Temporary scaffold for vessel preparation

Abstract

A biodegradable scaffold and methods of vessel preparation and drug delivery using the biodegradable scaffold are described. The biodegradable scaffold may be used to treat vessel dissection, restore vessel elasticity, and to provide long term release of drugs to prevent smooth muscle cell proliferation.

Description

CASPM.001WO PATENTTEMPORARY SCAFFOLD FOR VESSEL PREPARATIONINCORPORATION BY REFERENCE TO ANY PRIORITY APPLICATIONS

[0001] Any and all applications for which a priority claim is identified in the PCT Request as filed with the present application are hereby incorporated by reference under 37 CFR 1.57.BACKGROUNDField

[0002] The present disclosure relates to biodegradable scaffolds for vessel preparation and drug delivery.Description of the Related Art

[0003] The present treatments of vessel restenosis include drug eluting stents (DES) and drug coated balloons (DCB). Both of these treatment modalities benefit from the use of a vessel preparation device (e.g., scoring balloon, atherectomy) to restore vessel elasticity and improve drug uptake. While both of these treatment methods have been shown to be effective, they have significant drawbacks as well.

[0004] The use of DES involves the implantation of scaffolds or stents (e.g,, permanent metallic implants or biodegradable implants) having a coating that provides for controlled drug release. While clinically effective in controlling restenosis, DES can have long-term adverse effects such as late stent thrombosis. Biodegradable scaffolds may be used to mitigate the long-term adverse effects, however, thicker struts are used to compensate for lower mechanical strength. A typical biodegradable polymer scaffold can have a degradation time that ranges between 2-3 years. When the polymer based biodegradable scaffold breaks down, the acidic byproduct forms and can cause long-term inflammation. Since a drug coating may be released within the first 1-3 months of scaffold use, the drug may no longer be present to counter inflammation when the biodegradable polymer scaffold start to degrade close to 2- 3 years after being deployed.

[0005] DCBs are also used to treat vessel restenosis. DCBs have a limited time for drug delivery as all drug transfer must occur during balloon inflation. DCBs therefore havesignificant drawbacks such as inefficient vessel drug uptake, fast drug washout from the target tissue, and drug loss during navigation of the DCB to the target treatment site. There have also been instances of vessel dissection during DCB usage which must then be treated with a scaffold.SUMMARY

[0006] Presently disclosed is a drug coated biodegradable scaffold to improve drug delivery efficiency, minimize drug loss during navigation, and improve treatment of a target site. The biodegradable scaffold can be coated with an anti-restenotic agent like a limns drug. The biodegradable scaffold can include surface features that are designed to score and prepare the vessel as well as restore vessel elasticity at the time of scaffold deployment. The benefits of vessel preparation by the biodegradable scaffold can facilitate drug penetration into the tissue by disrupting the endothelium and penetrating into the media of the vessel wall. In some embodiments, the disclosed biodegradable scaffold is designed such that the rate of biodegradation is matched with the rate of drug release. The matched degradation of the scaffold and drug release prevents and / or ameliorates the inflammation associated with biodegradable implants.

[0007] In some aspects, a biodegradable scaffold is described. The biodegradable scaffold includes: a body having a thickness of 30 gm to 150 gm; a plurality of surface features positioned along the body, wherein the plurality of surface features has a height of between 30 pm and 200 gm, a lipophilic drug coating positioned on a surface of the biodegradable scaffold; and wherein the biodegradable scaffold includes a material configured to degrade in a period between 3 to 12 months, and wherein a degradation of the biodegradable scaffold coincides with a release of the lipophilic drug coating and healing of a patient’s blood vessel.

[0008] In some embodiments, the body includes a metal alloy and the metal alloy is selected from the group consisting of magnesium, iron, zinc, moly bdenum and combinations thereof. In some embodiments, the biodegradable scaffold is absent of a polymer. In some embodiments, the body includes a tubing, wherein a diameter of the tubing is 0.1 mm to 10 mm. In some embodiments, the body has a thickness between 30 gm and 60 gm. In some embodiments, the biodegradable scaffold further includes a base having a thickness of 40 gm and 80 um.

[0009] In some embodiments, the plurality of surface features includes 8 ribs to 128 ribs that are circumferentially spaced along the tubing. In some embodiments, the plurality of surface features includes a rib surface height of between 40 pm and 80 pm. In some embodiments, the plurality of surface features has the height of between 30 pm and 70 pm. In some embodiments, the plurality of surface features includes a number of protrusions between 16 protrusions to 32 protrusions. In some embodiments, the number of protrusions includes a rectangular shape, a square shape, a triangular with rounded peak shape, or needle shape. In some embodiments, a ratio between the height of the plurality' of surface features and the biodegradable scaffold is 0.5:1 to 3:1.

