Adhesive device and its use

Abstract

The present invention features an adhesive device for fixedly holding objects (eg, bone fragments) together.

Description

[Technical field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims priority to U.S. Patent Application No. 63 / 194,297, filed May 28, 2021, the entire contents of which are incorporated herein by reference. [Background technology]

[0002] Surgical adhesives designed to come into contact with tissue, especially those for internal use, must be biocompatible, easy to apply, and able to adhere to living tissue under wet, dry, clean, and / or biofouled conditions. However, these requirements have significantly limited the application of surgical adhesives in biomedical applications, and currently commercially available surgical adhesives exhibit one or more of the following: undesirable strength, toxicity, difficult workflow, and / or require clean, dry surfaces for optimal performance.

[0003] Severe traumatic craniomaxillofacial (CMF) fractures commonly occur due to high-energy trauma, such as motor vehicle accidents, sports injuries, war injuries, and physical assaults. Many of these fractures require surgical stabilization and / or reconstruction. Current adhesives used to stabilize CMFs and other fractures suffer from one or more of the following deficiencies: high water solubility, weak bond strength, too slow or too fast setting times, irreversible rigid setting that does not allow adequate reduction, and lack of biocompatibility. Thus, new bioadhesives are needed. Summary of the Invention [Problem to be solved by the invention]

[0004] The invention features an adhesive device for holding objects (eg, bone fragments) fixedly in place relative to one another.

[0005] In a first aspect, the invention features a method of stabilizing bone fragments in a body, the method including the steps of: (i) forming a first anchor on a first bone fragment by (a) heating an adhesive composition to form a softened adhesive composition, contacting the softened adhesive composition with a first bone fragment, and (b) allowing the softened adhesive composition to cool to form a first anchor secured to the first bone fragment; (ii) forming a second anchor on the second bone fragment by (a) heating the adhesive composition to form a softened adhesive composition, contacting the softened adhesive composition with a second bone fragment, and (b) allowing the softened adhesive composition to cool to form a second anchor secured to the second bone fragment. Including, Here, the adhesive composition has a tackifying temperature of at least 40° C. (e.g., at least 42° C., at least 45° C., at least 50° C., at least 55° C., or from 40° C. to 55° C.), The first anchor and the second anchor are connected to a support structure for stabilizing the bone fragment.

[0006] In some embodiments, the support structure is a flexible support comprising a biodegradable and biocompatible polymer that connects the first anchor to the second anchor. In some embodiments, the support structure, first anchor, and second anchor are formed from a tape that includes (x) a non-adhesive upper layer, which is the support structure, and (y) a lower layer that becomes adhesive when softened to form the first anchor and second anchor.

[0007] In some embodiments, the adhesive composition is not water soluble (e.g., has a water solubility of less than 30 mg / L, 25 mg / L, 20 mg / L, or 15 mg / L at 25° C.), while in other embodiments, the adhesive composition is water soluble (e.g., has a water solubility of more than 30 mg / L or 50 mg / L at 25° C.).

[0008] In some embodiments, the adhesive composition includes an inorganic particulate additive heat transfer agent. In some embodiments, the heat transfer agent {e.g., sodium chloride, iron (III) phosphate dihydrate, iron (III) citrate monohydrate, hydroxyapatite, tetracalcium phosphate, tricalcium phosphate, dicalcium phosphate, and sodium carbonate, or a combination thereof (e.g., hydroxyapatite)} is present in an amount that allows the softened adhesive composition to cool and harden in 120 seconds or less (e.g., 10 seconds or less). In some embodiments, the heat transfer agent is present in an amount that allows the adhesive composition to soften within 120 seconds (e.g., 10 seconds or less) after application of energy. In certain embodiments, the heat transfer agent is present in an amount that allows the adhesive composition to soften within 10 seconds after application of energy to the non-adhesive top layer. In some embodiments, the adhesive composition comprises about 0.5-60% (w / w) heat transfer agent (e.g., 7.5±2.5%, 10±5%, 15±5%, 20±5%, 25±10%, 37.5%±5%, 50±10%, or 35-60% (w / w)).

[0009] In some embodiments of the second aspect, the adhesive layer comprises a particulate filler. In some embodiments, the particulate filler prevents loss of the adhesive composition upon heating. In some embodiments, the particulate filler is insoluble.

[0010] In some embodiments, the adhesive composition comprises a polymer having a structure of formula (I).

[0011] [ka]

[0012] During the ceremony, n is an integer from 0 to 4 (e.g., n=1, 2, 3, or 4); Block B comprises an oligomer derived from a polyester, polyether, polyalkylene glycol, polysilicone, or polycarbonate with a MW<10,000 g / mol (e.g., 2±1 KDa, 4±2 KDa, 5±2.5 KDa, or 8±2 KDa); Block A comprises an optionally substituted C1-C6 alkylene, and Block A is derived from a diisocyanate crosslinker; Block W comprises an optionally substituted C0-C3 alkyl-benzene-diol or an optionally substituted C0-C3 alkyl-benzene-triol; the linker L' comprises a carbamate; and The linker L comprises a urea.

[0013] In some embodiments, block B comprises an oligomer derived from a polyester, a polyalkylene glycol, a polysilicone, or a polycarbonate. In certain embodiments, the block B oligomer has a MW≦4,000 g / mol (e.g., 1±0.5 KDa, 2±0.5 KDa, or 3±1 KDa).

[0014] In some embodiments, block B has formula (II):

[0015] [ka]

[0016] wherein each o is independently an integer from 0 to 20 (e.g., n=0 to 4, 2 to 6, 4 to 10, 5 to 15, or 10 to 20).

[0017] In some embodiments, block B has formula (III):

[0018] [ka]

[0019] wherein each o is independently an integer from 0 to 20 (e.g., n=0 to 4, 2 to 6, 4 to 10, 5 to 15, or 10 to 20).

[0020] In some embodiments, block B has formula (IV):

[0021] [ka]

[0022] wherein each o is independently an integer from 0 to 20 (e.g., n=0 to 4, 2 to 6, 4 to 10, 5 to 15, or 10 to 20).

[0023] In some embodiments, block B has formula (V):

[0024] [ka]

[0025] where each o is independently an integer from 0 to 20 (eg, n=0-4, 2-6, 4-10, 5-15, or 10-20).

[0026] In some embodiments, block B has formula (VI):

[0027] [ka]

[0028] where each o is independently an integer from 0 to 20 (eg, n=0-4, 2-6, 4-10, 5-15, or 10-20).

[0029] In some embodiments, block A has formula (VII):

[0030] [ka]

[0031] wherein R 1 is C1-C3 alkyl.

[0032] In some embodiments, the linker L' is

[0033] [ka]

[0034] It has the structure:

[0035] In some embodiments, the linker L is

[0036] [ka] It has the structure:

[0037] In some embodiments, block W is

[0038] [ka] It has the structure:

[0039] In some embodiments, the adhesive composition comprises 30-70% (w / w) filler.

[0040] In some embodiments, the filler includes polycaprolactone (PCL), polydioxanone (PDX), poly(lactic-co-glycolic acid) (PLGA), poly-3-hydroxybutyric acid (P3HB), polylactic acid (PLA), polyglycolide (PGA), poly-4-hydroxybutyric acid (P4HB), polyethylene carbonate (PEC), polypropylene carbonate (PPC), poly(trimethylene carbonate) (PTMC), polysulfone, polyethylene glycol (PEG), hydroxyapatite (HA), tetracalcium phosphate (TTCP), tricalcium phosphate (TCP), dicalcium phosphate (DCP), or copolymers thereof, or blends thereof. In some embodiments, the filler includes polycaprolactone (PCL), polydioxanone (PDX), poly(lactic-co-glycolic acid) (PLGA), or poly-3-hydroxybutyric acid (P3HB), or copolymers thereof, or blends thereof.

[0041] In some embodiments, steps (i) and (ii) are repeated to stabilize multiple bone fragments in a subject, in some embodiments, 2-5, 6-10, 11-15, 16-20, 21-25, 26-30, 31-35, 36-40, 41-45, 46-50, or more bone fragments are stabilized in a subject.

[0042] In any of the embodiments of the above method, the heating includes applying an energy source. For example, the energy source can be ultrasonic energy, or any other energy source described herein. In certain embodiments, the ultrasonic energy is applied at a frequency of 35 kHz to 70 kHz (e.g., 45±10 kHz, 55±10 kHz, or 60±10 kHz, or 70 kHz), and optionally, 1.5 to 5.0 J of energy is applied (e.g., 2.0±0.5 J, 3.0±0.5 J, 4.0±0.5 J, or 4.5±0.5 J). In certain embodiments, the ultrasonic energy is applied at a frequency and amount sufficient to transfer fluid between the adhesive composition and the bone fragments prior to formation of the first anchor and the second anchor. The ultrasonic energy can be applied using an ultrasonic welder. In certain embodiments, the ultrasonic welder includes a horn tip having individual texture elements, the individual texture elements being equally spaced at a uniform depth of up to 0.127 mm.

[0043] In an embodiment of any of the above methods, the method includes one or more of the following features: (i) the bone fragment is reversibly stabilized, (ii) the first anchor and the second anchor are reversible anchors, (iii) the adhesive composition does not rely on an in situ curing reaction for adhesion, and / or (iv) the adhesive composition reversibly softens at a temperature of 45±5° C. or 55±5° C.

[0044] In any embodiment of the above method, the support structure, the first anchor, and the second anchor are formed from a tape including (x) a non-adhesive upper layer that is the support structure, and (y) a lower layer that softens and becomes adhesive to form the first anchor and the second anchor.

[0045] In an embodiment of any of the above methods, (i) a support structure and (ii) at least one of the first anchor and the second anchor are arranged to form an adhesive portion and a support portion forming a backing for the adhesive portion. The adhesive portion can be softened upon heating without deforming the support portion. The backing portion can have a thickness of 0.05 to 0.31 mm. In some embodiments, the backing portion has a thickness of 0.12 to 0.20 mm. The adhesive portion can have a thickness of 0.05 to 0.16 mm. In some embodiments, the adhesive portion has a thickness of 0.075±0.025 mm or 0.13±0.03 mm.

[0046] In some embodiments, the heat includes applying the heat using a welder via a series of continuous welding tacks perpendicular to the application surface to cover the entire surface, hi some embodiments, the heat includes continuously sliding the welder across the device surface in a brush stroke or painting motion.

[0047] In a second aspect, the invention features an apparatus for stabilizing bone fragments in a body, the apparatus comprising: (i) a first anchor attachable to a first bone fragment, the first anchor comprising an adhesive composition that softens upon heating and forms the first anchor upon cooling; (ii) a second anchor attachable to a second bone fragment, the second anchor comprising an adhesive composition that softens upon heating and forms a second anchor upon cooling; (iii) a support structure connecting the first anchor to the second anchor, capable of stabilizing the bone fragment; Including, Here, the adhesive composition has a tackifying temperature of at least 40°C (eg, at least 42°C, at least 45°C, at least 50°C, at least 55°C, or from 40°C to 55°C).

[0048] In some embodiments of the second aspect, the support structure is a flexible support comprising a biodegradable and biocompatible polymer that connects the first anchor to the second anchor. In some embodiments, the support structure, the first anchor, and the second anchor are formed from a tape comprising (x) a non-adhesive top layer, which is the support structure, and (y) a bottom layer that softens to become adhesive and form the first anchor and the second anchor.

[0049] In some embodiments of the second aspect, the adhesive composition is not water soluble.

[0050] In some embodiments of the second aspect, the adhesive composition includes a heat transfer agent. In some embodiments, the heat transfer agent is an inorganic particulate additive heat transfer agent. In some embodiments, the heat transfer agent (e.g., sodium chloride, iron (III) phosphate dihydrate, iron (III) citrate monohydrate, hydroxyapatite, tetracalcium phosphate, tricalcium phosphate, dicalcium phosphate, and sodium carbonate, or a combination thereof (e.g., hydroxyapatite)) is present in an amount that allows the softened adhesive composition to cool and harden within 120 seconds (e.g., within 10 seconds). In some embodiments, the heat transfer agent is present in an amount that allows the adhesive composition to soften within 120 seconds (e.g., within 10 seconds) after the application of energy. In some embodiments, the heat transfer agent comprises about 0.5-60% (w / w) of the adhesive composition (e.g., 7.5±2.5%, 10±5%, 15±5%, 20±5%, 25±10%, 37.5±5%, 50±10%, or 35-60% (w / w)).

[0051] In some embodiments of the second aspect, the adhesive layer comprises a particulate filler. In some embodiments, the particulate filler prevents loss of the adhesive composition upon heating. In some embodiments, the particulate filler is insoluble.

[0052] In some embodiments of the second aspect, the adhesive composition comprises a polymer having a structure of formula (I).

[0053] [ka]

[0054] During the ceremony, n is an integer from 0 to 4 (e.g., n=1, 2, 3, or 4); Block B comprises an oligomer derived from a polyester, polyether, polyalkylene glycol, polysilicone, or polycarbonate with a MW<10,000 g / mol (e.g., 2±1 KDa, 4±2 KDa, 5±2.5 KDa, or 8±2 KDa); Block A comprises an optionally substituted C1-C6 alkylene, and Block A is derived from a diisocyanate crosslinker; Block W comprises an optionally substituted C0-C3 alkyl-benzene-diol or an optionally substituted C0-C3 alkyl-benzene-triol; the linker L' comprises a carbamate; and The linker L comprises a urea.

[0055] In some embodiments, block B comprises an oligomer derived from a polyester, a polyalkylene glycol, a polysilicone, or a polycarbonate. In certain embodiments, the block B oligomer has a MW≦4,000 g / mol (e.g., 1±0.5 KDa, 2±0.5 KDa, or 3±1 KDa).

[0056] In some embodiments of the second aspect of the present invention, block B has formula (II):

[0057] [ka]

[0058] wherein each o is independently an integer from 0 to 20 (e.g., n=0 to 4, 2 to 6, 4 to 10, 5 to 15, or 10 to 20).

[0059] In some embodiments of the second aspect of the present invention, block B has formula (III):

[0060] [ka]

[0061] wherein each o is independently an integer from 0 to 20 (e.g., n=0 to 4, 2 to 6, 4 to 10, 5 to 15, or 10 to 20).

[0062] In some embodiments of the second aspect of the present invention, block B has formula (IV):

[0063] [ka]

[0064] wherein each o is independently an integer from 0 to 20 (e.g., n=0 to 4, 2 to 6, 4 to 10, 5 to 15, or 10 to 20).

[0065] In some embodiments of the second aspect of the present invention, block B has formula (V):

[0066] [ka]

[0067] where each o is independently an integer from 0 to 20 (eg, n=0-4, 2-6, 4-10, 5-15, or 10-20).

[0068] In some embodiments of the second aspect of the present invention, block B is represented by formula (VI):

[0069] [ka]

[0070] where each o is independently an integer from 0 to 20 (eg, n=0-4, 2-6, 4-10, 5-15, or 10-20).

[0071] In some embodiments of the second aspect of the present invention, block A has formula (VII):

[0072] [ka]

[0073] wherein R 1 is C1-C3 alkyl.

[0074] In some embodiments of the second aspect of the invention, the linker L' is

[0075] [ka]

[0076] It has the structure:

[0077] In some embodiments of the second aspect of the invention, the linker L is

[0078] [ka]

[0079] It has the structure:

[0080] In some embodiments of the second aspect of the invention, the block W is

[0081] [ka]

[0082] It has the structure:

[0083] In some embodiments of the second aspect of the invention, the adhesive composition comprises 30-70% (w / w) of a filler, such as polycaprolactone (PCL), polydioxanone (PDX), poly(lactic-co-glycolic acid) (PLGA), poly-3-hydroxybutyrate (P3HB), polylactic acid (PLA), polyglycolide (PGA), poly-4-hydroxybutyrate (P4HB), polyethylene carbonate (PEC), polypropylene carbonate (PPC), poly(trimethylene carbonate) (PTMC), polysulfone, polyethylene glycol (PEG), hydroxyapatite (HA), tetracalcium phosphate (TTCP), tricalcium phosphate (TCP), dicalcium phosphate (DCP), or copolymers thereof, or blends thereof. In some embodiments, the filler comprises polycaprolactone (PCL), polydioxanone (PDX), poly(lactic-co-glycolic acid) (PLGA), or poly-3-hydroxybutyric acid (P3HB), or copolymers thereof, or blends thereof. In certain embodiments, the filler comprises hydroxyapatite (HA).

[0084] In some embodiments of the second aspect of the present invention, the device includes a plurality of bone anchors and a plurality of support structures capable of stabilizing a plurality of bone fragments within a subject.

[0085] In one embodiment of any of the above devices, (i) the support structure and (ii) at least one of the first anchor and the second anchor are arranged to form an adhesive portion and a support portion forming a backing for the adhesive portion. The adhesive portion is capable of softening upon heating without deforming the support portion. The backing portion may have a thickness of 0.05 to 0.31 mm. In some embodiments, the backing portion has a thickness of 0.12 to 0.20 mm. The adhesive portion may have a thickness of 0.05 to 0.16 mm. In some embodiments, the adhesive portion has a thickness of 0.075±0.025 mm or 0.13±0.03 mm.

