Biodegradable drug-eluting stents

Abstract

The biodegradable drug eluting stent comprises a first non-biodegradable end section, a biodegradable middle section coupled to the first non-biodegradable end section, and a second non-biodegradable end section coupled to the biodegradable middle section. The stent also comprises a plurality of connectors connecting the first and second end sections to the middle section, each connector comprising a biodegradable connector arm coupled to and extending away from an end of the middle section, and a non-biodegradable arm receiver coupled to an end of the first or second end section. The connector arm has an end tab, and the arm receiver is configured to mate with the end tab. The end sections are drug eluting and configured to expand at a faster rate than that of the middle section in response to an expansion force from an expandable balloon over which the stent is crimped.

Description

[Technical field]

[0001] (cross reference) This PCT application claims priority to PCT Application No. PCT / CN2021 / 108897, filed July 28, 2021, which is incorporated herein by reference.

[0002] The present disclosure relates to medical devices, systems, and methods, in particular to stents and vascular scaffoldings. [Background technology]

[0003] (background) In medicine, a stent is a metal or plastic tube inserted into a duct to keep the lumen or passageway of an anatomical vessel open, and stenting is the placement of a stent. There are a wide variety of stents used for different purposes, from expandable coronary artery, vascular, and biliary stents to simple plastic stents used to allow the flow of urine between the kidneys and bladder.

[0004] The most commonly used stents are coronary and vascular stents. Coronary stents are placed during coronary angioplasty. The most common use for coronary stents is in the coronary arteries, into which bare metal stents, drug eluting stents, bioabsorbable stents, dual therapy stents (combination of both drug and bioengineered stents), or possibly coated stents are inserted. Vascular stents are a common treatment for advanced peripheral and cerebrovascular disease. Common sites treated with vascular stents include the carotid, iliac, and femoral arteries.

[0005] Drug-eluting stents and bioresorbable stents have seen more widespread use and technological advances in recent years. Drug-eluting stents (DES) are peripheral or coronary stents (i.e., scaffolds) that are placed into narrowed, diseased peripheral or coronary arteries to slowly release drugs and block cell growth. The release of the drug prevents fibrosis, along with blood clots (i.e., thrombus), that would otherwise block the stented artery, a process called restenosis. Stents are usually placed in peripheral or coronary arteries during angioplasty procedures by interventional cardiologists or interventional radiologists. Bioresorbable stents, often also called bioresorbable scaffolds, biodegradable stents, or naturally dissolving stents, serve the same purpose as stents, but are made from materials that can dissolve or be absorbed in the body.

[0006] Although drug-eluting stents have many advantages and have proven superior to bare metal stents in some cases, with a lower rate of major adverse cardiac events, they are not without drawbacks. In at least some cases, the metal may remain permanently in the vessel after drug release, causing thrombosis and, in at least some cases, necessitating long-term antiplatelet drug therapy, which increases the risk of bleeding for the patient. In at least some cases, the stent may interfere with the suturing of any bridge vessels if the patient requires a surgical bypass procedure at the stented site in the future. Furthermore, in at least some cases, heavy metal residues may be found in the sustained release membrane, which may be harmful to the patient.

[0007] Bioresorbable stents or vascular scaffolds may have advantages over drug-eluting and bare metal stents in that they can be degraded over time, typically over three years, allowing future bypass surgery and reducing the risk of thrombosis and heavy metal residues. However, bioresorbable stents may suffer from disadvantages in other areas. In at least some cases, in the process of biodegradation, the ends of the stent are susceptible to crushing, leading to one or more ends of the stent being suspended within the vessel lumen, thus increasing the risk of thrombus formation. In at least some cases, bioresorbable stents are made of biodegradable materials that are too thick to allow such stents to be implanted in an overlapping or nested manner, which may be required for diffuse or long lesions. Furthermore, at least in some cases, bioresorbable stents are not applicable to bifurcation lesions, where two stents are required, because such stents cannot be overlapped or nested with one another due to the relatively larger wall thickness of such stents.