[0010] In some embodiments, the lipophilic drug coating includes a drug coating thickness of between 2 pm and 10 pm. In some embodiments, the lipophilic drug coating includes a limus drug.

[0011] In some aspects, a method of vessel preparation and drug delivery is described. The method includes: delivering a biodegradable scaffold to a treatment site; expanding the biodegradable scaffold; scoring the treatment site with a plurality of surface features on the biodegradable scaffold; delivering a drug from a lipophilic drug coating on the biodegradable scaffold to the treatment site, wherein the drug is delivered for a first period of time; degrading the biodegradable scaffold over a second period of time, wherein the second period of time is the same or shorter than the first period of time.

[0012] In some embodiments, the method further includes pressing the biodegradable scaffold with a radial force pressure between 400 mmHg to 500 mmHg. In some embodiments, the method further includes coating the biodegradable scaffold with the lipophilic drug coating prior to delivering the drug. In some embodiments, the method further includes facilitating the drug to transfer through an arterial wall of the treatment site.

[0013] In some embodiments, degrading the biodegradable scaffold degrades a metal alloy material of the biodegradable scaffold. In some embodiments, degrading the biodegradable scaffold degrades layer-by-layer.BRIEF DESCRIPTION OF THE DRAWINGS

[0014] These and other features, aspects and advantages are described below with reference to the drawings, which are intended for illustrative purposes and should in no waybe interpreted as limiting the scope of the embodiments. Furthermore, various features of different disclosed embodiments can be combined to form additional embodiments, which are part of this disclosure. In the drawings, like reference characters denote corresponding features consistently throughout similar embodiments. The following is a brief description of each of the drawings.

[0015] FIG. 1A illustrates an embodiment of surface features formed on a biodegradable magnesium tubing.

[0016] FIG. IB is a scanning electron microscopy (SEM) image illustrating another embodiment of surface features formed on a biodegradable magnesium tubing.

[0017] FIG. 2A is an SEM image illustrating an embodiment of a biodegradable magnesium scaffold laser cut from the tubing of FIG. 1A.

[0018] FIG. 2B is an SEM image illustrating an embodiment of a biodegradable magnesium scaffold laser cut from a profiled magnesium alloy tubing.

[0019] FIG. 2C is an SEM image illustrating another embodiment of a biodegradable magnesium scaffold laser cut from a profiled magnesium alloy tubing,

[0020] FIG. 3A is a schematic illustration of a scaffold strut having a rectangular cross-section and no surface feature, according to some embodiments.

[0021] FIG. 3B is a schematic illustration of a cross-sectional view of a scaffold strut with a surface feature formed on the scaffold strut, according to some embodiments.

[0022] FIG. 3C is a schematic illustration of a perspective side view of the scaffold strut with the surface feature shown in FIG. 3B.

[0023] FIG. 4A illustrates a scaffold crimped onto a balloon prior to inflation, according to some embodiments.

[0024] FIG. 4B illustrates a scaffold crimped onto an inflated balloon after expansion, according to some embodiments.

[0025] FIG. 5 illustrates a histology diagram of a rabbit iliac artery with an implanted biodegradable scaffold, according to some embodiments.

[0026] FIG. 6A is an SEM image illustrating a rabbit iliac artery with scaffold struts covered with endothelial cells, according to some embodiments.

[0027] FIG. 6B is a higher-magnification SEM image of FIG. 6A illustrating a rabbit iliac artery with scaffold struts covered with endothelial cells, according to some embodiments.

[0028] FIG. 6C is another higher-magnification SEM image of FIG. 6A illustrating a rabbit iliac artery with scaffold struts covered with endothelial cells, according to some embodiments.

[0029] FIG. 6D is another higher-magnification SEM image of FIG. 6A illustrating a rabbit iliac artery with scaffold struts covered with endothelial cells, according to some embodiments.DETAILED DESCRIPTIONOverview

[0030] The presently disclosed scaffold addresses the limitations of existing DESs and DCBs by preparing the vessel during scaffold deployment, preventing vessel dissections, and delivery drug from the implant surface. The scaffold can include a plurality7of surface features that are configured to score the vessel wall. This not only reduces the risk of elastic recoil but also minimizes the need for a scaffold with a high radial strength. In turn, this allows for the disclosed scaffold to be thinner than existing scaffolds with a biodegradation time closer to the time it takes for vessel healing. In some embodiments, the thinner structure of the biodegradable scaffold may also allow for improved control of degradation. In some embodiments, the disclosed scaffold can be configured to degrade in 3 months, 4 months, 5 months, 6 months, 7 months, 8 months, 9 months, 10 months, 1 1 months, 12 months, between 3 to 4 months, between 3 to 5 months, between 3 to 6 months, between 3 to 12 months, between 9 to 12 months, between 4 to 5 months, between 4 to 6 months, between 5 to 6 months, between 2 to 7 months, between 1 to 8 months, and any value in between ranges listed, including endpoints. In some embodiments, the drug, coated on the scaffold surface, can be delivered in a controlled manner during the period the scaffold is degrading. In some embodiments, a drug coating may be coated on the biodegradable scaffold for control release of the drug. Moreover, the surface features, coated with the drug, can facilitate drug transfer through the arterial wall.Man ufacturing O verview

