esters, N-hydroxysulfosuccinimide esters, aldehydes, imide esters, epoxides, isocyanates, catechols, and combinations thereof; (iii) the one or more crosslinkers may be selected from gelatin methacrylate, hyaluronic acid methacrylate, oxidized methacrylic alginate, polycaprolactone diacrylate, N,N'-bis(acryloyl)cystamine, N,N'-methylenebis(acrylamide), polyethylene glycol diacrylate, polyethylene glycol dimethacrylate, and combinations thereof. The dry adhesive material may comprise poly(acrylic acid) crosslinked with biodegradable gelatin methacrylate grafted with N-hydroxysuccinimide esters and may further comprise one or more biodegradable biopolymers. The one or more biodegradable biopolymers may be selected from gelatin, chitosan, and combinations thereof. The negatively charged carboxylic acid groups in the poly(acrylic acid) grafted with N-hydroxysuccinimide esters promote liquid absorption and swelling of the dry adhesive material, and can further form intermolecular bonds with one or more wet tissue surfaces within less than 60 seconds after contact between the dry adhesive material and one or more wet surfaces. The N-hydroxysuccinimide esters grafted in the poly(acrylic acid) can form covalent bonds with primary amine groups present on one or more wet surfaces. After covalent crosslinks are formed between the one or more amine coupling groups and one or more wet surfaces, the swollen dry adhesive material can be converted into a hydrogel layer. The hydrogel has a hydrogel resistance of at least 1,000 J / m. -2The dry adhesive material may have a fracture toughness of 1000 . The dry adhesive material may be in the form of a flat sheet, a perforated sheet, a double-sided tape or film, and a perforated double-sided tape or film. The dry adhesive material may have an upper surface and a lower surface and may further include one or more backing material layers disposed on at least one of the upper and lower surfaces. The backing material may be a removable backing material made of polyethylene, hydrophobic polymer-coated paper, poly(methyl methacrylate), a hydrophobic polymer film, or a combination thereof. The backing material may also be a non-removable material layer made of a silicone elastomer, a thermoplastic polyurethane, a hydrogel, a biocompatible material that is non-adhesive to wet tissue, or a combination thereof. The dry adhesive material may further include one or more engineering solids and / or devices adhered to one or more surfaces of the dry adhesive material. The one or more engineering solids may be selected from hydrogel, silicon, titanium, polydimethylsiloxane, polyimide, polycarbonate, and a combination thereof. The dry adhesive material may be biodegradable. (i) one or more polymers and / or (iii) one or more crosslinkers may be selected to modify biodegradability characteristics.

[0010] According to another aspect, the present invention provides a therapeutic agent delivery device for attachment to one or more wet tissue surfaces and for releasing one or more therapeutic agents to a target site, the therapeutic agent delivery device comprising: (i) a dry adhesive material having an upper surface and a lower surface; and (ii) one or more therapeutic agent-loaded patches disposed on one or more of the upper and lower surfaces of the dry adhesive material. The dry adhesive material layer comprises one or more hydrophilic polymers, one or more amine coupling groups, and one or more crosslinking agents, wherein the dry adhesive material is in the form of a film or tape having an upper surface and a lower surface. Further, the dry adhesive material has a liquid content such that, upon placing one or more of the upper and / or lower surfaces of the dry adhesive material in contact with one or more wet surfaces, the dry adhesive material absorbs liquid from the one or more wet surfaces, swells, and forms temporary crosslinks between the dry adhesive material and the wet surfaces, and forms covalent crosslinks between the one or more amine coupling groups and the one or more wet surfaces.

[0011] According to another aspect, the present invention provides a device for providing electrical measurement of cardiac motion, the device including: (i) a dry adhesive material layer having an upper surface and a lower surface; and (ii) one or more strain sensors disposed on one or more of the upper and lower surfaces of the dry adhesive material. The dry adhesive material layer includes one or more hydrophilic polymers, one or more amine coupling groups, and one or more crosslinkers, the dry adhesive material being in the form of a film or tape having an upper surface and a lower surface. The dry adhesive material has a liquid content such that, upon placing one or more of the upper and / or lower surfaces of the dry adhesive material in contact with one or more wet surfaces, the dry adhesive material absorbs liquid from the one or more wet surfaces, swells, and forms temporary crosslinks between the dry adhesive material and the wet surfaces, and forms covalent crosslinks between the one or more amine coupling groups and the one or more wet surfaces.

[0012] According to another aspect, the present invention provides a method of adhering wet tissues together, the method comprising providing a dry adhesive material comprising (i) one or more hydrophilic polymers, (ii) one or more amine coupling groups, and (iii) one or more crosslinking agents; placing the dry adhesive material in contact with one or more wet tissue surfaces; causing the dry adhesive material to absorb liquid from the one or more wet surfaces, thereby swelling the adhesive material; causing instantaneous crosslinking by intermolecular interactions between the adhesive material and the one or more wet surfaces; and causing rapid covalent crosslinking between the adhesive material and the one or more wet surfaces.

[0013] According to another aspect, the present invention provides a method for delivering a therapeutic agent to a target site, the method comprising: providing a therapeutic agent delivery device comprising: (i) a dry adhesive material comprising one or more hydrophilic polymers, one or more amine coupling groups, and one or more crosslinking agents; and (ii) one or more therapeutic agent-loaded patches disposed on one or more of a top surface and a bottom surface of the dry adhesive material; placing one or more of the top surface and the bottom surface of the dry adhesive material in contact with one or more wet tissue surfaces; causing the dry adhesive material to absorb liquid from the one or more wet surfaces, thereby swelling the adhesive material; causing instantaneous crosslinking by intermolecular interactions between the adhesive material and the one or more wet surfaces; causing rapid covalent crosslinking between the adhesive material and the one or more wet surfaces; and releasing the therapeutic agent into the one or more therapeutic agent-loaded patches and delivering it to the target site.

[0014] According to another aspect, the present invention provides a method for providing electrical measurement of cardiac motion, the method including providing an electrical measurement device including: (i) a dry adhesive material layer having an upper surface and a lower surface, the dry adhesive material layer including one or more hydrophilic polymers, one or more amine coupling groups, and one or more crosslinkers; and (ii) one or more strain sensors disposed on one or more of the upper and lower surfaces of the dry adhesive material; placing one or more of the upper and lower surfaces of the dry adhesive material in contact with one or more wet tissue surfaces; causing the dry adhesive material to absorb liquid from the one or more wet surfaces, thereby swelling the adhesive material; causing instantaneous crosslinking by intermolecular interactions between the adhesive material and the one or more wet surfaces; causing rapid covalent crosslinking between the adhesive material and the one or more wet surfaces; and causing the one or more strain sensors to electrically measure cardiac motion.

[0015] Other systems, methods, and features of the invention will be or become apparent to one with skill in the art upon examination of the following figures and detailed description. It is intended that all such additional systems, methods, and features be included within this specification, be within the scope of the invention, and be protected by the accompanying claims. [Brief explanation of the drawings]

[0016] The accompanying drawings are included to provide a further understanding of the invention, and are incorporated in and constitute a part of this specification. The components in the drawings are not necessarily to scale, emphasis instead being placed upon clearly illustrating the principles of the invention. The drawings illustrate embodiments of the invention and, together with the description, serve to explain the principles of the invention.

