Patent Description:
Medical devices designed for implantation in a subject, such as stents, may experience gradual migration from a target location within the subject at which the device was initially positioned. The migration tendencies of said medical devices may be caused by the compressible and/or flexible configurations of said devices, and influenced by peristalsis (e.g., involuntary constriction and relaxation of muscles of the esophagus, intestine, colon, etc.) or the generally lubricious environment of the target location. Movement of the implantable device may minimize the effectiveness of the device in treating the target location, and may cause further health complications for the subject. Some procedures may involve fixing the implantable device to the target location through use of ancillary tools, such as sutures or tape, to reduce migration. However, these approaches generally require subsequent removal of said ancillary tools from the target location, thereby necessitating the subject to undergo additional procedures. Devices and methods for fixing an implantable device within a subject without requiring use of ancillary tools to fix said device at the target location may be limited.

<CIT> discloses a stent having an inner surface and an outer surface. At least a portion of the outer surface of the stent comprising a dissolvable adhesive polymer or a degradable adhesive polymer is disposed on at least a portion of the outer surface of the stent. The adhesive is activated by exposure to an aqueous environment. The dissolvable adhesive polymer dissolves over time in an aqueous environment. The dissolvable adhesive polymer or the degradable adhesive polymer has a surface tack of about <NUM> kPa to about <NUM> kPa (<NUM> psi to about <NUM> psi).

The present invention relates to a medical device comprsiing a body; a polymer matrix over the body, wherein the polymer matrix comprises a plurality of fibers defining a plurality of pores to permit tissue growth therethrough; and a bio-adhesive coating at least partially covering the polymer matrix. The bio-adhesive coating is biodegradable.

Any one of the medical devices described herein may include any of the following features. The plurality of fibers may have a diameter ranging from about <NUM> to about <NUM>. The bio-adhesive coating may be chemically bonded to the plurality of fibers. The body may include an expandable stent having a plurality of struts and a plurality of openings between adjacent struts, the plurality of fibers being positioned over the plurality of struts. The plurality of fibers may be electro-spun over the body. The medical device may include silicone between at least a portion of the body and the polymer matrix. The bio-adhesive coating may comprise a polysaccharide cross-linked with a linker molecule. The polysaccharide may comprise chitosan. The linker molecule may comprise polyethylene glycol. The polymer matrix may comprise a fluoropolymer. The body may comprise a biocompatible metal or metal alloy configured to move from a compressed configuration to an expanded configuration. In the compressed configuration, for example, the body may have a first length and a first diameter, and in the expanded configuration, the body may have a second length greater than the first length and a second diameter smaller than the first diameter.

According to one example, the medical device includes an expandable body including a plurality of openings; a polymer matrix disposed along an exterior surface of the body and within at least a portion of the plurality of openings, wherein the polymer matrix comprises a plurality of fibers; and a bio-adhesive coating chemically bonded to the polymer matrix, wherein the bio-adhesive coating is biodegradable. The medical device may further include silicone between at least a portion of the body and the polymer matrix. The bio-adhesive coating may comprise chitosan. The chitosan may be cross-linked. The polymer matrix may comprise a thermoplastic polymer.

Methods of treatment are also disclosed For example, the method may include treating a subject by delivering a medical device to target tissue of the subject, wherein the medical device includes: an expandable body; a polymer matrix comprising a plurality of fibers over the body; and a bio-adhesive coating at least partially covering the polymer matrix; wherein the bio-adhesive coating adheres the polymer matrix and the body to the tissue; and wherein the medical device promotes cell growth from the tissue through the bio-adhesive coating and the polymer matrix. The bio-adhesive coating may maintain contact with the tissue, e.g., for <NUM> hours to <NUM> months.

Implantable medical devices with features for facilitating attachment within a patient, e.g., to minimize migration of the device, are included herein. A target treatment site for placing the implantable medical device may include a tissue wall, such as an esophagus or other part of the gastrointestinal system of the patient. The devices herein may include features to inhibit migration from the initial, target treatment site at which the device was originally placed.

