WO2020084629A1

WO2020084629A1 - Scaffold graft having self-expandable scaffold and method of manufacturing thereof

Info

Publication number: WO2020084629A1
Application number: PCT/IN2018/050822
Authority: WO
Inventors: Deveshkumar Mahendralal KOTHWALA; Rajnikant Gandalal Vyas; Pramod Kumar Minocha
Original assignee: Meril Life Sciences Pvt Ltd
Priority date: 2018-10-23
Filing date: 2018-12-08
Publication date: 2020-04-30

Abstract

Scaffold graft having self-expandable scaffold and method of manufacturing thereof is disclosed. The scaffold graft comprises of a self-expandable scaffold. The scaffold includes an inner surface and an outer surface. The scaffold also includes a first layer coated on at least the outer surface 5 of the self-expandable scaffold resulting in a scaffold graft. The first layer includes at least a polymer dissolved in at least a solvent in the concentration in the range of 0.6%-0.8% (w/v). The thickness of the first layer ranges from 30-60 micron. The reduced profile of the scaffold graft ranges from 1.6 mm-2.4 mm.

Description

SCAFFOLD GRAFT HAVING SELF-EXPANDABLE SCAFFOLD AND METHOD OF MANUFACTURING

THEREOF

FIELD OF INVENTION

[001] The present disclosure relates to a graft, more specifically, the disclosure relates to a biodegradable graft coated on a self-expandable scaffold.

BACKGROUND

[002] Stents (or scaffolds) are medical devices that are generally used to keep the lumen of blood vessels intact and to facilitate adequate blood flow to the organs. However, the walls of vessels may suffer from dissection or tear during percutaneous interventions. Vessel perforation, ischemia, aneurysms etc may be a consequence of guide wire advancement, balloon or scaffold advancement, balloon or scaffold inflation, over sizing or ruptured balloon or scaffold, or from sub-intimal passage of the balloon or scaffold into a vessel with severe dissection during the percutaneous interventions.

[003] Moreover, increased blood flow in the vessel may cause the bulging out of the weakened portion of the vessel wall leading to the condition of the aneurysm. The most detrimental stage of the aneurysm is reached when the balloon (and/or bulged out portion) is burst (and/or ruptured) leading to stroke, massive internal bleeding, etc.

[004] Covered scaffolds have revolutionized the management of peripheral blood vessel perforation. The covered metal scaffolds have been extensively used in occluding the aneurysms (coronary, peripheral and neurovascular). Conventionally, metal scaffolds are covered by a synthetic material like PTFE or a processed biological material like treated pericardium tissue which are not bioresorbable and require long term monitoring.

[005] However, the metal scaffold grafts are permanent implants which may lead to long term complications like in-scaffold restenosis, inflammation and the implant requires lifetime follow up to the site.

SUMMARY

[006] The present invention relates to a scaffold graft comprising of a self-expandable scaffold.

The scaffold includes an inner surface and an outer surface. The scaffold also includes a first layer which is coated on at least the outer surface of the self-expandable scaffold to form a scaffold graft. The first layer includes at least a polymer dissolved in at least a solvent in the concentration in the range of 0.6%-0.8% (w/v). The thickness of the first layer ranges from 30-60 micron. The reduced profile of the scaffold graft ranges from 1.6 mm-2.4 mm.

[007] A method for manufacturing of the scaffold graft includes the following steps: providing a self-expandable scaffold, coating a first layer on the outer surface of the self-expandable scaffold to form a covered scaffold, and annealing the covered scaffold at an annealing temperature and an annealing time to form a scaffold graft having a reduced profile ranges from 1.6 mm to 2.4 mm.

BRIEF DESCRIPTION OF THE DRAWINGS

[008] The summary above, as well as the following detailed description of illustrative embodiments, is better understood when read in conjunction with the appended drawings. For the purpose of illustrating the present disclosure, exemplary constructions of the disclosure are shown in the drawings. However, the disclosure is not limited to specific methods and instrumentalities disclosed herein. Moreover, those in the art will understand that the drawings are not to scale.

[009] FIG.l illustrates a schematic view of the scaffold graft in accordance with an embodiment of the present invention.

[0010] FIG.2 illustrates a flowchart depicting steps involved in manufacturing of the scaffold graft in accordance with an embodiment of the present invention.