[0017] [Figure 1A-C] 1A and 1B are schematic illustrations of tissue adhesives according to the prior art, where FIG. 1A depicts an existing tissue adhesive in liquid form, FIG. 1B depicts an existing tissue adhesive in the form of a wet hydrogel, and FIG. 1C depicts a schematic illustration of the mechanism of existing tissue adhesives that rely on the diffusion of monomers or polymers into the polymer network of the tissue for bonding. [Figure 2A-B] 2A schematically illustrates a dry double-sided material in the form of a tape according to an embodiment of the present invention, where FIG. 2A depicts the placement of a dry double-sided tape (hereinafter sometimes referred to as "DST") between two wet tissues according to an embodiment of the present invention (left), and the attachment of a hydrogel and / or various other materials to the wet tissue surface using a DST according to an embodiment of the present invention (right), and FIG. 2B depicts the dry crosslinking mechanism of a DST according to an embodiment of the present invention, which integrates drying of the interfacial liquid (e.g., water) due to swelling of the DST, instantaneous temporary crosslinking, and rapid covalent crosslinking. [Figure 3A-E] 3A schematically illustrates various features of DST according to embodiments of the present invention. FIG. 3A depicts various shapes of DST based on high manufacturing flexibility. FIG. 3B illustrates DST stained with red food dye for visualization in the swollen state (due to water absorption) and stretched to 9 and 16 times its original unstretched length. FIG. 3C shows the nominal stress versus elongation curve for the DST in FIG. 3B stretched to more than 16 times its original unstretched length. FIG. 3D is a photograph (left) and a graph (right) of the in vitro biocompatibility of DST based on a Live / Dead assay of mouse embryonic fibroblasts (mEFs) after 24 hours of culture. FIG. 3E graphically illustrates the in vitro biodegradation of gelatin-based DST in DPBS using collagenase. [Figure 4A-B] Photographs of a DST according to one embodiment of the present invention, where FIG. 4A illustrates the DST initially prepared in a dry state in the form of a thin tape (approximately 100 μm dry thickness) and FIG. 4B illustrates the use of the DST together with a backing material. [Figure 5] 1A-1C schematically illustrate the application of DST according to an embodiment of the present invention, where the DST provides adhesion between two wet surfaces. [Figure 6A-D]The properties and adhesive performance of chitosan-based DST according to embodiments of the present invention are graphically illustrated: FIG. 6A shows the nominal stress versus elongation curve for swollen chitosan-based DST; FIG. 6B shows the clamp-to-clamp force versus displacement curves for unnotched and notched chitosan-based DST for fracture toughness measurements; FIG. 6C shows the interfacial toughness and shear and tensile strength between wet porcine skin adhered with chitosan-based DST; and FIG. 6D shows the in vitro biodegradation of chitosan-based DST in Dulbecco's PBS (DPBS) using collagenase, lysozyme, and NAGase. [Figure 7] 1 graphically illustrates fracture toughness for a gelatin-based DST, according to one embodiment of the present invention. [Figure 8A-C] 8A and 8B show schematic diagrams illustrating mechanical test setups for evaluating the adhesive performance of DSTs according to embodiments of the present invention, where FIG. 8A shows the test setup for measuring interfacial toughness based on a standard 180-degree peel test (ASTM F2256), FIG. 8B shows the test setup for measuring shear strength based on a standard lap shear test (ASTM F2255), and FIG. 8C shows the test setup for measuring tensile strength based on a standard tensile test (ASTM F2258). [Figure 9A-E] The adhesive performance of DST according to embodiments of the present invention is illustrated graphically. Figure 9A shows the interfacial toughness and shear and tensile strength versus time after compression for wet porcine skin adhered with DST containing an NHS ester. Figure 9B shows the interfacial toughness and shear and tensile strength versus time after compression for wet porcine skin adhered with DST containing an NHS ester. Figure 9C shows the interfacial toughness and shear and tensile strength versus time after compression for wet porcine skin adhered with DST without an NHS ester. Figure 9D shows the interfacial toughness and shear and tensile strength versus time after compression for wet porcine skin adhered with DST without an NHS ester. Figure 9E shows a comparison of adhesive performance between DST and a commercially available tissue adhesive. Values in Figures 9A-E represent the mean and standard deviation (n = 3-5). [Figure 10]Illustrating DST between adhered tissues according to an embodiment of the present invention, FIG. 10A shows darkfield and brightfield images overlaid with green fluorescent microscope images of pig skin adhered with DST immediately after application, and FIG. 10B shows darkfield and brightfield images overlaid with green fluorescent microscope images of pig skin adhered with DST 24 hours after application. [Figure 11] 1 is a graph showing the thickness dependence of adhesive performance of a DST according to one embodiment of the present invention. Values represent the mean and standard deviation (n=3-5). [Figure 12] 1 is a graphical comparison of adhesive performance between a DST according to one embodiment of the present invention and several existing tissue adhesives. Values represent the mean and standard deviation (n=3-5). [Figures 13A-N] Illustrating instantaneous, strong adhesion of various wet tissues and engineered solids by DST according to embodiments of the present invention, FIG. 13A graphically illustrates the interfacial toughness and shear and tensile strength between various tissues bonded by DST, FIGS. 13B-G show photographs of various tissues bonded by DST, FIG. 13H graphically illustrates the interfacial toughness and shear and tensile strength between pig skin and various engineered solids by DST, and FIGS. 13I-N show photographs of pig skin and various engineered solids bonded by DST. [Figure 14A-C] Representative curves for mechanical testing of various tissues bonded with DST according to embodiments of the present invention are graphically illustrated: FIG. 14A shows the force / width vs. displacement curve for 180-degree peel testing of various tissues bonded with DST; FIG. 14B shows the shear stress vs. displacement curve for lap shear testing of various tissues bonded with DST; and FIG. 14C shows the tensile stress vs. displacement curve for tensile testing of various tissues bonded with DST. [Figure 15A-C]Surface functionalization of engineered solids is depicted schematically in Figure 1. Figure 5A is a schematic diagram of primary amine functionalization of silicon, titanium, and PDMS and subsequent covalent bonding between the primary amine groups and NHS ester groups in DST according to embodiments of the present invention; Figure 15B is a schematic diagram of primary amine functionalization of polycarbonate and subsequent covalent bonding between the primary amine groups and NHS ester groups in DST according to embodiments of the present invention; and Figure 15C shows a schematic diagram of primary amine functionalization of polyimide and subsequent covalent bonding between the primary amine groups and NHS ester groups in DST according to embodiments of the present invention. [Figures 16A-C] Representative curves from mechanical testing of pig skin and various engineered solids bonded with DST according to embodiments of the present invention are graphically illustrated: FIG. 16A shows the force / width vs. displacement curves for 180-degree peel tests and 90-degree peel tests (for silicone) of pig skin and various engineered solids bonded with DST; FIG. 16B shows the shear stress vs. displacement curves for lap shear tests of pig skin and various engineered solids bonded with DST; and FIG. 16C shows the tensile stress vs. displacement curves for tensile tests of pig skin and various engineered solids bonded with DST. [Figures 17A-D] 17A and 17B illustrate sealing a lacerated porcine trachea with air leakage, FIG. 17B illustrates sealing a lacerated porcine lung lobe with air leakage, FIG. 17C illustrates sealing a porcine stomach with fluid leakage, and FIG. 17D illustrates sealing a damaged porcine small intestine by forming an anastomosis with DST according to embodiments of the present invention. [Figures 18A-D]18A and 18B schematically illustrate the integration of various devices into wet tissue enabled by DST according to embodiments of the present invention: FIG. 18A illustrates the adhesion of a drug-loaded patch to an incised, beating porcine heart; FIG. 18B graphically illustrates the diffusion of a simulated drug (fluorescein) from the DST-adhered drug patch of FIG. 18A into cardiac tissue over time; FIG. 18C illustrates the adhesion of a DST-strain sensor hybrid to a beating porcine heart; and FIG. 18D illustrates the normalized electrical resistance of the DST-adhered strain sensor of FIG. 18C over time to measure deformation of the beating heart. [Figure 19] 1A-1C illustrate schematically the fabrication of a DST-strain sensor hybrid according to an embodiment of the present invention. [Figure 20] 1 graphically illustrates the adhesive performance of DSTs according to embodiments of the present invention during long-term storage up to two weeks. Values represent the mean and standard deviation (n=3-5). DETAILED DESCRIPTION OF THE INVENTION

[0018] The following definitions are useful in interpreting terms applied to features of the embodiments disclosed herein and are meant only to define elements within the present disclosure.

[0019] As used herein, the term "dry" when describing the double-sided material of the present invention refers to a material that has a lower than equilibrium moisture content than the material being used. Thus, when the dry double-sided material of the present invention is placed in contact with wet tissue or other wet or moistened (e.g., saline-moistened) surface to which it adheres, the material will absorb water, saline, moisture, and physiological fluids, such as plasma, interstitial fluid, lymphatic fluid, cerebrospinal fluid, and gastrointestinal fluid, from the moist or moistened surface. Generally, a dry adhesive material will have a liquid content of less than about 50% by weight, based on the total weight of the dry adhesive material.

[0020] As used herein, the term "absorb," when describing the mechanism by which a dry double-sided material absorbs water, saline, moisture, and physiological fluids such as plasma, interstitial fluid, lymphatic fluid, cerebrospinal fluid, and gastrointestinal fluid from a wet surface with which it is placed in contact, refers to atoms or molecules from the liquid on the wet surface crossing the surface of the dry double-sided material.

[0021] As used herein, the terms "tape" or "film" when describing the double-sided materials of the present invention refer to structures that have a relatively large area compared to their thickness. Such structures provide flexibility.

[0022] As used herein, the term "double-sided" when describing the adhesive material of the present invention refers to an adhesive tape or film that provides adhesive properties on both the top and bottom adhesive surfaces. It should be noted that while the adhesive material may be referred to as double-sided, the adhesive properties of one or both sides of the adhesive material may be utilized in a given application. For example, it may be desirable to utilize the adhesive properties of only one side of the adhesive material during use, with the adhesive properties of the second side being rendered inaccessible, for example, by maintaining a material layer or backing material disposed on the second side during use to block the adhesive properties of that second side. In such an example, the material layer or backing material may be initially disposed on both the first and second sides, with the material layer or backing material being removed from only the first side prior to application, allowing use of only the adhesive properties of the first side.

[0023] As used herein, the term "wet tissue" refers to biological tissue that contains or is covered by an aqueous medium, including water, saline, moisture, and physiological fluids such as plasma, interstitial fluid, lymphatic fluid, cerebrospinal fluid, and gastrointestinal fluid.

[0024] As used herein, the term "instantaneous" when used to describe instantaneous, temporary crosslinking between a double-sided material and one or more wet surfaces refers to a time that elapses from the moment the double-sided material contacts one or more wet surfaces of greater than zero seconds up to or within about 1 minute, more preferably about 50 seconds or less, more preferably about 40 seconds or less, more preferably about 30 seconds or less, more preferably about 20 seconds or less, more preferably about 15 seconds or less, more preferably about 10 seconds or less, more preferably about 9 seconds or less, more preferably about 8 seconds or less, more preferably about 7 seconds or less, more preferably about 6 seconds or less, more preferably about 5 seconds or less.