[0008] For at least these reasons, improvements to stents, particularly drug-eluting and bioresorbable stents, are desirable.

[0009] The following references may be relevant: US20170181872A1, US20070288084A1, US10932928B2, US9907644B2, US9326870B2, US8814927B2, US8603154B2, US7789906B2, and WO2019138416A1. [Prior art documents] [Patent documents]

[0010] [Patent Document 1] US Patent Application Publication No. 2017 / 0181872 [Patent Document 2] US Patent Application Publication No. 2007 / 0288084 [Patent Document 3] U.S. Pat. No. 10,932,928 [Patent Document 4] U.S. Pat. No. 9,907,644 [Patent Document 5] U.S. Patent No. 9,326,870 [Patent Document 6] U.S. Pat. No. 8,814,927 [Patent Document 7] U.S. Pat. No. 8,603,154 [Patent Document 8] U.S. Pat. No. 7,789,906 [Patent Document 9] International Publication No. 2019 / 138416 Summary of the Invention [Means for solving the problem]

[0011] (summary) The present disclosure provides a biodegradable drug-eluting stent that addresses at least some of the shortcomings of drug-eluting and bioresorbable stents described above. An exemplary stent may comprise a first non-biodegradable end section, a biodegradable middle section having a first end connected to an end of the first non-biodegradable end section, and a second non-biodegradable end section having an end connected to a second end of the biodegradable middle section. The end sections may be drug-eluting and non-biodegradable. By providing non-biodegradable end sections, multiple such stents may be overlapped or nested, making such stents applicable for bifurcation lesions. The middle section of the stent may degrade over time, leaving the non-biodegradable end sections in place. If restenosis occurs, such as where the biodegraded middle section was, a shorter stent may be implanted in its place.

[0012] The exemplary stent may also include a plurality of connectors connecting the first and second end sections to the intermediate section. Each connector may include a biodegradable connector arm coupled to and extending away from a first or second end of the biodegradable intermediate section, and a non-biodegradable arm receiver coupled to an end of the first or second end section. The biodegradable connector arm may have an end tab. The arm receiver may be configured to mate with the end tab. The connector may provide a mortise and tenon joint between the non-biodegradable end section and the biodegradable intermediate section, which may prevent the lateral ends of the biodegradable end section from collapsing as the material degrades.

[0013] The first and second end sections may be configured to expand at a first rate in response to an expansion force. The middle section may be configured to expand at a second rate in response to an expansion force. The first rate may be faster than the second rate. The first end section may comprise at least one ring of struts arranged in a first non-biodegradable strut pattern. The second end section may comprise at least one ring of struts arranged in a second non-biodegradable strut pattern. The middle section may comprise at least one ring of struts arranged in a biodegradable strut pattern. The biodegradable strut pattern of the middle section may be denser than the first and second non-biodegradable strut patterns of the first and second non-biodegradable end sections, which may cause a differential expansion response of the end and middle sections. During expansion of the stent, typically by expansion of a balloon or other expandable member (such as a malecot) over which the stent is crimped, the non-biodegradable end sections typically expand first, which can promote stabilization of the biodegradable middle section. Such stabilization can prevent any displacement of the biodegradable middle section and the connector parts coupled thereto, and can prevent any damage to the mortise and tenon structure of the connector.

[0014] Additionally, the non-biodegradable end sections are typically made from metal or other materials that are highly visible to fluoroscopy or other medical imaging and thus can facilitate precise delivery and positioning of the stent.

[0015] Additional aspects and advantages of the present disclosure will become readily apparent to those skilled in the art from the following detailed description, in which only illustrative embodiments of the present disclosure are shown and described. As will be realized, the present disclosure is capable of other and different embodiments, and its several details are capable of modification in various obvious respects, all without departing from the present disclosure. Thus, the drawings and description are to be regarded as illustrative in nature, and not as restrictive.