[0031] The surface features on the scaffold can be formed in a variety of ways. As shown in FIG. 1, axially profiled features can be formed by laser etching a biodegradable magnesium tubing. Other methods of creating the profiled tubing include chemical etching, mechanical abrasion of tubing surface and electrochemical etching of masked tubing. In some embodiments, radially threaded profiled features can be formed by laser etching a biodegradable magnesium tubing. In some embodiments, the tubing is about 1.7 mm in diameter and includes 32 axial protrusions formed as ribs that are spaced about the surface of the tubing. Typical number of ribs range from 8 to 128 circumferentially spaced along the tubing. In some embodiments, the height of each of the rib surface features is 60 gm.

[0032] In some embodiments, the diameter of the tubing is, is about, is at least, is at least about, 0.1 mm, 0.2 mm, 0.3 mm, 0.4 mm, 0.5 mm, 0.6 mm, 0.7 mm, 0.8 mm, 0.9 mm, 1 mm, 1.1 mm, 1.2 mm, 1.3 mm, 1.4 mm, 1.5 mm, 1.6 mm, 1.7 mm, 1,8 mm, 1.9 mm, 2 mm, 2.1 mm, 2,2 mm, 2.3 mm, 2.4 mm 2,5 mm, 2.6 mm, 2.7 mm, 2,8 mm, 2.9 mm, 3 mm, 4 mm, 5 mm, 6 mm, 7 mm, 8 mm, 9 mm or 10 mm, or any range of values therebetween. In some embodiments, the diameter of the tubing is, is about, is at least, is at least about, 0.1 mm to 1 mm, 0.2 mm to 1 mm, 0.3 mm to 1 mm, 0.4 mm to 1 mm, 0.5 mm to 1 mm, 0.6 mm to 1 mm, 0.7 mm to 1 mm, 0,8 mm to 1 mm, 0.9 mm to 1 mm, 1 mm to 2 mm, 1.1 mm to 2 mm, 1.2 mm to 2 mm, 1.3 mm to 2 mm, 1.4 mm to 2 mm, 1 .5 mm to 2 mm, 1 .6 mm to 2 mm, 1.7 mm to 2 mm, 1.8 mm to 2 mm, 1.9 mm to 2 mm, 2 mm to 3 mm, 2.1 mm to 3 mm, 2.2 mm to 3 mm, 2.3 mm to 3 mm, 2.4 mm to 3 mm, 2.5 mm to 3 mm, 2.6 mm to 3 mm, 2,7 mm to 3 mm, 2,8 mm to 3 mm, 2.9 mm to 3 mm, 1 mm to 10 mm, 2 mm to 10 mm, 3 mm to 10 mm, 4 mm to 10 mm, 5 mm to 10 mm, 6 mm to 10 mm, 7 mm to 10 mm, 8 mm to 10 mm or 9 mm to 10 mm, or any range of values therebetween.

[0033] In some embodiments, the number of ribs circumferentially spaced along the tubing is, is about, is at least, is at least about, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 38, 40, 42, 44, 46, 48, 50, 52, 54, 56, 58, 60, 62, 64, 66, 68, 70, 72, 74, 76, 78, 80, 82, 84, 86, 88, 90, 92, 94, 96, 98, 100, 102, 104, 106, 108, 110, 112, 114, 116, 118, 120, 122, 124, 126 or 128, or any range of values therebetween.

[0034] In some embodiments, the height of each of the rib surface features is, is about, is at least, is at least about, 40 pm, 42 gm, 44 pm, 46 pm, 48 pm, 50 pm, 52 pm, 54gm, 56 gm, 58 gm, 60 gm, 62 gm, 64 gm, 66 pm, 68 pm, 70 pm, 72 gm, 74 gm, 76 gm, 78 gm or 80 gm, or any range of values therebetween.

[0035] As shown in FIGS. 2A, 2B and 2C, the biodegradable magnesium scaffold can be laser cut from the tubing of FIG. 1. The presence of surface protrusions on the biodegradable magnesium scaffold can allow the scaffold to be thinner to allow for quicker biodegradation. Typically, the scaffold thickness of the base ranges from 20 gm to 100 gm, with the ideal thickness ranging between 40 pm to 80 gm to provide for adequate initial radial strength and quick biodegradation.

