Device for endoscopic delivery of multiple strips

Abstract

Disclosed herein are devices, kits and methods for delivering a plurality of strips to a site of a tissue defect to facilitate coverage and / or closure of the tissue defect. The kit may include: a first medical device configured to push a plurality of straps received therein through a distal opening; and a second medical device defining a working channel for insertion of the first medical device. The method may comprise introducing a distal portion of a medical device containing a plurality of strips comprising a biocompatible material into the gastrointestinal tract; positioning a distal portion of the device proximate a target site comprising a wall of defective gastrointestinal tract tissue; and applying the plurality of strips to the target site by pushing the plurality of strips out of the distal opening of the device.

Description

Cross-citation to related applications

[0001] This application claims priority to U.S. Provisional Application No. 63 / 431,075, filed on December 8, 2022, the entire contents of which are incorporated herein by reference. Technical Field

[0002] The present disclosure generally relates to medical devices, kits, and methods of use thereof. More particularly, the present disclosure encompasses devices, kits, and methods for endoscopic medical procedures, such as applying a plurality of strips to a tissue defect site to promote coverage and / or closure of the tissue defect. Background Art

[0003] Various medical procedures can be used to treat tissue. For example, endoscopic surgery of the gastrointestinal (GI) tract or other organ systems can be performed for intervention and / or therapeutic purposes, such as treating submucosal lesions, removing precancerous mucosal tissue or tumors, and removing lesions. Such procedures may cause perforations, postoperative leakage, or other wounds that need to be repaired. Internal wounds or tissue defects, such as inflammation, ulcers, etc., can form naturally and can also benefit from treatment. In order to treat internal wounds, medicaments such as hemostatics can be applied to the target site via a medical device. For example, hemostatic particles can be sprayed on the wound or tissue defect. However, applying hemostatics to internal tissue defects, for example, via spraying, may bring special challenges, including being distributed to the undesirable parts of the body by the defect. Summary of the Invention

[0004] The present disclosure includes medical devices, kits, and methods of using the same, such as a method of applying a plurality of strips to a tissue defect site to promote coverage and / or closure of the tissue defect. For example, the present disclosure includes a kit comprising a first medical device defining a lumen for accommodating an axis and a chamber near the distal end of the first medical device, wherein the chamber accommodates a plurality of strips comprising a biocompatible material, and the axis is movable along the lumen to push the plurality of strips through the distal opening of the first medical device. The kit also includes a second medical device defining a working channel into which the first medical device is insertable. In some examples herein, the biocompatible material comprises chitosan, cellulose, poly(2-hydroxyethyl methacrylate), polystyrene, collagen, gelatin, fibrin, polyethylene glycol (PEG), hyaluronic acid, a block copolymer, or a combination thereof. In some examples, the plurality of strips include chitosan or a derivative thereof, such as thiolated chitosan, chitosan cross-linked with tripolyphosphate, and / or carboxymethylcellulose chitosan cross-linked with polyethylene glycol amine (PEG amine). The plurality of strips may be bioresorbable. According to some aspects of the present disclosure, the second device may be an endoscope.

[0005] Additionally or alternatively, each of the plurality of strips may have a length ranging from about 5 mm to about 40 mm, a width ranging from about 1.5 mm to about 5 mm, and / or a thickness ranging from about 1 μm to about 100 μm. In some examples, the plurality of strips may include strips of different lengths and / or widths. According to some aspects of the present disclosure, the strips of the plurality of strips may be planar. In at least one example, the plurality of strips include at least one strip having a thickness that is variable along the length of the at least one strip. For example, with respect to the first device, the shaft may include a distal end having a cross-sectional dimension that is larger than a cross-sectional dimension of the shaft such that when the shaft moves along the lumen, the distal end of the shaft contacts the wall of the lumen and slides along the wall of the lumen. The kit may also include a balloon device.

[0006] The present disclosure also encompasses the use of the kit for treating a target site of tissue. For example, the second device may be an endoscope, and the tissue may be tissue of the gastrointestinal tract. In some examples, the target site may comprise a tissue defect, and the plurality of strips may fill, cover, and / or repair the tissue defect. In at least one example, in connection with the use of the kit, the plurality of strips may be configured to transition from a flat configuration when housed in the first device to a curled configuration when applied to the target site.

[0007] The present disclosure also includes a method of treating a subject, the method comprising: introducing a distal portion of a medical device into the gastrointestinal tract of the subject, wherein the distal portion contains a plurality of strips comprising a biocompatible material; positioning the distal portion of the device near a target site in a wall of gastrointestinal tissue comprising a defect; and applying the plurality of strips to the target site by pushing the plurality of strips out of the distal opening of the device, wherein the plurality of strips at least partially fill the defect or form a layer over the defect. The biocompatible material may comprise chitosan, cellulose, poly(2-hydroxyethyl methacrylate), polystyrene, collagen, gelatin, fibrin, polyethylene glycol (PEG), hyaluronic acid, a block copolymer, or a combination thereof. For example, the biocompatible material may comprise thiolated chitosan, chitosan cross-linked with tripolyphosphate, or carboxymethylcellulose chitosan cross-linked with polyethylene glycol amine. In some examples, the biocompatible material may be bioabsorbable.