[0016] (Incorporated by reference) All publications, patents, and patent applications mentioned herein are incorporated by reference to the same extent as if each individual publication, patent, or patent application was specifically and individually indicated to be incorporated by reference. To the extent that the publications and patents or patent applications incorporated by reference conflict with the disclosure contained herein, the present specification is intended to supersede and / or take precedence over any such conflicting material. [Brief description of the drawings]

[0017] The novel features of the invention are set forth with particularity in the appended claims. A better understanding of the features and advantages of the present invention will be obtained by reference to the following detailed description that sets forth illustrative embodiments, in which the principles of the invention are utilized, and the accompanying drawings (also referred to herein as "Figure" and "FIG.").

[0018] [Figure 1] FIG. 1 shows a side view of an exemplary stent according to embodiments herein.

[0019] [Diagram 2]FIG. 2 shows a side view of another exemplary stent according to embodiments herein.

[0020] [Figure 3A] FIG. 3A shows an enlarged side view of an illustration of connectors for the end and middle sections of a stent described herein, according to an embodiment.

[0021] [Figure 3B] FIG. 3B illustrates a cross-sectional view of the connector embodiment of FIG. 3A.

[0022] [Figure 3C] FIG. 3C illustrates a cross-sectional view of the connector embodiment of FIG. 3A.

[0023] [Figure 3D] FIG. 3D shows an enlarged side view of a connector of the stent of FIG.

[0024] [Figure 3E] FIG. 3E shows an enlarged side view of a connector of the stent of FIG.

[0025] [Figure 4] FIG. 4 shows an illustration of a stent section pattern for a stent described herein, according to an embodiment.

[0026] [Figure 5-1] 5A-5F show the expansion of an exemplary stent, according to embodiments herein. [Figure 5-2] 5A-5F show the expansion of an exemplary stent, according to embodiments herein. [Figure 5-3] 5A-5F show the expansion of an exemplary stent, according to embodiments herein.

[0027] [Figure 6A]Figures 6A, 6B, 6C, and 6D show optical coherence tomography (OCT) images of blood vessels with a bare metal stent (Figure 6A), a drug-eluting stent (Figure 6B), and a hybrid stent according to embodiments herein (Figures 6C-6D) immediately after deployment, at one-month follow-up (Figure 6A-6C), and at three-month follow-up (Figure 6D), respectively. [Figure 6B] Figures 6A, 6B, 6C, and 6D show optical coherence tomography (OCT) images of blood vessels with a bare metal stent (Figure 6A), a drug-eluting stent (Figure 6B), and a hybrid stent according to embodiments herein (Figures 6C-6D) immediately after deployment, at one-month follow-up (Figure 6A-6C), and at three-month follow-up (Figure 6D), respectively. [Figure 6C] Figures 6A, 6B, 6C, and 6D show optical coherence tomography (OCT) images of blood vessels with a bare metal stent (Figure 6A), a drug-eluting stent (Figure 6B), and a hybrid stent according to embodiments herein (Figures 6C-6D) immediately after deployment, at one-month follow-up (Figure 6A-6C), and at three-month follow-up (Figure 6D), respectively. [Figure 6D] Figures 6A, 6B, 6C, and 6D show optical coherence tomography (OCT) images of blood vessels with a bare metal stent (Figure 6A), a drug-eluting stent (Figure 6B), and a hybrid stent according to embodiments herein (Figures 6C-6D) immediately after deployment, at one-month follow-up (Figure 6A-6C), and at three-month follow-up (Figure 6D), respectively. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0028] (Detailed Description) While various embodiments of the present invention have been shown and described herein, it will be apparent to those skilled in the art that such embodiments are provided by way of example only. Numerous variations, changes, and substitutions may occur to those skilled in the art without departing from the invention. It is understood that various alternatives to the embodiments of the present invention described herein may be employed.

[0029] Whenever the terms "at least," "greater than," or "greater than or equal to" precede the first number in a series of two or more numbers, the terms "at least," "greater than," or "greater than or equal to" apply to each and every number in the series. For example, "greater than or equal to 1, 2, or 3" is equivalent to "greater than or equal to 1," "greater than or equal to 2," or "greater than or equal to 3."