[0086] In one embodiment of any of the above devices, the device includes one or more of the following features: (i) the first anchor and the second anchor are capable of adhering to wet or dry bone fragments, respectively; (ii) the first anchor and the second anchor are reversible anchors; (iii) the adhesive composition does not rely on an in situ curing reaction for adhesion; and / or (iv) the adhesive composition reversibly softens at a temperature of 45±5° C. or 55±5° C.

[0087] In a third aspect, the invention features an adhesive composition that includes: (i) 0 to 70% (w / w) of a bulking agent; and (ii) 30 to 100% (w / w) (e.g., 30 to 35% (w / w)) of a polymer having a structure of formula (I):

[0088] [ka]

[0089] During the ceremony, n is an integer from 0 to 4 (e.g., n=1, 2, 3, or 4); Block B comprises an oligomer derived from a polyester, a polyalkylene glycol, a polysilicone, or a polycarbonate with a MW<10,000 g / mol (e.g., 2±1 KDa, 4±2 KDa, 5±2.5 KDa, or 8±2 KDa); Block A comprises an optionally substituted C1-C6 alkylene, and Block A is derived from a diisocyanate crosslinker; Block W comprises an optionally substituted C0-C3 alkyl-benzene-diol or an optionally substituted C0-C3 alkyl-benzene-triol; the linker L' comprises a carbamate; and The linker L comprises a urea, The adhesive composition has a sticking temperature of at least 40° C. (eg, at least 42° C., at least 45° C., at least 50° C., at least 55° C., or between 40° C. and 55° C.).

[0090] In some embodiments, block B comprises an oligomer derived from a polyester, a polyalkylene glycol, a polysilicone, or a polycarbonate. In certain embodiments, the block B oligomer has a MW≦4,000 g / mol (e.g., 1±0.5 KDa, 2±0.5 KDa, or 3±1 KDa).

[0091] In some embodiments of the third aspect, the adhesive composition is not water soluble.

[0092] In some embodiments of the third aspect, the adhesive composition comprises a heat transfer agent {e.g., sodium chloride, iron(III) phosphate dihydrate, iron(III) citrate monohydrate, hydroxyapatite, tetracalcium phosphate, tricalcium phosphate, dicalcium phosphate, and sodium carbonate, or a combination thereof (e.g., hydroxyapatite)}. In some embodiments, the heat transfer agent is present in an amount that allows the softened adhesive composition to cool and harden in 120 seconds or less (e.g., 10 seconds or less). In some embodiments, the heat transfer agent is present in an amount that allows the adhesive composition to soften within 120 seconds (e.g., 10 seconds or less) after the application of energy. In some embodiments, the heat transfer agent comprises about 0.5-60% (w / w) of the adhesive composition (e.g., 7.5±2.5%, 10±5%, 15±5%, 20±5%, 25±10%, 37.5±5%, 50±10%, or 35-60% (w / w)).

[0093] In some embodiments of the third aspect, block B has formula (II):

[0094] [ka]

[0095] wherein each o is independently an integer from 0 to 20 (e.g., n=0 to 4, 2 to 6, 4 to 10, 5 to 15, or 10 to 20).

[0096] In some embodiments of the third aspect of the present invention, block B has formula (III):

[0097] [ka]

[0098] wherein each o is independently an integer from 0 to 20 (e.g., n=0 to 4, 2 to 6, 4 to 10, 5 to 15, or 10 to 20).

[0099] In some embodiments of the third aspect of the present invention, block B has formula (IV):

[0100] [ka]

[0101] wherein each o is independently an integer from 0 to 20 (e.g., n=0 to 4, 2 to 6, 4 to 10, 5 to 15, or 10 to 20).

[0102] In some embodiments of the third aspect of the present invention, block B has formula (V):

[0103] [ka]

[0104] where each o is independently an integer from 0 to 20 (eg, n=0-4, 2-6, 4-10, 5-15, or 10-20).

[0105] In some embodiments of the third aspect of the present invention, block B has formula (VI):

[0106] [ka]

[0107] where each o is independently an integer from 0 to 20 (eg, n=0-4, 2-6, 4-10, 5-15, or 10-20).

[0108] In some embodiments of the third aspect of the present invention, block A has formula (VII):

[0109] [ka]

[0110] wherein R 1 is C1-C3 alkyl.

[0111] In some embodiments of the third aspect of the invention, the linker L' is

[0112] [ka]

[0113] It has the structure:

[0114] In some embodiments of the third aspect of the invention, the linker L is

[0115] [ka] It has the structure:

[0116] In some embodiments of the third aspect of the invention, the block W is

[0117] [ka] It has the structure:

[0118] In some embodiments of the third aspect, the filler includes polycaprolactone (PCL), polydioxanone (PDX), poly(lactic-co-glycolic acid) (PLGA), poly-3-hydroxybutyric acid (P3HB), polylactic acid (PLA), polyglycolide (PGA), poly-4-hydroxybutyric acid (P4HB), polyethylene carbonate (PEC), polypropylene carbonate (PPC), poly(trimethylene carbonate) (PTMC), polysulfone, polyethylene glycol (PEG), hydroxyapatite (HA), tetracalcium phosphate (TTCP), tricalcium phosphate (TCP), dicalcium phosphate (DCP), or copolymers thereof, or blends thereof. In some embodiments, the filler includes polycaprolactone (PCL), polydioxanone (PDX), poly(lactic-co-glycolic acid) (PLGA), or poly-3-hydroxybutyric acid (P3HB), or copolymers thereof, or blends thereof. In certain embodiments, the filler includes hydroxyapatite (HA).

[0119] In a fourth aspect, the invention features a tape that includes (i) a non-adhesive polymeric overlayer and (ii) an underlayer that includes the adhesive composition of any one of the preceding embodiments.

[0120] In one embodiment of the layered tape, (i) a support structure and (ii) at least one of the first anchor and the second anchor are arranged to form an adhesive portion and a support portion forming a backing for the adhesive portion, where the adhesive portion is capable of softening upon heating without deforming the support portion. The thickness of the backing portion can be 0.05-0.31 mm. In some embodiments, the backing portion has a thickness of 0.12 to 0.20 mm. The thickness of the adhesive portion can be 0.05-0.16 mm. In some embodiments, the adhesive portion has a thickness of 0.075±0.025 mm or 0.13±0.03 mm. In one embodiment of the layered tape, the tape includes one or more of the following features: (i) the first anchor and the second anchor are each capable of adhering to wet or dry bone fragments; (ii) the first anchor and the second anchor are reversible anchors; and (iii) the adhesive composition does not rely on an in situ curing reaction for adhesion. and / or (iv) the adhesive composition reversibly softens at a temperature of 45±5°C or 55±5°C.

[0121] In some embodiments of the fourth aspect, the non-adhesive polymeric top layer comprises polycaprolactone (PCL), polydioxanone (PDX), poly(lactic-co-glycolic acid) (PLGA), poly-3-hydroxybutyric acid (P3HB), polylactic acid (PLA), polyglycolide (PGA), poly-4-hydroxybutyric acid (P4HB), polyethylene carbonate (PEC), polypropylene carbonate (PPC), poly(trimethylene carbonate) (PTMC), polysulfone, polyethylene glycol (PEG), or copolymers thereof.

[0122] In a fourth aspect, the invention features a method of making an apparatus of the invention or a tape of the invention, the method including: a) contacting (i) a first portion including an adhesive composition of the invention with (ii) a second portion including a support structure; and b) applying heat to bond the first portion and the second portion. In certain embodiments, the method further includes applying a force to compress the first portion and the second portion. For example, a force of at least 800 kg can be applied. In some embodiments, the first and second portions can be joined by lamination, hi certain embodiments, one or both of the first and second portions are in the form of a sheet.

[0123] definition As used herein, the term "about" refers to values ​​within a range of ±10% of the value following the term "about."

[0124] The term "adhesive section" as used herein refers to a portion of the device of the present disclosure that includes an adhesive composition. For example, the adhesive section of the device of the present invention may be composed of 30-100% (w / w) of one or more adhesive compositions (e.g., polymers having the structure of formula (I) described herein), 0-70% (w / w) of one or more fillers (e.g., non-sticky polymers), and 0.5-60% (w / w) of one or more heat transfer agents. The adhesive section adheres to at least one object (e.g., bone fragments). The adhesive section may be on one side (e.g., the adhesive side; the face of the adhesive side) of the device.

[0125] As used herein, the term "adhesive side" refers to a coating or layer that includes: 1) one or more adhesives (e.g., preferably multiple adhesives); 2) one or more fillers; and 3) one or more heat transfer agents. The adhesive side can soften when exposed to energy, such as, for example, ultrasonic energy, infrared, radio frequency (RF), etc.

[0126] As used herein, the term "adhesive composition" refers to compounds and mixtures capable of adhering one or more objects or materials together. The adhesive composition may be a polymer having the structure of formula (I) as described herein.

[0127] As used herein, the term "biocompatible" means that the material does not adversely affect cells, tissues, or biological functions in the indicated application, or meets the limits specified by internationally recognized testing standards governing biocompatible materials for medical applications.

[0128] As used herein, the term "biodegradable" means that a material can be broken down by the action of living organisms (e.g., in vivo physiological environment), particularly into harmless products. Biodegradable materials may be hydrolytically or enzymatically degradable.

[0129] The term "filler" as used herein refers to a non-adhesive material or substance that is added to modify properties such as, but not limited to, adhesive strength, adhesion temperature, cytotoxicity, tensile strength, cure time, and viscosity. For example, the filler can be, for example, polycaprolactone (PCL), polydioxanone (PDX), poly(lactic-co-glycolic acid) (PLGA), poly-3-hydroxybutyric acid (P3HB), polylactic acid (PLA), polyglycolide (PGA), poly-4-hydroxybutyric acid (P4HB), polyethylene carbonate (PEC), polypropylene carbonate (PPC), poly(trimethylene carbonate) (PTMC), polysulfone, polyethylene glycol (PEG), hydroxyapatite (HA), tetracalcium phosphate (TTCP), tricalcium phosphate (TCP), dicalcium phosphate (DCP), or copolymers thereof.

[0130] As used herein, the term "thermal transfer agent" refers to a compound that promotes the formation of a softened adhesive. The thermal transfer agent may be, for example, a salt such as sodium chloride, iron (III) phosphate dihydrate, iron (III) citrate monohydrate, hydroxyapatite, tetracalcium phosphate (TTCP), tricalcium phosphate (TCP), dicalcium phosphate (DCP), or sodium carbonate.

[0131] As used herein, the term "set (stiffen)" refers to an increase in the stiffness of a material or substance. For example, the adhesive section (or adhesive side) of the present disclosure can soften (e.g., within 120 seconds (e.g., within 10 seconds)) after being exposed to energy. The adhesive section (or adhesive side) can then set (i.e., harden) within 120 seconds (e.g., within 10 seconds). The solidification of the adhesive section (or adhesive side) that secures two (or more) bone fragments to each other allows the fracture to heal.

[0132] As used herein, the term "softening" refers to a decrease in the stiffness of a material or substance. For example, the device or adhesive side of the present disclosure can soften after being exposed to energy, and within 120 seconds or less (e.g., 10 seconds or less), the softened adhesive side (the surface of the adhesive side) can flow and conform to the shape of biological tissue or other substrate.

[0133] As used herein, the term "tackifying temperature" refers to the temperature at which an adhesive blend or formulation goes from non-flowable to thread-forming when contacted with a glass pipette tip. The adhesive blend or formulation may lose stiffness (e.g., reversible phase transition temperature). For example, the device or adhesive side of the present disclosure may soften (e.g., the device or adhesive side of the present disclosure) upon reaching the tackifying temperature.

[0134] As used herein, the term "subject" refers to a human or a non-human animal (eg, a mammal such as a non-human primate, horse, cow, pig, or dog).

[0135] As used herein, the term "support structure" refers to a portion of the device of the present disclosure that physically supports the adhesive portion. For example, the device of the present invention may be composed of 40-100% of one or more non-adhesive polymers (e.g., as a support). The support structure is between two adhesive portions. For example, the support structure may be on one side (e.g., the support side) of the device.

[0136] As used herein, the term "support side" refers to a support structure that is disposed as a backing for the adhesive side of the device of the present invention. The support side can be formed from one or more non-adhesive polymers, such as, for example, polycaprolactone (PCL), polydioxanone (PDX), poly(lactic-co-glycolic acid) (PLGA), poly-3-hydroxybutyric acid (P3HB), polylactic acid (PLA), polyglycolide (PGA), poly-4-hydroxybutyric acid (P4HB), polyethylene carbonate (PEC), polypropylene carbonate (PPC), poly(trimethylene carbonate) (PTMC), polysulfone, polyethylene glycol (PEG), or copolymers thereof. For example, when the device is a bone tape, the support side can constitute a non-adhesive backing that structurally supports the adhesive portion on the adhesive side of the bone tape.

[0137] As used herein, the term "surface fouling" refers to an adhesive, or a mixture of two or more adhesives, that has lost its ability to adhere to a surface in the presence of aqueous liquids (e.g., water, blood, serum, plasma). The adhesive portion of the device of the present invention can be formulated to resist surface fouling.

[0138] As used herein, the term "water-soluble" refers to a material or substance that dissolves in water. A "water-insoluble" material or substance (e.g., the adhesive part (or adhesive side) of the present disclosure) refers to a material or substance in which less than 30 mg of the material or substance dissolves in 1 L of water at 25°C.

[0139] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by those skilled in the art to which this invention belongs. Methods and materials for use in this disclosure are described herein. Other suitable methods and materials known in the art can also be used. Materials, methods, and examples are merely illustrative and are not intended to be limiting. All publications, patent applications, patents, sequences, database entries, and other references mentioned herein are incorporated by reference in their entirety. In case of discrepancy, the present specification, including definitions, will prevail.

[0140] The details of one or more embodiments of the invention are set forth in the description below. Other features, objects, and advantages of the invention will become apparent from the description and the claims.

[0141] chemical terms It is to be understood that the terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting.

[0142] At various places herein, substituents of the compounds of the present disclosure are disclosed in groups or ranges. It is specifically intended that the present disclosure includes every individual subcombination of the members of such groups and ranges. For example, the term "C1-C6 alkyl" is specifically intended to individually disclose methyl, ethyl, propyl, butyl, pentyl, and hexyl. Furthermore, when a compound includes multiple positions where a substituent is disclosed in a group or range, unless otherwise indicated, the present disclosure is intended to cover the group (e.g., genera and subgenera) of compounds including each individual compound and every individual, including each and every individual subcombination of the members at each position.

[0143] The term "alkyl," as used herein, refers to a branched or straight-chain monovalent saturated aliphatic hydrocarbon radical of 1 to 20 carbon atoms (e.g., 1 to 16 carbon atoms, 1 to 10 carbon atoms, or 1 to 6 carbon atoms). In some embodiments, an alkyl group is unbranched (i.e., straight chain). In some embodiments, an alkyl group is branched. Alkyl groups are exemplified by methyl, ethyl, n- and iso-propyl, n-, sec-, iso- and tert-butyl, neopentyl, and the like.

[0144] As used herein, the term "alkylene" refers to a saturated bivalent linker having a particular size (e.g., C 1-6 refers to -alkylene). They include straight chain, branched chain, and cyclic forms, and combinations thereof, and contain only C and H when unsubstituted. They are divalent, and therefore capable of linking two parts of a molecule. Examples include -CH2-, -CH2CH2-, -CH2CH2CH2-, -CH2CH2CH2CH2-, -CH2CH2CH2CH2CH2-, and -CH2CH2CH2CH2CH2CH2-. These groups can be substituted with groups typically suitable as substituents on alkyl groups as described herein.

[0145] As used herein, the terms "C0-C3 alkyl-benzene-diol" and "C0-C3 alkyl-benzene-triol" refer to a substituent optionally containing an alkyl chain of 0 to 3 carbons in length and terminating in a benzene-diol or benzene-triol. The substituent can have the formula:

[0146] [ka]

[0147] where m is 0, 1, 2, or 3. p is 2 or 3.

[0148] As used herein, phrases of the form "optionally substituted X" (e.g., optionally substituted alkyl) are intended to be equivalent to "X, where X is optionally substituted" (e.g., "said alkyl is optionally substituted alkyl"). This does not imply that the feature "X" (e.g., alkyl) itself is optional. In certain embodiments, substitution with a given structure is required, where optionally substituted refers to one or more additional substituents. For example, the moiety -L 2 -R 4 In L 2 is alkyl, the moiety is a group R 4 Alkyl substituted by "L 2 ". In some embodiments, the term optionally substituted X means that X is optionally substituted with one or more (e.g., 1, 2, 3, 4, 5, or 6) substituents, which may independently be any of the substituents described herein. Exemplary substituents include, but are not limited to, alkyl, hydroxyl, alkoxy, aryloxy, halogen, fluoroalkyl, carboxyl, carboxyalkyl, amino, aminoalkyl, monosubstituted amino, disubstituted amino, and quaternary amino groups containing 0-6 carbon atoms and 0-4 heteroatoms selected from O, N, F, Cl, Br, and I. Substituents include methyl, ethyl, carboxymethyl, acyl, CF3, fluoro, and chloro. [Brief description of the drawings]

[0149] [Figure 1] Graph showing the cytotoxicity of materials compared to negative and positive controls (DMEM and 5% DMSO, respectively). Results are expressed as mean ± standard deviation; n=4. [Diagram 2] 1 is a graph showing the change in stick temperature of an adhesive when blended with other adhesive compounds (normalized to the temperature of the adhesive with the lowest stick temperature). DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0150] The present disclosure features adhesive devices for fixing and holding objects (e.g., bone fragments) together. The disclosed devices are useful for attaching to bone or fastening materials to tissue to provide stability or support. The disclosed devices can eliminate or reduce the need to use staples, sutures, tacks, screws, etc. to fix or repair damaged tissue (or bone) or to secure implants within the body.