[0025] As used herein, the term "temporary" when used to describe instantaneous temporary crosslinks between a double-sided material and one or more wet surfaces refers to a range of times ranging from the time that the instantaneous temporary crosslinks are formed to a sufficiently long time that the temporary crosslinks have been formed, such as 24 hours or more.

[0026] As used herein, "fast" or "rapid" when used to describe rapid covalent crosslinking between a double-sided material and one or more wet surfaces refers to a time that elapses from the moment the double-sided material contacts one or more wet surfaces of from greater than zero seconds up to and including 5 minutes, more preferably about 4.5 minutes or less, more preferably about 4 minutes or less, more preferably about 3.5 minutes or less, more preferably about 3 minutes or less, more preferably about 2.5 minutes or less, more preferably about 2 minutes or less, more preferably about 1.5 minutes or less, more preferably about 1 minute or less.

[0027] As used herein, "swelling," when used to describe the absorption and swelling of a dry adhesive material upon contact with one or more wet surfaces, generally refers to an increase in size by the dry adhesive material, which is generally in the form of a tape or film and becomes thicker upon taking up liquid.

[0028] As used herein, "biodegradable" when used to describe a dry adhesive material refers to the partial or total degradation and / or subsequent removal of the implanted material within a living animal by endogenous enzymes and / or water within the animal.

[0029] As used herein, "engineered solids" refers to solid materials that are not living tissue, including synthetic materials such as plastics, metals, glasses, ceramics, and elastomers, as well as biological materials processed from natural sources.

[0030] The present invention generally provides an adhesive material that can adhere to wet surfaces and can bond wet surfaces, particularly wet tissue surfaces, together. The adhesive material is a dry adhesive material that is engineered to provide a new dry crosslinking mechanism for instantly and strongly bonding wet surfaces. In particular, the dry adhesive material is engineered so that when placed in contact with one or more wet surfaces, it absorbs liquid from the one or more wet surfaces, thereby causing the adhesive material to swell. This absorption of interfacial liquid allows for instant crosslinking via intermolecular interactions between the adhesive material and the one or more wet surfaces, followed by rapid covalent crosslinking between the adhesive material and the one or more wet surfaces (see Figures 2A-B).

[0031] The dry adhesive material of the present invention thereby overcomes the above-mentioned limitations of existing adhesive materials (as further depicted in Figures 1A-C). Rather than relying on molecular diffusion toward the tissue as required by existing adhesives, the dry adhesive material achieves instant, strong adhesion to wet surfaces through a synergistic combination of drying of interfacial liquids due to swelling of the dry adhesive material, instantaneous temporary crosslinking, and rapid covalent crosslinking between the adhesive material and one or more wet surfaces.

[0032] As further described below, ex vivo and in vitro models demonstrate that the dry adhesive material can form strong bonds between a variety of wet dynamic tissues (e.g., skin, tendon, stomach, muscle, heart, and liver) and engineered solids (e.g., hydrogel, silicone, titanium, polydimethylsiloxane, polyimide, and polycarbonate) within 5 seconds, with a force of approximately 1,150 Jm. -2 We demonstrate that this dry adhesive material can achieve interfacial toughness on the order of 100 kPa and shear and tensile strength on the order of 160 kPa, while still providing low shear modulus (approximately 10 kPa) and high stretchability (more than 10 times) similar to those found in living tissue, high biocompatibility, and controllable biodegradation. Thus, this dry adhesive material not only offers a new paradigm in wet adhesion, but also enables new opportunities in diverse applications such as tissue adhesives, bioscaffolds, drug delivery, and wearable and implantable devices.

[0033] Reference will now be made in detail to embodiments of the invention, examples of which are illustrated in the accompanying drawings. Wherever possible, the same reference numbers are used in the drawings and the description to refer to the same or like parts.

[0034] According to one aspect, the present invention provides an adhesive material comprising a combination of (i) one or more hydrophilic polymers, (ii) one or more amine coupling groups, and (iii) one or more crosslinkers. When the adhesive material is placed in contact with one or more wet surfaces, such as wet tissue, it absorbs liquid from the one or more wet surfaces and removes any interfacial liquid present between the adhesive material and the wet surface, in the form of a dry material. This liquid absorption causes the dry material to swell. The liquid absorption and swelling of the dry adhesive material provide instantaneous temporary crosslinking between the adhesive material (particularly carboxylic acid groups, hydroxyl groups, sulfonic acid groups, amine groups, and catechol groups in the adhesive) and the wet surface, and further allows rapid subsequent covalent bonding or crosslinking between one or more amine coupling groups (e.g., NHS ester groups, sulfo-NHS ester groups, aldehyde groups, imide ester groups, epoxide groups) and the one or more wet surfaces via amine groups naturally present on the one or more wet surfaces.

[0035] According to an embodiment of the present invention, (i) the one or more hydrophilic polymers are selected from any conventional hydrophilic polymer that absorbs water in a dry state, including, but not limited to, polyacrylic acid, polyacrylamide, polyvinyl alcohol, polyhydroxyethyl methacrylate, polyethylene glycol, polyvinylpyrrolidone, polystyrene sulfonate, casein, albumin, gelatin, collagen, chitosan, hyaluronic acid, alginic acid, oxidized alginate, pectin, and combinations thereof. Because the adhesive material can be used in a wide variety of biomedical applications, the polymers used in the present invention are preferably biocompatible (although non-biomedical applications do not necessarily require the use of exclusively biocompatible polymeric materials). According to a preferred embodiment, the one or more hydrophilic polymers contain one or more negatively charged groups, such as poly(acrylic acid), casein, albumin, and alginic acid, which impart moisture-wicking properties that are desirable for rapid absorption and removal of interfacial liquids from wet surfaces.

[0036] According to an embodiment of the present invention, (ii) the one or more amine coupling groups are selected from conventional amine coupling groups, including, but not limited to, N-hydroxysuccinimide esters, A-hydroxysulfosuccinimide esters, aldehydes, imide esters, epoxides, isocyanates, catechols, and combinations thereof. Because the adhesive material can be used in a wide variety of biomedical applications, the amine coupling groups used in the present invention are preferably biocompatible (although non-biomedical applications do not necessarily require the use of biocompatible amine coupling groups). Such amine coupling groups are configured such that one or more hydrophilic polymers can be grafted with the one or more amine coupling groups, which then form covalent crosslinks with the wet surface to which the adhesive material is applied.

[0037] According to embodiments of the present invention, (iii) the one or more crosslinkers are selected from conventional crosslinkers, including, but not limited to, gelatin methacrylate, hyaluronic acid methacrylate, oxidized methacrylic alginate, polycaprolactone diacrylate, N,N'-bis(acryloyl)cystamine, N,N'-methylenebis(acrylamide), polyethylene glycol diacrylate, polyethylene glycol dimethacrylate, and combinations thereof. Because the adhesive materials can be used in a wide variety of biomedical applications, the crosslinkers used in the present invention are preferably biocompatible (although for non-biomedical applications, it is not necessary to utilize only biocompatible crosslinkers).

[0038] According to a preferred embodiment, the adhesive material is a gelatin-based adhesive material. The gelatin-based adhesive material according to embodiments of the present invention, in its as-prepared (before drying) form, preferably comprises about 20 wt % to about 40 wt %, more preferably about 25 wt % to about 35 wt %, even more preferably about 30 wt % polyacrylic acid, about 5 wt % to about 15 wt %, more preferably about 10 wt % gelatin, about 0.5 wt % to about 1.5 wt % PAAc-NHS ester, more preferably about 1 wt % PAAc-NHS ester, about 0.05 wt % to about 0.15 wt % gelatin methacrylate, more preferably about 0.1 wt % gelatin methacrylate, and the balance deionized water.

[0039] According to an exemplary embodiment, the gelatin-based DST, in its as-prepared (pre-dried) form, comprises about 30 wt. % polyacrylic acid, about 10 wt. % gelatin, about 1 wt. % PAAc-NHS ester, about 0.1 wt. % gelatin methacrylate, and the balance deionized water.

[0040] According to a preferred embodiment, the adhesive material is a chitosan-based adhesive material. The chitosan-based adhesive material according to embodiments of the present invention, in its as-prepared (before drying) form, preferably comprises about 20 wt % to about 40 wt %, more preferably about 25 wt % to about 35 wt %, even more preferably about 30 wt % polyacrylic acid, about 1 wt % to about 3 wt %, more preferably about 2 wt % chitosan, about 0.5 wt % to about 1.5 wt % PAAc-NHS ester, more preferably about 1 wt % PAAc-NHS ester, about 0.05 wt % to about 0.15 wt % gelatin methacrylate, more preferably about 0.1 wt % gelatin methacrylate, and the balance deionized water.

[0041] According to an exemplary embodiment, the chitosan-based DST, in its as-prepared (pre-dried) form, comprises about 30 wt. % poly(acrylic acid), about 2 wt. % chitosan, about 1 wt. % PAAc-NHS ester, about 0.1 wt. % gelatin methacrylate, and the balance deionized water.