[0036] In some embodiments, the scaffold thickness of the base is, is about, is at least, is at least about, 20 gm, 22 pm, 24 gm, 26 gm, 28 gm, 30 pm, 32 gm, 34 gm, 36 pm, 38 pm, 40 pm, 42 gm, 44 gm, 46 gm, 48 gm, 50 gm, 52 pm, 54 pm, 56 pm, 58 pm, 60 gm, 62 gm, 64 gm, 66 gm, 68 pm, 70 pm, 72 pm, 74 gm, 76 gm, 78 gm, 80 gm, 82 gm, 84 gm, 86 gm, 88 pm, 90 gm, 92 pm, 94 gm, 96 gm, 98 gm or 100 gm or any range of values therebetween.

[0037] In some embodiments, the ideal scaffold thickness of the base is, is about, is at least, is at least about, 40 gm, 42 pm, 44 gm, 46 gm, 48 gm, 50 pm, 52 gm, 54 gm, 56 gm, 58 gm, 60 pm, 62 gm, 64 gm, 66 pm, 68 gm, 70 gm, 72 gm, 74 pm, 76 gm, 78 gm or 80 gm, or any range of values therebetween.Surface Features

[0038] As discussed above, while many existing scaffolds include surface features, many of these are too low to effectively score the vessel wall. In some embodiments, the surface features are provided to denude the endothelium layer to allow the delivered drug to penetrate the tissue more effectively.

[0039] In some embodiments, clinically meaningful vessel scoring and improved drug uptake require scoring elements with a height of at least 30 gm, at least 40 gm, at least 50 gm, at least 60 gm, at least 70 gm, at least 80 gm, at least 90 pm, at least 100 gm, at least 110 gm, at least 120 gm, at least 130 pm, at least 140 gm, at least 150 gm, at least 160 pm, at least 170 gm, at least 180 pm, at least 190 gm, at least 200 gm, between about 30 pm and about 200 gm, between about 30 gm and about 180 gm, between about 30 gm and about 160 gm, between about 30 gm and about 140 gm, between about 30 gm and about 120 pm, betweenabout 30 pm and about 100 pm, between about 30 pm and about 80 pm, between about 30 pm and about 60 pm, between about 30 pm and about 40 pm, between about 40 pm and about 200 pm, between about 40 pm and about 180 pm, between about 40 pm and about 160 pm, between about 40 pm and about 140 pm, between about 40 pm and about 120 pm, between about 40 pm and about 100 pm, between about 40 pm and about 80 pm, between about 40 pm and about 60 pm, between about 50 pm and about 200 pm, between about 50 pm and about 180 pm, between about 50 pm and about 160 pm, between about 50 pm and about 140 pm, between about 50 pm and about 120 pm, between about 50 pm and about 100 pm, between about 50 pm and about 80 pm, between about 50 pm and about 60 pm, between about 60 pm and about 200 pm, between about 60 pm and about 180 pm, between about 60 pm and about 160 pm, between about 60 pm and about 140 pm, between about 60 pm and about 120 pm, between about 60 pm and about 100 pm, between about 60 pm and about 80 pm, between about 70 pm and about 200 pm, between about 70 pm and about 180 pm, between about 70 pm and about 160 pm, between about 70 pm and about 140 pm, between about 70 pm and about 120 pm, between about 70 pm and about 100 pm, between about 70 pm and about 80 pm, between about 80 pm and about 200 pm, between about 80 pm and about 180 pm, between about 80 pm and about 160 pm, between about 80 pm and about 140 pm, between about 80 pm and about 120 pm, between about 80 pm and about 100 pm, between about 90 pm and about 200 pm, between about 90 pm and about 180 pm, between about 90 pm and about 160 pm, between about 90 pm and about 140 pm, between about 90 pm and about 120 pm, between about 90 pm and about 100 pm, between about 100 pm and about 200 pm, between about 100 pm and about 180 pm, between about 100 pm and about 160 pm, between about 100 pm and about 140 pm, between about 100 pm and about 120 pm, between about 110 pm and about 200 pm, between about 110 pm and about 180 pm, between about 110 pm and about 160 pm, between about 110 pm and about 140 pm, between about 110 pm and about 120 pm, between about 120 pm and about 200 pm, between about 120 pm and about 180 pm, between about 120 pm and about 160 pm, between about 120 pm and about 140 pm, between about 130 pm and about 200 pm, between about 130 pm and about 180 pm, between about 130 pm and about 160 pm, between about 130 pm and about 140 pm, between about 140 pm and about 200 pm, between about 140 pm and about 180 pm, between about 140 pm and about 160 pm, between about 150 pm and about 200 pm, between about 150 pm and about 180 pm, between about 150 pmand about 160 gm, between about 160 gm and about 200 gm, between about 160 gun and about 180 gm, between about 170 gm and about 200 gm, between about 170 gm and about 180 .urn, between about 180 gm and about 200 gm, between about 190 gm and about 200 gm, and any value in between ranges listed, including endpoints.