[0151] Device The devices of the present disclosure can be used to hold two or more objects (e.g., bone fragments, ligaments, tendons) in place relative to one another. The devices of the present disclosure can be made from a gradient of a mixture of one or more adhesives (e.g., polymers having the structure of formula (I) described herein) and one or more fillers (e.g., non-adhesive polymers).

[0152] Adhesive, filler, and heat transfer agent blending (gradient) The device of the present disclosure may have different compositions in different parts of the device. For example, the device may have at least two parts: (i) at least one adhesive portion (e.g., a portion of the device comprised of 30-100% (w / w) of one or more adhesives (e.g., polymers having the structure of Formula (I) described herein), 0-70% (w / w) of one or more fillers (e.g., non-adhesive polymers), and 0.5-60% (w / w) of one or more heat transfer agents) that attach to at least one object (e.g., tissue such as a bone fragment, ligament, tendon, etc.); and (ii) at least one support structure {e.g., a portion of a device that is comprised of 40-100% (w / w) of one or more fillers (e.g., non-sticky polymers), and 0-60% (w / w) of zero or more adhesives and zero or more heat transfer agents} may include. The support structure may be formed from an anchoring material, such as polycaprolactone. The adhesive (e.g., a portion of the device comprised of a sufficiently large amount of adhesive) may be non-tacky at room temperature, but may soften when exposed to energy, such as ultrasonic energy, infrared radiation, or radio frequency (RF). The softened adhesive can conform to the shape of the object (e.g., bone fragment) it comes into contact with. When exposure to energy ceases, the adhesive cools and hardens, bonding the object (e.g., bone fragment) it comes into contact with. This process is repeated for the second object (and third, fourth, fifth, or however many objects are secured to the previous object). This reversible softening feature of the adhesive is advantageous for ease of handling, positioning, workflow, and control of device application.

[0153] The adhesive and support structure may be arranged to form two sides (faces) of the device: an adhesive side (where the adhesive is a coating of one or more adhesives mixed with one or more fillers) that contacts and adheres to two or more objects (e.g., bone fragments), and a support side (support side face) that backs up the adhesive side. In this case, energy (e.g., ultrasonic energy, infrared, radio frequency (RF)) is delivered to the support side of the device through which heat is transferred to the adhesive side (contacting the objects) without significant deformation of the support structure. This selective softening of the adhesive component relative to the support component element is advantageous for retaining the strength and / or performance of the support structure.

[0154] The adhesive (or adhesive side) may be comprised of a mixture of an adhesive (e.g., a polymer having the structure of formula (I) described herein) and a filler that can be varied to change properties of the device of the present disclosure, such as, for example, adhesive strength, adhesion temperature, cytotoxicity, tensile strength, cure time, surface stain resistance, brittleness, viscosity, etc.

[0155] The support structure (or support side) may be comprised of a mixture of filler and adhesive and may be modified to modify the properties of the support, such as, for example, porosity (e.g., having pores or texture that may be filled with adhesive), brittleness (e.g., the support structure (or support side) preferably can be bent or twisted 90° without delaminating), flexibility, surface staining properties, and tensile strength. Additionally, the support structure (or support side) may include a sensible pattern or texture to aid in determining the direction and orientation of application. This pattern may include a pattern that provides both visual and / or tactile senses for determining direction.

[0156] The devices of the present disclosure (and their components, e.g., the adhesive and non-adhesive polymers that make up the adhesive portion (and adhesive side) and the support structure (and support side)) may optionally be biodegradable and, optionally, biocompatible. Additionally, the devices (and their components described herein) may optionally be bioabsorbable.

[0157] Adhesives of the Present Disclosure The devices of the present disclosure may include a mixture of one or more adhesives having the structure of formula (I).

[0158] [ka]

[0159] n is an integer from 0 to 4 (e.g., n=1, 2, 3, or 4); Block B comprises an oligomer derived from a polyester, polyether, polyalkylene glycol, polysilicone, or polycarbonate with a MW<10,000 g / mol (e.g., 2±1 KDa, 4±2 KDa, 5±2.5 KDa, or 8±2 KDa); Block A comprises an optionally substituted C1-C6 alkylene, and Block A is derived from a diisocyanate crosslinker; Block W comprises an optionally substituted C0-C3 alkyl-benzene-diol or an optionally substituted C0-C3 alkyl-benzene-triol; the linker L' comprises a carbamate; and The linker L comprises a urea.

[0160] In some embodiments, block B comprises an oligomer derived from a polyester, a polyalkylene glycol, a polysilicone, or a polycarbonate. In certain embodiments, the block B oligomer has a MW≦4,000 g / mol (e.g., 1±0.5 KDa, 2±0.5 KDa, or 3±1 KDa).

[0161] Block B can have a structure of formula (II), formula (III), formula (IV), formula (V), or formula (IV).

[0162] [ka]

[0163] In the formula, each o is independently an integer from 0 to 20 (e.g., n=0 to 4, 2 to 6, 4 to 10, 5 to 15, or 10 to 20).

[0164] Block A is represented by formula (VII):

[0165] [ka] In the formula, R 1 is C1-C3 alkyl.

[0166] The linker L' has the structure:

[0167] [ka]

[0168] may have the following structure:

[0169] The linker L has the structure:

[0170] [ka]

[0171] may have the following structure:

[0172] Block W has the structure:

[0173] [ka]

[0174] may have the following structure:

[0175] The isolated adhesive compound may have a tack temperature of at least 10° C., at least 15° C., at least 20° C., at least 25° C., or between 10° C. and 55° C. The blended material containing the adhesive compound may have a tackification temperature of at least 40° C. (e.g., at least 42° C., at least 45° C., at least 50° C., at least 55° C., or between 40° C. and 55° C.).

[0176] The adhesive or adhesive mixture of the present disclosure may be optionally biodegradable and optionally biocompatible. Additionally, the adhesive or adhesive mixture may optionally be bioabsorbable. The adhesive or adhesive mixture of the present disclosure may have a water solubility of less than 30 mg per liter of water.

[0177] Generally, all adhesives used in biomedical devices as seen in the prior art use monomers (e.g., monomers) or teach the assembly of irreversible crosslinked networks with large polymer assemblies chemically formed from monomers (US20140311673A1, WO2017044896A1, WO2014158288A1, US20120029559A1, US20160346424A1, WO2016134304A1, PCT / CA2020051781). They teach that low molecular weight molecules with low viscosity must be used to flow before curing, or that if large solid polymeric materials are used, solvents or other diluents are required to make them flowable. However, the use of solvents in biomedical adhesives introduces unnecessary toxicity or prevents the adhesive from curing or bonding. Additionally, flowable systems are susceptible to leakage or leaching of reactive adhesive components and / or oxidizing agents from the application site, and / or retention of unreacted species, all of which may manifest as an inflammatory response in vivo.

[0178] Compared to the prior art, adhesives of formula I do not rely on an in situ curing reaction for adhesion and are less susceptible to adhesive leaching / flowing out of the application site, which can lead to unwanted side reactions and inflammatory complications. Furthermore, the nature of block B also means that these adhesives are particularly resistant to swelling and therefore less susceptible to inflammatory complications due to device swelling in vivo. The reversible softening properties of the adhesive at temperatures close to physiological temperatures result in advantages such as no need for solvents to wet the surface, non-tacky at room temperature facilitating workflow, and no need for high temperatures to soften the adhesive, reducing the risk of tissue necrosis.

[0179] Filler The device of the present disclosure may contain one or more fillers in various amounts (or gradients). The filler may be a non-adhesive material or a substance that may be added to change the properties of the device of the present disclosure, such as adhesive strength, adhesion temperature, cytotoxicity, tensile strength, curing time, and viscosity. For example, the filler may be, for example, polycaprolactone (PCL), polydioxanone (PDX), poly(lactic-co-glycolic acid) (PLGA), poly-3-hydroxybutyric acid (P3HB), polylactic acid (PLA), polyglycolide (PGA), poly-4-hydroxybutyric acid (P4HB), polyethylene carbonate (PEC), polypropylene carbonate (PPC), poly(trimethylene carbonate) (PTMC), polysulfone, polyethylene glycol (PEG), hydroxyapatite (HA), tetracalcium phosphate (TTCP), tricalcium phosphate (TCP), dicalcium phosphate (DCP), or copolymers thereof. Preferably, the support structure (or the support side) can comprise one or more of polycaprolactone (PCL), polydioxanone (PDX), poly(lactic-co-glycolic acid) (PLGA), or poly-3-hydroxybutyric acid (P3HB), and copolymers thereof. More preferably, the support structure exhibits a melting temperature at least 20° C. higher than the melting temperature of the adhesive component (e.g., at least 20° C., 25° C., 30° C., 35° C., 40° C., 45° C., 50° C., 55° C., 60° C., 65° C., 70° C., 75° C., 80° C., 85° C., 90° C., 95° C., 100° C., 105° C., 110° C., 115° C., 120° C., 125° C., 130° C., 135° C., 140° C., 145° C., or 150° C. higher than the temperature of the adhesive component). Even more preferably, the support structure exhibits a melting temperature at least 100° C. higher than the melting temperature of the adhesive component.

[0180] The filler or mixture of fillers of the present disclosure may be optionally biodegradable and optionally biocompatible. Additionally, the filler or mixture of fillers may optionally be bioabsorbable.

[0181] Heat Transfer Agent The adhesive portion (or adhesive side) may include one or more heat transfer agents (e.g., compounds that may facilitate the formation of a softened adhesive) in the adhesive portion or adhesive side of the device. The heat transfer agent may be, for example, a salt such as sodium chloride, iron (III) phosphate dihydrate, iron (III) citrate monohydrate, hydroxyapatite, tetracalcium phosphate (TTCP), tricalcium phosphate (TCP), dicalcium phosphate (DCP), or sodium carbonate.

[0182] Softening and hardening of the device The adhesive (or adhesive side) can reversibly soften (e.g., decrease in stiffness) or solidify (e.g., increase in stiffness) upon exposure to energy (e.g., ultrasonic energy, infrared radiation, radio frequency (RF)) or upon cooling (e.g., cooling at ambient temperature without exposure to the energy described herein). When the adhesive or adhesive mixture undergoes a phase transition from a solid state to a softened state (hard to malleable), the adhesive (or adhesive side) can soften and form a softened polymer thread upon contact with a glass pipette tip. Once softened, the adhesive (or adhesive side) can be contacted with one or more attachment objects. The softened adhesive (or adhesive side) can harden within 120 seconds (e.g., less than 10 seconds) after the adhesive (or adhesive side) is no longer exposed to energy (e.g., ultrasonic energy, infrared radiation, radio frequency (RF)). Preferably, the disclosed adhesive (or adhesive side) has a tackifying temperature of 40° C. or greater.

[0183] Device dimensions The devices of the present disclosure may have a thickness of 0.02-1.5 mm (e.g., 0.3±0.2 mm). Depending on the application and the mass of tissue / bone to be stabilized, this thickness will vary. For example, thinner devices (e.g., 0.05 mm thick) may be used for soft tissue applications, while thicker devices may be used for bone stabilization (e.g., 1.0 mm thick). Thus, the time required for the adhesive portion (or adhesive side) to soften is proportional to the thickness of the device. Furthermore, the time required for hardening is proportional to the thickness of the device.

[0184] The devices of the present disclosure can be prepared as sheets up to 100 mm long and up to 100 mm wide (e.g., 60 mm x 60 mm) (with all the components of the device described herein (e.g., adhesives, support structures)). The sheets can be cut to any size and shape (e.g., 10 mm x 40 mm) with thicknesses as described herein.

[0185] Surface stain prevention properties The device of the present disclosure (specifically, the adhesive or adhesive side) can resist surface staining in the presence of an aqueous medium (e.g., blood). The adhesive or adhesive mixture described herein can bond to an object (e.g., wet or dry tissue) as described herein. Once bonded, the adhesive or mixture can remain bonded to the object in the presence of an aqueous medium (such as blood). For example, the device of the present disclosure can bond two (or more) objects in the presence of blood (e.g., horse blood or sheep blood).

[0186] Uses and Treatments The disclosed devices are useful for attaching to an object (e.g., bone) or fastening an object to another object (e.g., a substance to tissue) to provide stability or support. The disclosed devices can eliminate or reduce the need to use staples, sutures, tacks, screws, etc. to fasten or repair damaged tissue (or bone) or to fasten implants within the body.

[0187] Attachment to bone The devices of the present disclosure may be useful for holding bone fragments (eg, bone fragments within or from a subject) fixed to one another.

[0188] Two or more bone fragments may be bonded (and thus fixed) to one or more devices disclosed herein. The bone fragment may be in contact with the adhesive portion (or adhesive side) of the device. Another bone fragment may be in contact with the same adhesive portion (or adhesive side) or may be in contact with a second adhesive portion of the device. The contacted adhesive portion may then be softened using an energy source, such as ultrasonic energy, infrared, radio frequency (RF), etc. After cooling, the adhesive portion solidifies and bonds with the bone fragment. The process may then be repeated for each adhesive portion and bone fragment contact area. The bonded device may thus stabilize the fracture and maintain the physiological alignment required for bone union. The process may also be performed in situ or ex situ (e.g., the fragments may be removed from the body, bonded to the adhesive portion (or adhesive side) of the device, and then returned to their original position for further fixation).

[0189] The devices of the present disclosure may secure and hold two or more (e.g., 2-5, 6-10, 11-15, 16-20, 21-25, 26-30, 31-35, 36-40, 41-45, 46-50 or more) bone fragments together. The bone fragments may be secured together using at least one device. In some cases, two or more (e.g., 2-5, 6-10, 11-15, 16-20, 21-25, 26-30, 30-40, 40-50 or more) of the disclosed devices may be used to secure and hold two or more bone fragments together.

[0190] The devices of the present disclosure can be used in combination with current standards of care, such as, for example, stabilizing traditional plates or holding communitions or scaffolds in place in load-bearing areas.

[0191] Tissue Scaffold The devices of the present disclosure can be used to hold a tissue scaffold or filler material in place within a defect to allow regeneration to occur.

[0192] Installation on already installed equipment The devices of the present disclosure may be used to attach to an object (e.g., bone) or to secure an object to another object (e.g., material to tissue) by applying additional devices over a previously attached device of the present disclosure to increase the rigidity of the fixation.

[0193] Enumeration of embodiments Some specific embodiments are listed below. The embodiments listed below should not be construed as limiting the scope of the present disclosure, but rather the following embodiments are presented as some examples of the utility of the present disclosure.

[0194] 1. A method for stabilizing bone fragments in a body, comprising: (i) forming a first anchor on a first bone fragment by (a) heating an adhesive composition to form a softened adhesive composition, contacting the softened adhesive composition with a first bone fragment, and (b) allowing the softened adhesive composition to cool to form a first anchor secured to the first bone fragment; (ii) forming a second anchor on the second bone fragment by (a) heating the adhesive composition to form a softened adhesive composition, contacting the softened adhesive composition with a second bone fragment, and (b) allowing the softened adhesive composition to cool to form a second anchor secured to the second bone fragment. Including, wherein the adhesive composition has a tackifying temperature of at least 40° C. The first anchor and the second anchor are connected to a support structure for stabilizing the bone fragment. A method for stabilizing bone fragments within the body.

[0195] 2. The method of embodiment 1, wherein the support structure is a flexible support comprising a biodegradable and biocompatible polymer that connects the first anchor to the second anchor.

[0196] 3. The method of embodiment 2, wherein the support structure, first anchor, and second anchor are formed from a tape including (x) a non-adhesive upper layer that is the support structure, and (y) a lower layer that becomes adhesive when softened to form the first anchor and second anchor.

[0197] 4. The method of any one of embodiments 1 to 3, wherein a) the adhesive composition is not water-soluble.

[0198] 5. The method of any one of the preceding claims, wherein the adhesive composition comprises a heat transfer agent.

[0199] 6. The method of embodiment 5, wherein the heat transfer agent is present in an amount that enables the softened adhesive composition to cool and harden in 120 seconds or less.

[0200] 7. The method of embodiment 6, wherein the heat transfer agent is present in an amount that enables the softened adhesive composition to cool and harden in 10 seconds or less.

[0201] 8. The method of any one of embodiments 5-7, wherein the heat transfer agent is present in an amount that allows the adhesive composition to soften within 120 seconds of the application of energy.