DETAILED DESCRIPTION OF THE DRAWINGS

[0011] Prior to describing the invention in detail, definitions of certain words or phrases used throughout this patent document will be defined: the terms "include" and "comprise", as well as derivatives thereof, mean inclusion without limitation; the term "or" is inclusive, meaning and/or; the phrases "coupled with" and "associated therewith", as well as derivatives thereof, may mean to include, be included within, interconnect with, contain, be contained within, connect to or with, couple to or with, be communicable with, cooperate with, interleave, juxtapose, be proximate to, be bound to or with, have, have a property of, or the like; Definitions of certain words and phrases are provided throughout this patent document, and those of ordinary skill in the art will understand that such definitions apply in many, if not most, instances to prior as well as future uses of such defined words and phrases.

[0012] Particular embodiments of the present disclosure are described herein below with reference to the accompanying drawings, however, it is to be understood that the disclosed embodiments are merely examples of the disclosure, which may be embodied in various forms. Well-known functions or constructions are not described in detail to avoid obscuring the present disclosure in unnecessary detail. Therefore, specific structural and functional details disclosed herein are not to be interpreted as limiting, but merely as a basis for the claims and as a representative basis for teaching one skilled in the art to variously employ the present disclosure in virtually any appropriately detailed structure.

[0013] In accordance with the present disclosure, a scaffold graft for treatment of traumatic vascular lesions, vessel perforations, aneurysmatic lesions, and atherosclerotic obstructive lesions in the peripheral vasculature and method of manufacturing the same is provided. In an embodiment, the scaffold is a self-expanding scaffold. The scaffold may be made of a metal alloy, say, nitinol. The graft may be made of a biodegradable material. An outer surface of the graft is coated with a layer coating solution. The layer of the coating solution includes without limitation, one or more bioresobable polymer and one or more solvents.

[0014] The layer of the coating solution of the present invention which is coated over the metallic scaffold is biocompatible as well as elastic and/or flexible. The layer of the coating solution of the present invention withstands the forces applied during the deployment of the scaffold graft and at the treatment site. The coating of present invention degrades in about 4 to 6 months thereby avoiding the need of long term follow up.

[0015] The scaffold graft may be additionally coated with an anti-proliferative drug. The anti proliferative drug is coated above the layer of the coating solution. The anti-proliferative drug reduces neointimal proliferation and/or prevents any inflammatory reaction of the vessel due to introduction of the scaffold graft.

[0016] Now referring specifically to the drawings, FIG. 1 illustrates a schematic view of the scaffold graft 100. The scaffold graft 100 has high radial strength and durability. The radial strength of the scaffold graft 100 may vary depending upon the size of the scaffold graft 100. For instance, radial strength of scaffold graft 100 having dimensions 5 X 30 mm (D x L) ranges from 30N to 40N.

[0017] The scaffold graft 100 includes a scaffold 1 and a graft 3. In an embodiment, the scaffold graft 100 may be constructed by coating a graft 3 over the scaffold 1.

[0018] The scaffold 1 may be a self-expandable scaffold. The scaffold 1 may be made of stainless steel, nitinol, magnesium alloys, and cobalt chromium or their alloy. In an embodiment, the scaffold 1 is made of nitinol. Nitinol is selected for the fabrication of the scaffold 1 as it shows shape memory effect, super elastic behavior, high tensile strength, good corrosion resistance and biocompatibility.

[0019] The scaffold 1 may be manufactured using a known process such as laser cutting and braiding. In an embodiment, the scaffold 1 is manufactured using laser cutting technique. In an embodiment, the scaffold 1 is manufactured by laser cutting a nitinol tube to form a predefined pattern. Alternately, a plurality of nitinol wires are braided together to form a braided scaffold 1.

[0020] In an embodiment, the scaffold 1 has a strut thickness of 160-200pm.

[0021] The scaffold 1 which is a tubular structure includes a proximal end la, a distal end lb, an outer surface lc and an inner surface (not shown).

[0022] In an embodiment, the scaffold 1 is provided with a plurality of markers 5. The markers 5 may be disposed on each of the joints of the proximal end la and distal end lb of scaffold strut. In an embodiment, the scaffold 1 includes three markers at the joints of the proximal end la and three markers at the distal end lb of the scaffold strut. The markers 5 may include, without limitation, radiopaque markers. The radiopaque markers may be made of without limitation platinum, tantalum, gold, etc. In an embodiment, the radiopaque markers used in the present invention are made of tantalum.

[0023] In an embodiment, the graft 3 is coated on the outer surface lc of the scaffold 1. The graft 3 may at least partially cover the outer surface lc of the scaffold. In an embodiment, the graft 3 covers the entire outer surface lc. Alternately, the graft 3 covers 70% of the outer surface lc.