[0042] According to a preferred embodiment, the adhesive material, in its as-prepared (pre-dried) form, comprises: (i) from about 20 w / w% to about 55 w / w% of one or more hydrophilic polymers; (ii) from about 0.5 w / w% to about 1.5 w / w% of one or more amine coupling groups; and (iii) from about 0.05 w / w% to about 0.15 w / w% of one or more crosslinking agents, with the balance being deionized water.

[0043] In a specific embodiment of the proposed mechanism, the dry adhesive material comprises (i) poly(acrylic acid), (ii) grafted with an N-hydroxysuccinimide ester (PAAc-co-NHS ester), and (iii) crosslinked with biodegradable gelatin methacrylate, and (i) one or more biodegradable biopolymers (e.g., gelatin or chitosan). This dry adhesive material is preferably in the form of a film or tape. The negatively charged carboxylic acid groups in the PAAc-co-NHS ester promote rapid swelling of the dry adhesive material, allowing it to dry quickly on the wet surfaces of various tissues. At the same time, the carboxylic acid groups in the PAAc-NHS ester form instantaneous intermolecular bonds (e.g., hydrogen bonds and electrostatic interactions) with the tissue surface under brief (e.g., less than 5 seconds) gentle pressure (e.g., 1 kPa pressure) (Figures 2B and 5). The grafted NHS ester groups in the PAAc-co-NHS ester further form covalent bonds with primary amine groups present on various tissues within minutes without further pressure, providing strong, long-term adhesion (Figures 2B and 5). After adhering to the tissue surface, the swollen, dried adhesive material exhibits a resistance of 1,000 J / m based on the double network structure formed between the stretchable PAAc-co-NHS ester network and the biopolymer network. -2 This results in a thin layer of hydrogel with ultra-high fracture toughness (Figures 6 and 7).

[0044] According to an embodiment of the present invention, the adhesive material has an upper surface and a lower surface. Preferably, the adhesive material is generally in the form of a sheet, tape, or film having an upper surface and a lower surface (all of which may be perforated, partially perforated, or non-perforated). In a preferred embodiment, the adhesive material includes a removable backing layer or an integral (non-removable) material layer disposed on one or more adhesive surfaces. For example, one or more removable backing material layers can be disposed on one or more adhesive surfaces to, among other things, aid in handling the adhesive material and provide protection against moisture. Optionally, one or more integral material layers can be disposed on one or more adhesive surfaces to, among other things, provide one or more non-adhesive sides or side portions for single-sided or partial-sided use.

[0045] For example, a removable backing layer may be disposed over the entire upper surface of the adhesive material, while an integral material layer may be disposed over the entire lower surface. Thus, only the adhesive properties of the upper surface of the adhesive material can be utilized in application by removing the backing layer before use. Similarly, removable backing layers may be disposed on both the upper and lower surfaces, thereby allowing the adhesive properties of both the upper and lower surfaces of the adhesive material to be utilized in application by removing the backing layers before use. In some applications, it may be desirable for the adhesive material to have a combination of one or more removable backing layers disposed on a single surface (e.g., upper surface) and one or more integral material layers also disposed on the same single surface (e.g., upper surface), thereby allowing the adhesive properties of only the portions of the surface (e.g., upper surface) where the removable backing layer is disposed to be utilized by removing the backing layer from those portions, while the adhesive properties of the portions of the surface (e.g., upper surface) where the integral backing material layer is disposed are not utilized. For example, a unitary layer of material may be disposed on a central portion of the top surface of the adhesive material, while one or more removable backing layers may be disposed on portions of the top surface surrounding the central portion, providing a configuration in which the top surface of the adhesive material will adhere to wet surfaces along the outer portions or periphery of the adhesive material upon removal of the removable backing layer, while the central portion of the adhesive material will not adhere due to the unremoved unitary layer of material.

[0046] The integral material layer or removable backing layer is provided to prevent adhesion of the material prior to the intended use time. Therefore, the removable backing layer or integral material layer blocks the adhesive properties of the material. The integral material layer or removable backing layer is provided to prevent adhesion of the material to non-target tissue during and after application to wet tissue. Therefore, the integral material layer or removable backing layer is non-adhesive to wet biological tissue. The removable backing layer or integral material layer can be placed directly on one or more surfaces of the adhesive material (i.e., without anything interposed therebetween). In some embodiments, a layer, glue, or other substance used to attach the materials together is placed between one or more surfaces of the adhesive material and the integral material layer or removable backing layer. The removable backing layer or integral material layer can be made of any material that prevents the adhesive material from adhering to wet surfaces. The integral material layer or removable backing layer can be made of any material that is non-adhesive to wet biological tissue. In particular, as described herein, the adhesive material is in the form of a dry material that, when placed in contact with a wet surface, absorbs liquid from the wet surface, causing the dry material to swell. This liquid absorption and swelling of the dry adhesive material provides an instantaneous, temporary crosslink between the adhesive material and the wet surface, and further allows for rapid subsequent covalent bonding or crosslinking between the adhesive material and the wet surface. Therefore, the removable backing layer or integral material layer can generally be made of any material that prevents liquid from contacting the surface of the adhesive material. Therefore, the integral material layer or backing material layer can generally be made of any material that does not form an adhesive interface with wet biological tissue. Due to the use of the adhesive material of the present invention, the removable backing layer or integral material layer should be made of a biocompatible material. According to an embodiment of the present invention, the removable backing layer is made of polyethylene or any hydrophobic polymer-coated paper and poly(methyl methacrylate) or any hydrophobic polymer film.Such a removable backing layer can be directly adhered to one or more surfaces of the adhesive material, or can be adhered together with a layer of other adhesive, such as a glue or acrylic adhesive. According to embodiments of the present invention, the one-piece material layer is fabricated from a silicone elastomer, a thermoplastic polyurethane, a hydrogel, or any other biocompatible material that does not adhere to wet tissue. Such a one-piece material layer can be directly adhered to one or more surfaces of the adhesive material.

[0047] To achieve instant and strong adhesion of the strain sensor, the DST-strain sensor hybrid was attached to a beating pig heart after removing the backing. The strain sensor attached to the beating pig heart was kept at room temperature for 12 hours and then connected to a digital multimeter to monitor the deformation of the beating heart.

[0048] As shown in Figure 5, adhesive materials in the form of dry double-sided tape (DST) can be applied directly to the target wet tissue surface after removing the removable or backing material layer provided on one or more surfaces of the DST without any other preparation process (Steps 3-4). Upon contact with the wet surface, the dry adhesive material rapidly swells by absorbing the interfacial liquid (e.g., water) and dries the wet surface (Step 5). At the same time, the carboxylic acid groups in the DST instantly form intermolecular bonds with the tissue surface (Step 6), followed by rapid covalent bond formation between the NHS ester groups (amine coupling groups) in the adhesive and the amine groups on the tissue (Step 7).

[0049] After adhering to the tissue, the swollen adhesive material (DST) becomes a thin layer of hydrogel, thereby providing a strong bond between the surfaces (step 8).

[0050] As shown graphically in Figures 6A-D, this embodiment of the chitosan-based dry adhesive material exhibits excellent properties and adhesive performance. As shown in Figure 6A, the nominal stress vs. elongation curve for the swollen chitosan-based DST indicates that the chitosan-based DST also exhibits a low shear modulus (approximately 30 kPa) and high stretchability (>6-fold), comparable to soft biological tissue. The chitosan-based dry adhesive material exhibited a shear modulus of 1,700 Jm², as depicted in the force vs. displacement curves between clamps for the unnotched and notched chitosan-based DST in Figure 6B. -2 The results showed excellent fracture toughness measurements of 100%. Furthermore, as depicted in Figure 6C, excellent interfacial toughness and shear and tensile strength were measured between wet porcine skin adhered with the chitosan-based material of the present invention. Figure 6D further demonstrates that desirable in vitro biodegradation of the chitosan-based dry adhesive material in DPBS using collagenase, lysozyme, and NAGase was achieved. The values in Figures 6C-D represent the mean and standard deviation (n = 3-5).

[0051] 7 further illustrates in a graph the fracture toughness of this embodiment of the gelatin-based dry adhesive material. As shown, the force versus displacement between the clamps for the unnotched and notched gelatin-based adhesive material for the fracture toughness measurement was 1,120 Jm -2 The fracture toughness of the gelatin-based adhesive material was measured. For the fracture toughness measurements in Figures 6B and 7, F represents the force applied to the sample, L represents the displacement between the clamps, and L c denotes the critical displacement between the clamps at which the notched gel breaks, a0 is the width of the unnotched sample, b0 is the thickness of the unnotched sample, and U(L c )teeth,

number

[0052] The high processability of the dry adhesive material allows for flexible fabrication into various shapes, such as flat sheets, perforated sheets, and tape-like rolls, to meet various needs (see Figure 3A). The dry adhesive material also has several favorable properties for biological applications. In particular, the swollen dry adhesive material exhibits a shear modulus of approximately 2.5 to approximately 5 kPa and an extensibility greater than 16 times its original unswollen length, mechanically matching these properties of soft tissue (Figure 3B-C). Based on its composition, the dry adhesive material is highly biocompatible and biodegradable (Figure 3D-E). The biocompatibility of the dry adhesive material-conditioned medium is the same as that of control tissue culture medium (Dulbecco's Modified Eagle's Medium (DMEM)) and shows no observable in vitro cytotoxicity to mouse embryonic fibroblasts (mEFs) after 24 hours of culture (Figure 3D). The values in Figure 3D-E represent the mean and standard deviation (n = 3-5).