[0008] The method may further include applying a therapeutic agent to the target site after the plurality of strips are applied to the target site. According to certain aspects of the present disclosure, the therapeutic agent may be a hemostatic agent. In certain examples herein, applying the therapeutic agent may include spraying the therapeutic agent onto the target site. In certain examples, pushing the plurality of strips out of the distal opening of the device may include advancing the shaft of the device distally to push the plurality of strips with the distal end of the shaft. In these examples, the cross-sectional dimensions of the distal end of the shaft may be larger than the cross-sectional dimensions of the shaft so that when the shaft moves along the lumen, the distal end of the shaft contacts and slides along the wall of the lumen. According to certain aspects of the present disclosure, each of the plurality of strips may range in length from about 5 mm to about 40 mm, in width from about 1.5 mm to about 5 mm, or in thickness from about 1 mm to about 100 mm.

[0009] The method may further include applying a biocompatible liquid or a balloon to the plurality of strips after applying the plurality of strips to the target site. In some examples, the plurality of strips may be configured to transition from a planar configuration when contained within the device to a curled configuration when applied to the target site. In at least one example, the plurality of strips may include at least one strip having a variable thickness along the length of the at least one strip.

[0010] Also disclosed herein is a method for treating a subject, the method comprising: introducing a distal portion of a medical device into the gastrointestinal tract of the subject, wherein the distal portion of the device defines a lumen for accommodating a shaft and a chamber near the distal end of the device, wherein the chamber accommodates a plurality of strips comprising a biocompatible material; positioning the distal portion of the device near a target site comprising a tissue wall having a defect; advancing the shaft distally to push the plurality of strips out of the distal opening of the device and onto the target site; and applying a biocompatible liquid, therapeutic agent, or balloon to the target site after applying the plurality of strips. The biocompatible material may include chitosan, cellulose, poly(2-hydroxyethyl methacrylate), polystyrene, collagen, gelatin, fibrin, polyethylene glycol (PEG), hyaluronic acid, a block copolymer, or a combination thereof. In some examples, the biocompatible material may be a bioabsorbable material, a hemostatic material, or both. For example, the method may include applying a therapeutic agent to the target site after applying the plurality of strips, the therapeutic agent being a hemostatic agent.

[0011] The present disclosure also includes a method of treating a subject, the method comprising: introducing a distal portion of a medical device into the gastrointestinal tract of the subject, wherein the distal portion of the device comprises a chamber that houses a plurality of strips comprising chitosan or a derivative thereof; positioning the distal portion of the device near a target site comprising a wall of gastrointestinal tissue having a defect; and applying the plurality of strips to the target site by pushing the plurality of strips out of a distal opening of the device; wherein each of the plurality of strips has a thickness that varies along the length of the strip, and wherein the plurality of strips transform from a planar configuration when housed in the device to a curled configuration when applied to the target site. The method may further comprise applying a biocompatible liquid, a therapeutic agent, or a balloon to the target site after the plurality of strips are applied to the target site. For example, the method may comprise spraying water or an aqueous solution having an acidic pH onto the target site after the plurality of strips are applied to the target site. BRIEF DESCRIPTION OF THE DRAWINGS

[0012] The accompanying drawings, which are incorporated in and constitute a part of this specification, illustrate various exemplary embodiments and, together with the description, serve to explain the principles of the disclosed embodiments.

[0013] According to some aspects of the present disclosure, Figure 1A An exemplary device for delivering multiple strips to a target site is shown.

[0014] Figures 1B to 1C Show Figure 1A components of the device.

[0015] According to some aspects of the present disclosure, Figure 2 Exemplary strip sizes are shown.

[0016] According to some aspects of the present disclosure, Figure 3Delivery of multiple strips to a target site is shown.

[0017] According to some aspects of the present disclosure, Figure 4 The delivery of multiple strips to another target site is shown.

[0018] According to some aspects of the present disclosure, Figure 5 An exemplary system for adhering multiple strips to tissue is shown.

[0019] According to some aspects of the present disclosure, Figure 6 Another exemplary system for adhering multiple strips to tissue is shown. DETAILED DESCRIPTION

[0020] Specific aspects of the present disclosure are described in more detail below. In the event of a conflict in terms and / or definitions incorporated by reference, the terms and definitions provided herein shall prevail.

[0021] As used herein, the terms "comprises," "comprising," or any other variations thereof are intended to encompass a non-exclusive inclusion, such that a process, method, article, or apparatus that includes a list of elements includes not only those elements but may also include other elements not expressly listed or inherent to such process, method, article, or apparatus. The term "exemplary" is used in the sense of an example rather than an ideal.

[0022] As used herein, the singular forms "a," "an," and "the" include plural references unless the context indicates otherwise. The terms "approximately" and "about" refer to being substantially the same as the referenced number or value. As used herein, the terms "approximately" and "about" should be understood to include ±5% of the specified amount or value. All ranges should be understood to be inclusive, for example, a diameter range of 10 mm to 40 mm includes 10 mm, 40 mm, and all values ​​therebetween.