[0030] Whenever the term "less than", "less than", or "less than or equal to" precedes the first number in a series of two or more numbers, the term "less than", "less than", or "less than or equal to" applies to each and every number in the series. For example, "less than or equal to 3, 2, or 1" is equivalent to "less than or equal to 3", "less than or equal to 2", or "less than or equal to 1".

[0031] Certain embodiments of the invention herein contemplate numerical ranges. When a range exists, the range includes the range endpoints. In addition, all subranges and values ​​within the range exist as if explicitly written out. The term "about" or "approximately" may mean within an acceptable error range for a particular value, which will depend in part on how the value is measured or determined, e.g., the limitations of the measurement system. For example, "about" may mean within 1 or more than 1 standard deviation, according to the practice in the art. Alternatively, "about" may mean a range of up to 20%, up to 10%, up to 5%, or up to 1% of a given value. When a particular value is described in the present application and claims, the term "about" may be assumed to mean within an acceptable error range for the particular value, unless otherwise stated.

[0032] As shown at least in Figures 1 and 2, an exemplary stent 100 according to embodiments herein may comprise a first non-biodegradable end section 110, a biodegradable intermediate section 130 having a first end and a second end coupled to an end of the first non-biodegradable end section 110, and a second non-biodegradable end section 120 having an end coupled to the second end 130 of the biodegradable intermediate section.

[0033] The first end section 110 and the second end section 120 may be configured to expand at a first rate in response to an expansion force, for example from a balloon 500 or other expandable member (such as a malecot) over which the stent 100 is crimped. The intermediate section 130 may be configured to expand at a second rate in response to the same expansion force, the first rate being faster than the second rate. During expansion of the stent, the non-biodegradable end sections 110, 120 typically expand first, which may facilitate stabilization of the biodegradable intermediate section 130. Such stabilization may prevent any displacement of the biodegradable intermediate section 130 and the connector 140, and may prevent any damage to the connector 140.

[0034] The first end section 110 comprises at least one ring of struts 115 arranged in a first non-biodegradable strut pattern. The second end section 120 may comprise at least one ring of struts 125 arranged in a second non-biodegradable strut pattern. The middle section 130 may comprise at least one ring of struts 135 arranged in a biodegradable strut pattern. The biodegradable strut pattern of the middle section may be denser than the first and second non-biodegradable strut patterns of the first and second non-biodegradable end sections. This increased density may contribute at least in part to the increased stiffness of the middle section 130 and its expansion in response to the same expansion force slower than the first end section 110 and the second end section 140.

[0035] 1 and 2, for example, first end section ring 115, second end section ring 125, and mid section ring 135 may be arranged in a zigzag or sinusoidal pattern. The repetition of these patterns may be greater for mid section 130 than for first end section 110 and second end section 120. Although zigzag and sinusoidal strut patterns are shown in Figures 1 and 2, other strut patterns are also contemplated. As shown in FIG. 4, for example, the struts of the end and / or intermediate section rings may have a rectangular pattern 405, a diamond pattern 410, a pentagonal pattern 415, a hexagonal pattern 420, an octagonal pattern 430, a triangular pattern 435, an oval pattern 440, or a star-shaped pattern (such as a five-pointed star 450, a six-pointed star 445, or more, e.g., a fourteen-pointed star 455, etc.), to name a few, or combinations thereof.

[0036] 1-2, as well as FIGS. 3A-3E, the stent 100 may further comprise a number of connectors 140 connecting the first and second end sections 110, 120 to the intermediate section 130. Each connector 140 may comprise a biodegradable connector arm 142 coupled to and extending away from a first or second end of the biodegradable intermediate section 130, a biodegradable connector arm 142 having an end tab 146, and a non-biodegradable arm receiver 144 coupled to an end of the first or second end section 110, 120 and configured to mate with the end tab 146 of the biodegradable connector arm 142. One or more of the connector arms 142 may have a length of 0.1 to 1 mm.