[0202] 9. The method of embodiment 8, wherein the heat transfer agent is present in an amount that enables the adhesive composition to soften within 10 seconds of applying energy to the non-adhesive top layer.

[0203] 10. The method of any one of embodiments 5-9, wherein the heat transfer agent is selected from the group consisting of sodium chloride, iron(III) phosphate dihydrate, iron(III) citrate monohydrate, hydroxyapatite, tetracalcium phosphate, tricalcium phosphate, dicalcium phosphate, and sodium carbonate, or a combination thereof.

[0204] 11. The method of embodiment 10, wherein the heat transfer agent is hydroxyapatite.

[0205] 12. The method of any one of claims 5 to 11, wherein the adhesive composition comprises about 0.5 to 60% (w / w) of a heat transfer agent.

[0206] 13. The adhesive composition comprises about 35-60% (w / w) of a heat transfer agent; 13. The method of embodiment 12.

[0207] 14. The method of any one of the preceding embodiments, wherein the adhesive composition comprises a polymer having a structure of formula (I). [ka] (In the formula, n is an integer from 0 to 4 (e.g., n=1, 2, 3, or 4); Block B comprises an oligomer derived from a polyester, a polyalkylene glycol, a polysilicone, or a polycarbonate, with a MW≦4,000 g / mol; Block A comprises an optionally substituted C1-C6 alkylene, and Block A is derived from a diisocyanate crosslinker; Block W comprises an optionally substituted C0-C3 alkyl-benzene-diol or an optionally substituted C0-C3 alkyl-benzene-triol; the linker L' comprises a carbamate; and The linker L comprises a urea.

[0208] 15. Block B is of formula (II): [ka] (In the formula, each o is independently an integer of 0 to 20.) 15. The method of embodiment 14, having the structure:

[0209] 16. Block B is of formula (III): [ka] (In the formula, each o is independently an integer of 0 to 20.) 15. The method of embodiment 14, having the structure:

[0210] 17. Block B is of formula (IV): [ka] (In the formula, each o is independently an integer of 0 to 20.) 15. The method of embodiment 14, having the structure:

[0211] 18. Block B is a compound of formula (V): [ka] (In the formula, each o is independently an integer of 0 to 20.) 15. The method of embodiment 14, having the structure:

[0212] 19. Block A is of formula (VII): [ka] (In the formula, R 1 is C1-C3 alkyl. 19. The method of any one of embodiments 14 to 18, having the structure:

[0213] 20. The linker L' is [ka] 20. The method of any one of embodiments 14 to 19, having the structure:

[0214] 21. The linker L is [ka] 21. The method of any one of embodiments 14 to 20, having the structure:

[0215] 22. Block W is [ka] 22. The method of any one of embodiments 14 to 21, having the structure:

[0216] 23. The method of any one of the preceding embodiments, wherein the adhesive composition comprises 30-70% (w / w) of a filler.

[0217] 24. The method of embodiment 23, wherein the filler comprises polycaprolactone (PCL), polydioxanone (PDX), poly(lactic-co-glycolic acid) (PLGA), poly-3-hydroxybutyrate (P3HB), polylactic acid (PLA), polyglycolide (PGA), poly-4-hydroxybutyrate (P4HB), polyethylene carbonate (PEC), polypropylene carbonate (PPC), poly(trimethylene carbonate) (PTMC), polysulfone, polyethylene glycol (PEG), hydroxyapatite (HA), tetracalcium phosphate (TTCP), tricalcium phosphate (TCP), dicalcium phosphate (DCP), or copolymers thereof, or blends thereof.

[0218] 25. The method of embodiment 24, wherein the filler comprises polycaprolactone (PCL), polydioxanone (PDX), poly(lactic-co-glycolic acid) (PLGA), or poly-3-hydroxybutyric acid (P3HB), hydroxyapatite (HA), or copolymers thereof, or blends thereof.

[0219] 26. A method according to any one of embodiments 1 to 25, wherein steps (i) and (ii) are repeated to stabilize multiple bone fragments in the subject.

[0220] 27. The method of embodiment 26, wherein 2 to 5, 6 to 10, 11 to 15, 16 to 20, 21 to 25, 26 to 30, 31 to 35, 36 to 40, 41 to 45, 46 to 50 or more bone fragments are stabilized as the object.

[0221] 28. The method of any one of the preceding embodiments, wherein the heating comprises applying an energy source.

[0222] 29. The method of embodiment 28, wherein the energy source is ultrasonic energy.

[0223] 30. The method of embodiment 29, wherein the ultrasonic energy is applied at a frequency of 35 kHz to 70 kHz.

[0224] 31. The method of embodiment 30, wherein the frequency of the ultrasonic energy is 70 kHz.

[0225] 32. A method according to any one of embodiments 28 to 31, wherein an energy of 1.5 to 5.0 J is applied.

[0226] 33. The method of any one of embodiments 29-32, wherein ultrasonic energy is applied at a frequency and in an amount sufficient to transfer fluid between the adhesive composition and the bone fragments prior to formation of the first anchor and the second anchor.

[0227] 34. The method of any one of embodiments 29-33, wherein the ultrasonic energy is applied using an ultrasonic welder.

[0228] 35. The method of embodiment 34, wherein the ultrasonic welding machine includes a horn tip having individual texture elements, the individual texture elements being equally spaced at a uniform depth of up to 0.127 mm.

[0229] 36. A method according to any one of embodiments 1 to 35, comprising reversibly stabilizing the bone fragments.

[0230] 37. The method of any one of embodiments 1 to 36, wherein the first anchor and the second anchor are reversible anchors.

[0231] 38. The method of any one of the preceding embodiments, wherein the adhesive composition does not rely on an in situ curing reaction for adhesion.

[0232] 39. The method of any one of embodiments 1 to 38, wherein the adhesive composition reversibly softens at a temperature of 45±5° C.

[0233] 40. The method of any one of embodiments 1-39, wherein the support structure, first anchor, and second anchor are formed from a tape including (x) a non-adhesive upper layer that is the support structure, and (y) a lower layer that softens and becomes adhesive to form the first anchor and second anchor.

[0234] 41. The method of any one of embodiments 1 to 40, comprising: (i) a support structure; and (ii) at least one of the first anchor and the second anchor, arranged to form an adhesive portion and a support portion that forms a backing for the adhesive portion, the adhesive portion being capable of softening when heated without deforming the support portion.

[0235] 42. The method of embodiment 41, wherein the backing portion has a thickness of 0.05 to 0.31 mm, and optionally, the backing portion has a thickness of 0.12 to 0.20 mm.

[0236] 43. The method of embodiment 41 or 42, wherein the adhesive portion has a thickness of 0.05 to 0.16 mm, and optionally, the adhesive portion has a thickness of 0.075±0.025 mm.

[0237] 44. The method of embodiment 43, wherein the adhesive portion has a thickness of 0.13±0.03 mm.

[0238] 45. The method of any one of the preceding embodiments, wherein the heat is applied using a welder via a series of continuous welding studs perpendicular to the application surface to cover the entire surface.

[0239] 46. ​​The method of any one of the preceding claims, wherein the heating comprises continuously sliding a welder across the surface of the device in a brush stroke or painting motion.

[0240] 47. A device for stabilizing bone fragments, comprising: (i) a first anchor attachable to a first bone fragment, the first anchor comprising an adhesive composition that softens upon heating and forms the first anchor upon cooling; (ii) a second anchor attachable to a second bone fragment, the second anchor comprising an adhesive composition that softens upon heating and forms a second anchor upon cooling; (iii) a support structure connecting the first anchor to the second anchor, capable of stabilizing the bone fragment; and the adhesive composition has a tackification temperature of at least 40°C. A device for stabilizing bone fragments.

[0241] 48. The device described in embodiment 47, wherein the support structure is a flexible support comprising a biodegradable and biocompatible polymer that connects the first anchor to the second anchor.

[0242] 49. The device of embodiment 48, wherein the support structure, first anchor, and second anchor are formed from a tape including (x) a non-adhesive upper layer that is the support structure, and (y) a lower layer that becomes adhesive upon softening to form the first anchor and the second anchor.

[0243] 50. The device of any one of embodiments 47-49, wherein the adhesive composition is not water-soluble.

[0244] 51. The device of any one of embodiments 47 to 50, wherein the adhesive composition includes a heat transfer agent.

[0245] 52. The apparatus of embodiment 51, wherein the heat transfer agent is present in an amount that enables the softened adhesive composition to cool and harden within 120 seconds.

[0246] 53. The apparatus of embodiment 51 or 52, wherein the heat transfer agent is present in an amount that enables the softened adhesive composition to cool and harden within 10 seconds.

[0247] 54. The device of any one of embodiments 51-53, wherein the heat transfer agent is present in an amount that enables the adhesive composition to soften within 120 seconds after application of energy.

[0248] 55. The device of embodiment 54, wherein the heat transfer agent is present in an amount that enables the adhesive composition to soften within 10 seconds of applying energy to the non-adhesive top layer.

[0249] 56. The device of any one of embodiments 51 to 55, wherein the heat transfer agent is selected from the group consisting of sodium chloride, iron(III) phosphate dihydrate, iron(III) citrate monohydrate, hydroxyapatite, tetracalcium phosphate, tricalcium phosphate, dicalcium phosphate, and sodium carbonate, or a combination thereof.

[0250] 57. The device of embodiment 56, wherein the heat transfer agent is hydroxyapatite.

[0251] 58. The device of any one of embodiments 51 to 57, wherein the adhesive composition comprises about 0.5 to 60% (w / w) of a heat transfer agent.

[0252] 59. The apparatus of embodiment 58, wherein the adhesive composition comprises about 35-60% (w / w) of a heat transfer agent.

[0253] 60. The device of any one of embodiments 47-59, wherein the adhesive composition comprises a polymer having a structure of formula (I). [ka] (In the formula, n is an integer between 0 and 4 (e.g., n=1, 2, 3, or 4); Block B comprises an oligomer derived from a polyester, a polyalkylene glycol, a polysilicone, or a polycarbonate with a MW of <4,000 g / mol; Block A comprises an optionally substituted C1-C6 alkylene, and Block A is derived from a diisocyanate crosslinker; Block W comprises an optionally substituted C0-C3 alkyl-benzene-diol or an optionally substituted C0-C3 alkyl-benzene-triol; the linker L' comprises a carbamate; and The linker L comprises a urea.

[0254] 61. Block B is of formula (II): [ka] (In the formula, each o is independently an integer of 0 to 20.) 61. The device of embodiment 60, having the structure:

[0255] 62. Block B is of formula (III): [ka] (In the formula, each o is independently an integer of 0 to 20.) 61. The device of embodiment 60, having the structure:

[0256] 63. Block B is of formula (IV): [ka] (In the formula, each o is independently an integer of 0 to 20.) 61. The device of embodiment 60, having the structure:

[0257] 64. Block B is a compound of formula (V): [ka] (In the formula, each o is independently an integer of 0 to 20.) 61. The device of embodiment 60, having the structure:

[0258] 65. Block A is represented by formula (VII): [ka] (In the formula, R 1 is C1-C3 alkyl. The device according to any one of embodiments 60 to 64, having the structure:

[0259] 66. The linker L' is [ka] The device according to any one of embodiments 60 to 65, having the structure:

[0260] 67. The linker L is [ka] The device according to any one of embodiments 60 to 66, having the structure:

[0261] 68. Block W: [ka] The device according to any one of embodiments 60 to 67, having the structure:

[0262] 69. The device of any one of embodiments 47 to 68, wherein the adhesive composition comprises 30 to 70% (w / w) of a filler.

[0263] 70. The device of embodiment 69, wherein the filler comprises polycaprolactone (PCL), polydioxanone (PDX), poly(lactic-co-glycolic acid) (PLGA), poly-3-hydroxybutyrate (P3HB), polylactic acid (PLA), polyglycolide (PGA), poly-4-hydroxybutyrate (P4HB), polyethylene carbonate (PEC), polypropylene carbonate (PPC), poly(trimethylene carbonate) (PTMC), polysulfone, polyethylene glycol (PEG), hydroxyapatite (HA), tetracalcium phosphate (TTCP), tricalcium phosphate (TCP), dicalcium phosphate (DCP), or copolymers thereof, or blends thereof.

[0264] 71. The device of embodiment 70, wherein the filler comprises polycaprolactone (PCL), polydioxanone (PDX), poly(lactic-co-glycolic acid) (PLGA), or poly-3-hydroxybutyric acid (P3HB), hydroxyapatite (HA), or copolymers thereof, or blends thereof.

[0265] 72. A device described in any one of embodiments 47 to 71, comprising multiple bone anchors and multiple support structures capable of stabilizing multiple bone fragments.

[0266] 73. A device described in any one of embodiments 47 to 72, wherein (i) the support structure and (ii) at least one of the first anchor and the second anchor are arranged to form an adhesive portion and a support portion that forms a backing for the adhesive portion, and the adhesive portion can soften when heated without deforming the support portion.

[0267] 74. A device described in any one of embodiments 47 to 73, wherein the first anchor and the second anchor are each capable of adhering to wet or dry bone fragments.

[0268] 75. A device described in any one of embodiments 47 to 74, wherein the first anchor and the second anchor are reversible anchors.

[0269] 76. The device of any one of embodiments 47 to 75, wherein the adhesive composition does not rely on an in situ curing reaction for adhesion.

[0270] 77. The device of any one of embodiments 47 to 76, wherein the adhesive composition reversibly softens at a temperature of 45±5°C.

[0271] 78. A device described in any one of embodiments 73 to 77, wherein the backing portion has a thickness of 0.05 to 0.31 mm.

[0272] 79. The device of embodiment 78, wherein the backing portion has a thickness of 0.12 to 0.20 mm.

[0273] 80. The device of any one of embodiments 73 to 78, wherein the adhesive portion has a thickness of 0.05 to 0.16 mm.

[0274] 81. The device of embodiment 80, wherein the adhesive portion has a thickness of 0.075±0.025 mm.

[0275] 82. The device of embodiment 80, wherein the adhesive portion has a thickness of 0.13±0.03 mm.

[0276] 83. (i) 0 to 70% (w / w) of a bulking agent; and (ii) 30 to 100% (w / w) of formula (I): [ka] (In the formula, n is an integer from 0 to 4 (e.g., n=1, 2, 3, or 4); Block B comprises an oligomer derived from a polyester, a polyalkylene glycol, a polysilicone, or a polycarbonate, with a MW≦4,000 g / mol; Block A comprises an optionally substituted C1-C6 alkylene, and Block A is derived from a diisocyanate crosslinker; Block W comprises an optionally substituted C0-C3 alkyl-benzene-diol or an optionally substituted C0-C3 alkyl-benzene-triol; the linker L' comprises a carbamate; and The linker L comprises a urea. The polymer comprises a polymer having a structure have a stick temperature of at least 40°C; Adhesive composition.

[0277] 84. The adhesive composition of embodiment 83, wherein the adhesive composition is not water soluble.

[0278] 85. The adhesive composition of embodiment 83 or 84, wherein the adhesive composition comprises a heat transfer agent.

[0279] 86. The adhesive composition of embodiment 85, wherein the heat transfer agent is present in an amount that enables the softened adhesive composition to cool and harden within 120 seconds.

[0280] 87. The adhesive composition of embodiment 86, wherein the heat transfer agent is present in an amount that enables the softened adhesive composition to cool and harden within 10 seconds.

[0281] 88. The adhesive composition of any one of embodiments 85-87, wherein the heat transfer agent is present in an amount that enables the adhesive composition to soften within 120 seconds after the application of energy.

[0282] 89. The adhesive composition of embodiment 88, wherein the heat transfer agent is present in an amount that enables the adhesive composition to soften within 10 seconds of applying energy to the non-adhesive top layer.

[0283] 90. The adhesive composition of any one of embodiments 85 to 89, wherein the heat transfer agent is selected from the group consisting of sodium chloride, iron(III) phosphate dihydrate, iron(III) citrate monohydrate, hydroxyapatite, tetracalcium phosphate, tricalcium phosphate, dicalcium phosphate, and sodium carbonate, or a combination thereof.

[0284] 91. The adhesive composition of embodiment 90, wherein the heat transfer agent is hydroxyapatite.

[0285] 92. The adhesive composition of any one of embodiments 85 to 91, wherein the adhesive composition comprises about 0.5 to 60% (w / w) of a heat transfer agent.

[0286] 93. The adhesive composition of embodiment 92, wherein the adhesive composition comprises about 35-60% (w / w) of the heat transfer agent.