[0053] Furthermore, the (i) one or more polymers and / or (iii) one or more crosslinkers utilized in the present dry double-sided materials can be selected to provide desired biodegradable properties. For example, as shown in Figures 3E and 6D, the crosslinker for PAAc-co-NHS ester (i.e., gelatin methacrylate) and the biopolymer in the adhesive (i.e., gelatin or chitosan) are biodegradable at various rates by endogenous enzymes (e.g., collagenase, lysozyme, NAGase). As shown, gelatin typically degrades much faster than chitosan under physiological conditions. Therefore, the biodegradation rate of the adhesive can be controlled as desired by adjusting its composition, from one week (for gelatin-based DSTs) to several months (for chitosan-based DSTs), as shown in Figures 3E and 6D.

[0054] To evaluate the adhesive performance of the dry adhesive, three different mechanical tests were performed according to tissue adhesive testing standards (ASTM F2256 for peel test, ASTM F2255 for lap shear test, and ASTM F2258 for tensile test) to measure interfacial toughness (by peel test), shear strength (by lap shear test), and tensile strength (by tensile test), respectively (Figures 8A-C). In these tests, wet porcine skin was selected as a model tissue for adhesive performance evaluation because of its close similarity to human skin and its mechanical robustness. The adhesive material of the present invention exhibited a high strength (710 Jm) between wet porcine skin after contact with gentle pressure for less than 5 seconds. -2 The adhesive material can establish fast bonds (e.g., maximum bond strength can be achieved within 30-60 seconds or even less) that are strong (over 120 kPa shear and tensile strength) and have interfacial toughness exceeding 100 kPa (Figure 9A). Tissues bonded by the adhesive material exhibit stable, long-term, strong bonds (over 24 hours after initial gentle compression for 5 seconds), as shown in Figures 9B and 10, with negligible reduction in measured interfacial toughness and strength. In particular, Figures 10A-B illustrate a dry adhesive material in the form of a double-sided tape (DST) between bonded tissues according to an embodiment of the present invention. Figure 10A shows dark-field and bright-field images overlaid with green fluorescent microscopy images of porcine skin bonded by the DST immediately after application, and Figure 10B shows the image 24 hours after application. As shown, the DST further expanded after 24 hours by absorbing moisture from the wet tissue while maintaining a strong and conformal bond between two wet porcine skins.

[0055] The adhesive performance of the dry adhesive material is affected by the thickness of the dry adhesive material. As shown in the graph of FIG. 11, thicker dry adhesive materials have an adhesive strength of about 800 J / m when the thickness of the as-prepared dry adhesive material is greater than 210 μm. -2 It tends to provide relatively high interfacial toughness between wet porcine skin until a plateau value of

[0056] The dry adhesive material of the present invention forms excellent adhesion to wet tissues based on a synergistic combination of drying of the interfacial liquid due to swelling of the dry adhesive material, instantaneous temporary crosslinking, and rapid covalent crosslinking. Therefore, the components of the dry adhesive material that provide drying, swelling, instantaneous temporary crosslinking, and rapid covalent crosslinking are important in providing adhesive properties. For example, the effect of instantaneous intermolecular bonding followed by rapid covalent bonding on the adhesive performance of the dry adhesive material was tested by analyzing the adhesive performance of a dry adhesive material formed without the grafted NHS ester in PAAc. This composition did not form covalent bonds with wet tissues, as shown in Figures 9C-D. The dry adhesive material without the NHS ester instantly became strong (500 Jm) when applied between wet porcine skin. -2 Although the dry adhesive can provide strong (>80 kPa shear and tensile strength) and stable adhesion (>80 kPa interfacial toughness) (Figure 9C), the adhesive performance shows significant deterioration over time (Figure 9D). This deterioration is believed to be due to the unstable and temporary nature of the instantaneous intermolecular bonds in a wet environment. Therefore, the dry adhesive material can provide stable and strong adhesion to wet surfaces through the inclusion and use of materials that provide both instantaneous temporary adhesion and subsequent rapid covalent bonding (Figure 2B).

[0057] The dry adhesive material of the present invention further provides superior adhesive performance compared to existing tissue adhesives, including commercially available cyanoacrylate adhesives (e.g., Histoacryl Flex™, Dermabond™), albumin-based adhesives (e.g., Bioglue™), polyethylene glycol-based adhesives (e.g., CoSeal™, DuraSeal™), fibrin glues (e.g., Tisseel™), as well as nanoparticle solutions and UV-curable surgical glues. These existing tissue adhesives require relatively long times (1 minute or more) to form a bond and exhibit limited adhesive performance on wet tissue (20 J m -2Interfacial toughness of less than 10 kPa and shear / tensile strength of less than 10 kPa (see Figures 9E and 12). In Figure 9E, data for commercially available tissue adhesives are obtained from the literature (see Vakalopoulos, K.A. et al. Mechanical strength and rheological properties of tissue adhesives with regard to colorectal anastomosis: an ex vivo study. Annals of Surgery 261, 323-331 (2015)). In Figure 12, typical values for interfacial toughness, shear and tensile strength, and application time for bond formation are compared between the dry adhesive material (between hydrogel and porcine skin) and various existing tissue adhesives.The data for commercially available adhesives (Histoacryl Flex™, Derma-bond™, CoSeal™, DuraSeal™, Tisseel™, and Bioglue™), UV-curable surgical glue, nanoparticle solutions, and tough hydrogel adhesives in Figure 12 are taken from the literature and application manuals (for commercially available tissue adhesives) (Vakalopoulos, K.A. et al. Mechanical strength and rheological properties of tissue adhesives with regard to colorectal anastomosis: an ex vivo study. Annals of Surgery 261, 323-331 (2015); Roche, E.T. et al. Soft robotic sleeve supports heart function. Science Translational Medicine 9, eaaf3925 (2017); Rose, S. et al. Nanoparticle solutions as adhesives for gels and biological tissues. Nature 505, 382-385 (2014); Li, J. et (See Reece, T.B., Maxey, T.S. & Kron, I.L.A. prospectus on tissue adhesives. The American Journal of Surgery 182, S40-S44 (2001)). N / R indicates not reported. As shown, the dry adhesive material of the present invention exhibits much higher interfacial toughness (up to 1,150 Jm) than existing tissue adhesives within less than 5 seconds. -2 ), providing shear and tensile strength (up to 160 kPa) (see Figures 8E and 12).

[0058] The dry adhesive material of the present invention is applicable to a wide range of wet tissues, including skin, tendons, stomach, muscle, heart, and liver. In particular, Figures 13A-G illustrate the instantaneous and strong adhesion of various wet tissues by the dry adhesive material. For example, Figure 13A graphically illustrates the interfacial toughness and shear and tensile strength between various tissues adhered by the dry adhesive material, and Figures 13B-G show photographs of various tissues adhered by the dry adhesive material for pig skin 13B, tendon 13C, stomach 13D, muscle 13E, heart 13F, and liver 13G.

[0059] The remarkable versatility of the present dry adhesive material also allows it to provide instant, strong adhesion between wet tissue and a variety of engineered solids, including hydrogels, silicone, titanium, polydimethylsiloxane (PDMS), polyimide, and polycarbonate, which cannot be achieved with existing tissue adhesives (Figures 13H-N). In other words, the present dry adhesive material can be used to attach one or more various engineered solids to one or more wet tissue surfaces (see Figures 13I-N). As shown, such attachment to one or more wet tissue surfaces provides high interfacial toughness and shear and tensile strength between porcine skin and a variety of engineered solids (Figure 13H).

[0060] 14A-C further graphically illustrate representative curves for mechanical testing of various tissues adhered with dry adhesive materials according to embodiments of the present invention, where FIG. 14A shows the force / width vs. displacement curve for 180-degree peel testing of various tissues adhered with DST, FIG. 14B shows the shear stress vs. displacement curve for lap shear testing of various tissues adhered with DST, and FIG. 14C shows the tensile stress vs. displacement curve for tensile testing of various tissues adhered with DST. As shown, the dry adhesive materials exhibit high interfacial toughness (710 Jm for skin) and excellent adhesion to skin. -2 , 820 Jm for tendons -2 , 450 Jm for the stomach -2 , 570 Jm for muscles -2 , 340 Jm for the heart -2, 190 Jm for liver -2 ) and high shear and tensile strength (greater than 120 kPa for skin, 140 kPa for tendon, 70 kPa for stomach, 80 kPa for muscle, 70 kPa for heart, and 20 kPa for liver) (Figures 13A and 14).