[0037] The plurality of connectors 140 may define a first connecting section between an end of the first end section 110 and a first end of the intermediate section 130, and a second connecting section between an end of the second end section 120 and a second end of the intermediate section 130. Such a connecting section may be defined as the longitudinal area of ​​the stent 100 between adjacent rings 115, 125 of the end sections 110, 120 and a ring 135 of the intermediate section 130. One or both of the first and second connecting sections may have a length of 0.5 to 1 mm.

[0038] 1 and further enlarged in FIG. 3D, the non-biodegradable arm receiver 144 may include a socket 148 shaped to receive an end tab 146 of the biodegradable connector arm 142. In some embodiments, the end tab 146 may have an opening 147 through which a suture or tether 149 or other structure may pass to further secure the end tab 146 to the non-biodegradable arm receiver 144, as shown in FIG. 1 and FIG. 3D.

[0039] 2 and further enlarged in FIG. 3E, the non-biodegradable arm receiver 144 comprises a post 144s configured to hook over an end tab 146 of the biodegradable connector arm 142. In some embodiments, the end tab 146 may have an opening 147 through which the post 144s loops and secures the end tab 146, as shown in FIG. 1 and FIG. 3D. The post 144s may be integral with the non-biodegradable tab 145, which may be molded to fit, at least in part, within the opening 147.

[0040] The connector 140 may provide a mortise and tenon joint between the non-biodegradable end sections 110, 120 and the biodegradable middle section 150, which may prevent the lateral ends of the biodegradable end section 150 from collapsing as the material degrades. Figures 3A-3C show schematic diagrams of an exemplary connector 140 in a side view (Figure 3A) and in cross-sectional views orthogonal to the side view (Figures 3B, 3C). As shown in Figure 3A, the end tab 146 of the connector arm 142 may have an oval shape that is sized to fit within a socket 148 of the receiver 144. The complementary shapes of the end tabs 144 and sockets 148 may help prevent the end sections 110, 120 from decoupling from the intermediate section 130, particularly in the longitudinal direction of the stent 100 (i.e., parallel to the longitudinal axis of the stent 110), such as during deployment and expansion of the stent 100, as well as during the process of implantation when the intermediate section 130 may at least partially degrade or undergo migration of the vessel in which it is embedded. Although oval complementary shapes for the end tabs 144 and sockets 148 are shown, other shapes may alternatively be used, including elliptical, circular, polygonal, triangular, rectangular, pentagonal, hexagonal, or the like. In some embodiments, the thickness of the receiver 144 exceeds that of the connector arms 142 and end tabs 146, and the increased thickness can enable the socket 148 to have a support base 148s, as shown in FIG. 3B, which can help prevent the end sections 110, 120 from decoupling from the intermediate section, particularly in the radial direction of the stent 100 (i.e., transverse to the longitudinal axis of the stent 110), such as during deployment and expansion of the stent 100, as well as during the process of implantation when the intermediate section 130 may at least partially degrade or undergo movement of the vessel in which it is embedded. In some embodiments, the thickness of the receiver 144 is substantially the same as that of the connector arms 142 and end tabs 146, and a support base 148s is not provided, as shown in FIG. 3C.

[0041] Although the connector arm 142 is described above as extending from and / or coupled to a longitudinal end of the intermediate section 130 with the connector receptacle 144 extending from and / or coupled to a longitudinal end of the end section 110 or 120, the connector arm 142 and the connector receptacle 144 may alternatively or in combination be reversed. That is, the connector arm 142 may extend from and / or be coupled to a longitudinal end of the end section 110 or 120, and the connector receptacle 144s may extend from and / or be coupled to a longitudinal end of the intermediate section 130.

[0042] Referring back to the stent 100, the first and second non-biodegradable end sections 110, 120 may be drug eluting. For example, the first and second non-biodegradable end sections 110, 120 may be at least partially coated with a therapeutic agent, such as an mTOR inhibitor, rapamycin, paclitaxel, sirolimus, or combinations thereof, to name a few. By providing non-biodegradable end sections 110, 120, multiple hybrid stents 100 may be overlapped or nested, making such stents 100 applicable for bifurcation lesions. The middle section 130 may degrade over time, leaving the non-biodegradable end sections 110, 120 in place. If restenosis occurs, such as where the biodegraded middle section 130 was, a shorter stent may be implanted in its place.