[0023] Embodiments of the present disclosure include medical devices, kits, and methods for treating a target site, such as endoscopic delivery of multiple strips to a target tissue site. The methods herein include applying multiple strips to a target tissue site, such as a tissue defect, to fill and / or repair the target tissue site. The multiple strips can be applied to the target tissue site before an agent, such as a hemostatic agent, is applied to the target tissue site. The kits and devices herein can be pre-loaded with multiple strips near the distal end for delivery of the multiple strips to the target tissue site. After application to a tissue site, such as a tissue defect, the multiple strips can cover and / or fill the tissue defect.

[0024] The multiple strips described herein can be used as defect closures and / or barriers to prevent certain agents from spreading through the defect to other parts of the body outside the target area or beyond the target area. For example, the multiple strips described herein can be used to repair (e.g., close) an opening in a tissue defect or to form a layer above a tissue defect. The layer formed by the multiple strips can be used as a protective layer, barrier, or covering. The multiple strips described herein can also be used to fill certain defects. In some examples, the multiple strips can be used to seal perforations. Once applied to the defect, the multiple strips of the present disclosure can provide a surface or structure for applying agents such as hemostats thereon. In some examples, the multiple strips described herein can be applied to the connection between sutures (e.g., as part of an anastomotic resection), acting as a barrier to prevent leakage by reinforcing and / or sealing the sutures. Additionally or alternatively, applying the multiple strips to the defect can inhibit or prevent hemostats and / or other agents applied to the target area (e.g., the tissue defect area) from passing through the defect and reaching undesirable areas of the body, such as by spraying.

[0025] In some examples, multiple strips may comprise the same or different materials as agents, such as hemostats, that are subsequently applied to the target tissue site. For example, multiple strips may comprise hemostatic materials. In addition to being used to fill and / or repair defects, multiple strips comprising hemostatic materials may also assist in stopping bleeding when applied to the target tissue site. Multiple strips may be used to treat various types of tissue, including injured or diseased tissue, such as lesions, ulcers, perforations, microperforations, and other areas requiring treatment or repair. In some examples, the multiple strips disclosed herein may be used in a multi-step treatment process. For example, in an initial step or a set of steps, multiple strips may be applied to a tissue defect. Subsequently, a hemostatic agent may be applied to the same area, such as multiple strips, to prevent or inhibit tissue bleeding. Multiple strips may be made of the same material as the hemostatic agent to be applied subsequently, or may be made of a material different from the hemostatic agent.

[0026] Exemplary sites to which multiple strips may be applied herein include, but are not limited to, gastrointestinal tissues such as the esophagus, stomach, small intestine (e.g., duodenum, jejunum, or ileum) and / or large intestine (e.g., cecum, colon, rectum, or anal canal). In some examples, multiple strips may be applied to defects in gastrointestinal tissues. Multiple strips may be applied to various tissue defects, including perforations, microperforations, leaks, and fistulas. Based on the depth or thickness of the defect, the defect may be classified as a partial thickness defect or a full thickness defect. Exemplary thicknesses of the defect range from approximately 3 mm to 50 mm. For example, a partial thickness tissue defect may be non-transmural, while a full thickness tissue defect may be transmural. A full thickness tissue defect may include perforations, leaks, or fistulas. In some examples, small or large bowel anastomotic resection may result in the risk of leakage between sutures. The plurality of strips described herein can be applied to such a junction, for example, prior to administering a medicament, to serve as a barrier to areas outside the target area. In other examples, the plurality of strips described herein can be applied to a fistula, such as an intestinal fistula, for example, prior to administering a medicament, to serve as a barrier to areas outside the target area.

[0027] According to aspects of the present disclosure, multiple strips can be delivered endoscopically, optionally after or in conjunction with a medical procedure such as endoscopic mucosal resection (EMR), endoscopic submucosal dissection (ESD), or a tissue biopsy. For example, multiple strips can be delivered endoscopically to a target site to fill and / or repair tissue defects caused by ulceration of a layer or mucosal layer removed via ESD. Multiple strips can include one or more biocompatible materials (including, for example, one or more materials derived from biological materials) that can be at least partially or completely bioabsorbable. For example, when applied to tissue, at least a portion of each strip may dissolve or degrade over time. Exemplary biocompatible materials suitable for use in the multiple strips described herein include, but are not limited to, polysaccharides such as chitosan (including thiolated chitosan and other functionalized chitosans or chitosan derivatives), cellulose, poly(2-hydroxyethylmethacrylate) (polyHEMA), polystyrene, collagen, gelatin, thrombin (including, for example, thrombin / gelatin), fibrin, polyethylene glycol (PEG), hyaluronic acid, block copolymers, and combinations thereof. Without being bound by theory, it is believed that the use of block copolymers or combinations of these materials can improve the durability of the overall matrix of the strip and can enhance the degradability, cohesion, and / or adhesion of the strip. For example, the type of monomer and copolymer units and their arrangement can be selected based on the type of target site to be treated to provide the desired strength and degradation properties of the strip. The multiple strips herein can also be cross-linked, such as via ionic cross-linking or covalent cross-linking, to enhance the matrix provided by the strip. In some examples, the strips can be made of a film or sheet comprising a biocompatible material. Each strip can be cut to the desired size. In other examples, the tapes can be prepared by extruding the polymer.