[0061] As shown in Figures 15A-C, attaching various engineered solids to wet tissue using the present dry adhesive material was achieved by first functionalizing one or more surfaces of the engineered solid with primary amines to provide rapid covalent bonding with the dry adhesive material. The dry adhesive material is then adhered to the desired wet tissue surface as described herein. In particular, Figure 15A depicts a schematic diagram of primary amine functionalization of silicon, titanium, and PDMS, and subsequent covalent bonding between the primary amine groups and NHS ester groups in DST according to embodiments of the present invention. Figure 15B shows a schematic diagram of primary amine functionalization of polycarbonate, and subsequent covalent bonding between the primary amine groups and NHS ester groups in DST according to embodiments of the present invention. Figure 15C shows a schematic diagram of primary amine functionalization of polyimide, and subsequent covalent bonding between the primary amine groups and NHS ester groups in DST according to embodiments of the present invention. Thus, the present materials and methods provide for the attachment of various engineered solids to wet surfaces.

[0062] The adhesive performance of such composites (where composite refers to the dry adhesive material of the present invention with one or more engineered solids attached) was evaluated by adhering the composite to wet porcine skin (Figure 16). Adhesion between wet tissue and various engineered solids by the dry adhesive material exhibited high interfacial toughness (1,150 Jm for hydrogels). -2 , 800Jm for silicon -2 , 680Jm for titanium -2 , 480 Jm for PDMS -2 , 720 Jm for polyimide -2 , 410Jm for polycarbonate -2(greater than 80 kPa for hydrogels, 160 kPa for silicon, 150 kPa for titanium, 100 kPa for PDMS, 100 kPa for polyimide, and 70 kPa for polycarbonate) (see Figure 13H).

[0063] Thus, the capabilities and versatility of the dry adhesive material of the present invention can enable an unprecedented range of functions, such as instantly sealing damaged tissue and attaching various devices to wet, dynamic tissue (Figure 17). In ex vivo tests, a pig's air-leaking trachea and a cut lung lobe were rapidly sealed within one minute using the dry adhesive material of the present invention with a hydrogel patch attached (a composite dry adhesive material with a hydrogel patch placed and attached), thereby restoring the function of the air-leaking pig's trachea without air leakage (Figures 17A-B). Similarly, a pig's stomach with a 1 cm diameter hole that was leaking fluid was quickly sealed within one minute using the dry adhesive material of the present invention with a hydrogel patch attached (a composite dry adhesive material with a hydrogel patch placed and attached), easily stopping the leakage of flowing water (Figure 17C). Furthermore, the instantaneous, strong adhesive ability of DST enabled the easy repair of damaged pig intestines, forming a fluid-tight anastomosis (Figure 17D). This rapid sealing of damaged tissue with the dry adhesive material of the present invention may therefore find particular utility in surgical repair or wound closure as a viable alternative to suturing or stapling.

[0064] The rapid and strong adhesive properties of dry adhesive materials are also highly desirable for attaching various functional devices to dynamic and deformable tissues, including, but not limited to, skin, tendons, and the heart. For example, dry adhesive materials can be used to adhere fluorescein-filled hydrogels to a beating pig heart with one or more incisions to demonstrate the ability to attach drug delivery devices to dynamic, wet tissue (Figure 18A). This was achieved by forming a composite containing the dry adhesive material with drug delivery device(s) attached to one or more sides of the dry adhesive material and subsequently adhering this composite to the dynamic, wet tissue. In this example, a pressurized air inlet was injected into an ex vivo pig heart to mimic the beating heart. Flexibility in the fabrication of dry adhesive materials is further enhanced by the use of perforated dry adhesive materials to facilitate the delivery of one or more materials (e.g., the mimetic drug fluorescein, as shown in Figure 18A) from the drug delivery device(s) toward the wet tissue (e.g., cardiac tissue, as shown in Figure 18A) to which the dry adhesive material is adhered. Notably, the high stretchability and rapid adhesion of the dry adhesive material allow for adaptive application of drug devices (e.g., drug patches) by stretching the DST patch to closely match or correspond to the size and shape of an incision in the target wet tissue (e.g., the beating pig heart in Figure 18A). As shown, the adhered DST patch maintained adhesion without detachment on the beating heart for over 12 hours, achieving gradual delivery of drugs to the cardiac tissue (Figure 18B).

[0065] As another example, a stretchable strain sensor was adhered to a beating pig heart (Figure 18C). The fast and strong adhesion of a dry adhesive material in the form of DST (dry double-sided tape) allows for easy attachment of the strain sensor to the dynamic and curved surface of the beating pig heart and for long-term electrical measurement of cardiac motion (Figure 18C). Notably, a stretchable DST-sensor hybrid was prepared by printing a conductive ink onto a DST-Ecoflex hybrid substrate (Figure 19), which offers convenience in application due to its ready-to-use properties (Figure 18C). Notably, as shown in Figure 19, a DST-strain sensor hybrid can be prepared using hydrogel-elastomer hybrid technology, where the strain sensor is fabricated by printing a conductive ink (such as an ink based on Eco-flex™ resin and carbon black (CB)). The resulting DST-strain sensor hybrid can be easily adhered to wet tissue, and deformation can be measured by monitoring the change in the strain sensor's electrical resistance (Figure 18D). Such a DST device hybrid can serve as a universal platform for wearable and implantable devices to be attached to various parts of the human body.

[0066] Thus, the present invention provides improved tissue adhesives in the form of dry adhesive materials, preferably in the form of dry films or tapes, such as dry double-sided films or tapes (DSTs), that rely on a novel dry crosslinking mechanism to rapidly and strongly bond a variety of wet tissues and devices. The dry-storable and ready-to-use nature of the adhesive materials allows for easy storage, distribution, and use over extended periods (e.g., greater than two weeks) without compromising performance. This is illustrated in Figure 20, which graphically depicts the adhesive performance (interfacial toughness of the bonded materials) between wet porcine skin and dry adhesive materials stored dry at -20°C for various periods: as-prepared, 1 day after preparation, 3 days after preparation, 1 week after preparation, and 2 weeks after preparation.

[0067] The dry adhesive material of the present invention thus eliminates the storage of perishable liquids or wet gels and the difficulties of mixing reagents immediately before each use, which are common in existing tissue adhesives. Furthermore, this pre-defined dry adhesive material has a unique thin tape shape and a simple composition that allows for high manufacturing flexibility. This can therefore provide substantial economic advantages and facilitate the rapid and widespread dissemination and translation of materials. These novel capabilities of the theoretical adhesive material address a series of long-term challenges for existing tissue adhesives and may offer new opportunities for future developments in tissue engineering, drug delivery, and biointegrated devices. The novel dry crosslinking mechanism for wet adhesion will further inspire the design of future adhesives in wet and underwater environments.

[0068] Materials and methods for experimental data Materials. All chemicals were obtained from Sigma-Aldrich and used without further purification unless otherwise stated. To prepare double-sided tape (DST), acrylic acid, gelatin methacrylate (Type A Bloom 90-100 from porcine skin with 60% substitution), acrylic acid N-hydroxysuccinimide ester (AAc-NHS), α-ketoglutaric acid, gelatin (Type A Bloom 300 from porcine skin), and chitosan (75-85% deacetylated) were used. In the example, α-ketoglutaric acid is the photoinitiator used to polymerize the monomers into polymeric form during preparation. To visualize DST, red food dye (McCormick) and FITC-gelatin (Thermo Fisher Scientific) were used for photographs and microscopic images, respectively. For in vitro biodegradation testing, Dulbecco's phosphate-buffered saline (DPBS; containing calcium and magnesium, Gibco), collagenase, lysozyme, and NAGase were used. Acrylamide and the photoinitiator Irgacure 2959 (I2959) were used for the preparation of hydrogels. (3-aminopropyl)triethoxysilane (APTES) and hexamethyldiamine (HMDA) were used for surface functionalization of engineered solids. Ecoflex 00-30 (Smooth-On), silicone cure retarder (SLO-JO, Smooth-On), and carbon black (Alfa Aesar) were used for the preparation of stretchable strain sensors. All engineered solids were obtained from McMaster Carr unless otherwise stated. Pig skin, tendons, stomach, muscle, heart, liver, and blood were purchased from a local grocery store.

[0069] Preparation of dry double-sided tape (DST). Dry DST was prepared based on either gelatin or chitosan. To prepare gelatin-based DST, 30 w / w% acrylic acid, 10 w / w% gelatin, 1 w / w% AAc-NHS, 0.1 w / w% gelatin methacrylate, and 0.2 w / w% α-ketoglutaric acid were dissolved in deionized water. The mixture was then filtered through a 0.2 μm sterile syringe filter and poured into a glass mold with a spacer. The DST was cured in a UV chamber (284 nm, 10 W output) for 20 min and completely dried under a nitrogen stream. The dried DST was further immersed in ethanol for 12 h to leach out unreacted reagents and then completely dried in a vacuum chamber to remove the ethanol. The final dry DST was sealed in a plastic bag and stored at -20 °C before use. Chitosan-based DST was prepared by replacing 10 w / w% gelatin with 2 w / w% chitosan. In the experiments, gelatin-based DST with an as-prepared thickness of 210 μm was used unless otherwise noted. To prepare DST of various shapes, large sheets of dried DST were cut into each design using a laser cutter (Epilog). Polyethylene-coated paper was used as the backing for the DST. To aid in visualization of the DST, 0.5 w / w% red food coloring (for photographs) or 0.2 w / w% FITC-gelatin (for fluorescence microscopy images) was added to the DST precursor solution before hardening.