[0024] The graft 3 is in the form of a first layer. The first layer of the graft 3 may be made of without limitation a non-degradable or a biodegradable material. In an embodiment, the graft 3 is made of one or more bioresorbable polymers. The bioresorbable graft 3 acts as a support layer/base layer which enhances the tissue growth. In case of biodegradable grafts, the graft 3 has a controlled degradation rate inside the body. The degradation rate is dependent upon the properties of the biodegradable material used for making the graft 3.

[0025] The bioresorbable polymer(s) may include without limitation, aliphatic polyesters, natural polymers, polyanhydrides, poly (orthoesters), polyphosphazenes, poly (aminoacids), polyalkylcyanoacrylates, poly (propylene fumarate), poly (ester-ether), and poly (vinyl alcohol), poly-L-lactide (PLLA) and poly-D-lactide (PDLA), poly-dl-lactic acid (PDLLA), poly-L-lactide-co- glycolide (PLG), poly-L-lactide-co-s-caprolactone (PLCL), polyglycolide or their combinations.

[0026] In an embodiment, the graft 3 is made of aliphatic polyesters. The aliphatic polyesters may include without limitation, polylactic acid (PLA), polyglycolic acid (PGA), poly-e- caprolactone (PCL), polyhydroxybutyrate (PHB), and poly (3-hydroxy valerate). In an embodiment, the graft 3 is made of poly-L-lactide-co-s-caprolactone (PLCL).

[0027] Poly-L-lactide-co-s-caprolactone (PLCL) is used for the formation of the graft 3 due to its good elasticity. The concentration of lactide to caprolactone in the copolymer PLCL may range from 25-85%, more preferably 40-70%. The inherent viscosity of the copolymer (PLCL) may be between 1.2 and 1.8 dl/g, more preferably between 1.4 and 1.6 dl/g. The degradation of PLCL initiates from the fourth month from the placement of the scaffold graft 100. The use of PLCL for preparing the graft 3 eliminates the risk of tearing or breaking of the graft 3 during expansion of the scaffold graft 100.

[0028] In an embodiment, the graft 3 may be a single layer graft or a multi-layer graft. The graft 3 on the scaffold 1 increases expansion performance, prevents any micro cracks and notches at the strut edges of the scaffold 1.

[0029] The graft 3 is coated over the outer surface lc of the scaffold by depositing a layer of a coating solution. The layer of the coating solution is a solution of the biodegradable polymer(s) (as disclosed in paragraphs 18 & 19) and may additionally include one or more drugs or anti inflammatory agents. The layer of the coating solution is prepared by dissolving the aforesaid components in one or more solvents. Alternately, the layer of the coating solution of graft 3 comprises of one or more bioresorbable polymers and one or more solvents while a layer of one or more drugs or anti-inflammatory agents is coated over the graft 3. The layer of the coating solution of the present invention which is coated over the metallic scaffold is biocompatible as well as elastic and/or flexible. The layer of the coating solution of the present invention withstands the forces applied during the deployment of the scaffold graft and at the treatment site. The coating of present invention degrades in about 4 to 6 months thereby avoiding the need of long term follow up.

[0030] In an embodiment, the bioresorbable polymer used is poly-L-lactide-co-s-caprolactone (PLCL). The amount of PLCL used may vary between 0.1% w/v to 1.3% w/v, preferably between 0.4% w/v and 1.0% w/v, more preferably between 0.6% w/v and 0.8% w/v. [0031] The solvent may include without limitation, water, dimethyl sulfoxide (DMSO), Dichloromethane (DCM) N,N'- dimethylformamide (DMF), N,N'-dimethylacetamide (DMAC), N- methyl-2-pyrrolidone (NMPO), chloroform, l,3-dimethyl-2-imidazolidinone (DMEU), 1,3-dimethyl- 3,4,5,6-tetrahydro-2-(lH)-pyrimidinone (DMPU), methanol, ethanol, 1-propanol, isopropanol, acetone, diethyl ether, methyl acetate, ethyl acetate, xylene, and mixtures thereof. In present invention, solvents used are dichloromethane, chloroform and acetone.

[0032] The concentration of dichloromethane used may be in the range of 20%-100% (v/v). The concentration of chloroform may range up to 50% (v/v). The concentration of acetone may range up to 80% (v/v).

[0033] In an embodiment, the solvents used are dichloromethane and acetone. The ratio of dichloromethane and acetone ranges from 2:8 to 1:9. In another embodiment, only dichloromethane may be used. In yet another embodiment, the solvents used are dichloromethane and chloroform. The ratio of dichloromethane and chloroform ranges from 5:5 to 7:3.