[0028] In some embodiments herein, the plurality of strips comprise chitosan and / or its derivatives, including but not limited to thiolated chitosan, pegylated chitosan, catechol-modified chitosan, quaternary ammonium chitosan, and / or carboxymethyl chitosan. Chitosan is a linear polysaccharide formed from glucosamine units derived from chitin, a structural component of the exoskeleton of crustaceans. Chitosan is typically prepared by deacetylation of chitin with an alkaline agent such as sodium hydroxide to produce a water-soluble substance. Chitosan has antimicrobial properties and possesses natural bioadhesive and hemostatic properties, enabling it to bind to negatively charged surfaces such as mucous membranes. As discussed further below, where an agent, such as a hemostatic agent, is applied to the plurality of strips, the agent may comprise chitosan or a derivative thereof.

[0029] The plurality of strips described herein may comprise chitosan in the form of a salt. For example, salts may be prepared by combining chitosan with a suitable conjugate acid such as acetic acid (forming chitosan acetate) or lactic acid (forming chitosan lactate). Other possible organic acids include, but are not limited to, succinic acid (chitosan succinate), glutamic acid (chitosan glutamate), glycolic acid (chitosan glycolate), and citric acid (chitosan citrate). In an exemplary process for preparing a chitosan salt, chitosan is suspended in water at room temperature, followed by addition of an organic acid (e.g., acetic acid and / or citric acid) to form a gel. The gel is then dried into a film or sheet of the desired thickness and size. Without being bound by theory, it is believed that the acid provides the cross-linked structure. In some embodiments, the plurality of strips may comprise chitosan cross-linked with a tripolyphosphate, such as sodium tripolyphosphate, or carboxymethyl chitosan cross-linked with polyethylene glycol amine.

[0030] The plurality of strips herein can be formed to have any suitable size, for example, based on the type of target site, such as the size and shape of the tissue defect. In some examples, the length of each individual strip can be in the order of millimeters, for example, ranging from about 5 mm to about 40 mm, about 10 mm to about 35 mm, about 15 mm to about 30 mm, or about 20 mm to about 25 mm. In some examples, the width of each individual strip can be in the order of millimeters, for example, ranging from about 1.5 mm to about 5 mm, or from about 2.0 mm to about 4 mm, for example, a width of about 1.5 mm, about 2.0 mm, about 2.5 mm, about 3 mm, or about 3.5 mm. In some examples, the thickness of each individual strip may be micron-sized, for example, ranging from about 1 μm to about 300 μm, for example, from about 1 μm to about 50 μm, about 10 μm to about 100 μm, about 50 μm to about 150 μm, about 75 μm to about 250 μm, about 100 μm to about 300 μm, or about 150 μm to about 275 μm. The thickness of the strip may be uniform or variable. For example, a variable thickness may cause the strip to curl when applied to the target site. The strips herein may have a regular geometric shape, such as a rectangular or cylindrical shape, or an irregular shape. In some examples, each individual strip can change configuration to fill a tissue defect. According to some aspects, each of the multiple strips may have substantially the same size and / or shape (e.g., the same length, width, and thickness). According to some aspects, the multiple strips may include strips of different sizes and / or shapes (e.g., different lengths, widths, and / or thicknesses).

[0031] The plurality of strips can be substantially dry prior to use, for example, when contained within a delivery device or kit prior to application to a target site. In some examples herein, the plurality of strips can be moistened after being dispensed from the delivery device or kit. For example, after the strips are applied to the target site, water or an aqueous solution can be applied to the strips via a fluid channel of an endoscope. In some examples, upon exposure to moisture (moisture present at the target site and / or moisture applied via an endoscope or other device), the strips may absorb the fluid, causing the strips to swell. According to certain aspects of the present disclosure, moistening the plurality of strips, in addition to moisture present at the target site, can aid in their adhesion to tissue. In some cases, the plurality of strips can be substantially planar when contained within the device and, upon application to the target site, optionally, upon moistening the strips with liquid present at the target site and / or with a biocompatible liquid, such as water, saline, or other aqueous solution, applied to the target site after application of the plurality of strips, can assume a curled configuration.