[0070] Mechanical Testing. For tissue samples stored for more than 1 hour before mechanical testing, after applying the DST, the sample surface was sprayed with 0.1 wt% aqueous sodium azide and sealed in a plastic bag to prevent tissue degradation and dehydration. After rinsing the surface with water, all tissues and engineered solids were bonded with the DST, followed by a 5-second press. To measure interfacial toughness, 2.5-cm-wide bonded samples were prepared and tested using a mechanical testing machine (2.5 kN load cell, Zwick / Roell Z2.5) using a standard 180-degree peel test (ASTM F2256) or 90-degree peel test (ASTM D2861) (for hard substrates such as silicone). All tests were performed at 50 mm min. -1The peeling test was performed at a constant peel rate of 100 s. Once the peeling process reached a steady state, the measured force reached a plateau. The interfacial toughness was determined by dividing the plateau force (for 180° peel tests) or twice the plateau force (for 90° peel tests) by the width of the tissue sample. A poly(methyl methacrylate) film (50 μm thick, Goodfellow) was applied using cyanoacrylate glue (Krazy Glue) as a stiff backing for the tissue and hydrogel.

[0071] To measure tensile strength, adhesive samples with a bonded area of 2.5 cm width and 1 cm length were prepared and tested using a mechanical testing machine using the standard lap shear test (ASTM F2255). All tests were performed at 50 mm min -1 The shear strength was determined by dividing the maximum force by the adhesive area. Poly(methyl methacrylate) film was applied using cyanoacrylate glue as a stiff backing for the tissue and hydrogel.

[0072] To measure the tensile strength, adhesive samples with a bonded area of 2.5 cm width and 2.5 cm length were prepared and tested using a mechanical testing machine with a standard tensile test (ASTM F2258). All tests were performed at 50 mm min -1 The test was carried out at a constant pulling rate of 1000 kJ / min. The tensile strength was determined by dividing the maximum force by the bonded area. Cyanoacrylate glue was used to apply aluminum fixtures and provide grips for the tensile test.

[0073] To characterize the mechanical properties of DST, the DST was equilibrated in DPBS before testing. The tensile properties and fracture toughness of DST were measured by pure shear tensile tests on thin rectangular samples (10 mm long, 30 mm wide, and 0.5 mm thick) using a mechanical testing machine (20 N load cell, Zwick / Roell Z2.5). All tests were performed for 50 mm min. -1The fracture toughness of the DST was calculated according to a previously reported method based on tensile tests of unnotched and notched samples with a notch length of 1 cm.

[0074] Preparation of engineered solids. To prepare hydrogels for adhesion testing of engineered solids, 20 w / w% acrylamide, 10 w / w% gelatin, 0.2 w / w% gelatin methacrylate, and 0.5 w / w% I2959 were dissolved in deionized water. The mixture was then filtered through a 0.2 μm sterile syringe filter and poured into a glass mold with a spacer. The hydrogels were cured in a UV chamber (284 nm, 10 W power) for 60 minutes. To facilitate covalent bonding with DST, all engineered solids except the hydrogel were functionalized with primary amines. For silicon, titanium, and PDMS, the substrates were first treated with oxygen plasma (30 W power, Harrick Plasma) for 2 minutes to activate the surface. The plasma-treated substrates were then covered with an APTES solution (1 w / w% APTES in 50% ethanol) and incubated at room temperature for 3 hours. The substrates were then thoroughly washed with isopropyl alcohol and dried under a stream of nitrogen. For polyimide and polycarbonate, the substrates were immersed in a HMDA solution (10% v / v in deionized water) at room temperature for 24 hours. The substrates were then thoroughly washed with deionized water and dried under a stream of nitrogen.

[0075] In vitro biodegradation tests. In vitro biodegradation tests of DSTs were conducted based on enzymatic degradation media according to a previously reported protocol (see Boutry, C. M. et al. A stretchable and biodegradable strain and pressure sensor for orthopedic application. Nature Electronics 1, 314-321 (2018)). To prepare the in vitro enzymatic biodegradation media for gelatin-based DSTs, 5 mg of collagenase was added to 100 mL of DPBS. To prepare the in vitro enzymatic biodegradation media for chitosan-based DSTs, 5 mg of collagenase, 5 mg of lysozyme, and 1 mg of lysozyme were added to 100 mL of DPBS. -1 Ten microliters of the NAGase solution was added to 100 mL of DPBS. The dried DST was cut into small samples (10 mm wide and 10 mm long) and accurately weighed. Before immersion in the enzyme medium, the samples were sterilized with 75% ethanol for 15 minutes and washed three times with DPBS. Each sample was then immersed in 15 mL of enzyme medium in a glass scintillation vial and incubated at 37°C with shaking at 60 rpm. Approximately 0.01 w / v% sodium azide was added to the enzyme medium to prevent microbial growth during the test. At each time interval, the DST was removed from the incubation medium, thoroughly washed with deionized water, and freeze-dried. Weight loss was determined as the percentage of the mass of the freeze-dried sample at each time interval, normalized by the dry mass of the original sample.

[0076] In vitro biocompatibility testing. In vitro biocompatibility testing was performed using DST-conditioned medium for cell culture (see Darnell, MC et al. Performance and biocompatibility of extremely tough alginate / polyacrylamide hydrogels. Biomaterials 34, 8042-8048 (2013)). To prepare DST-conditioned medium for in vitro biocompatibility testing, 20 mg of DST was incubated in 1 mL of Dulbecco's modified Eagle's medium (DMEM) at 37°C for 24 hours. Fresh DMEM was used as a control. Wild-type mouse embryonic fibroblasts (mEFs) were plated in 96-well plates (N = 10 in each case). The cells were then treated with DST-conditioned medium and incubated at 37°C in 5% CO2 for 24 hours. Cell viability was determined using a Live / Dead Viability / Cytotoxicity Kit for Mammalian Cells (Thermo Fisher Scientific) by adding 4 μM calcein and ethidium homodimer-1 to the culture medium. A confocal microscope (SP 8, Leica) was used to image live cells with excitation / emission at 495 nm / 515 nm and dead cells at 495 nm / 635 nm, respectively.

[0077] Preparation of DST-strain sensor hybrids. DST-strain sensor hybrids were prepared by printing conductive ink onto a DST-elastomer hybrid substrate. First, the elastomer substrate was prepared by pouring Ecoflex 00-30 resin into a laser-cut acrylic mold. Subsequently, a thin layer of DST (100 μm dry thickness) was introduced onto the underside of the Ecoflex substrate, following a previously reported protocol for hydrogel-elastomer hybrids (see Yamagishi, K. et al., Tissue-adhesive wirelessly powered optoelectronic device for metronomic photodynamic cancer therapy. Nature Biomedical Engineering 3, 27–36 (2019)). The strain sensors were fabricated by printing conductive ink onto a DST-Ecoflex hybrid substrate using a custom direct ink writing (DIW) 3D printer (see Yuk, H. & Zhao, X. A., "A new 3D printing strategy by harnessing deformation, instability, and fracture of viscoelastic inks." Advanced Materials 30, 1704-028 (2018)). Briefly, the conductive ink was prepared by mixing 10 w / w% carbon black and 1 w / w% silicone cure retarder into Ecoflex 00-30 resin using a planetary mixer (AR-100, Thinky). The printing path was generated by creating G-code to control the XYZ motion of a robotic gantry (Aerotech). Conductive ink was printed onto the substrate using a pressure-based microdispenser (Ultimus V, Nordson EFD) with a 200 μm diameter nozzle (Smoothflow tapered tip, Nordson EFD) through a custom Lab VIEW interface (National Instruments).The change in electrical resistance of the strain sensor caused by deformation was monitored by a digital multimeter (34450A, Keysight).

[0078] Instantaneous sealing of pig lungs. This ex vivo experiment was performed using fresh pig lungs purchased from a local grocery store. An incision was made in the pig's trachea and lung lobes with a razor blade. A tube was then connected to the pig's trachea to inflate and deflate the pig's lungs (3 kPa or 22.5 mmHg pressure). A hydrogel patch (2.5 cm wide and 5 cm long) was attached to the injured pig's trachea and lung lobes with DST and pressed for 5 seconds to instantly seal the incision. To monitor the robustness of the DST-based instantaneous seal over a long period of time, the sealed pig lungs were kept at room temperature for 12 hours.

[0079] Instantaneous sealing of a pig stomach. This ex vivo experiment was performed using fresh pig stomachs purchased from a local grocery store. A 10 mm diameter hole was drilled in the stomach. A water tube was then connected to the stomach, allowing water to flow continuously through the hole. A 40 mm diameter hydrogel patch was attached to the injured pig stomach using DST and pressed for 5 seconds, instantly sealing the hole. To monitor the robustness of the DST-based instantaneous seal over a long period of time, the sealed pig stomach was kept at room temperature for 12 hours.