[0043] The first and second non-biodegradable end sections 110, 120 may be made from a metal, such as stainless steel, cobalt chrome, or alloys thereof. By being made from a metal or other material that is highly visible to fluoroscopy or other medical imaging, the end sections 110, 120 can facilitate precise delivery and positioning of the stent 100.

[0044] The intermediate section 130 may be made from a bioresorbable metal, metal alloy, or polymer, such as iron, magnesium, zinc, or alloys thereof in the case of a bioresorbable metal, or polylactic acid (PLA), poly-L-lactic acid (PLLA), or polylactic-co-glycolic acid (PLGA) in the case of a bioresorbable polymer.

[0045] The first end section 110 may have a first length, the second end section 120 may have a second length, and the intermediate section 130 may have a third length that is greater than one or both of the first and second lengths. One or both of the lengths of the first end section or the second end section 110, 120 may be between 0.5 and 5 mm. The length of the intermediate section 130 may be between 5 and 25 mm. One or both of the first and second end sections 110, 120 may have a thickness between 60 and 100 μm. The intermediate section may have a thickness between 50 and 120 μm, for example 80 μm.

[0046] 5A-5F show how the stent 100 may be deployed and expanded. As shown in FIG. 5A, the stent 100 may be crimped over an inflatable balloon 500 or other expandable member (such as a malecot) in a collapsed or undeployed configuration. As shown in FIG. 5B, as the balloon 500 begins to be inflated, the end sections 110, 120 may begin to expand while the middle section 130 remains collapsed. As shown in FIG. 5C, as the balloon 500 is further inflated, the end sections 110, 120 may further expand, causing the end portions 130e of the middle section 130 to expand with them, although not to the same extent as the end sections 110, 120, while the central portion 130c of the middle section 130 remains collapsed. As shown in Figure 5D, as the balloon 500 is further inflated, the end sections 110, 120 may further expand, along with both the end section 130e and the central section 130 of the middle section 130, while the central section 130c may not expand as much as the end section 130e. As shown in Figure 5E, as the balloon 500 is further inflated, the end sections 110, 120 and the middle section 130 may now expand to approximately the same diameter. As shown in Figure 5F, as the balloon 500 is further inflated to its maximum diameter, the stent 100 may now expand to its full extent, i.e., its fully expanded or deployed configuration, including the end sections 110, 120 and the middle section 130.

[0047] Although the above steps illustrate a method of deploying a biodegradable drug-eluting stent, according to an embodiment, one of ordinary skill in the art will recognize many variations based on the teachings described herein. Steps may be completed in different orders. Steps may be added or deleted. Some of the steps may include sub-steps. Many of the steps may be repeated as many times as is beneficial or advantageous.

[0048] (Experimental Research) A pig-based animal study was conducted to compare bare metal stents (BMS), drug eluting stents (DMS), and a hybrid stent (test stent) according to embodiments herein.

[0049] FIG. 6A shows optical coherence tomography (OCT) images of the left circumflex artery (LCX) and left anterior descending artery (LAD) in which the BMS was deployed. Images were taken immediately after stent deployment and at one-month follow-up. Images were taken at the distal edge, body, and proximal edge of the stent. Stent struts can be observed as white arrows. For the LCX, the BMS was well attached immediately after stenting (post-stenting) without edge dissection or thrombus formation (similar to findings from QCA (quantitative comparative analysis) described below with reference to Table 1). At one-month follow-up, both edges (proximal and distal) have mild proliferation, but the stent body has severe intimal proliferation (as shown within the two circles marked on the individual images). For the LAD, similar to the LCX, there were no post-procedural complications. At 1-month follow-up, proliferation at either the proximal or distal margin was less severe than that at the LCX, however proliferation in the stent body (as shown within the two circles marked on the individual images) was significantly more severe than that at the LCX.