Examples of the disclosure include systems, devices, and methods for attaching an implantable medical device to a target treatment site within a subject (e.g., patient). In examples, accessing a patient's esophagus includes endoluminal placement of the medical device into the target treatment site. Placement of the medical device may be via a catheter, scope (endoscope, bronchoscope, colonoscope, etc.), tube, or sheath, inserted into an anatomical passageway via a natural orifice or via laparoscopy. The orifice can be, for example, the nose, mouth, or anus, and the placement can be in any portion of the GI tract, including the esophagus, stomach, duodenum, large intestine, or small intestine. Placement also can be in other organs or other bodily spaces reachable via the GI tract, other body lumens, or openings in the body, including via laparoscopy. This disclosure is not limited to any particular medical procedure or treatment site within a body.

Reference will now be made in detail to aspects of the disclosure, examples of which are illustrated in the accompanying drawings. Wherever possible, the same or similar reference numbers will be used through the drawings to refer to the same or like parts. The term "distal" refers to a portion farthest away from a user when introducing a device into a patient. By contrast, the term "proximal" refers to a portion closest to the user when placing the device into the subject. As used herein, the terms "comprises," "comprising," or any other variation thereof, are intended to cover a non-exclusive inclusion, such that a process, method, article, or apparatus that comprises a list of elements does not necessarily include only those elements, but may include other elements not expressly listed or inherent to such process, method, article, or apparatus. The term "exemplary" is used in the sense of "example," rather than "ideal. " As used herein, the terms "about," "substantially," and "approximately," indicate a range of values within +/- <NUM>% of a stated value.

Examples of the disclosure may relate to devices and methods for performing various medical procedures and/or treating portions of the large intestine (colon), small intestine, cecum, esophagus, any other portion of the gastrointestinal tract, and/or any other suitable patient anatomy (collectively referred to herein as a "target treatment site"). As mentioned above, this disclosure is not limited to any specific medical device or method, and aspects of the disclosure may be used in connection with any suitable medical tool and/or medical method, at any suitable site within the body. Various examples described herein include single-use or disposable medical devices.

<FIG> shows an exemplary medical device <NUM> in accordance with one or more examples of this disclosure. Medical device <NUM> comprises a body <NUM> having a longitudinal length defined between a first end <NUM> and a second end <NUM>. One or more of first end <NUM> or second end <NUM> optionally may be flared radially outward relative to a cross-sectional profile of body <NUM>. Body <NUM> may be flexible and configured to expand axially and/or radially when transitioning from a compressed configuration to an expanded configuration. Stated differently, body <NUM> may have a first length and a first diameter when in a first, compressed configuration. Body <NUM> may further have a second length and a second diameter when in a second, expanded configuration. The second length and/or the second diameter may be greater than the first length and/or the first diameter, respectively. Optionally, the second length may be greater than the first length and the second diameter may be greater than the first diameter.

Body <NUM> may include a lumen defined between first end <NUM> and second end <NUM>, a first opening <NUM> at first end <NUM>, and a second opening <NUM> at second end <NUM>. First opening <NUM> and second opening <NUM> may be in fluid communication with one another through the lumen of body <NUM>. As shown, body <NUM> includes an expandable stent assembly having a plurality of struts <NUM> and a plurality of openings <NUM> defined between adjacent struts <NUM>. Body <NUM> may be formed of various suitable materials having flexible characteristics, including, for example, a biocompatible metal, a metal alloy, a shape memory material, etc. Medical device <NUM> may further include a biocompatible matrix <NUM> disposed over at least a portion of body <NUM> between first end <NUM> and second end <NUM>, wherein matrix <NUM> may comprise one or more polymers. In some embodiments, polymer matrix <NUM> may be positioned over a substantial portion of the longitudinal length of body <NUM>, such that polymer matrix <NUM> includes a longitudinal length that is substantially similar to body <NUM>. In other embodiments, polymer matrix <NUM> may be positioned over a portion of body <NUM> that is less than the longitudinal length of body <NUM>, such that one or more portions of body <NUM> are uncovered by polymer matrix <NUM>.