[0287] 94. a) Block B is a compound of formula (II): [ka] (In the formula, each o is independently an integer of 0 to 20.) 94. The adhesive composition of any one of embodiments 83 to 93, having the structure:

[0288] 95. Block B is a compound of formula (III): [ka] (In the formula, each o is independently an integer of 0 to 20.) 94. The adhesive composition of any one of embodiments 83 to 93, having the structure:

[0289] 96. Block B is represented by formula (IV): [ka] (In the formula, each o is independently an integer of 0 to 20.) 94. The adhesive composition of any one of embodiments 83 to 93, having the structure:

[0290] 97. Block B is a compound of formula (V): [ka] (In the formula, each o is independently an integer of 0 to 20.) 94. The adhesive composition of any one of embodiments 83 to 93, having the structure:

[0291] 98. Block A is represented by formula (VII): [ka] (In the formula, R 1 is C1-C3 alkyl. 94. The adhesive composition of any one of embodiments 83 to 93, having the structure:

[0292] 99. The linker L' is [ka] The adhesive composition of any one of embodiments 83 to 98, having the structure:

[0293] 100. The linker L is [ka] 99. The adhesive composition of any one of embodiments 83 to 99, having the structure:

[0294] 101. Block W [ka] The adhesive composition according to any one of embodiments 83 to 100, having the structure:

[0295] 102. The adhesive composition of any one of embodiments 83 to 101, wherein the filler comprises polycaprolactone (PCL), polydioxanone (PDX), poly(lactic-co-glycolic acid) (PLGA), poly-3-hydroxybutyrate (P3HB), polylactic acid (PLA), polyglycolide (PGA), poly-4-hydroxybutyrate (P4HB), polyethylene carbonate (PEC), polypropylene carbonate (PPC), poly(trimethylene carbonate) (PTMC), polysulfone, polyethylene glycol (PEG), hydroxyapatite (HA), tetracalcium phosphate (TTCP), tricalcium phosphate (TCP), dicalcium phosphate (DCP), or copolymers thereof, or blends thereof.

[0296] 103. The adhesive composition of embodiment 102, wherein the filler comprises polycaprolactone (PCL), polydioxanone (PDX), poly(lactic-co-glycolic acid) (PLGA), or poly-3-hydroxybutyric acid (P3HB), hydroxyapatite (HA), or copolymers thereof, or blends thereof.

[0297] 104. A tape comprising (i) a non-adhesive polymeric upper layer and (ii) an underlayer comprising the adhesive composition of any one of embodiments 83-103.

[0298] 105. The tape of embodiment 104, wherein the non-adhesive polymeric top layer comprises polycaprolactone (PCL), polydioxanone (PDX), poly(lactic-co-glycolic acid) (PLGA), poly-3-hydroxybutyric acid (P3HB), polylactic acid (PLA), polyglycolide (PGA), poly-4-hydroxybutyric acid (P4HB), polyethylene carbonate (PEC), polypropylene carbonate (PPC), poly(trimethylene carbonate) (PTMC), polysulfone, polyethylene glycol (PEG), or copolymers thereof.

[0299] 106. The tape of embodiment 104 or 105, wherein the non-adhesive polymeric top layer has a thickness of 0.05 to 0.31 mm.

[0300] 107. The tape of embodiment 106, wherein the non-adhesive polymeric top layer has a thickness of 0.12 to 0.20 mm.

[0301] 108. The tape of any one of embodiments 104 to 107, wherein the underlayer has a thickness of 0.05 to 0.16 mm.

[0302] 109. The tape of embodiment 108, wherein the underlayer has a thickness of 0.075±0.025 mm.

[0303] 110. The tape of embodiment 108, wherein the underlayer has a thickness of 0.13±0.03 mm.

[0304] 111. The apparatus of any one of embodiments 47-82 or the method of manufacturing a tape of any one of claims 104-110, comprising: a) contacting (i) a first part comprising the adhesive composition of any one of embodiments 93-103 with (ii) a second part comprising a support structure; b) applying heat to bond the first and second parts; A manufacturing method comprising:

[0305] 112. The method of embodiment 111, further comprising applying a force to compress the first portion and the second portion.

[0306] 113. The method of embodiment 112, wherein a force of at least 800 kg is applied.

[0307] 114. The method of embodiment 111, wherein the first and second parts are joined by lamination.

[0308] 115. The method of any one of embodiments 111-114, wherein one or both of the first and second parts are in the form of a sheet. EXAMPLES

[0309] The examples described herein are intended to illustrate the present invention, but are not intended to limit the present invention.

[0310] Abbreviation: DSC Differential Scanning Calorimetry DMAc Dimethylacetamide DMSO Dimethyl sulfoxide H time LDI Ethyl Ester L-Lysine Diisocyanate min MW molecular weight mL Milliliters MS mass spectrometry m / v mass / volume NMR nuclear magnetic resonance PCL Polycaprolactone PDX Polydioxanone TEA Triethylamine TGA thermogravimetric analysis THF Tetrahydrofuran

[0311] <<Example 1: Synthesis of adhesive>> compound 1 Compound 1 was synthesized by a three-step one-pot method under N2 atmosphere (Scheme 1). PCL polyol (polycaprolactone diol; MW 1250 g / mol) was dried in a two-neck round-bottom flask under vacuum at 75 °C for 2 h, then dissolved in DMAc solvent (~1:5 m / v ratio) and allowed to cool to room temperature under N2 atmosphere. 2.1 molar equivalents of LDI (ethyl ester L-lysine diisocyanate) were added and the reaction was stirred at room temperature for 1 h, warmed to 75 °C over 2 h, held at 75 °C for 1 h, and finally stirred at room temperature overnight. Dopamine hydrochloride (2 molar equivalents) was then added to the reaction and stirred until completely dissolved. The reaction was placed in an ice bath and triethylamine (TEA; 2 molar equivalents) was added dropwise. The reaction was allowed to proceed overnight. The reaction was filtered to remove the triethylamine hydrochloride by-product, and the resulting filtrate was stirred overnight in a large excess (~10 times the volume of the reaction solution) of ether to precipitate the adhesive. The supernatant was decanted and the precipitated adhesive was redissolved in a minimum amount of hot acetone / ethanol (90:10 v / v) and reprecipitated by solvent exchange centrifugation with ether (x3; 1:9 v / v). After prolonged drying under vacuum at room temperature, compound 1 was obtained as a white crystalline powder (n ≈5 (average)). 100% dopamine functionalization was observed. 1 Confirmed by H-NMR.

[0312] [ka]

[0313] compound 2 Compound 2 was synthesized in a three-step one-pot procedure under N2 atmosphere (Scheme 2). PCL polyol (polycaprolactone diol; MW 2000 g / mol) was dried in a two-neck round-bottom flask under vacuum at 75 °C for 2 h, then dissolved in DMAc solvent (~1:5 m / v ratio) and allowed to cool to room temperature under N2 atmosphere. 2.1 molar equivalents of LDI (ethyl ester L-lysine diisocyanate) were added and the reaction was stirred at room temperature for 1 h, warmed to 75 °C over 2 h, held at 75 °C for 1 h, and finally stirred at room temperature overnight. Dopamine hydrochloride (2 molar equivalents) was then added to the reaction and stirred until completely dissolved. The reaction was placed in an ice bath and triethylamine (TEA; 2 molar equivalents) was added dropwise. The reaction was allowed to proceed overnight. Upon completion, the reaction mixture was filtered to remove the triethylamine hydrochloride by-product. The adhesive was then precipitated by solvent exchange centrifugation with ether (x3; 1:9 v / v) and then filtered under vacuum. The adhesive was then redissolved in a minimum amount of hot acetone / ethanol (90:10 v / v) and reprecipitated with ether as above. After prolonged drying under vacuum at room temperature, compound 2 was obtained as a hard, white, waxy solid (n approx. 8.3 (average)). 1 H-NMR analysis confirmed 73% dopamine functionalization.

[0314] [ka]

[0315] compound 3 Compound 3 was synthesized in a three-step one-pot procedure under N2 atmosphere (Scheme 3). PCL polyol (polycaprolactone diol; MW 4000 g / mol) was dried in a two-neck round-bottom flask under vacuum at 100 °C for 2 h, then dissolved in DMAc solvent (~1:5 m / v ratio) and allowed to cool to room temperature under N2 atmosphere. Two molar equivalents of LDI (ethyl ester L-lysine diisocyanate) were added and the reaction was stirred at room temperature for 1 h, warmed to 75 °C over 2 h, held at 75 °C for 1 h, and finally stirred at room temperature overnight. Dopamine hydrochloride (2 molar equivalents) was then added to the reaction and stirred until completely dissolved. The reaction was placed in an ice bath and triethylamine (TEA; 2 molar equivalents) was added dropwise. The reaction was allowed to warm to room temperature and the reaction was allowed to proceed overnight. Once complete, the adhesive was precipitated by stirring in a large excess (~10 times the reaction volume) of acidic water. The adhesive was then vacuum filtered and washed with copious amounts of distilled water until the filtrate was no longer acidic. After extensive freeze-drying, compound 3 was obtained as a fluffy white powder (n approx. 17 (average)). 1 H-NMR analysis confirmed 82% dopamine functionalization.

[0316] [ka]

[0317] compound 4 Compound 4 was synthesized by a three-step one-pot method under N2 atmosphere (Scheme 4). PCL polyol (polycaprolactone triol; MW 300 g / mol) was dried in a two-neck round-bottom flask under vacuum at 75 °C for 2 h, then dissolved in DMAc solvent (~1:5 m / v ratio) and allowed to cool to room temperature under N2 atmosphere. Three molar equivalents of LDI (ethyl ester L-lysine diisocyanate) were added and the reaction was stirred at room temperature for 1 h, warmed to 75 °C over 2 h, held at 75 °C for 1 h, and finally stirred at room temperature overnight. Dopamine hydrochloride (3.1 molar equivalents) was then added to the reaction and stirred until completely dissolved. The reaction was placed in an ice bath and triethylamine (TEA; 3 molar equivalents) was added dropwise. The reaction was allowed to proceed overnight. Upon completion, the reaction was filtered to remove triethylamine hydrochloride residues and the adhesive was precipitated by solvent exchange centrifugation with acidic water (×1; 1:3 v / v). The adhesive was then washed with water (1:4 v / v) and ether (x4; 1:9 v / v) by solvent exchange centrifugation until neutral. The adhesive was redissolved in a minimum amount of hot acetone / ethanol (90:10 v / v) and reprecipitated by solvent exchange centrifugation with ether (x3; 1:9 v / v). After prolonged drying under vacuum at room temperature, compound 4 was finally obtained as a white crystalline powder (n ≈ 0.5 (average)). 1 H-NMR analysis confirmed 80% dopamine functionalization.

[0318] [ka]

[0319] compound 5 Compound 5 was synthesized in a three-step one-pot procedure under N2 atmosphere (Scheme 5). PCL polyol (polycaprolactone triol; MW 900 g / mol) was dried in a two-neck round bottom flask under vacuum at 75 °C for 2 h, then dissolved in DMAc solvent (~1:5 m / v ratio) and allowed to cool to room temperature under N2 atmosphere. 3.1 molar equivalents of LDI (ethyl ester L-lysine diisocyanate) were added and the reaction was stirred at room temperature for 1 h, warmed to 75 °C over 2 h, held at 75 °C for 1 h, and finally stirred at room temperature overnight. Dopamine hydrochloride (3.1 molar equivalents) was then added to the reaction and stirred until completely dissolved. The reaction was placed in an ice bath and triethylamine (TEA; 3 molar equivalents) was added dropwise. The reaction was allowed to proceed overnight. Upon completion, the reaction was filtered to remove triethylamine hydrochloride residues and the adhesive was precipitated by solvent exchange centrifugation with acidic water (x1; 1:3 v / v). The adhesive was then washed with water (1:4 v / v) and ether (x4; 1:9 v / v) until neutral by solvent exchange centrifugation. The adhesive was redissolved in a minimum amount of hot acetone / ethanol (90:10 v / v) and reprecipitated by solvent exchange centrifugation with ether (x3; 1:9 v / v). After prolonged drying under vacuum at room temperature, compound 5 was finally obtained as a pale yellow hard glassy solid (n approx. 2.3 (average)). The results of the analysis showed that the solubility of compound 5 in water was approximately 1.0% (n approx. 2.0%). 1 H-NMR analysis confirmed 77% dopamine functionalization.

[0320] [ka]

[0321] compound 6 Compound 6 was synthesized in a three-step one-pot procedure under N2 atmosphere (Scheme 6). PCL polyol (polycaprolactone triol; MW 2000 g / mol) was dried in a two-neck round bottom flask under vacuum at 85 °C for 2 h, then dissolved in DMAc solvent (~1:5 m / v ratio) and allowed to cool to room temperature under N2 atmosphere. Three molar equivalents of LDI (ethyl ester L-lysine diisocyanate) were added and the reaction was stirred at room temperature for 1 h, warmed to 75 °C over 2 h, held at 75 °C for 1 h, and finally stirred at room temperature overnight. Dopamine hydrochloride (3.1 molar equivalents) was then added to the reaction and stirred until completely dissolved. The reaction was placed in an ice bath and triethylamine (TEA; 3 molar equivalents) was added dropwise. The reaction was allowed to warm to room temperature and the reaction was allowed to proceed overnight. Upon completion, the mixture was filtered to remove triethylamine hydrochloride by-product residues and the adhesive was precipitated by solvent exchange centrifugation with acidic water (x1; 1:3 v / v). The adhesive was then washed with water (1:4 v / v) and ether (x4; 1:9 v / v) until neutral by solvent exchange centrifugation. The resulting adhesive was redissolved in a minimum amount of hot acetone / ethanol (90:10 v / v) and reprecipitated by solvent exchange centrifugation with ether (x4; 1:9 v / v) followed by prolonged drying under vacuum at room temperature to give compound 6 as a white fluffy powder (n approx. 5.5 (average)). The results are shown in Table 1. 1 H-NMR analysis confirmed 90% dopamine functionalization.

[0322] [ka]

[0323] compound 7 Compound 7 was synthesized in a three-step one-pot procedure under N2 atmosphere (Scheme 7). PCL polyol (polycaprolactone tetol; MW 1000 g / mol) was dried in a two-neck round bottom flask under vacuum at 75 °C for 2 h, then dissolved in DMAc solvent (~1:5 m / v ratio) and allowed to cool to room temperature under N2 atmosphere. Four molar equivalents of LDI (ethyl ester L-lysine diisocyanate) were added and the reaction was stirred at room temperature for 1 h, warmed to 75 °C over 2 h, held at 75 °C for 1 h, and finally stirred at room temperature overnight. Dopamine hydrochloride (3.1 molar equivalents) was then added to the reaction and stirred until completely dissolved. The reaction was placed in an ice bath and triethylamine (TEA; 4 molar equivalents) was added dropwise. The reaction was allowed to warm to room temperature and the reaction was allowed to proceed overnight. Upon completion, the mixture was filtered to remove triethylamine hydrochloride by-product residues and the adhesive was precipitated by solvent exchange centrifugation with acidic water (x1; 1:3 v / v). The adhesive was then washed with water (1:4 v / v) and ether (x4; 1:9 v / v) until neutral by solvent exchange centrifugation. The resulting adhesive was redissolved in a minimum amount of hot acetone / ethanol (90:10 v / v) and reprecipitated by solvent exchange centrifugation with ether (x4; 1:9 v / v) followed by prolonged drying under vacuum at room temperature to give compound 7 as a white spongy solid (n approx. 1.9 (average)). The results are shown in Table 1. 1 H-NMR analysis confirmed 89% dopamine functionalization.

[0324] [ka]

[0325] compound 8 Compound 8 was synthesized in a three-step one-pot procedure under N2 atmosphere (Scheme 8). PEE polyol (polyethyl ether hexol; MW 815 g / mol) was dried in a two-neck round bottom flask under vacuum at 75 °C for 2 h, then dissolved in DMAc solvent (~1:5 m / v ratio) and allowed to cool to room temperature under N2 atmosphere. Six molar equivalents of LDI (ethyl ester L-lysine diisocyanate) were added and the reaction was stirred at room temperature for 1 h, warmed to 75 °C over 2 h, held at 75 °C for 1 h, and finally stirred at room temperature overnight. Dopamine hydrochloride (6.1 molar equivalents) was then added to the reaction and stirred until completely dissolved. The reaction was placed in an ice bath and triethylamine (TEA; 6 molar equivalents) was added dropwise. The reaction was allowed to warm to room temperature and the reaction was allowed to proceed overnight. Upon completion, the mixture was filtered to remove triethylamine hydrochloride by-product residues and the adhesive was precipitated by solvent exchange centrifugation with acidic water (x1; 1:3 v / v). The adhesive was then washed with water (1:4 v / v) and ether (x4; 1:9 v / v) until neutral by solvent exchange centrifugation. The resulting adhesive was redissolved in a minimum amount of hot acetone / ethanol (90:10 v / v) and reprecipitated by solvent exchange centrifugation with ether (x4; 1:9 v / v) followed by prolonged drying under vacuum at room temperature to give compound 8 as a white pale yellow hard glassy solid. 1 H-NMR analysis confirmed 78% dopamine functionalization.

[0326] [ka]

[0327] <<Example 2. Adhesive blend>> Adhesive blends were prepared using either a cryogenic grinding process or a microcompounding procedure based on the amount of blended product required. The adhesive blends include an adhesive as described herein, a polymer such as PCL (MW=50 kDa, Polysciences, USA), and soluble or insoluble particles such as sodium chloride (Bioshop, USA), hydroxyapatite (Sigma, SS-nano, USA), tetracalcium phosphate (TCP) (Himed, USA) or sodium carbonate (Bioshop USA).