[0032] According to the present disclosure, a medical device for delivering a plurality of strips to a target site, such as a delivery device, may include a lumen and / or chamber for delivering the plurality of strips, wherein the strips are made of a biocompatible material or a combination of biocompatible materials described herein. The delivery device may be inserted into a working channel of an endoscope. In some examples, the delivery device may include a shaft, the distal end of which contacts the plurality of strips to push the plurality of strips out of a distal opening of the delivery device. For example, the plurality of strips may be housed in a chamber located proximal to the distal end of the delivery device and distal to the shaft that is longitudinally movable along the lumen of the delivery device. When a user pushes the shaft distally, the distal end of the shaft can push the plurality of strips out of the chamber and through the distal opening. The kits and medical systems described herein may include a device comprising a plurality of strips to be delivered to a subject (such a device also referred to herein as a delivery device), and optionally an endoscope or other medical device for advancing the delivery device to the target site. For example, an exemplary kit may include a first medical device housing a plurality of strips comprising a biocompatible material (eg, pre-loaded with the plurality of strips) and a second medical device defining a working channel into which the first device is insertable. Figures 1A to 1C , 3 and 4 show an exemplary first medical device of such a kit. Figure 5 and 6 An exemplary second medical device of such a kit is shown.The devices described herein and kits including such devices are not limited to the devices and features depicted in the figures; rather, various variations are contemplated and described in this disclosure.

[0033] According to certain aspects of the present disclosure, Figure 1AAn exemplary delivery device 100 is depicted, shown in an assembled state. Device 100 houses a plurality of strips 150 at a distal portion 170 and includes a mechanism for delivering strips 150 to a target site. This mechanism is depicted as including a shaft 120, with a distal end 130 proximal to the strips 150. For example, shaft 120 may be part of a plunger having a proximal handle 110 to allow a user to move shaft 120 along a lumen of the device. The lumen may be defined by a catheter 140. The lumen may extend from the proximal portion of device 100 to the distal end of device 100, e.g., communicating with a distal opening through which strips 150 may exit device 100. The distal portion of device 100 may be sized to fit within the working channel of an endoscope. For example, catheter 140 may have any suitable outer cross-sectional dimensions to fit within the working channel of an endoscope. The catheter 140 can be flexible so that the device 100 can be advanced through an endoscope working channel in a body cavity, which can have a tortuous anatomical structure. The handle 110 can be operatively connected to the distal end 130 of the shaft 120. By manipulating the handle 110, the shaft and its distal end 130 can be moved along the body cavity.

[0034] The plurality of strips 150 comprise a biocompatible material, which in some examples may comprise chitosan. The plurality of strips 150 may be housed within a distal portion of the device 100, for example, within a chamber near the distal end of the device 100. The plurality of strips 150 in the device 100 may have a uniform length and / or width (e.g., the strips are rectangular or square in shape), or the length and / or width may vary. In some examples, the length of each strip 150 may range from about 5 mm to about 40 mm, and the width of each strip may range from about 1.5 mm to about 5 mm. For example, a plurality of strips having a length of about 20 mm, about 25 mm, and about 30 mm may be used to treat a target site having a cross-sectional size ranging from about 10 mm to about 20 mm (e.g., a perforation having a cross-sectional size of about 15 mm). Each of the plurality of strips 150 may have a substantially flat or planar configuration when housed in the device 100 prior to application to the target site. For example, each of the plurality of straps may be configured to prevent bending of the straps and / or bunching of the straps when housed in the device 100 .

[0035] Figures 1B to 1C Components of the delivery device 100 are depicted. For example Figure 1B The catheter 140 is shown having a proximal end 160, a distal portion 170, and an outlet or distal opening 180. The distal portion 170 may be located within a chamber of the device 100 to accommodate a catheter such as Figure 1A A plurality of strips 150 are shown. A plurality of strips 150 may be pre-loaded into the distal portion 170 of the device 100. The user may load the desired number of strips 150 into the distal portion 170 before inserting the device 100 into the endoscope.

[0036] FIG1 illustrates a mechanism for delivering a strip 150, comprising a handle 110 and a shaft 120 having a distal end 130. For example, the mechanism may collectively form a plunger assembly capable of ejecting or dispensing a plurality of strips 150 from the device 100. The distal end 130 of the shaft 120 may be configured to be slidably received within a lumen of the device 100. For example, the distal end 130 may be configured to move distally within the lumen of the catheter 140. The handle 110 may be used to move the shaft 120 and its distal end 130 distally toward the strip 150. The handle 110 and / or the distal end 130 may be integrally formed with the shaft 120, or may be operably coupled to the shaft 120 via, for example, crimping, welding, gluing, or other securing mechanisms. The shaft 120 may be both flexible and sufficiently rigid to transmit the force of movement of the handle 110 to the distal end 130 of the shaft 120. However, the shaft 120 may also be sufficiently flexible so as not to inhibit the flexibility of the catheter 140. For example, the shaft 120 may comprise a material in a flexible configuration, such as nickel-titanium alloy, stainless steel, plastic or other polymers, braided coils, or nylon-12. In at least one example, the shaft 120 comprises a wire, such as a nickel-titanium alloy wire.