As seen in <FIG>, polymer matrix <NUM> comprises a plurality of fibers <NUM> defining a plurality of pores <NUM> (e.g., interstices). The plurality of fibers <NUM> may be disposed over the plurality of struts <NUM> and the plurality of openings <NUM> of body <NUM>, e.g., providing a porous matrix over body <NUM>. Each fiber of the plurality of fibers <NUM> may have a diameter ranging from about <NUM> nanometers (nm) to about <NUM>, such as from about <NUM> to about <NUM>, about <NUM> to about <NUM>, or about <NUM> to about <NUM>. The thickness of polymer matrix <NUM> may range from at least <NUM> micron (µm) to at least one millimeter (mm), such as, e.g., from about <NUM> to about <NUM>, from about <NUM> to about <NUM>, from about <NUM> to about <NUM>, from about <NUM> to about <NUM>, from about <NUM> to about <NUM>, from about <NUM> to about <NUM>, or about <NUM> to about <NUM>. Each fiber <NUM> may have the same diameter, or the plurality of fibers <NUM> may include fibers of differing dimensions. It should be appreciated that the diameter(s) of the fibers <NUM> may be at least partially determinative of the size(s) of the pores <NUM> defined between adjacent fibers <NUM>.

Being porous, polymer matrix <NUM> may allow passage of one or more materials through polymer matrix <NUM>. For example, as described in further detail herein, polymer matrix <NUM> may permit tissue growth between the plurality of fibers <NUM> and through the plurality of pores <NUM>. The dimensions of the plurality of pores <NUM> may at least partially determine a rate of tissue growth through polymer matrix <NUM>. The dimensions (e.g., thickness, diameter, etc.) of the plurality of fibers <NUM> may at least partially determine the rate of tissue growth through polymer matrix <NUM>. In some embodiments, the plurality of fibers <NUM> may be sintered to strengthen a material composition of the plurality of fibers <NUM> and reduce a friability of the polymer matrix <NUM>. According to some examples herein, the porosity of polymer matrix <NUM> may remain substantially consistent when sintering the plurality of fibers <NUM>. Further, for example, the porosity of polymer matrix <NUM> may be fine-tuned to allow for adequate degradation and cell growth infiltration between the plurality of fibers <NUM> and through the plurality of pores <NUM>.

Polymer matrix <NUM> may be formed over body <NUM> by any suitable technique, including, for example, electrospinning. For example, a polymer material may be electro-spun over body <NUM> to form polymer matrix <NUM>. Exemplary polymer materials include, but are not limited to, thermoplastic polymers, including fluoropolymers, which may be electro-spun while in liquid solution form. The material(s) may be delivered with high electrical forces such that the material(s) may be deposited over an exterior of body <NUM> in a randomized, asymmetrical, and/or irregular pattern. Solvent(s) in the liquid solution may evaporate and polymer chains form, e.g., becoming mechanically entangled. The resulting structure may comprise the plurality of fibers <NUM> deposited onto body <NUM>. In some embodiments, polymer matrix <NUM> may comprise polyvinylidene fluoride, polyvinylidene difluoride (PVDF), and/or hexafluoropropylene (HFP).

As seen in <FIG>, the plurality of fibers <NUM> may be intertwined with one another over the plurality of struts <NUM>. It should be appreciated that the plurality of fibers <NUM> may be further intertwined with an exterior surface of body <NUM> to secure polymer matrix <NUM> to body <NUM>. For example, medical device <NUM> may include a material between body <NUM> and the plurality of fibers <NUM>, e.g., the material disposed as one or more outer layers along the exterior surface of body <NUM>. The plurality of fibers <NUM> may comingle with the material of the outer layer(s). The outer layer(s) may comprise a polymer, such as, for example, silicone. Accordingly, during an electrospinning process of generating polymer matrix <NUM> over body <NUM>, the material electro-spun onto body <NUM> (e.g., fluoropolymer) may be mechanically entangled with the outer layer.