[0040] FIG. 3A illustrates an embodiment of a rectangular cross-section of a scaffold strut with no surface features. The rectangular cross-section of the scaffold strut with no surface features has a scaffold strut thickness 310. In some embodiments, the scaffold strut can have a scaffold strut thickness of about 95 gm to about 180 gm. In some embodiments, the scaffold strut can have a scaffold strut thickness of about 120 gm

[0041] In some embodiments, the scaffold strut thickness is about 95 gm, about 100 uni, about 105 gm, about 110 gm, about 115 gm, about 120 gm, about 125 gm, about 130 uni, about 135 gm, about 140 gm, about 145 gm, about 150 gm, about 155 gm, about 160 gm, about 165 gm, about 170 gm, about 175 uni or about 180 gm, or any range of values therebetween.

[0042] FIGS. 3B and 3C illustrate an embodiment of a scaffold strut with a surface feature positioned on the scaffold strut. FIG. 3B illustrates a rectangular cross-section of the scaffold strut with a surface feature. As shown in FIG. 3B, the scaffold strut with the surface feature may have a scaffold strut height 320, FIG. 3C illustrates a perspective view of the scaffold structure with the surface feature of FIG. 3B. In some embodiments, a plurality of surface features positioned on the scaffold strut, can have a scaffold strut height of about 70 gm.

[0043] In some embodiments, the scaffold strut height is, is about, is at least, is at least, about, 30 gm, 32 gm, 34 gm, 36 gm, 38 gm, 40 gm, 42 gm, 44 gm, 46 gm, 48 gm, 50 gm, 52 gm, 54 gm, 56 gm, 58 gm, 60 gm, 62 gm, 64 gm, 66 gm, 68 gm or 70 gm, or any range of values therebetween.

[0044] In some embodiments, the surface features formed are in the form of peaks and valleys. The peaks can provide a scoring feature to score the vessel in order to release the stress of the arteries. In some embodiments, the peaks and valleys surface feature can also increase the surface area of the scaffold so as to increase the drug provided to the vessel wall without needing to increase the thickness of the drug coating.

[0045] As shown in FIGS. 3A and 3B, the surface features formed can have a triangular cross-section to form a peak on the scaffold strut. However, other shapes, configurations, and dimensions are also envisioned. For example, the protrusions can be rectangular, square, triangular with rounded peak, or needle shaped.

[0046] In some embodiments, the surface features can be spaced apart from each other. In some embodiments, the spacing may be dictated by the tubing diameter and number of protrusions. For ease of manufacturing, the protrusions may be evenly spaced. In some embodiments, the scaffold can have 32 number of protrusions. In some embodiments, the number of protrusions is, is about, is at least, is at least about, 16, 18, 20, 22, 24, 26, 28, 30 or 32, or any range of values therebetween.

[0047] In some embodiments, the scaffold can have a ratio of 0.5: 1 to 3: 1 between the height of the surface feature and the strut. In some embodiments, the ratio between the height of the surface feature and the strut is, is about, is at least, is at least about, 0.5:1, 0.6:1, 0.7: 1 , 0.8: 1, 0.9:1, 1.0: 1, 1.1: 1, 1.2:1, 1.3: 1, 1.4: 1 , 1.5: 1, 1.6:1, 1.7: 1, 1.8: 1, 1.9:1, 2.0: 1, 2.1: 1 , 2.2: 1, 2.3:1, 2.4:1, 2.5: 1, 2.6: 1, 2.7: 1, 2.8: 1, 2,9: 1 or 3.0: 1, or any range of values therebetween,

[0048] In some embodiments, the surface of the biodegradable scaffold may have sand-blasted surface features. In some embodiments, the plurality' of sand-blasted surface features has an average roughness of about 0.7 pm, about 0,8 pm, about 0.9 pm, or about 1 pm, or any range of values therebetween (such as between about 0.7 pm and about 1 pm, about 0.7 pm and about 0.9 pm, between about 0.8 pm and about 1 pm, or between 0.8 pm and about 0 9 pm). In some embodiments, the plurality of surface features has an average height of about 6 pm, about 7 pm, about. 8 pm, about 9 pm, about 10 pm, about 11 pm, or about 12 pm, or any range of values therebetween. In some embodiments, the plurality of surface features has a mean width of about 17 pm, about 18 pm, about 19 pm, about 20 pm, about 21 pm, about 22 pm, about 23 pm, about 24 pm, about 25 pm, about 26 pm, about 27 pm, about 28 pm, about 29 pm, about 30 pm, about 31 pm, about 32 pm, about 33 pm, about 34 pm, or about 35 pm, or any range of values therebetween.

[0049] For example, the sand-blasted surface features can be formed on a biodegradable magnesium tubing having an average roughness (Ra) of about 0.85 pm with a lower limit roughness of about 0.75 pm and upper limit roughness of about 0.97 gm, an average height (Rz = average height of the tallest 5-10 peaks and the deepest 5-10 valleys) ofabout 8 gm with a lower limit height of about 6.66 gm and an upper limit height of about 10.78 gm, and a mean width (Rstn = average spacing between adjacent peaks or valleys) of about 25.69 um with a lower limit spacing of about 17.44 gm and an upper limit spacing of about 33.94 gm.