[0037] Device 100 can be inserted into the working channel of an endoscope or other delivery device, allowing distal portion 170 of device 100 to be positioned endoscopically near a target site, such as a tissue wall of the gastrointestinal tract. For example, a user can use an endoscope to position the working channel and device 100 therein at the target site. Once distal portion 170 of device 100 is near the target site, handle 110 can be used to distally advance shaft 120, advancing distal end 130 within distal portion 170 toward multiple strips 150. Shaft 120 can push multiple strips 150 through distal opening 180. Pausing distal advancement of shaft 120 or pulling shaft 120 proximally via handle 110 can stop dispensing strips 150. In some examples, device 100 can be part of a kit. For example, device 100 can be the first medical device in a kit that includes a second medical device. For example, the second medical device can be an endoscope. The device 100 may be inserted from the kit into a working channel of an endoscope for positioning at a target site.

[0038] Figure 2 Illustrative dimensions of strips according to some examples herein are shown (not to scale). For example, Figure 1A The plurality of strips 150 may include strips having Figure 2In some or all of the exemplary strips of the dimensions shown, for example, the plurality of strips 150 may be substantially rectangular. In some examples, the width of the plurality of strips 150 may range from about 1.5 mm to about 5 mm, such as a width of about 3 mm. The length of each strip 150 may range from about 10 mm to about 40 mm, such as a length of about 10 mm, about 15 mm, about 20 mm, about 25 mm, about 30 mm, about 35 mm, or about 30 mm. In at least one example, each of the plurality of strips 150 may have the same length and width, such as a length of about 10 mm and a width of about 3 mm, or a length of about 40 mm and a width of about 3 mm. The size of the plurality of strips 150 used in the device 100 may be selected based on the size and shape of the tissue defect to be treated.

[0039] According to some aspects of the present disclosure, Figure 3 and Figure 4 An exemplary method of delivering a plurality of strips 150 to target sites 300 and 400 is shown, respectively. Specifically, the distal portion 170 of the device 100 is positioned adjacent to the respective target sites 300 and 400. For ease of illustration, partial thickness tissue defects can be distinguished from full thickness tissue defects based on size. Partial thickness tissue defects can exhibit a larger surface area, while full thickness tissue defects can exhibit a smaller surface area.

[0040] Figure 3 , a plurality of strips 150 are shown housed within a distal portion 170 of the device 100 , proximate a distal opening of the device 100 , which faces a target site 300 containing a tissue defect 302 . Figure 3 The distal end 130 of the shaft 120 is also depicted as being proximal to and adjacent to the plurality of strips 150. When the handle 110 is actuated (e.g., the handle 110 is advanced in a distal direction toward the plurality of strips 150), the distal end 130 of the shaft 120 is advanced distally to contact the plurality of strips 150. The distal end 130 is shown pushing the plurality of strips out of the catheter 140 and onto the target site 300 to contact the defect 302 at the target site 300. Figure 3 Multiple strips 150 are shown being applied simultaneously. The defect 302 at the target site 300 may be a partial thickness tissue defect, whereby the defect or the depth of the defect does not extend completely through the tissue. Figure 3 The defect shown can be treated by covering or repairing the surface rather than completely filling the defect. Figure 3 As shown, the plurality of strips 150 form a layer or barrier having a two-dimensional surface over the defect 302 of the target site 300. The plurality of strips 150 are depicted as forming an overlapping structure across the surface of the target site 300 including the defect 302.

[0041] The plurality of strips 150 can maintain a flat, planar configuration when housed within the device 100. When applied to the target site 300, the plurality of strips 150 can be dispersed across the defect 302 located on the surface of the target site 300. At least some of the plurality of strips 150 distributed across the defect 302 can overlap. The user can continue to apply the strips 150 by dispensing the strips 150 from the delivery device until the defect 302 is substantially or completely covered. The user can add additional strips 150 as needed or as necessary. In at least one example, when the strips 150 of the device 100 are exhausted, the user can remove the device 100 and replace it with another device preloaded with the plurality of strips 150. In another example, when the strips 150 are exhausted, the user can add additional strips 150. For example, a user can add more strips 150 to the proximal end of the device 100 (optionally after removing the plunger assembly, e.g., plunger 110, shaft 120, and distal end 130 of shaft 120) and use the plunger assembly to push the strips 150 to the distal portion 170 of the device 100. In some examples, additional strips 150 or a replacement device pre-loaded with multiple strips 150 can be included in a kit that includes the device 100 and, optionally, another second medical device, such as an endoscope.

[0042] Figure 4 In, with Figure 3 In a similar manner to that shown, a plurality of strips 150 are applied to a target site 400 having a defect 402. The target site 400 may comprise a full-thickness tissue defect, such as a defect 402 that extends through the entire tissue wall of the target site 400. For example, the defect 402 may be a perforation. Such full-thickness tissue defects may be treated using a plurality of strips 150 to extend into the tissue defect and at least partially fill the tissue defect. Figure 4 As shown, the plurality of strips 150 are dispensed from the device 100 in a planar configuration. Once applied to the tissue, each of the plurality of strips 150 will assume a curled or twisted shape to fit the defect 402 at the target site 400. Figure 4 As depicted, the configuration of the plurality of strips 150 may change after they exit the device 100 and contact tissue. This configuration change enables the strips 150 to fit within certain tissue defects (e.g., full-thickness tissue defects) rather than being spread across the surface. The user may continue to dispense the strip 150 from the device 100 until the defect 402 at the target site 400 is substantially or completely filled with the strip 150 .