The outer layer may be positioned between at least a portion of body <NUM> and polymer matrix <NUM>. For example, silicone or other suitable polymer material of the outer layer(s) may be disposed within at least a portion of the plurality of openings <NUM> between the plurality of the struts <NUM>, and the plurality of fibers <NUM> may be deposited over the plurality of struts <NUM> and/or the plurality of openings <NUM>. To minimize constraining a flexibility of body <NUM>, the plurality of fibers <NUM> may be concentrated over the plurality of struts <NUM> during the electrospinning process of polymer matrix <NUM>. Further, the plurality of fibers <NUM> may be selectively guided over the plurality of struts <NUM> during the electrospinning process to preserve a profile of the plurality of openings <NUM> defined therebetween. With polymer matrix <NUM> formed along an exterior of body <NUM>, polymer matrix <NUM> may provide and maintain a barrier about the lumen of body <NUM>. As described in detail herein, polymer matrix <NUM> may provide a first, long-term (e.g., permanent) fixation mechanism for securing medical device <NUM> to a target treatment site within a subject.

Medical device <NUM> includes a bio-adhesive coating <NUM> disposed over, and at least partially covering, polymer matrix <NUM>. The bio-adhesive coating <NUM> may be chemically bonded to polymer matrix <NUM>. Accordingly, polymer matrix <NUM> may be disposed between the bio-adhesive coating <NUM> and body <NUM> such that the bio-adhesive coating <NUM> is separated from body <NUM> by polymer matrix <NUM>. The bio-adhesive coating <NUM> may comprise a biodegradable material, such that the bio-adhesive coating <NUM> may be resorbed or otherwise degrade after a period of time. As described in further detail herein, the bio-adhesive coating <NUM> may maintain contact with a target treatment site (e.g., tissue) for a desired amount of time, which may depend on chemical characteristics and/or the thickness of the bio-adhesive coating <NUM>. For example, the bio-adhesive coating <NUM> may maintain contact with the target treatment site from approximately <NUM> hours to approximately <NUM> months, such as from about <NUM> days to about <NUM> week, from about <NUM> week to about <NUM> weeks, from about <NUM> month to about <NUM> months, or about <NUM> months to about <NUM> months. The degradation time may be controlled by various factors, including, for example, the nature of the biodegradable material and/or quantity (e.g., thickness) of the bio-adhesive coating <NUM> on polymer matrix <NUM>. The thickness of bio-adhesive coating <NUM> over polymer matrix <NUM> may range from about at least <NUM> to at least <NUM>, such as, e.g., from about <NUM> to about <NUM>, from about <NUM> to about <NUM>, from about <NUM> to about <NUM>, from about <NUM> to about <NUM>, from about <NUM> to about <NUM>, from about <NUM> to about <NUM>, or about <NUM> to about <NUM>. Further, bio-adhesive coating <NUM> may be chemically modified on an exterior surface of polymer matrix <NUM>.

Exemplary materials suitable for the bio-adhesive coating <NUM> include, but are not limited to, polysaccharides such as chitosan. The polysaccharide may be cross-linked with a linker molecule. Such linker molecules include, for example, polyethylene glycol (PEG). PEG may provide a hydrophilic scaffold along polymer matrix <NUM>, and may serve as an anchor for bio-adhesive coating <NUM> to attach to polymer matrix <NUM>. The hydrophilic properties of PEG may provide adhesive capabilities for securing bio-adhesive coating <NUM> to polymer matrix <NUM>. Other suitable materials for bio-adhesive coating <NUM> may include, but are not limited to, polymers such as chitosan optionally modified with thiol groups, PEG modified with thiol groups, and oxidized cellulose. The bio-adhesive coating <NUM> may have hemostatic properties for simulating a healing response from a target treatment site (e.g., tissue) when in contact thereto. Stated differently, the bio-adhesive coating <NUM> may treat injuries at the target treatment site, such as wounds, hemorrhages, damaged tissues, bleeding, etc. The bio-adhesive coating <NUM> may serve as a wound dressing to inhibit excessive bleeding and/or promote rapid healing. Additionally, the bio-adhesive coating <NUM> may have adhesion characteristics capable of securing body <NUM> to the target treatment site.