[0328] To cryogenically grind the adhesive blends, 1–3 g of the total mass of the adhesive components was added to a steel canister containing four hardened ball bearings. Grinding was performed in a Retsch Cryomill (Retsch, DE) equipped with liquid nitrogen at 30 Hz and −196 °C using three 5 min grinding cycles with automatic precooling and 5 min cooling between cycles. The mixture was allowed to warm to room temperature in the canister and then transferred to a glass scintillation vial.

[0329] Alternatively, compounded adhesive filaments were prepared using a 10 mL Xplore Twin Screw Micro-compounder at about 200 rpm for about 2 minutes at about 105° C. The blended adhesive was extruded into filaments and pelletized.

[0330] Regardless of blending method, all adhesive blends were dried under vacuum at room temperature for at least 2 hours, sealed, and stored at -20°C prior to use. Table 1a shows the adhesive blends of the present disclosure. [Table 1a] [Table 1a-2] [Table 1a-3] [Table 1a-4]

[0331] <<Example 3. Manufacturing the support part>> Filaments of polymer blends were made using a microcompounding procedure. Briefly, the polymers were dried overnight at room temperature under vacuum before use. For films composed of blends of polymers, the polymers were first mixed (compounded) and filamentized using a 10 mL Xplore Twin Screw Micro-compounder at a suitable temperature to melt the polymers (115-220 °C based on the polymers being blended) at 200 rpm for approximately 5 minutes. The polymers were extruded into filaments and pelletized.

[0332] The pellets were dried under vacuum and then compression molded into thin films at 1000-2000 kg in a Carver Automated heated press. Briefly, the platens were heated to the appropriate melting temperature. The filaments were cut to lengths of approximately 3 cm for the specific mass depending on the size of the sheet to be pressed. A Teflon liner (Teflon is a registered trademark) and die were used to prevent the molten polymer from adhering to the steel platens. In selected cases, the Teflon liner was textured to impart texture to the resulting sheet (see Example 4). The Teflon die had a thickness of 0.1-0.5 mm. The molding was performed by stacking the steel plate, the Teflon liner, the Teflon die and the polymer material, the Teflon liner, and the steel plate. The layered mold sandwich was placed on the bottom platen and elevated to approximately 1 mm below the top platen. The polymer was allowed to melt for 10 minutes without the application of force. After melting, the force was increased manually to approximately 100-300 kg. Once the force had dropped to approximately 0-100 kg, the hydraulic pressure was released to allow air bubbles to dissipate. The force was then increased to 1000-2000 kg (depending on the desired thickness) at 15% speed in automatic mode for 5 minutes. The set-up layered mold was transferred to 37°C and allowed to cool naturally before the sheet was removed from the mold. The sheet was trimmed to remove excess material and stored in a desiccator before use. Table 1b shows the polymers of the invention that make up the support side.

[0333] [Table 1b]

[0334] <<Example 4. Texturing a polymer sheet>> To create texture on the adhesive side of the polymer sheet, subtractive laser etching was used to texture a Teflon liner, giving the polymer sheet positive features (convex shapes) during compression molding. The texture was created using computer-aided design in Autocad. The texture was laser etched into the Teflon sheet with a 60W CO2 laser engraving machine (Universal Laser Systems, VLS3.5). After etching, the textured Teflon sheet was cleaned with isopropanol and compressed air to remove excess material. To further clean the textured liner before use, one polymer sheet was pressed onto the freshly etched Teflon liner and removed. The dimensions of the features were adjusted using more passes or higher power if necessary, but generally measured 100-200 μm in depth. The textured sheet was then used as a liner during compression molding of the polymer sheet, forming positive features approximately 100-150 μm in height.

[0335] <<Example 5. Device Assembly>> Method 1: Press The freeze-ground / formulated adhesive, adhesive blend or adhesive mixture was hot pressed onto the polymer sheet / film. Briefly, the polymer sheet / film (prepared as reported in Example 4) was plasma treated for at least 2 min under partial oxygen atmosphere using a benchtop plasma cleaner (Harrick Plasma, USA). Meanwhile, a hot press (Carver, USA) was heated to 75 °C (upper platen) and 70 °C (lower platen). Approximately 0.8 g of adhesive, adhesive blend or adhesive mixture was placed at the center of the polymer sheet. The sheet was then placed, adhesive side up, into a lamination mold similar to that used for compression molding of sheets. The thickness of the mold was set to set the adhesive thickness. The mold was placed on the platen and raised so that the upper platen was <1 mm from the mold. The material was allowed to melt for 5-10 min without pressure. After the melting step, a force of 800 kg was automatically applied at 15% speed and held for an additional 5 min. The mold was removed and cooled to room temperature before removing the resulting polymer sheet / adhesive composite.

[0336] Method 2: Lamination The lamination method involves laminating pre-pressed sheets of the support polymer and adhesive layer together. The adhesive sheets were prepared by a modified version of the compression molding method used for the support side polymer (Example 4). Briefly, a compounded rod of adhesive blend was cut lengthwise into 5 mm pieces and approximately 0.8-1.0 g was placed into a compression molding apparatus. This mold was then placed in a hot press maintained at 105 °C on both platens, maximizing heating by ensuring that the compression mold was less than 1 mm from the top platen. The adhesive was allowed to melt for 5 minutes, after which a force of 1000-4000 kg (depending on the desired thickness) was applied for 2 minutes. The mold was then removed from the hot press, cooled to room temperature, and the adhesive layers were removed for lamination. Separately, a polymer sheet / film (prepared as reported in Example 4) was plasma treated for at least 2 minutes under partial oxygen atmosphere using a benchtop plasma cleaner (Harrick Plasma, USA). For lamination, the backing layer was placed on top of the adhesive layer between two Teflon sheets and placed in a laminator set at approximately 150-250° F. (depending on the thickness of the adhesive). The resulting sheet was allowed to cool to room temperature, after which the lamination tape was peeled off the Teflon sheets.

[0337] [Table 1c] [Table 1c-2]

[0338] <<Example 6 Analysis of thermal stability and volatile substance content of adhesive compounds>> The volatile content of the adhesive compounds was determined from simulated TGA experiments. 100 mg of each adhesive compound was placed in a heat-resistant glass vial at room temperature. The samples were heated to 160°C under vacuum conditions for 1 hour. After 1 hour, the samples were left under vacuum for an additional hour to cool. The mass of the samples was recorded after cooling. The residual solvent was calculated from the percentage of mass loss obtained at 160°C. Two samples were tested for each adhesive.

[0339] The results are shown in Table 1d. Table 1d shows the thermal stability / volatiles content of the adhesive obtained by simulated thermogravimetric analysis (sTGA) obtained as the mass loss of material up to a pre-set temperature (boiling point of the highest boiling solvent) - in our case DMAc 160 °C. Thermal stability is important to ensure that the adhesive remains stable during processing, storage, shipping etc. Briefly, 100 mg adhesive samples were heated to 160 °C under vacuum for 1 h and then cooled for another hour under vacuum before the final adhesive was produced whose final mass was determined. Thermal stability / volatiles content was obtained as the difference in mass before and after heating.

[0340] [Table 1d]

[0341] <<Example 8. Analysis of water solubility and swelling of adhesives>> The solubility and swelling potential of the adhesive compounds were evaluated. Briefly, 0.200 g adhesive samples were dried under vacuum at 40 °C for 48 h and weighed to obtain the initial dry mass. 25.0 mL of deionized water was added to each sample and the samples were incubated at room temperature (approximately 21 °C) for 48 h with intermittent mixing. After 48 h, the aqueous phase was decanted, lyophilized, and then vacuum dried overnight at 40 °C to measure the mass of material extracted into the water. The ratio of the mass of the extracted material to the aqueous solution was used to estimate the water solubility of each adhesive. Residual adhesive swelling was taken as the mass percent of water increased relative to the initial adhesive mass and was determined by removing excess water with a Kimwipe before weighing the samples after incubation. Table 2 shows the solubility and swelling potential of the adhesive compounds.

[0342] [Table 2]

[0343] All adhesives tested clearly had low aqueous solubility. The highest average solubility was less than 1 mg / g water (0.66 mg / g for compound 2). However, the majority of adhesives tested showed solubilities an order of magnitude lower. In two cases (compounds 4 and 6), the extractable mass was too small to be recorded reliably.

[0344] <<Example 9. Analysis of thermal properties of adhesive>> The glass transition and / or melting temperatures of the pure adhesives were obtained from differential scanning calorimetry (DSC) experiments performed on a DSC7020 thermal analysis system (Hitachi High Technologies Canada Inc., Ontario, CA) equipped with an electrical cooling system. Samples (5–15 mg) were loaded into open 40 μL aluminum DSC pans and introduced into the DSC sample chamber. The chamber was continuously purged with a dry nitrogen flow of 40 mL / min. Each sample was equilibrated at 150 °C for 5 min to erase its thermal history, cooled to -90 °C at a rate of 20 °C / min, held isothermally for 5 min, heated again to 150 °C at a rate of 5 °C / min, held isothermally for 5 min, then cooled again to -90 °C at a rate of 5 °C / min, held isothermally for 5 min, and finally heated again to 180 °C at a rate of 5 °C / min. The melting (TM) and / or glass transition (Tg) temperatures were calculated from the thermograms using NEXTA standard analytical software, v2.0. The thermal properties of the pure adhesive and adhesive blends are shown in Table 4.

[0345] The tack temperature of the neat adhesive was measured as follows: 100 mg adhesive samples were placed in scintillation glass vials and equilibrated in a room temperature (23°C) water bath for 5 minutes. Using the rate programmable feature on the heating plate, the temperature of the water bath was increased at a rate of 1°C / min to 75°C. The tack temperature was measured as the temperature at which the adhesive changed from a non-flowable, rigid / glassy state to a viscous, amorphous state that simply pulled a string when poked with a pipette. The results are shown in Table 3.

[0346] [Table 3]

[0347] <<Example 10. Analysis of adhesive strength>> The lap shear strength of the adhesive was obtained by performing a standard lap shear test using an Instron universal testing machine in tension mode with a 1000N load cell and an applied strain rate of 25mm / min. Samples (n=6) were 2x1cm 2 The adhesive was sandwiched between aluminum substrates with a contact area of ​​10 mm and incubated overnight at room temperature before testing. The results are shown in Table 4.

[0348] [Table 4]

[0349] <<Example 11. In vitro cytotoxicity>> The in vitro cytotoxicity of adhesive compounds 4, 6 and 7, as well as the polymeric films and tape devices, was tested by the WST assay. Materials were 10 mg / mL for the compounds and 7 mm for the polymeric films and devices. 2 The materials were extracted into growth medium (DMEM) at a concentration of 10,000 / mL. Positive and negative controls were treated with 5% DMSO and growth medium, respectively. Cells were seeded at a density of 10,000 cells per well. Cell viability was measured 24 and 72 hours after contact of the materials with A10 cells. All materials showed cell viability above the minimum cell viability of 70% required for FDA submission, except for compound 4, which had approximately 10% cell viability at both time points (Figure 1). The cytotoxicity of the materials was analyzed by direct contact with A10 cells for 24 and 72 hours and compared to negative and positive controls (DMEM and 5% DMSO, respectively). Cell viability (%) values ​​were determined by WST-1 colorimetric assay. Results are expressed as mean ± standard deviation. n=4.

[0350] Example 12. Effect of adhesive composition on device performance The adhesive performance can be tuned by varying the composition of the adhesive components. However, this is not a simple task, as can be seen in Figure 2. This is because of the dissimilar and therefore non-trivial dependence of adhesive properties such as tackification temperature (Figure 2) for different adhesive components.

[0351] The tack temperature and adhesion properties of the adhesive and adhesive blend mixtures were evaluated. Blends were prepared by hot mixing the adhesive components in the selected weight ratio. 100 mg of adhesive sample was placed in a scintillation glass vial and equilibrated in a water bath at room temperature (23 °C) for 5 min, after which the temperature of the water bath was increased at 1 °C / min to 75 °C using the programmable function of the heating plate. The tack temperature was measured at the temperature at which the adhesive mixture changed from a non-flowing solid to a viscous amorphous state that was stringy when poked with a pipette. The adhesion properties were measured on the resulting adhesive film using an AutoC-PL,H laboratory press (Carver Inc, USA). Approximately 0.1 g of adhesive was placed between Teflon liners and left on the press for 5 min to allow thermal equilibration to the set temperature of 80 °C. The sample was then compressed at 80 °C with a load of 600 kg for 5 min, removed from the press and cooled to room temperature over 20 min. The Teflon liners were then separated to observe the adhesive blending. The adhesive blends were qualitatively evaluated for 1) adhesion to Teflon and tack of the film, 2) stiffness / plasticity / brittleness by bending the Teflon and observing the film cracking, and 3) cohesiveness of the film when peeled off the Teflon surface.

[0352] Table 5 shows the effect of adhesive and adhesive blends, Table 6 shows the effect of polymer fillers in the adhesive blends, and Table 7 shows the effect of particulate adhesives on the adhesive blends.

[0353] [Table 5]

[0354] The effect of polymer fillers on the performance of bone tape device C was evaluated, where the adhesive component consisted of 50% w / w% adhesive blend 4a and 50% of the listed polymer fillers, with the support side consisting of polymer 3. To mimic in vivo application, the device was applied to the cheekbone covered in citrated horse blood using an ultrasonic energy source prior to application. The performance of the tape was assessed qualitatively by looking at the adhesion, ease of application, peel strength, and tensile strength of the tape, where a score of 0 = no adhesion to bone, 5 = good application, and adhesion to bone, and good tensile strength or good peel strength, and 10 = desirable adhesion, peel resistance, and tensile strength. The results are shown in Table 6.

[0355] [Table 6]

[0356] Table 6 shows that polymeric fillers can be used to improve adhesive performance. Without being bound by theory, this occurs when the polymeric filler positively impacts the physical and / or mechanical properties of the adhesive, thereby acting as a second phase toughener.

[0357] For example, polymer fillers with softening temperatures that are too low (e.g. PLC7015) or too high (e.g. LG824s, L210s HA) limit the performance of the adhesive layer below that of the control adhesive (no filler) itself. Higher molecular weight polymers improve tensile resistance (e.g. PCL50 vs. PCL14, PBA), while softer polymers (e.g. PBA) contribute to improved peel performance.

[0358] Inorganic fillers such as HA do not provide the same level of second phase reinforcement as compatible polymeric fillers. Without wishing to be bound by theory, inorganic particulates are typically void fillers, whereas polymeric fillers contribute to improved elongation / tensile properties through long chain entanglement interactions.

[0359] Polymers that are not miscible with the adhesive compound (evident from separate adhesive and polymer Tg domains on the DSC thermograms), such as LG824 and L210sHA, also do not perform well. This is probably because their phase strengthening mechanisms are reduced primarily due to void filling, in the absence of chain entanglement and the associated intermolecular interaction effects promoted by phase mixing of the polymer phase with the adhesive compound. This is supported by device C-7 (Table 6), which shows that the best scores are obtained when another adhesive compound with suitable mechanical and / or physical properties is incorporated into the adhesive layer as a polymer filler component.

[0360] Polymer fillers that increase the overall hydrophilicity of the adhesive layer, e.g., PF127, will increase the swelling capacity and / or solubility of the adhesive layer, ultimately leading to bone tape failure due to delamination from the bone and / or side supports. On the other hand, polymer fillers that decrease the hydrophilicity of the adhesive layer (e.g., PCL) are desirable to mitigate bone tape failure due to water ingress in vivo.

[0361] Example 13: Effect of particulate additives on the performance of bone tape devices. The effect of particle additives on the performance of bone tape devices D and F was evaluated. Various amounts of the listed particles were mixed into adhesive formulations containing 50 wt% Adhesive Blend 4a or Adhesive Blend 9a, and 50% polymer filler, and evaluated for application and adhesion to rabbit cheekbones. The bone tape devices were applied to cheekbones covered with citrated horse blood using an ultrasonic energy source. The weight percentage reflects the amount of inorganic particles added relative to the organic mass of the adhesive formulation. The performance of the tape was evaluated qualitatively by looking at the adhesion, ease of application, peel strength, and tensile strength of the tape. A score of 0=no adhesion to bone, 5=good application and adhesion to bone, and good or good tensile strength, and 10=desirable adhesion, peel resistance, and tensile strength. The results are shown in Table 7.

[0362] [Table 7]

[0363] Addition of additives at concentrations below 2.5 wt% resulted in no effect or reduced performance. At additive levels of 2.5 wt%, application of the tape was facilitated but no improvement in performance was observed. At additive levels of 5-10%, application and fluid displacement were improved but strength was not significantly improved. Without wishing to be bound by theory, it is hypothesized that the presence of these additives in appropriate amounts enhances energy transfer from the backing material to the adhesive component, allowing the adhesive component to reach tack temperature without compromising the supporting component of the bone tape.