[0050] FIG. 4A illustrates a scaffold crimped onto a balloon prior to inflation, according to some embodiments. FIG. 4B illustrates a scaffold crimped onto an inflated balloon after expansion, according to some embodiments. As shown in FIG. 4A, a scaffold 410A is configured to crimped onto a balloon 420 A. Once the balloon is inflated as shown in FIG. 4B, an expanded scaffold 410B is formed on an inflated balloon 420B.Scaffold Material Properties

[0051] The scaffold can be constructed of a fast-degrading material that completely biodegrades or corrodes to match the duration for vessel healing. In some embodiments, the scaffold can degrade in 3 months, 4 months, 5 months, 6 months, between 3 to 4 months, between 3 to 5 months, between 3 to 6 months, between 4 to 5 months, between 4 to 6 months, between 5 to 6 months, between 2 to 7 months, between 1 to 8 months, and any value in between ranges listed, including endpoints.

[0052] To achieve this level of degradation, the scaffold can comprise a metal alloy, such as a magnesium alloy, an iron alloy or alloys based on zinc or molybdenum. In some embodiments, the scaffold may be absent of a polymer or a biodegradable polymer. In some embodiments, the scaffold can comprise a polymer or a biodegradable polymer such as PLGA. In some embodiments, a body of the scaffold can comprise a biodegradable polymer, copolymer, blend, composite or combinations thereof In some embodiments, the biodegradable polymer can be selected from the group consisting of polylactic acid, polyglycolic acid and their copolymers, polydioxanone, polycaprolactone, polyphosphazene, collagen, gelatin, chitosan, glycosaminoglycans, and combinations thereof. In some embodiments, the body of the scaffold can have a body thickness of, of about, of at least, of at least about 30 gm, 32 gm, 34 gm, 36 um, 38 gm, 40 gm, 42 um, 44 gm, 46 gm, 48 gm, 50 gm, 52 gm, 54 gm, 56 gm, 58 um or 60 gm, or any range of values therebetween. In some embodiments, the body of the scaffold can have a body thickness of about 50 gm. In some embodiments, the body of the scaffold can have a body thickness of about 30 gm to about 150gm. In some embodiments, the body of the scaffold can have a body thickness of about 90 gm to about 100 gm. In some embodiments, the scaffold may be a stent. In some embodiments, the disclosed scaffold can be thinner than existing scaffolds. This can not only ensure a quicker tinier for degradation but can allow the scaffold to have a more predictable degradation. Scaffold body with thicker structures (e.g., at least about 150 gm can degrade inside out which can lead to a catastrophic breakdown of the scaffold. By contrast, a scaffold body with a thinner structure (e.g., at most about 100 gm) can ensure that the scaffold degrades layer-by- layer.Coating Properties

[0053] In some embodiments, the scaffold surface can be coated with an antiproliferative agent like a limus drug (e.g., Biolimus AS?) which has a high lipophilicity, long tissue residence time, and preferred adhesion to fatty tissue. In some embodiments, the drug can be directly coated on the scaffold or mixed with a biodegradable polymer to further control the release rate from the scaffold surface. In some embodiments, the drug coating may be a lipophilic drug coating. In some embodiments, the drug coating comprising biolimus may be about or at least about ten-fold more lipophilic than a drug coating comprising sirolimus. In some embodiments, the drug coating may comprise a lipophilic coating and a drug.

[0054] In some embodiments, the thickness of the drug coating is, is about, is at least, is at least about, 2.0 gm, 2.2 gm, 2,4 gm, 2.6 gm, 2.8 gm, 3.0 gm, 3.2 gm, 3.4 gm, 3.6 gm, 3.8 gm, 4.0 gm, 4.2 gm, 4.4 gm, 4.6 gm, 4.8 gm, 5.0 gm, 5.2 gm, 5.4 gm, 5.6 gm, 5.8 gm, 6.0 gm, 6.2 gm, 6.4 gm, 6.6 gm, 6.8 gm, 7.0 gm, 7.2 gm, 7.4 gm, 7.6 gm, 7.8 gm, 8.0 gm, 8.2 gm, 8.4 gm, 8.6 gm, 8.8 gm, 9.0 gm, 9.2 gm, 9.4 gm, 9.6 gm, 9.8 gm or 10.0 gm, or any range of values therebetween.Method of Delivery