[0043] According to certain aspects of the present disclosure, after the plurality of strips 150 are applied to the target site (e.g., on a tissue defect), further steps may be performed to promote adhesion and / or curling of the plurality of strips and achieve the following: Figure 4The configuration shown is for filling a tissue defect. After application of the multiple strips, adhesion, curling, or twisting of the multiple strips can be promoted by spraying a liquid, such as water or an aqueous solution (e.g., saline solution), onto the target area. To promote curling of the strips, the pH of the liquid can be altered based on the biocompatible material of the strips. For example, the liquid can be water or an aqueous solution with an acidic or neutral pH. For example, chitosan materials typically contain positively charged groups (e.g., protonated amine groups). When the multiple strips comprise chitosan or a derivative thereof, water or an acidic aqueous solution with a pH less than 7 can be applied to the target area after application to promote curling of the strips. In some examples, pure water with a pH of approximately 7 can be applied to strips made of biocompatible materials such as poly(2-hydroxyethyl methacrylate) (poly(HEMA)), which may curl in neutral pH systems.

[0044] In some examples, at least one or all of the strips applied to a target site using the device may have a variable thickness along the length and / or width of the strip. Such dimensions may cause the strip to curl when exposed to moisture at the target site and / or when a liquid, such as water or an aqueous solution, is applied to the target site to which the strip has been applied. For example, when water or an aqueous solution is applied to multiple strips comprising an adsorbent and / or a hydrophilic material, the strips may swell, and the variable thickness may cause each strip to curl at a different point after absorbing water. The water or aqueous solution may additionally or alternatively have a pH that promotes curling. For example, a strip comprising chitosan with positively charged groups and having a uniform thickness may curl when acidic water or an aqueous solution is applied, but not when water or an aqueous solution with a neutral or alkaline pH is applied; whereas a strip comprising chitosan with positively charged groups and having a non-uniform thickness may curl when water or an aqueous solution with a neutral pH is applied.

[0045] In the examples herein, a liquid (e.g., water or an aqueous solution) can be applied to the plurality of strips at the target site as a spray (e.g., a mist). For example, after the plurality of strips 150 are applied to the target site (e.g., a tissue defect), a liquid source (e.g., water or an aqueous solution) can be applied directly to the strips to promote adhesion of the strips and interaction between the plurality of strips at the target site. The amount of liquid applied can be selected based at least in part on the thickness of the plurality of strips.

[0046] Figure 5 and Figure 6 The application of multiple strips (e.g., using Figure 1A The device 100, such as Figure 3 ), an exemplary method of promoting adhesion of multiple strips to target tissue sites 500 and 600. For example, Figure 5 and Figure 6 Each depicts a plurality of strips 150 that have been applied across a tissue defect. Figure 5 A plurality of strips 150 are shown forming a layer or barrier comprising overlapping strips 150 over a defect 502 at a target site 500. The defect 502 at the target site 500 may be a partial thickness tissue defect such that the defect depth does not extend completely through the tissue wall. Similarly, Figure 6 A plurality of strips 150 are shown applied in an overlapping configuration to form a layer or barrier over a defect 602 at a target site 600. The defect 602 at the target site 600 may also be a partial thickness tissue defect.

[0047] Figure 5 , after the plurality of strips 150 are applied to the defect 502 at the target site 500, a liquid 594 can be applied to the plurality of strips 150 to promote adhesion to the tissue at the target site 500. The liquid 594 can be water or an aqueous solution. The liquid 594 can be sprayed or otherwise applied to the target site 500 using a suitable device, such as an endoscope 590, to contact the plurality of strips 150 at the target site 500. The liquid 594 can be dispensed through a working channel 592 of the endoscope 590. The endoscope 590 can also be used to apply the strips 150 in a previous step through the same working channel 592 or other channels, such as fluid channels, via the device 100. In some examples, the endoscope 590 can be part of a kit that also includes another medical device, such as the device 100, for applying the plurality of strips to the target site.

[0048] Figure 6 In FIG. 6 , after applying the plurality of strips 150 to the defect 602 at the target site 600, an inflation device, such as a balloon of balloon device 694, can be deployed and applied to the tops of the plurality of strips to contact the strips 150 and promote adhesion to the tissue. In some examples, rather than a portion of balloon device 694 being delivered to the target site 602 via working channel 692 as shown, the balloon can be coupled to the endoscope 690. The balloon can be connected to a fluid source, such as air or water, for inflation and deflation. After inflation at the target site, the balloon can contact, for example, gently press against, the strips 150 at the target site 600 to promote adhesion of the plurality of strips 150 to the tissue. In at least one example, the endoscope 690 can be part of a kit that also includes another medical device, such as device 100, for applying the plurality of strips to the target site. Optionally, the kit can also include a balloon device, such as balloon device 694.