[0364] However, the use of soluble additives at levels above 10 wt% compromises the integrity of the bone tape during application as the soluble additive components dissolve or leach leaving craters / voids in the bone tape. On the other hand, the use of insoluble additives, e.g., HA and TTCP, at levels above 20 wt% improves tensile strength and application compared to the control. Without being bound by theory, this is believed to be due to the ability of the insoluble additives to act as void-filling second phase tougheners in addition to aiding in the transfer of energy from the substrate to the adhesive components during application. Evidence of the role of these particulate additives as void-filling second phase tougheners can be seen in Table 7, from the comparison of Apparatus D-12 to D-14 through D-16, Apparatus F-1 to F-6, Apparatus F-1 to F-6, and Apparatus F-2 to F-7 and F-8. All of these indicate that for a given HA content, the nature of the polymer filler in the adhesive strongly influences the effectiveness of the additive (note that with the exception of PES, the polymer fillers in all of these apparatuses all exhibit similar melting points). Further evidence can be seen in devices F-2 vs. F-4, where the more porous but compositionally similar TTCP filler is less effective at filling voids compared to HA.

[0365] Apparatuses F-1 to F-3 in Table 7 show the effect of additive pH on the performance of the apparatus. From the prior art, it is known that basic additives induce in situ crosslinking of the catechol moiety of catechol-containing adhesives. This is also evident in the adhesive apparatus of this embodiment. Residual reactants in the HA additive give the additive an effective non-neutral pH. The real pH of HA was found to range from acidic to basic based on the supplier's manufacturing method. When used directly in the manufacture of bone tapes without further washing to remove non-neutral impurities, HA exhibiting basic pH characteristics will cause in situ pH-induced catechol-catechol crosslinking and / or dimerization at the high temperature manufacturing process conditions in the manufacture of bone tapes. However, as shown in Table 7 for the apparatus of this embodiment, it is also evident that while some improvements in bone tape performance may be observed in apparatuses where the adhesive undergoes in situ crosslinking / oligomerization (e.g., apparatus F-1), these improvements are only marginal (e.g., apparatuses F-2 and F-3). These results strongly support that the adhesive of this embodiment does not require crosslinking for desired adhesive and / or device performance. Furthermore, when said in situ induced adhesive crosslinking is present, the resulting bone tape is not the most aesthetically pleasing, as the color of the adhesive and resulting bone tape changes from white to dark brown / black with increasing pH-induced crosslinking. Thus, the non-crosslinked adhesive device of this embodiment produced using a particulate additive with a pH ≦7 meets the desired aesthetic and performance criteria for use in surgical procedures.

[0366] Bone tapes with an adhesive layer consisting only of the filler polymer PCL, without any adhesives or additives, do not stick to bone.

[0367] Example 14. Effect of Support Composition on the Performance of Bone Tape Devices The effect of support side composition was investigated for bone tape device E. Device E was fabricated with adhesive blend 6f on various support side compositions and evaluated for application and adhesion to rabbit cheekbones. Application was performed using an ultrasonic heating system. To mimic in vivo application, the cheekbones were covered with horse blood containing citric acid prior to application. Tape performance was assessed qualitatively by looking at tape adhesion, ease of application, peel strength, and tensile strength, where Y=yes; N=No. Scores were 0=fail, 3=average, and 5=excellent performance. Results are shown in Table 8.

[0368] [Table 8]

[0369] Table 8 shows that the performance of the bone tape is highly dependent on the properties of the supporting component.

[0370] Polymers that melt / soften below the tack temperature of the adhesive formulation (e.g., PCL, PLC7015) are not optimal when used alone. In these situations, the challenge is to apply the bone tape without introducing defects into the support that would compromise the tensile strength of the postoperative device. This is especially true for polymers with high crystalline content, such as PCL, that melt rapidly at or below the tack temperature of the adhesive layer. This is also true for polymers that exhibit polymorphic phase transitions and / or contain multiple polymorphs with phase transitions below the tack temperature of the adhesive formulation. For example, PDX has a final melt temperature of 110°C, but also undergoes several polymorphic transitions, including melt-mediated recrystallization, between room temperature and 50°C.

[0371] Polymers that melt / soften at temperatures that are too high compared to the tackification temperature of the adhesive formulation (e.g., PLC9517) also pose application challenges that compromise device performance. In these systems, the temperatures required to soften the support component to allow it to conform to the shape of the bone surface and to promote complete wetting of the bone surface by the adhesive component can actually cause adhesive to flow out from under the bone tape device, resulting in a compromised device with poor adhesive properties. Similar challenges can occur with polymers that have too high a modulus of elasticity (E tensile >0.5 GPa; LG824s, PLC8516, etc.), and generally require heating well above their glass transition temperature to develop sufficient flexibility to maintain a conformal shape to bone.

[0372] In general, polymers with desired melt profile, tensile strength, and / or modulus can be obtained by blending individual polymers, e.g., polymers 3 and 6 in Table 8 above. However, we note that substrate compositions without PCL or copolymers containing PCL generally do not adhere well to the adhesive layer, even with manufacturing adjustments such as introducing texture to the substrate surface at the adhesive-substrate interface or lamination-press protocols (Table 9). For example, pure PDX backing (polymer 2) and LG824s (polymer 5) backings result in adhesive layer delamination upon bending the tape, regardless of the introduction of texturing at the adhesive-substrate side interface (Table 9). On the other hand, in polymer blends, PCL (e.g., polymer blend 3) and / or PCL-containing copolymers (e.g., polymer blend 6), despite their incompatibility with nearly all other polymers, contribute to lower softening temperatures (Table 8), adhesive layer compatibility regardless of manufacturing method (Table 9), and strength retention due to hydrophobicity (Table 10).

[0373] [Table 9]

[0374] *Adhesive and support side compatibility is 0.5x1cm2 The bone tape pieces were then qualitatively evaluated based on a 180° flexibility test in which the pieces were folded in half and scored as follows: 0 = adhesive does not adhere to support side; 1 = adhesive peels easily from support side; 2 = adhesive peels from backing; 3 = adhesive peels from backing when picked; 4 = adhesive tears but does not peel from support side; 5 = adhesive layer cannot be separated from backing side.

[0375] **The performance of the bone tape device was qualitatively evaluated by applying it to rabbit cheekbones covered with citrated horse blood using an ultrasonic heating system. A score of 0 = no adhesion to bone, 5 = good application and adhesion to bone, and good tensile strength or good peel strength; 10 = desirable adhesion, peel resistance, and tensile strength.

[0376] Table 10: Mechanical properties of selected PCL-containing polymer blends over 7 weeks under physiological conditions to assess their utility for long-term use in vivo. Tensile specimens were cut to approximately 0.5 cm using a laser cutter and evaluated using a modified ASTM D882-18 standard. [Table 10]

[0377] Example 15. Effect of adhesive and backing thickness on bone tape performance Bone tapes can be manufactured using a variety of backing thicknesses and adhesive thicknesses. Adhesive Blend 9c and Polymer Blend 6 backings were used, and several combinations of adhesive and backing thicknesses were used to examine the effect of member thickness on the performance of laminated device F-2. Using a 70 kHz ultrasonic welder set at 2.5 J of energy, device F-2 was applied to the cheekbones of rabbits that had been covered in citrated horse blood prior to application to mimic in vivo application. Tape performance was assessed qualitatively by looking at tape adhesion, ease of application, peel strength, and tensile strength. A score of 0 = no adhesion to bone, 5 = good application and adhesion to bone, and good or good tensile strength, and 10 = desirable adhesion, peel resistance, and tensile strength.

[0378] [Table 11]

[0379] Table 11 shows that a very thick backing side polymer (0.31 mm) limits the flexibility and performance of the tape, while a very thin backing also limits the performance of the tape, but improves flexibility significantly. On the other hand, reducing the thickness of the adhesive layer improves the flexibility of the tape while maintaining a similar performance score. Thus, tapes with thinner adhesive and / or backing side layers are more suitable for applications requiring maximum flexibility, while tapes with thicker backing side layers provide the greatest stability / strength reinforcement to the tape.

[0380] Without wishing to be bound by theory, it is believed that a thin backing layer or a thin adhesive increases the energy transfer from the backing polymer to the adhesive layer, resulting in improved release. When the backing layer is at its thinnest, the heat energy lost to the backing layer is minimal. When the adhesive layer is at its thinnest, the energy required to melt the adhesive is minimal, regardless of the efficiency of energy transfer.

[0381] Example 16: Effect of Energy Application on the Performance of Bone Tape Devices As shown in Examples 12-15, careful and critical coordination of the selection of adhesive components, including fillers and / or particulate additives, and the selection of support side components is required to obtain optimal device properties and performance. However, in addition to the selection of device components, the performance of bone tape is also related to the application method. Table 12 shows the success of various applicators in the application of bone tape. Table 13 shows the temperature profile obtained during ultrasonic welding to bone. Tables 14-15 show the effect of ultrasonic device frequency on surgical flow characteristics such as welding time and welding force to achieve the desired bone tape performance. Table 16 shows the dependence of ultrasonic application on bone tape composition and thickness, and Table 17 shows the possibility of using the welder for various application styles. Unless otherwise stated, bone tape application was performed using a 70 kHz ultrasonic welder on rabbit cheekbones covered with citrated horse blood prior to application to mimic in vivo application, and the performance of the tape was qualitatively evaluated by looking at the adhesion, ease of application, peel strength, and tensile strength of the tape. A score of 0 = no adhesion to bone, 5 = good application and adhesion to bone, and good tensile strength or good peel strength, and 10 = desirable adhesion, peel resistance and tensile strength.

[0382] Table 12: Effect of energy source on bone tape performance The bone tape device F-2 was applied to the cheekbone using various heat sources, followed by manual bone peeling to measure the degree of adhesion, which was rated on a qualitative scale of 1 to 5: 1 = no adhesion under any circumstances; 5 = excellent adhesion and application / spreadability. In all cases, application was achieved by processing / pressing heated bone tape onto the substrate. To fully evaluate the potential of each method, the applied energy (ultrasound), time (heat gun, heat lamp, UV lamp), or temperature (soldering iron) were sequentially increased until bone tape failure occurred.

[0383] [Table 12]

[0384] Table 12 shows the superior performance of bone tape when ultrasonic energy is applied compared to other energy sources investigated. Without wishing to be bound by theory, it is believed that this success is due to the ability of the ultrasonic welder to selectively melt or soften the adhesive layer relative to the supporting polymer layer in situ during tape application. This selective in situ melting, combined with the constant vibrational force of the ultrasound under the applied welding force during application, acted to simultaneously displace fluids and drive the adhesive layer further into the bone hole, resulting in the superior adhesive properties observed. Conversely, other methods resulted in indiscriminate loss of heat energy to the environment, requiring longer heating times and / or higher heating temperatures to enhance tape shape conformance and / or adhesive tack. In addition to longer heating times and / or higher heating temperatures, the indiscriminate loss of heat energy to the environment resulted in increased opportunities for both damage to the supporting polymer layer and tissue damage from excessive / focused heating during application. Therefore, when applying the tape using these alternative methods, the tape had to be heated before application to avoid "shadows" on the tape and to avoid burns, resulting in suboptimal processes and time for the surgical workflow. On the other hand, ultrasonic welders demonstrated desirable adhesion with relatively short welding cycles (less than 1 second per weld) and did not reach or maintain welding temperatures that could cause tissue damage or necrosis with welding energies below 7 J (Table 13). However, for the 70 kHz welder used in these experiments, the 7 J energy setting was typically too high, causing damage to bone during bone tape application. This was evident as bleaching of the bone in contact with the welder and was believed to be due to the bone being overheated during application, causing dehydration. However, no charring of the bone was observed under these conditions, indicating that the welder did not reach and / or maintain temperatures that would cause thermal necrosis of healthy bone during application. Furthermore, as shown in Table 13, the severity of heat exposure under such harsh conditions can be mitigated by increasing the time between successive welds.

[0385] Table 13: Ultrasonic welding temperature profile when applying the Bone Tape Device F-2 to the wetted zygomatic bone using a 70 kHz ultrasonic welder. The temperature profile of the bone near the application site was assessed ex vivo using a fine-tip type E thermocouple. To accomplish this, half a cheekbone (sectioned) was cut from a rabbit cadaver and a small hole (0.69 mm diameter) was drilled into the end to accommodate the tip of the thermocouple (0.47 mm diameter). Given a bone thickness of 2.28 mm, the nominal distance from the bone surface to the thermocouple is approximately 0.9 mm. After wetting the bone with deionized water, the BoneTapeDeviceF-2 was applied to the cheekbone directly above the probe tip using either 2.5 J or 7 J per weld. Temperature profiles were recorded at 1-second intervals for each of four conditions: a single weld, five consecutive welds, ten consecutive welds, and five welds spaced 5 seconds apart.

[0386] [Table 13]

[0387] Tables 14 and 15 further illustrate the dependence of bone tape surgical workflow application on ultrasonic welding parameters.

[0388] Table 14: Dependence of surgical workflow (welding time and / or welding force) on ultrasonic frequency; in vitro proof of concept. The ability of 35 kHz and 70 kHz ultrasonic welding to apply the BoneTape Device D-12 to sawbones was investigated using horns matched in cross-sectional area and surface finish (e.g., knurling). The ultrasonic horn was mounted upside down with the weld part facing up, and a linear guide and calibrated mass were used to apply weld forces ranging from 0.5 N to 5.5 N. The quality of the welds was assessed qualitatively, primarily for adhesion and backing damage.

[0389] [Table 14]

[0390] Table 15: Application of Bone Tape Device F-2 to Wet Bone Using Ultrasonic Welding at 35 kHz and 70 kHz Investigated In Vitro. Using horns of matched cross-sectional area and surface finish, Bone Tape Device F-2 was applied freehand to the cheekbones of rabbits using either a 35 kHz or 70 kHz ultrasonic welding unit.

[0391] [Table 15]

[0392] Table 14 shows that the high frequency welder was able to successfully attach bone tape to the saw bone with only 1.5 J of ultrasonic energy at any welding force between 1.0 N and 5.5 N. In contrast, the low frequency welder was significantly dependent on the welding force. This indicates that the low frequency welder is highly dependent on the skill of the user (i.e., the force applied per weld), whereas the high frequency welder provides a desirable attachment regardless of the variation in the force applied by each user.

[0393] Both Tables 14 and 15 also show that the low frequency units required more energy and therefore substantially longer time to complete the weld compared to the high frequency units. Furthermore, the welds performed with the lower frequency units were generally qualitatively weaker than the welds created with the 70 kHz units. Because adhesive melting is directly related to the rate of energy delivery, i.e., its power, this result indicates that below a given power limit, not enough energy is delivered to melt the adhesive layer within a given weld cycle. If the power is too high, too much energy is delivered during the weld cycle, resulting in the supporting polymer melting and burning through. Overall, these results indicate that high frequency welders are favored in improving surgical workflow and should reduce the weld time and / or weld force required to achieve the desired weld of the bone tape to the bone.

[0394] The above results also show that the ability of bone tape to withstand high welding power is related to improved practicality of the procedure. Table 16 shows how the compositional features of bone tape affect its ability to withstand high welding energies, i.e. high welding powers.

[0395] [Table 16]

[0396] Table 16 shows that the energy resistance of bone tapes generally increases with increasing adhesive and / or support polymer layers. For a given support polymer thickness, regardless of adhesive thickness, increasing energy generally improves the tape's performance, particularly the peel score, up to a peak energy, after which further increases in energy decrease the overall tape score. The performance improvement is more pronounced with thinner adhesive layers, and the peak energy also occurs sooner with thinner adhesive layers compared to thicker adhesive layers. In other words, with less adhesive to dissolve, less energy is required to secure the device to the bone.

[0397] Furthermore, Table 16 shows that excellent adhesion and tensile strength could be achieved at energies less than optimal, but the greatest peel was only obtained at peak energies. This indicates that the adhesive itself does not need to become completely fluid, and that once the adhesive softens sufficiently to conform and contact the bone surface, it can form a strong tensile bond with the bone surface. However, to achieve optimal peel strength, the adhesive must completely melt and become fluid, which allows the adhesive to flow into the bone pores or remove the liquid from the bone surface. Thus, peel strength is considered to be a manifestation of both mechanical and physical bonding. If the energy is too high, the adhesive may become too fluid and be lost by flowing off the bone tape. The reduced post-peak scores observed with bone tapes containing thinner adhesive layers support this.

[0398] Table 17 shows the availability of ultrasonic welding machines with different horn geometries for different application styles.

[0399] Table 17: Effect of horn shape on surgical workflow and performance of bone tape device F-2 In all cases, the bone tape device was applied to the moist buccal bone using a 70 kHz welder equipped with various horn geometries at 2.5 J, then manually pulled off the bone to measure the degree of adhesion, which was rated on a qualitative scale of 1 to 5, where 1 = no adhesion under any circumstances and 5 = excellent adhesion and application. The stamp method refers to applying the bone tape using a welder via a series of continuous welding studs perpendicular to the application surface, covering the entire surface. On the other hand, the paint method refers to continuously sliding the welder over the entire tape surface in a drawing / brush stroke motion.

[0400] The horn textures listed in Table 17 are defined as follows:

[0401] - Fine: The individual texture elements are evenly spaced and have a uniform depth of up to 0.127mm, which corresponds to 30-80% of the total tape thickness. - Coarse: The individual texture elements are evenly spaced and have a uniform depth of ≥ 0.381 mm, which corresponds to 80-400% of the total tape thickness. - Sandblasted: The individual texture elements have a non-uniform shape and distribution, and the non-uniform depth is less than 30% of the total tape thickness. - Smooth: The ends of the horn shapes have no horn texture. - Round: Smooth horns without sharp corners.