As mentioned above, the bio-adhesive coating <NUM> may be chemically bonded to the polymer matrix <NUM>, including via the linker molecule. Accordingly, the linker molecule (e.g., PEG) may be cross-linked with the plurality of fibers <NUM> to facilitate a connection between the bio-adhesive coating <NUM> and polymer matrix <NUM>. In some examples, the linker molecule may become entangled with the polymer chains of polymer matrix <NUM> as the plurality of fibers <NUM> are formed on body <NUM>. In some examples, the bio-adhesive coating <NUM> may be prepared using plasma to cross-link the polysaccharide and linker molecule. As described in detail herein, the bio-adhesive coating <NUM> may provide a second, temporary fixation mechanism for securing medical device <NUM> to a target treatment site within a subject.

According to some aspects of the present disclosure, the plurality of fibers <NUM> may be selectively deposited over body <NUM> to control a fixation characteristic of medical device <NUM> to a target treatment site. For example, the plurality of fibers <NUM> may be deposited along one or more regions of body <NUM>, thereby controlling an area of tissue ingrowth into medical device <NUM> to the one or more specific regions. As discussed above, the bio-adhesive coating <NUM> may adhere to a surface area of polymer matrix <NUM>, such that medical device <NUM> may include the bio-adhesive coating <NUM> along the one or more regions of body <NUM> when the plurality of fibers <NUM> are selectively deposited thereon.

Referring now to <FIG>, an exemplary use of medical device <NUM> to treat a target treatment site (e.g., tissue) within a subject is depicted. It should be understood that medical device <NUM> may be positioned at the target treatment site through use of a medical instrument (e.g., an endoscope) that is inserted through the subject's body and navigated toward the target treatment site. It should be understood that medical device <NUM> of this disclosure may be used in various locations (target treatment sites) within a subject's body, including but not limited to, the gastrointestinal tract, an organ, or other tissue. In the example depicted in <FIG>, the target treatment site includes a tissue wall <NUM> within a subject's body <NUM>, and the tissue wall <NUM> has a mucous layer <NUM> disposed along an exterior of the tissue wall <NUM>. According to some examples herein, the bio-adhesive coating <NUM> of medical device <NUM> may have a positive charge, complementary to a negative charge of the mucous layer <NUM>.

Upon reaching the tissue wall <NUM>, medical device <NUM> may be inserted transluminally through medical instrument and deployed therefrom at the tissue wall <NUM>. One or more tools <NUM> may be received through the lumen of the body <NUM> to facilitate navigation of medical device <NUM> toward the tissue wall <NUM>, such as, for example, a guidewire. In some embodiments, the bio-adhesive coating <NUM> may provide a smooth, outer atraumatic surface to facilitate passage of medical device <NUM> through the subject <NUM> and/or inhibit injury to the tissue wall <NUM> by the polymer matrix <NUM> and/or body <NUM>. Medical device <NUM> may be pressed against the tissue wall <NUM> such that the bio-adhesive coating <NUM> contacts the mucous layer <NUM>. With body <NUM> having a flexible configuration, medical device <NUM> may conform to a profile of the tissue wall <NUM>.

With the bio-adhesive coating <NUM> being positively charged and the mucous layer <NUM> being negatively charged, the bio-adhesive coating <NUM> may be attracted to the mucous layer <NUM> and form chemical bonds with the tissue surface, thereby anchoring medical device <NUM> to the tissue wall <NUM>. The bio-adhesive coating <NUM> may maintain medical device <NUM> against the tissue wall <NUM> for at least a minimum duration until the bio-adhesive coating <NUM> is resorbed or otherwise degrades. Accordingly, the bio-adhesive coating <NUM> may serve a tissue adhesive mechanism for temporarily fixing medical device <NUM> to the tissue wall <NUM>, and inhibiting migration of medical device <NUM> from the target treatment site. Further, the bio-adhesive coating <NUM> may further promote healing of the tissue wall <NUM> via the hemostatic properties of the bio-adhesive coating <NUM> while the bio-adhesive coating <NUM> remains in contact with the tissue wall <NUM>.