[0050] FIG. 6B shows optical coherence tomography (OCT) images of the left circumflex artery (LCX) and left anterior descending artery (LAD) in which the DES was deployed. Images were taken immediately after stent deployment and at one-month follow-up. Images were taken at the distal edge, body, and proximal edge of the stent. Stent struts can be observed as white arrows. For the LCX, the DES was well attached immediately after stenting (post-stenting) without edge dissection or thrombus formation (similar to the findings from QCA (quantitative comparative analysis) described below with reference to Table 1). At one-month follow-up, both edges (proximal and distal) have mild proliferation, but the stent body has severe intimal proliferation (as shown within the two circles marked on the individual images). For the LAD, similar to the LCX, there were no post-procedure complications. At one-month follow-up, proliferation at the distal edge was not as severe as that at the LCX. However, proliferation in the stent body (as shown within the two circles marked on the individual images) was significantly more severe than that in the LCX.

[0051] FIG. 6C shows optical coherence tomography (OCT) images of the left circumflex artery (LCX) and left anterior descending artery (LAD) in which a hybrid stent according to an embodiment herein was deployed (similar to findings from QCA described below with reference to Table 1). Images were taken immediately after stent deployment and at one-month follow-up. Images were taken at the distal edge, distal link (between the distal non-biodegradable portion and the biodegradable portion), body, proximal link (between the biodegradable portion and the proximal non-biodegradable portion), and proximal edge of the stent. Stent struts can be seen as white arrows. For the LCX, the test stent was well-appointed immediately after stenting (post-stenting) without edge dissection or thrombus formation (identical to findings from QCA). At one-month follow-up, proliferation at the edge, link segment, and stent body was similar to that found in the LCX and LAD. For the LAD, as with the LCX, there were no postprocedural complications. At 1-month follow-up, proliferation through the stent (from the distal edge to the distal link, body, proximal link, and proximal edge) was not as severe as in the BMS and DES groups.

[0052] Table 1 below shows the quantitative coronary analysis at one month follow-up. The test hybrid stent is associated with less in-stent restenosis compared to BMS and DES. Thirteen pigs were studied in this experiment, three with bare metal stents (BMS), three with drug-eluting stents (DES), and seven in the test stent group. Both the left circumflex artery (LCX) and the left anterior descending artery (LAD) were stented using the same stent in each pig. There was no significant difference in stent length and stent diameter in either the LCX or LAD between the two groups. At one month follow-up, the test hybrid stent is associated with less in-stent restenosis (mean value=9.8%) compared to BMS (24.5%) and DES (31.0%, p=0.029) according to QCA analysis. [Table 1]

[0053] Table 2 below shows the analysis of OCT measurements at 1 month follow-up. The test hybrid stents tended to have a larger lumen area compared to the BMS and DES according to the OCT measurements. OCT measurements were performed in 13 pigs (3 in the BMS or DES group and 7 in the test stent group) 1 month after the stenting procedure. The minimum stent area (MSA) measured by OCT at the LCX was comparable among the 3 groups. The MSA at the LAD in the test hybrid stent group was 3.59 ± 1.16 mm in the BMS. 2 and 3.39 ± 0.27 mm in the DES group. 2 significantly greater (p=0.027). [Table 2]

[0054] Table 3 below shows an analysis of OCT measurements at 3-month follow-up. Figure 6D shows the OCT images themselves, i.e., images of the left circumflex artery (LCX) and the left anterior descending artery (LAD), in which a hybrid stent according to an embodiment herein is deployed, immediately after stent placement and at 3-month follow-up. Images were taken at the distal edge, distal link (between the distal non-biodegradable portion and the biodegradable portion), body, proximal link (between the biodegradable portion and the proximal non-biodegradable portion), and proximal edge of the stent. As shown by the images in Figure 6D and Table 6D, a large minimum lumen area is maintained throughout the 3-month follow-up period, with lower late lumen loss from OCT measurements in both the LCX and LAD. [Table 3]