[0055] The disclosed scaffold can be delivered in the same way as DCBs and DESs.The scaffold can be configured to provide sufficient radial force (e.g., pressure) to minimize artery recoil and spasm during the procedure. In some embodiments, the radial force pressure is, is about, is at least, is at least about, 300 mmHg, 305 mmHg, 310 mmHg, 315 mmHg, 320 mmHg, 325 mmHg, 330 mmHg, 335 mmHg, 340 mmHg, 345 mmHg, 350 mmHg, 355 mmHg, 360 mmHg, 365 mmHg, 370 mmHg, 375 mmHg, 380 mmHg, 385 mmHg, 390 mmHg, 395mmllg, 400 mmHg, 405 mmHg, 410 mmHg, 415 mmHg, 420 mmHg, 425 mmHg, 430 mmHg, 435 mmHg, 440 mmHg, 445 mmHg, 450 mmHg, 455 mmHg, 460 mmHg, 465 mmHg, 470 mmHg, 475 mmHg, 480 mmHg, 485 mmHg, 490 mmHg, 495 mmHg or 500 mmHg, or any range of values therebetween. In some embodiments, the radial force pressure is at least about 400 mmHg. In some embodiments, the scaffold is configured to allow7the operator to inflate the balloon multiple times and also to post dilate the scaffold to minimize malposition.Matched Rate of Degradation

[0056] In some embodiments, the presently disclosed scaffold has a degradation time that is matched with the duration of drug release and complete vessel healing. Existing biodegradable scaffolds cause long term inflammation as the material of the scaffold produces acidic byproducts that can cause inflammation of the vessel walls. By matching the degradation of the scaffold with the drug release, the inflammatory response of the patient is minimized by the anti-inflammatory drug released by the drug coating.Methods of Treatment

[0057] The presently disclosed scaffold can be used to treat coronary and peripheral artery disease (e.g., below the knee, neurovascular). In some embodiments, the scaffold can be used to prevent future restenosis.

[0058] In some embodiments, the disclosed scaffold is directed to the treatment of erectile dysfunction (ED). Pudendal artery blockages are a common cause of ED because pudendal arteries tend to show high elastic recoil. Existing studies have demonstrated some drawbacks of current ED treatments (e.g., Diehm et al, Early Recoil After Balloon Angioplasty of Erection-Related Arteries in Patients With Arteriogenic Erectile Dysfunction, 25(6):710-715. (“Diehm”) have showm that elastic recoil post-angioplasty without stenting ranges between 20-50%. This data v / as derived from clinical trials and studies examining coronary and peripheral artery interventions. Some of these drawbacks include using a plain old balloon angioplasty (POBA) with no drug elution, high rates of restenosis, no impact on recoil, using a DES having difficulty with repeat procedures and post implant imaging, and using a drug-eluting balloon (DEB) having no option for repeat procedures (e.g., post-dilation) and no impact on recoil. In contrast, the ED treatment disclosed in the present application addresses the above drawbacks while combining advantages of current offerings. The presentlydisclosed scaffold can be used to treat vessel dissection, restore vessel elasticity, and to provide long term release of limus drug to prevent smooth muscle cell proliferation.EXAMPLES

[0059] Example embodiments of the present disclosure, including processes, materials and / or resultant products, are described in the following examples.Example 1 - Biodegradable Scaffold

[0060] FIG. 5 illustrates a histology diagram of a rabbit iliac artery with an implanted biodegradable scaffold. The artery was explanted after 28 days. As shown in FIG. 5, when the artery is fully patent, stenosis, thrombosis, and adverse effects are not present.

[0061] FIGS. 6A-6D are SEM images illustrating a rabbit iliac artery with an implanted biodegradable scaffold. The artery was explanted after 28 days. In FIGS. 6A-6D, the scaffold struts are completely covered with endothelial cells indicating a healed treatment site.

[0062] It is to be understood that the embodiments of the invention herein described are merely illustrative of the appl ication of the principles of the invention. Reference herein to details of the illustrated embodiments is not intended to limit the scope of the claims, which themselves recite those features regarded as essential to the invention. The drawings are for the purpose of illustrating embodiments of the invention only, and not for the purpose of limiting it.[0063 [ It is contemplated that various combinations or subcombinations of the specific features and aspects of the embodiments disclosed above may be made and still fall within one or more of the inventions. Further, the disclosure herein of any particular feature, aspect, method, property, characteristic, quality, attribute, element, or the like in connection with an embodiment can be used in all other embodiments set forth herein. Accordingly, it should be understood that various features and aspects of the disclosed embodiments can be combined with or substituted for one another in order to form varying modes of the disclosed inventions. Thus, it is intended that the scope of the present inventions herein disclosed should not be limited by the particular disclosed embodiments described above. Moreover, while the invention is susceptible to various modifications, and alternative forms, specific examples thereof have been shown in the drawings and are herein described in detail. It should beunderstood, however, that the invention is not to be limited to the particular forms or methods disclosed, but to the contrary, the invention is to cover all modifications, equivalents, and alternatives falling within the spirit and scope of the various embodiments described and the appended claims. Any methods disclosed herein need not be performed in the order recited. The methods disclosed herein include certain actions taken by a practitioner; however, they can also include any third-party instruction of those actions, either expressly or by implication. For example, actions such as “deploying an instrument sterilized using the systems herein” include “instructing the deployment of an instrument sterilized using the systems herein.” In addition, where features or aspects of the disclosure are described in terms of Markush groups, those skilled in the art will recognize that the disclosure is also thereby described in terms of any individual member or subgroup of members of the Markush group.