Still referring to <FIG>, as the bio-adhesive coating <NUM> adheres medical device <NUM> to the mucous layer <NUM>, the bio-adhesive coating <NUM> may facilitate tissue growth from the tissue wall <NUM> through polymer matrix <NUM>. Stated differently, by maintaining polymer matrix <NUM> within close proximity to the tissue wall <NUM>, the bio-adhesive coating <NUM> may allow tissue cells from the tissue wall <NUM> to grow through the bio-adhesive coating <NUM> and into the plurality of pores <NUM>. The tissue cells may become intertwined with the plurality of fibers <NUM>, thereby anchoring medical device <NUM> to the tissue wall <NUM> and inhibiting migration of medical device <NUM> from the target treatment site. In other words, the plurality of pores <NUM> may serve as sites that permit tissue growth into polymer matrix <NUM>. The bio-adhesive coating <NUM> may maintain medical device <NUM> against the tissue wall <NUM> via bonding with the mucous layer <NUM>, to thereby allow the tissue cells sufficient time to grow through polymer matrix <NUM>.

As described further above, the size(s) of the plurality of pores <NUM> may at least partially control the rate of tissue cell growth through polymer matrix <NUM>, and the diameter(s) of the plurality of fibers <NUM> may at least partially determine the size(s) of the plurality of pores <NUM>. Further, the diameter(s) of the plurality of fibers <NUM> may correspond or correlate to a minimum required force for disengaging medical device <NUM> from a target treatment site. Stated differently, the plurality of fibers <NUM> may be sized and/or shaped to provide medical device <NUM> sufficient mechanical strength in inhibiting migration of medical device <NUM> from the target treatment site. For example, a minimum extraction force sufficient to move medical device <NUM> relative to the target treatment site may be at least partially associated with a size and/or shape of the plurality of fibers <NUM>. Accordingly, the diameter of the plurality of fibers <NUM> may at least partially contribute to inhibiting the unintentional release of medical device <NUM> from the tissue wall <NUM>.

Still referring to <FIG>, upon degradation of the bio-adhesive coating <NUM>, medical device <NUM> may remain anchored to the tissue wall <NUM> via an engagement of polymer matrix <NUM> to the tissue wall <NUM>. Accordingly, despite removal of the bio-adhesive coating <NUM> from between polymer matrix <NUM> and the tissue wall <NUM>, polymer matrix <NUM> and body <NUM> may remain attached to the tissue wall <NUM> in response to the tissue cell growth through polymer matrix <NUM>. Medical device <NUM> may be designed to treat strictures in a body lumen defined by the tissue wall <NUM>, and/or provide a fluid pathway for material (e.g., fluid, digested material, etc.) to flow through body <NUM> following an invasive medical procedure. By providing a physical barrier between body <NUM> and the tissue wall <NUM>, polymer matrix <NUM> may ensure a fluid pathway through body <NUM> is preserved. Further, polymer matrix <NUM> may facilitate removal of medical device <NUM> upon completion of a procedure. For instance, polymer matrix <NUM> may reduce a surface area of body <NUM> which may be anchored to the tissue wall <NUM>, thereby allowing medical device <NUM> to be removed from the subject <NUM> upon applying an application of force thereto. Further, for example, the thickness of medical device <NUM> including the thickness of polymer matrix <NUM> and an exposed portion of the plurality of fibers <NUM> may facilitate removal of medical device <NUM> from the subject <NUM>. Additionally, polymer matrix <NUM> may control an extent (e.g., depth) and/or degree of tissue ingrowth into medical device <NUM>, providing further control for the removal of medical device <NUM> upon completion of a procedure.

Claim 1:
An implantable medical device (<NUM>), comprising:
a body (<NUM>);
a polymer matrix (<NUM>) over the body (<NUM>), wherein the polymer matrix (<NUM>) comprises a plurality of fibers (<NUM>) defining a plurality of pores to permit tissue growth therethrough; and
a bio-adhesive coating (<NUM>) at least partially covering the polymer matrix (<NUM>),
wherein the bio-adhesive coating (<NUM>) is biodegradable.