[0055] Although preferred embodiments of the present invention have been shown and described herein, it will be apparent to those skilled in the art that such embodiments are provided by way of example only. It is not intended that the present invention be limited by the specific examples provided herein. Although the present invention has been described with reference to the foregoing specification, the description and illustration of the embodiments herein are not meant to be construed in a limiting sense. Numerous variations, changes, and substitutions will now occur to those skilled in the art without departing from the present invention. Furthermore, it should be understood that all aspects of the present invention are not limited to the specific depictions, configurations, or relative proportions described herein, which depend upon a variety of conditions and variables. It should be understood that various alternatives to the embodiments of the present invention described herein may be employed in practicing the present invention. It is therefore contemplated that the present invention also covers any such alternatives, modifications, variations, or equivalents. It is intended that the following claims define the scope of the present invention, and that methods and structures within the scope of these claims and their equivalents are covered thereby.

Claims

1. A stent comprising: a first non-biodegradable end section; a biodegradable intermediate section having a first end and a second end, the first end being coupled to an end of the first non-biodegradable end section; and a second non-biodegradable end section having an end coupled to the second end of the biodegradable intermediate section. The stent.

2. The stent according to claim 1, further comprising a plurality of connectors connecting the first and second end sections to the intermediate section.

3. Each connector comprises: a biodegradable connector arm coupled to and extending away from the first or second end of the biodegradable intermediate section, the biodegradable connector arm having an end tab; and a non-biodegradable arm receiver coupled to the end of the first or second end section and configured to couple with the end tab of the biodegradable connector arm. The stent according to claim 2.

4. The plurality of connectors define a first connection section between the end of the first end section and the first end of the intermediate section and a second connection section between the end of the second end section and the second end of the intermediate section, and optionally, one or both of the first and second connection sections have a length of 0.5 to 1 mm. The stent according to claim 2.

5. One or more of the connector arms have a length of 0.1 to 1 mm. The stent according to claim 4.

6. The non-biodegradable arm receiver comprises a socket shaped to receive the end tab of the biodegradable connector arm. The stent according to claim 3.

7. The non-biodegradable arm receiver comprises a strut configured to latch onto the end tab of the biodegradable connector arm. The stent according to claim 3.

8. The first and second end sections are configured to expand at a first rate in response to an expansion force, the intermediate section is configured to expand at a second rate in response to the expansion force, and the first rate is faster than the second rate. The stent according to claim 2.

9. The first end section comprises at least one ring of struts arranged in a first non-biodegradable strut pattern, the second end section comprises at least one ring of struts arranged in a second non-biodegradable strut pattern, the intermediate section comprises at least one ring of struts arranged in a biodegradable strut pattern, and the biodegradable strut pattern of the intermediate section has a higher density than the first and second non-biodegradable strut patterns of the first and second non-biodegradable end sections. The stent according to claim 2.

10. At least one ring of the struts in the first or second end section comprises a plurality of non-biodegradable struts arranged in a first zigzag or sine wave pattern with a first repeat, and at least one ring of the struts in the intermediate section comprises a plurality of biodegradable struts arranged in a second zigzag or sine wave pattern with a second repeat that exceeds the first repeat. The stent according to claim 9.

11. The first and second non-biodegradable end sections are drug eluting. The stent according to claim 1.

12. The first and second non-biodegradable end sections are at least partially coated with a therapeutic agent. The stent according to claim 1.

13. The first and second non-biodegradable end sections are made of metal. The stent according to claim 1.

14. The intermediate section is made of a bioresorbable metal, metal alloy, or polymer. The stent according to claim 1.

15. The stent is balloon expandable. The stent according to claim 1.

16. The first end section has a first length, the second end section has a second length, and the intermediate section has a third length that exceeds one or both of the first and second lengths. The stent according to claim 4.

17. One or both of the lengths of the first end section or the second end section is 0.5 to 5 mm. The stent according to claim 16.

18. The length of the intermediate section is 5 to 30 mm, and optionally 5 to 25 mm. The stent according to claim 1.

19. The intermediate section has a thickness of 50 to 150 μm, and optionally 50 to 120 μm. The stent according to claim 1.

20. The stent according to claim 1, wherein one or both of the first and second end sections have a thickness of 60 to 100 µm.

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