[0034] The drug may include without limitation, anti-inflammatory agent, angiotensin converting enzyme (ACE) inhibitors, antihistamines, steroidal or non-steroidal anti-inflammatory agents, matrix metalloproteinase (MMP) inhibitors, mucolytics, opioids, anti-proliferative agent, anticholinergics, antifungal agents, antiparasitic agents, antiviral agents, biostatic compositions, chemotherapeutic/antineoplastic agents, immunosuppressors, nucleic acids, peptides, proteins, vasoconstrictors, bioactive agents and combinations thereof. The anti-proliferative agent used may include without limitation, paclitaxel or its derivative, sirolimus, everolimus or other compounds of the -limus group and likewise. In an embodiment, the anti-proliferative agent is sirolimus. The dose of sirolimus may range from 0.95-1.55pg/mm², more preferably range from 1.15-1.35pg/mm². The drug used sirolimus is used because of localized drug release of anti proliferative effect for treatment of restenosis and rupture or damage during endovascular surgery.

[0035] The drug may be coated on outer surface and/or inner surface of the scaffold graft 100. In an embodiment, the drug is coated on the outer surface lc of the scaffold graft 100.

[0036] The coating of the graft 3 and/or a layer of drug may be carried out by any available coating methods which may include without limitation, spray coating, dip coating, spin coating, electro-spin coating, rolling, sputtering, vapor deposition, plasma coating. In an embodiment, spray coating is used to form the graft 3 on the outer surface lc of the scaffold 1.

[0037] FIG. 2 illustrates a flowchart depicting steps involved in manufacturing of the scaffold graft 100. The process of manufacturing the scaffold graft 100 commences at step 201.

[0038] At step 201, the fabrication of the scaffold 1 is carried out. In an embodiment, the scaffold 1 is manufactured by laser cutting a nitinol tube to form a predefined pattern. In an embodiment, the scaffold 1 has a strut thickness of 160-200pm.

[0039] At step 203, the graft 3 is formed on the outer surface lc of an expanded scaffold 1. The graft 3 which comprises of a coating solution is coated by any available coating methods like spray coating, dip coating, spin coating, electro-spin coating, rolling, sputtering, vapor deposition, plasma coating and the like. In an embodiment, the method of spray coating is used for the formation of the graft 3 on the outer surface lc of the scaffold 1. The coating parameters include the amount of coating solution, the distance between spray gun and the scaffold 1, the mandrel rotation, the nitrogen gas pressure, the oscillation rate and the coating solution flow rate.

[0040] In an embodiment, the volume of coating solution may vary from 2-25 ml, preferably 07-20 ml, more preferably 12-15 ml. The distance between the spray gun and the scaffold 1 may vary from 2-8 cm, more preferably 04-06 cm to achieve smooth and uniform for coating surface. The rotation of the mandrel may be between 10-50 rotations per minute and more preferably 25-45 rotations per minute. The pressure of inert nitrogen gas may range from 3-12 psi, preferably from 05-10 psi, more preferably from 6-08 psi. The oscillation rate may range from 20-70 oscillations per minute, preferably range from 30-60 oscillations per minute, more preferably from 40-50 oscillations per minute. The flow rate of the coating solution ranges from about 02- 5 ml per minute, preferably from 1-2.5 ml per minute, more preferably from 0.2-0.5 ml per minute.

[0041] The process of coating the scaffold 1 is performed in a clean room environment (class 10000) to avoid the interference of temperature and moisture during the spray coating. The temperature and humidity of clean room is maintained at 22±3°C and 45%, respectively.

[0042] The formation of the graft 3 on the outer surface lc of the scaffold 1 may be achieved by using a cylindrical mandrel having smooth surface or a plain balloon. In an embodiment, the plain balloon is used for the formation of the graft 3 on the outer surface lc of the scaffold 1. The plain balloon is used for the formation of the graft 3 as the surface of the plain balloon is highly smooth and it has deflation characteristic which helps in easy removal of the scaffold graft 100 without damaging the surface of the graft 3.

[0043] During the process of formation of the graft 3, the scaffold 1 is affixed on the plain balloon of appropriate size. The scaffold 1 is affixed by inflating the plain balloon. The affixation process of the scaffold 1 on the plain balloon allows the formation of the graft 3 as the surface of the plain balloon act as a support for the formation of thin film/layers of polymer on the outer surface lc of the scaffold 1.