[0080] Instantaneous adhesion of devices to beating pig hearts. These ex vivo experiments were performed using fresh pig hearts purchased from a local grocery store. A microdispenser was used to introduce a programmed, pressurized air infusion into the pig hearts, mimicking their heartbeat. After rinsing the surface with water, all devices were adhered to the beating pig hearts, followed by a 5-second press. For experiments lasting longer than 1 hour at ambient conditions, the beating pig hearts were covered with a wet towel soaked in 0.1 w / w% aqueous sodium azide solution to prevent dehydration and degradation. An incision was made in the pig heart to allow for instantaneous and strong adhesion of the drug delivery devices. To prepare the drug delivery devices, 0.5 w / w% fluorescein sodium salt was added to a hydrogel patch (2.5 cm wide and 5 cm long) as a drug simulant. The drug-loaded hydrogel patch was then stretched to fit the incision and adhered to the beating pig hearts with a perforated DST. The drug patch attached to the beating pig heart was kept at room temperature for 12 hours to allow the simulated drug to diffuse into the cardiac tissue. The diffusion of the simulated drug was imaged using a fluorescence microscope (LV100ND, Nikon). To ensure instantaneous and strong adhesion of the strain sensor, the DST-strain sensor hybrid was attached to the beating pig heart after removing the backing. The strain sensor attached to the beating pig heart was kept at room temperature for 12 hours and then connected to a digital multimeter to monitor the deformation of the beating heart.

[0081] The present invention provides a new type of tissue adhesive in the form of a dry double-sided tape (DST) to address the limitations of currently available materials and methods for adhering tissues and attaching devices to tissues. The dry adhesive material of the present invention, along with its dry crosslinking mechanism, is particularly desirable for the instantaneous adhesion of various tissues due to the inherent wettability of biological tissues and the frequent introduction of water to tissue surfaces during surgical processes (e.g., water flushing or irrigation). As a result, adhesion formation between various wet tissues (skin, tendon, stomach, muscle, heart, and liver) and engineered solids (hydrogels, silicon, titanium, polydimethylsiloxane, polyimide, and polycarbonate) is much more rapid (e.g., less than one minute, even less than five seconds) than existing materials and mechanisms, with excellent interfacial toughness (e.g., up to 1,150 Jm). -2 This is accompanied by improved shear and tensile strength (e.g., up to 160 kPa). Furthermore, as demonstrated, the dry adhesive material has a shear modulus and stretchability similar to that of soft tissue. Furthermore, the biocompatibility of the dry adhesive-conditioned medium is comparable to that of the control medium, and the biodegradation rate of the dry adhesive material can be controlled by adjusting its composition without appreciably degrading its properties. The dry adhesive material has further demonstrated unprecedented functionality in ex vivo experiments, including sealing air-leaking pig lungs and fluid-leaking pig stomachs, as well as adhering drug patches and strain sensors to beating pig hearts.

Claims

1. 1. A dry adhesive material for adhering one or more wet surfaces, comprising: (i) one or more hydrophilic polymers; (ii) one or more amine coupling groups, and (iii) one or more cross-linking agents; Including, the dry adhesive material is in the form of a film or tape having an upper surface and a lower surface; the dry adhesive material has a liquid content such that, upon placing one or more of the top and / or bottom surfaces of the dry adhesive material in contact with the one or more wet surfaces, the dry adhesive material absorbs liquid from the one or more wet surfaces, swells and forms temporary crosslinks between the dry adhesive material and the wet surfaces, and forms covalent crosslinks between the one or more amine coupling groups and the one or more wet surfaces; the hydrophilic polymer in the dry adhesive material is configured to include one or more poly(acrylic acid)s grafted with the one or more amine coupling groups and crosslinked with the one or more crosslinking agents; Dry adhesive material.

2. (i) the one or more hydrophilic polymers are selected from polyacrylic acid, polyacrylamide, polyvinyl alcohol, polyhydroxyethyl methacrylate, polyethylene glycol, polyvinylpyrrolidone, polystyrene sulfonate, casein, albumin, gelatin, collagen, chitosan, hyaluronic acid, alginic acid, oxidized alginate, pectin, and combinations thereof; The dry adhesive material of claim 1 .

3. (ii) the one or more amine coupling groups are selected from N-hydroxysuccinimide esters, N-hydroxysulfosuccinimide esters, aldehydes, imidoesters, epoxides, isocyanates, catechols, and combinations thereof; The dry adhesive material of claim 1 .

4. (iii) the one or more crosslinkers are selected from gelatin methacrylate, hyaluronic acid methacrylate, oxidized methacrylic alginate, polycaprolactone diacrylate, N,N'-bis(acryloyl)cystamine, N,N'-methylenebis(acrylamide), polyethylene glycol diacrylate, polyethylene glycol dimethacrylate, and combinations thereof; The dry adhesive material of claim 1 .

5. comprising poly(acrylic acid) grafted with N-hydroxysuccinimide esters and crosslinked with biodegradable gelatin methacrylate, and further comprising one or more biodegradable biopolymers; The dry adhesive material of claim 1 .

6. Further comprising one or more biodegradable biopolymers. The dry adhesive material of claim 1 .

7. the one or more biodegradable biopolymers are selected from gelatin, chitosan, and combinations thereof; 7. The dry adhesive material of claim 5 or 6.

8. the negatively charged carboxylic acid groups in the poly(acrylic acid) grafted with N-hydroxysuccinimide esters promote the absorption of liquid and swelling of the dry adhesive material, and further form intermolecular bonds with the one or more wet tissue surfaces within less than 60 seconds after contact between the dry adhesive material and the one or more wet surfaces; The dry adhesive material of claim 5.

9. the N-hydroxysuccinimide ester grafted on the poly(acrylic acid) forms a covalent bond with a primary amine group present on the one or more wetting surfaces; The dry adhesive material of claim 5.

10. and after the covalent crosslinks are formed between the one or more amine coupling groups and the one or more wet surfaces, the swollen, dried adhesive material transforms into a hydrogel layer. The dry adhesive material of claim 1 .

11. The hydrogel has a viscosity of at least 1,000 Jm －２ having a fracture toughness of The dry adhesive material of claim 10.

12. in the form of flat sheets, perforated sheets, double-sided tapes or films, and perforated double-sided tapes or films; The dry adhesive material of claim 1 .

13. the dry adhesive material includes an upper surface and a lower surface, the adhesive material further including one or more layers of backing material disposed on at least one of the upper surface and the lower surface; The dry adhesive material of claim 12.

14. the backing material layer is a removable backing material layer and is made of polyethylene, hydrophobic polymer-coated paper, poly(methyl methacrylate), hydrophobic polymer film, or a combination thereof; 14. The dry adhesive material of claim 13.

15. The backing material layer is a non-removable material layer and is made of a silicone elastomer, a thermoplastic polyurethane, a hydrogel, a biocompatible material that is non-adhesive to wet tissue, or a combination thereof; 14. The dry adhesive material of claim 13.

16. further comprising one or more engineered solids and / or devices adhered to one or more surfaces of said dry adhesive material; The dry adhesive material of claim 1 .

17. the one or more engineered solids are selected from hydrogels, silicones, titanium, polydimethylsiloxanes, polyimides, polycarbonates, and combinations thereof; 17. The dry adhesive material of claim 16.

18. the dry adhesive material is biodegradable; The dry adhesive material of claim 1 .

19. the (i) one or more polymers and / or the (iii) one or more crosslinkers are selected to modify biodegradability properties; 20. The dry adhesive material of claim 18.

20. A therapeutic agent delivery device for attachment to one or more wet tissue surfaces and for releasing one or more therapeutic agents to a target site, comprising: (i) a layer of dry adhesive material having an upper surface and a lower surface; one or more hydrophilic polymers, one or more amine coupling groups, and one or more cross-linking agents, a dry adhesive material layer in the form of a film or tape having an upper surface and a lower surface, the dry adhesive material layer having a liquid content such that, upon placing one or more of the upper and / or lower surfaces of the dry adhesive material layer in contact with the one or more wet surfaces, the dry adhesive material layer absorbs liquid from the one or more wet surfaces, swells, and forms temporary crosslinks between the dry adhesive material layer and the wet surfaces, and forms covalent crosslinks between the one or more amine coupling groups and the one or more wet surfaces, and the hydrophilic polymer in the dry adhesive material layer is configured to include one or more poly(acrylic acid)s grafted with the one or more amine coupling groups and crosslinked by the one or more crosslinking agents; (ii) one or more therapeutic agent-loaded patches disposed on one or more of the upper and lower surfaces of the dry adhesive material layer; 12. A therapeutic agent delivery device comprising:

21. 1. A device for providing electrical measurements of cardiac motion, comprising: (i) a layer of dry adhesive material having an upper surface and a lower surface; one or more hydrophilic polymers, one or more amine coupling groups, and one or more cross-linking agents, a dry adhesive material layer in the form of a film or tape having an upper surface and a lower surface, the dry adhesive material layer having a liquid content such that, upon placing one or more of the upper and / or lower surfaces of the dry adhesive material layer in contact with the one or more wet surfaces, the dry adhesive material layer absorbs liquid from the one or more wet surfaces, swells, and forms temporary crosslinks between the dry adhesive material layer and the wet surfaces, and forms covalent crosslinks between the one or more amine coupling groups and the one or more wet surfaces, and the hydrophilic polymer in the dry adhesive material layer is configured to include one or more poly(acrylic acid)s grafted with the one or more amine coupling groups and crosslinked by the one or more crosslinking agents; (ii) one or more strain sensors disposed on one or more of the top and bottom surfaces of the dry adhesive material layer; Devices that include:

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