[0049] In some examples, both a liquid and a balloon may be applied to the multiple strips applied to the tissue defect. Applying both water or another suitable liquid and the balloon may help enhance adhesion of the strips to the tissue. To promote adhesion, the application of the liquid and / or balloon may be performed after multiple strips have been applied to the partial-thickness tissue defect. In some examples, water or another suitable liquid may be applied to the strips at the target site prior to applying the balloon.

[0050] The present disclosure also includes methods for filling, repairing and / or covering tissue defects at a target tissue site using a plurality of strips comprising biocompatible materials, followed by application of one or more therapeutic agents to the target site. Exemplary therapeutic agents that can be used in the present disclosure include, but are not limited to, hemostatics, antimicrobial agents, coagulation cascade activators, growth factors, anti-inflammatory agents, and cancer therapeutics. The hemostatic agent may be natural or derived from natural materials, or may be at least partially derived from a synthetic material. For example, the hemostatic agent may include one or more polysaccharides, such as chitosan, natural gums, alginates, cellulose, starch (e.g., potato or other plant starch), and glycogen. In at least one example, the hemostatic agent may be charged, such as a cation. In some examples, the hemostatic agent may be in granular form, such as formulated into a powder, or may be in liquid form, such as mixed with a biocompatible liquid and formulated into a spray.

[0051] In some embodiments, a hemostatic agent or other therapeutic agent can be applied to a tissue defect via spraying. For example, a therapeutic agent can be sprayed onto a target site containing multiple strips previously applied to the tissue defect. In examples where a balloon is used to facilitate adhesion of the multiple strips to the tissue, the balloon can be deflated and removed from the site prior to applying the therapeutic agent.

[0052] The therapeutic agent can be administered to the target site at any time after the plurality of strips are applied to the target site. In some examples, the therapeutic agent can be administered within seconds to minutes after the plurality of strips are applied, for example, within about 10 minutes, about 5 minutes, about 1 minute, about 30 seconds, or about 5 seconds, for example, within 1 second to 10 minutes, 5 seconds to 5 minutes, or 10 seconds to 30 seconds.

[0053] According to various aspects of the present disclosure, applying multiple strips to a tissue defect can help prevent unwanted substances from passing through the tissue defect. The devices and methods of the present disclosure can allow therapeutic agents, such as hemostats, to be applied to a target site without the therapeutic agent passing through the tissue defect site to reach unwanted areas of the body.

[0054] Other embodiments of the present disclosure will be apparent to those skilled in the art from consideration of the specification and practice of the embodiments disclosed herein. It is intended that the specification and examples be considered exemplary only, with the true scope and spirit of the present disclosure being indicated by the following claims.

Claims

1. A kit comprising: a first medical device defining a lumen for receiving a shaft and a chamber proximate a distal end of the first device, wherein the chamber receives a plurality of strips comprising a biocompatible material, and the shaft is movable along the lumen to urge the plurality of strips through a distal opening of the first device; and A second medical device defines a working channel into which the first device is insertable.

2. The kit of claim 1, wherein the biocompatible material comprises chitosan, cellulose, poly(2-hydroxyethyl methacrylate), polystyrene, collagen, gelatin, fibrin, polyethylene glycol (PEG), hyaluronic acid, a block copolymer, or a combination thereof.

3. The kit according to claim 1 or 2, wherein the plurality of strips comprises chitosan or a derivative thereof, such as thiolated chitosan, chitosan cross-linked with tripolyphosphate, and / or carboxymethylcellulose chitosan cross-linked with polyethylene glycol amine.

4. The kit of any one of claims 1 to 3, wherein the plurality of strips are bioresorbable.

5. The kit according to any one of claims 1 to 4, wherein the second device is an endoscope.

6. The kit of any one of claims 1 to 5, wherein each of the plurality of strips has a length ranging from about 5 mm to about 40 mm, a width ranging from about 1.5 mm to about 5 mm, and / or a thickness ranging from about 1 μm to about 100 μm.

7. The kit of any one of claims 1 to 6, wherein the plurality of strips comprises strips of different lengths and / or widths.

8. The kit of any one of claims 1 to 7, wherein the strips of the plurality of strips are planar.

9. The kit of any one of claims 1 to 8, wherein the plurality of strips comprises at least one strip having a thickness that is variable along the length of the at least one strip.

10. The kit of any one of claims 1 to 9, wherein the shaft comprises a distal end having a cross-sectional dimension that is larger than a cross-sectional dimension of the shaft, such that when the shaft moves along the lumen, the distal end of the shaft contacts and slides along the wall of the lumen.

11. The kit of any one of claims 1 to 10, wherein the kit further comprises a balloon device.

12. Use of the kit according to any one of claims 1 to 11 for treating a target site of tissue.

13. The use according to claim 12, wherein the second device is an endoscope and the tissue is tissue of the gastrointestinal tract.

14. The use according to claim 12 or 13, wherein the target site comprises a tissue defect, and the plurality of strips fills, covers and / or repairs the tissue defect.

15. The use according to any one of claims 12 to 14, wherein the plurality of strips transform from a planar configuration when housed in the first device to a curled configuration when applied to the target site.

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