[0064] The ranges disclosed herein also encompass any and all overlap, sub-ranges, and combinations thereof. Language such as “up to,” “at least,” “greater than,” “less than,” “between,” and the like includes the number recited. Numbers preceded by a term such as “about” or “approximately” include the recited numbers. For example, “about 10 nanometers” includes “10 nanometers.”

[0065] Any titles or subheadings used herein are for organization purposes and should not be used to limit the scope of embodiments disclosed herein.

[0066] The terms “approximately”, “about”, and “substantially” as used herein represent an amount or characteristic close to the stated amount or characteristic that still performs a desired function or achieves a desired result. For example, the terms “approximately”, “about”, and “substantially” may refer to an amount in certain embodiments that, is within less than plus or minus 10% of, within less than plus or minus 5% of, within less than plus or minus 1% of, within less than plus or minus 0.1% of, and within less than plus or minus 0.01% of the stated amount or characteristic.

Claims

WHAT IS CLAIMED IS:

1. A biodegradable scaffold comprising: a body having a thickness of 30 gm to 150 gm; a plurality of surface features positioned along the body, wherein the plurality of surface features has a height of between 30 gm and 200 gm; and a lipophilic drug coating positioned on a surface of the biodegradable scaffold; wherein the biodegradable scaffold comprises a material configured to degrade in a period between 3 to 12 months, and wherein a degradation of the biodegradable scaffold coincides with a release of the lipophilic drug coating and healing of a patient’s blood vessel.

2. The biodegradable scaffold of Claim 1, wherein the body comprises a metal alloy and the metal alloy is selected from the group consisting of magnesium, iron, zinc, molybdenum and combinations thereof.

3. The biodegradable scaffold of Claim 1, wherein the biodegradable scaffold is absent of a polymer.

4. The biodegradable scaffold of Claim 1, wherein the body comprises a tubing, wherein a diameter of the tubing is 0.1 mm to 10 mm.

5. The biodegradable scaffold of Claim 4 wherein the plurality7of surface features comprises 8 ribs to 128 ribs that are circumferentially spaced along the tubing.

6. The biodegradable scaffold of Claim 1 , wherein the plurality of surface features comprises a rib surface height of between 40 gm and 80 gm.

7. The biodegradable scaffold of Claim 1, wherein the thickness of the body is between 30 gm and 60 gm.

8. The biodegradable scaffold of Claim 1 , wherein the plurality of surface features has the height of between 30 gm and 70 gm.

9. The biodegradable scaffold of Claim 1, wherein the lipophilic drug coating has a thickness of between 2 gm and 10 gm.

10. The biodegradable scaffold of Claim 1, wherein the lipophilic drug coating comprises a limus drug.

11. The biodegradable scaffold of Claim 1, wherein the plurality of surface features comprises a number of protrusions between 16 protrusions to 32 protrusions.

12. The biodegradable scaffold of Claim 11, wherein the number of protrusions comprises a rectangular shape, a square shape, a triangular with rounded peak shape, or needle shape.

13. The biodegradable scaffold of Claim 1, further comprising a base having a thickness of 40 pm to 80 pm.

14. The biodegradable scaffold of Claim 1, wherein a ratio between the height of the plurality of surface features and the biodegradable scaffold is 0.5: 1 to 3: 1.

15. A method of vessel preparation and drug deliver}' comprising: delivering a biodegradable scaffold to a treatment site; expanding the biodegradable scaffold; scoring the treatment site with a plurality of surface features on the biodegradable scaffold; delivering a drug from a lipophilic drug coating on the biodegradable scaffold to the treatment site, wherein the drug is delivered for a first period of time; and degrading the biodegradable scaffold over a second period of time, wherein the second period of time is the same or shorter than the first period of time.

16. The method of Claim 15, further comprising pressing the biodegradable scaffold with a radial force pressure between 400 mmHg to 500 mmHg.

17. The method of Claim 15, wherein degrading the biodegradable scaffold degrades a metal alloy material of the biodegradable scaffold.

18. The method of Claim 15, wherein degrading the biodegradable scaffold degrades layer-by-layer.

19. The method of Claim 15, further comprising coating the biodegradable scaffold with the lipophilic drug coating prior to delivering the drug.

20. The method of Claim 15, further comprising facilitating the drug to transfer through an arterial wall of the treatment site.

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