[0402] [Table 17]

[0403] As shown, bone tape can be successfully applied using a variety of methods and / or horn shapes. Some shapes are not suitable for bone tape application depending on the specific technique, for example, using a coarse horn with a painting motion causes significant damage to the tape and bone, while other shapes, such as fine shapes, are the preferred technique for any user. In general, painting techniques have a steeper learning curve, as the ultrasonic welder must be held perpendicular to the surface to apply / apply. However, stamping facilitates the first weld point to the anchor BT during installation, resulting in a more desirable surgical workflow. Overall, these results demonstrate the flexibility of bone tape application to changes in user technique, and therefore improved utility of the procedure.

[0404] Other embodiments While the invention has been described in relation to particular embodiments thereof, it will be understood that further modifications are possible and that the invention is intended to cover any variation, use, or adaptation of the invention in accordance with the principles of the invention in general, including departures from the present disclosure that are within known or customary practice in the art to which the invention pertains and that may be applicable to the essential features hereinbefore described.

Claims

**Claim 1** A method for stabilizing bone fragments in the body, comprising: (i) (a) heating an adhesive composition to form a softened adhesive composition, contacting the softened adhesive composition with a first bone fragment, and (b) allowing the softened adhesive composition to cool to form a first anchor fixed to the first bone fragment, thereby forming a first anchor on the first bone fragment; (ii) (a) heating an adhesive composition to form a softened adhesive composition, contacting the softened adhesive composition with a second bone fragment, and (b) allowing the softened adhesive composition to cool to form a second anchor fixed to the second bone fragment, thereby forming a second anchor on the second bone fragment; wherein: the adhesive composition has a tackifying temperature of at least 40°C; the first anchor and the second anchor are connected to a support structure for stabilizing the bone fragments; A method for stabilizing bone fragments in the body. **Claim 2** The method according to claim 1, wherein the support structure is a flexible support comprising a biodegradable and biocompatible polymer that connects the first anchor to the second anchor. **Claim 3** The support structure, the first anchor, and the second anchor are formed from a tape comprising: (x) a non-adhesive upper layer that is the support structure, and (y) a lower layer that softens to become adhesive for forming the first anchor and the second anchor; and / or the adhesive composition is not water-soluble; and / or the adhesive composition comprises a heat transfer agent; The method according to claim 1. **Claim 4** The heat transfer agent is present in an amount that enables the softened adhesive composition to cool and cure in 120 seconds or less, or the heat transfer agent is present in an amount that enables the softened adhesive composition to cool and cure in 10 seconds or less; and / or the heat transfer agent is present in an amount that enables the adhesive composition to soften within 120 seconds after applying energy, or the heat transfer agent is present in an amount that enables the adhesive composition to soften within 10 seconds after applying energy to the non-adhesive upper layer; and / or the adhesive composition comprises 0.5 to 60% (w / w) of the heat transfer agent, or the adhesive composition comprises 35 to 60% (w / w) of the heat transfer agent; The method according to claim 3. **Claim 5** The heat transfer agent is selected from the group consisting of sodium chloride, iron(III) phosphate dihydrate, iron(III) citrate monohydrate, hydroxyapatite, tetracalcium phosphate, tricalcium phosphate, dicalcium phosphate, and sodium carbonate, or a combination thereof, or the heat transfer agent is hydroxyapatite, The method according to claim 4.

6. The method according to claim 1, wherein the adhesive composition comprises a polymer having the structure of formula (I). 【Chemical Formula 1】 (In the formula, n is an integer from 0 to 4; Block B comprises an oligomer derived from polyester, polyalkylene glycol, polysilicon, or polycarbonate with MW ≤ 4,000 g / mol; Block A may be substituted with C １ ~C ６ contains alkylene, and block A is derived from a diisocyanate crosslinking agent; Block W may contain C which may be substituted ０ - C ３ alkyl - benzene - diol, or C which may be substituted ０ - C ３ alkyl - benzene - triol; Linker L’ comprises a carbamate; and Linker L comprises a urea.)

7. a) Block B has the structure of formula (II): [Chemical 2] (In the formula, each o is independently an integer from 0 to 20.) or b) Block B has the structure of formula (III): 【Chemical Formula 3】 (In the formula, each o is independently an integer from 0 to 20.) or c) Block B has the structure of formula (IV): 【Chemical 4】 (In the formula, each o is independently an integer from 0 to 20.) or d) Block B has the structure of formula (V): 【Chemical Formula 5】 (In the formula, each o is independently an integer from 0 to 20.) and / or e) Block A has the structure of formula (VII): ​ (wherein R １ is C １ -C ３ alkyl.) ; and / or f) Linker L’ has the structure of 【Chemical Formula 7】 ; and / or g) Linker L has the structure of [Chemical Formula 8] ; and / or h) Block W has the structure of 【Chemical Formula 9】 ; The method according to claim 6.

8. The adhesive composition comprises 30 - 70% (w / w) filler, The method according to claim 1.

9. The filler comprises polycaprolactone (PCL), polydioxanone (PDX), poly(lactic - co - glycolic acid) (PLGA), poly - 3 - hydroxybutyric acid (P3HB), polylactic acid (PLA), polyglycolide (PGA), poly - 4 - hydroxybutyric acid (P4HB), polyethylene carbonate (PEC), polypropylene carbonate (PPC), poly(trimethylene carbonate) (PTMC), polysulfone, polyethylene glycol (PEG), hydroxyapatite (HA), tetracalcium phosphate (TTCP), tricalcium phosphate (TCP), dicalcium phosphate (DCP), or a copolymer thereof, or a blend thereof, or The filler comprises polycaprolactone (PCL), polydioxanone (PDX), poly(lactic-co-glycolic acid) (PLGA), or poly-3-hydroxybutyric acid (P3HB), hydroxyapatite (HA), or a copolymer thereof, or a blend thereof, The method according to claim 8.

10. The method according to claim 1, wherein steps (i) and (ii) are repeated to stabilize a plurality of bone fragments in the subject, or steps (i) and (ii) are repeated to stabilize 2 to 5 or more bone fragments in the subject.

11. The method according to claim 1, wherein heating comprises applying an energy source.

12. The energy source is ultrasonic energy, a) the ultrasonic energy is applied at a frequency of 35 kHz to 70 kHz, or the frequency of the ultrasonic energy is 70 kHz; and / or b) an energy of 1.5 to 5.0 J is applied; and / or c) the ultrasonic energy is applied at a frequency and in an amount sufficient to move fluid between the adhesive composition and the bone fragment before the formation of the first and second anchors; and / or d) the ultrasonic energy is applied using an ultrasonic welder, The method according to claim 1.

13. a) the method comprises reversibly stabilizing the bone fragment; and / or b) the first and second anchors are reversible anchors; and / or c) the adhesive composition does not rely on an in-situ curing reaction for adhesion; and / or d) the adhesive composition reversibly softens at a temperature of 45 ± 5°C; and / or e) the support structure, the first anchor, and the second anchor are formed from a tape comprising (x) a non-adhesive upper layer that is the support structure and (y) a lower layer that softens to become adhesive and forms the first and second anchors; and / or f) (i) the support structure and (ii) at least one of the first and second anchors are arranged to form an adhesive portion and a support portion that underlies the adhesive portion, and the adhesive portion can soften without deforming the support portion when heated; and / or g) Does heating involve applying it using a welding machine via a series of continuous welding studs perpendicular to the application surface so as to cover the entire surface; or does heating involve continuously sliding the welding machine over the entire surface of the device in a brushing stroke or a painting operation? The method according to claim 1.

14. An apparatus for stabilizing bone fragments, (i) A first anchor that can be attached to a first bone fragment, the first anchor comprising an adhesive composition that softens upon heating and forms the first anchor upon cooling; (ii) A second anchor that can be attached to a second bone fragment, the second anchor comprising an adhesive composition that softens upon heating and forms the second anchor upon cooling; (iii) A support structure capable of stabilizing the bone fragments, connecting the first anchor to the second anchor having, and the adhesive composition has a tackifying temperature of at least 40°C. An apparatus for stabilizing bone fragments.

15. The apparatus according to claim 14, wherein the support structure is a flexible support comprising a biodegradable and biocompatible polymer that connects the first anchor to the second anchor.

16. The support structure, the first anchor, and the second anchor are formed from a tape comprising (x) a non-adhesive upper layer that is the support structure and (y) a lower layer that becomes adhesive upon softening and forms the first and second anchors; and / or the adhesive composition is not water-soluble; and / or the adhesive composition contains a heat transfer agent. The apparatus according to claim 14.

17. The heat transfer agent is present in an amount that enables the softened adhesive composition to cool and cure within 120 seconds, or the heat transfer agent is present in an amount that enables the softened adhesive composition to cool and cure within 10 seconds; and / or the heat transfer agent is present in an amount that enables the adhesive composition to soften within 120 seconds after applying energy, or the heat transfer agent is present in an amount that enables the adhesive composition to soften within 10 seconds after applying energy to the non-adhesive upper layer; and / or the adhesive composition contains 0.5 to 60% (w / w) of the heat transfer agent, or 35 to 60% (w / w) of the heat transfer agent. The apparatus according to claim 16.

18. The heat transfer agent is selected from the group consisting of sodium chloride, iron(III) phosphate dihydrate, iron(III) citrate monohydrate, hydroxyapatite, tetracalcium phosphate, tricalcium phosphate, dicalcium phosphate, and sodium carbonate, or a combination thereof, or the heat transfer agent is hydroxyapatite, the apparatus according to claim 17.

19. The adhesive composition contains a polymer having the structure of formula (I), the apparatus according to claim 14. 【Chemical 10】 (In the formula, n is an integer from 0 to 4; block B contains an oligomer derived from polyester, polyalkylene glycol, polysilicon, or polycarbonate with MW < 4,000 g / mol; Block A may be substituted with C １ ~C ６ contains alkylene and block A is derived from a diisocyanate crosslinking agent; Block W may contain a substituted C ０ to C ３ alkyl - benzene - diol, or a substituted C ０ to C ３ alkyl - benzene - triol; linker L' contains carbamate; and linker L contains urea.)

20. a) block B has the structure of formula (II): 【Chemical 11】 (In the formula, each o is independently an integer from 0 to 20.) or b) block B has the structure of formula (III): 【Chemical 12】 (In the formula, each o is independently an integer from 0 to 20.) or c) block B has the structure of formula (IV): 【Chemical 13】 (In the formula, each o is independently an integer from 0 to 20.) or d) block B has the structure of formula (V): 【Chemical 14】 (In the formula, each o is independently an integer from 0 to 20.) has; and / or e) block A has the structure of formula (VII): 【Chemical Formula 15】 (wherein, R １ is C １ -C ３ is alkyl.) has; and / or f) linker L' has 【Chemical Formula 16】 the structure of; and / or g) linker L has 【Chemical 17】 the structure of; and / or h) block W has 【Chemical Formula 18】 the structure of, the apparatus according to claim 19.

21. The adhesive composition contains 30 - 70% (w / w) filler, the apparatus according to claim 14.

22. The filler contains polycaprolactone (PCL), polydioxanone (PDX), poly(lactic-co-glycolic acid) (PLGA), poly-3-hydroxybutyric acid (P3HB), polylactic acid (PLA), polyglycolide (PGA), poly-4-hydroxybutyric acid (P4HB), polyethylene carbonate (PEC), polypropylene carbonate (PPC), poly(trimethylene carbonate) (PTMC), polysulfone, polyethylene glycol (PEG), hydroxyapatite (HA), tetracalcium phosphate (TTCP), tricalcium phosphate (TCP), dicalcium phosphate (DCP), or a copolymer thereof, or a blend thereof, or The filler comprises polycaprolactone (PCL), polydioxanone (PDX), poly(lactic-co-glycolic acid) (PLGA), or poly-3-hydroxybutyric acid (P3HB), hydroxyapatite (HA), or a copolymer thereof, or a blend thereof. The device according to claim 21.

23. a) The device comprises a plurality of bone anchors and a plurality of support structures capable of stabilizing a plurality of bone fragments; and / or b) (i) The support structure and (ii) at least one of the first anchor and the second anchor are arranged to form an adhesive portion and a support portion forming a backing of the adhesive portion, and the adhesive portion can be softened without deforming the support portion when heated; and / or c) The first anchor and the second anchor can each adhere to a wet or dry bone fragment; and / or d) The first anchor and the second anchor are reversible anchors; and / or e) The adhesive composition does not rely on an in-situ curing reaction for adhesion; and / or f) The adhesive composition reversibly softens at a temperature of 45 ± 5 °C; and / or g) The backing portion has a thickness of 0.05 to 0.31 mm, or the backing portion has a thickness of 0.12 to 0.20 mm; and / or h) The adhesive portion has a thickness of 0.05 to 0.16 mm, or the adhesive portion has a thickness of 0.075 ± 0.025 mm, or 0.13 ± 0.03 mm. The device according to claim 14.

24. (i) 0 to 70% (w / w) filler; and (ii) 30 to 100% (w / w) of a polymer having the structure of formula (I): 【Chemical 19】 (wherein n is an integer from 0 to 4; block B comprises an oligomer derived from a polyester, a polyalkylene glycol, a polysiloxane, or a polycarbonate with MW ≤ 4,000 g / mol; Block A may be replaced with C １ ~C ６ contains an alkylene, and block A is derived from a diisocyanate crosslinking agent; Block W may contain C which may be substituted ０ ~C ３ alkyl - benzene - diol, or C which may be substituted ０ ~C ３ alkyl - benzene - triol; linker L' comprises a carbamate; and linker L comprises a urea.) and having an adhesion temperature of at least 40 °C. An adhesive composition.

25. a) The adhesive composition is not water-soluble; and / or b) The adhesive composition contains a heat transfer agent. The adhesive composition according to claim 24.

26. ​ The heat transfer agent is present in an amount that enables the softened adhesive composition to cool and cure within 120 seconds, or the heat transfer agent is present in an amount that enables the softened adhesive composition to cool and cure within 10 seconds; and / or The heat transfer agent is present in an amount that enables the adhesive composition to soften within 120 seconds after applying energy, or the heat transfer agent is present in an amount that enables the adhesive composition to soften within 10 seconds after applying energy to the non - adhesive upper layer; and / or The adhesive composition contains 0.5 - 60% (w / w) of the heat transfer agent, or contains 35 - 60% (w / w) of the heat transfer agent, The adhesive composition according to claim 25.

27. The heat transfer agent is selected from the group consisting of sodium chloride, iron(III) phosphate dihydrate, iron(III) citrate monohydrate, hydroxyapatite, tetracalcium phosphate, tricalcium phosphate, dicalcium phosphate, and sodium carbonate, or combinations thereof, or the heat transfer agent is hydroxyapatite, the adhesive composition according to claim 25.

28. a) Block B has the structure of formula (II): 【Chemical 20】 (In the formula, each o is independently an integer from 0 to 20.) or b) Block B has the structure of formula (III): 【Chemical 21】 (In the formula, each o is independently an integer from 0 to 20.) or c) Block B has the structure of formula (IV): 【Chemical 22】 (In the formula, each o is independently an integer from 0 to 20.) or d) Block B has the structure of formula (V): 【Chemical 23】 (In the formula, each o is independently an integer from 0 to 20.) ; and / or e) Block A has the structure of formula (VII): 【Chemical 24】 (wherein, R １ is C １ -C ３ is alkyl.) ; and / or f) The linker L’ has 【Chemical 25】 the structure of; and / or g) The linker L has 【Chemical 26】 the structure of; and / or h) Block W has 【Chemical 27】 the structure of, The adhesive composition according to claim 24.

29. A tape comprising (i) a non - adhesive polymer upper layer and (ii) a lower layer comprising the adhesive composition of claim 24.

30. a) The non-adhesive polymer upper layer comprises polycaprolactone (PCL), polydioxanone (PDX), poly(lactic-co-glycolic acid) (PLGA), poly-3-hydroxybutyric acid (P3HB), polylactic acid (PLA), polyglycolide (PGA), poly-4-hydroxybutyric acid (P4HB), polyethylene carbonate (PEC), polypropylene carbonate (PPC), poly(trimethylene carbonate) (PTMC), polysulfone, polyethylene glycol (PEG), or copolymers thereof; and / or b) The non-adhesive polymer upper layer has a thickness of 0.05 to 0.31 mm, or the non-adhesive polymer upper layer has a thickness of 0.12 to 0.20 mm; and / or c) The lower layer has a thickness of 0.05 to 0.16 mm, or the lower layer has a thickness of 0.075 ± 0.025 mm or a thickness of 0.13 ± 0.03 mm, The tape according to claim 29.

31. A method for manufacturing the device according to claim 14 or the tape according to claim 29, the method comprising: a) (i) bringing a first part comprising the adhesive composition according to claim 24 into contact with (ii) a second part comprising a support structure; b) applying heat to join the first part and the second part, The manufacturing method comprising.

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