[0044] The ends of the plain balloon are tapered to form the layers of polymer and drug on the outer surface lc of the scaffold 1. The tapered ends of the plain balloon are covered with a protective sheath to form the polymer and drug coating layer at the specified area of the scaffold 1. The coating process may continue for a period of 30-60 minutes, more preferably from 30-40 minutes.

[0045] In another embodiment, the coating of the graft 3 on the scaffold 1 may be performed in discontinuous manner with coating (on) and resting (off) cycle. The coating cycle may range from 50-110 seconds, more preferably from 70-90 seconds. The resting cycle may range from 05-35 seconds, more preferably from 15-25 seconds. The scaffold graft 100 is kept on resting for about 10-15 minutes before detachment from the balloon. The discontinuous coating method allows the formation thin film, multilayered graft 3 having enhanced strength.

[0046] Detachment of the scaffold 1 immediately after coating may cause damage to the graft 3. The scaffold graft 100 may then be kept for another 10-12 hours under vacuum desiccators to remove the residual solvents.

[0047] The aforementioned parameters are set to form a thin, uniform and smooth transparent coating over the scaffold 1. The thickness of graft 3 may range from 10-90 pm, preferably between 20-70 pm and more preferably between 30-60 pm. [0048] At step 205, the annealing process of the scaffold graft 100 is performed. The scaffold graft

100 is mounted and fixed on the mandrel that has an outer diameter (OD) less than the inner diameter (ID) of the scaffold 1. The mandrel may be made of without limitation, teflon or a similar material. The mandrel with the scaffold graft 100 is then kept in a vacuum oven for a predefined annealing time at a specific temperature. [0049] In an embodiment, the annealing temperature of the scaffold graft 100 ranges between 30-150°C, preferably between 45-135°C, more preferably between 70-110°C under the vacuum of 700 mmHg. The annealing time of the scaffold graft 100 may vary between 6-26 hours, preferably 10-22 hours, and more preferably 14-18 hours. The scaffold graft 100 is allowed to cool-down after annealing till the scaffold graft 100 reaches the ambient temperature before detaching the scaffold graft 100 from the mandrel.

[0050] Annealing of the scaffold graft 100 helps in relieving the internal stresses from the polymeric graft 3 and further enhances the smoothness and transparency of the graft 3. Further, annealing and cooling may be performed in one or more cycles to improve the strength of the graft 3.

[0051] Optionally/additionally, at step 207, the process of coating the drug over the scaffold graft 100 is performed. The coating of drug over the scaffold graft 100 may be performed in a clean room having a predefined drug coating temperature and a predefined humidity.

[0052] In an embodiment, the drug coating temperature is in the range of 19-22°C. The humidity is in the range of 25-50%. The aforementioned parameters are critical to form a uniform and transparent film over the scaffold graft 100.

[0053] The coating of the drug is performed by using a mixture of a blend of sirolimus and poly- DL-lactic acid (PDLLA) polymer (herein referred as the drug formulation). In an embodiment, the ratio of the polymer and the drug agent may range of 20:80 to 80:20, more preferably 50:50. The mixture of sirolimus and poly-DL-lactic acid (PDLLA) polymer is used to achieve controlled release of sirolimus. The scaffold graft 100 coated with anti-proliferative agent is kept in desiccators overnight to evaporate the residual solvent out of the scaffold graft 100.

[0054] The release pattern and tissue residence time of the drug may be configured by additional treatment like plasma coating and solvent vapor annealing. In one embodiment, crystalline form of drug is preferred whereas, in other invention, amorphous form is preferred and in another one combination of amorphous and crystalline drug is preferred. As crystalline drug form has greater residence times in tissue, and may be beneficial when a longer period of drug delivery is desired. In discrepancy where shorter periods of drug delivery are needed, more amorphous form of drug in the coating is achieved. [0055] At step 209, the process of loading and deployment of the scaffold graft 100 is performed. The scaffold graft 100 may be loaded in the tube with or without coating of the drug. The loading parameters of scaffold graft 100 are critical for undamaged loading of the scaffold 1. The loading parameters may include quill speed, strut position, final position, load diameter, hold diameter and final diameter.

[0056] The quill speed, strut position, final position, load diameter, hold diameter and final diameter may range from 0.2-0.8mm/sec, 120-180mm, 200-260mm, 12-18mm, 4.5-6.5mm and 1.50-1.90mm, respectively.

[0057] The scaffold graft 100 coated with/without the drug is loaded in to a delivery catheter which is compatible up to 6F catheter. In an embodiment, the scaffold graft 100 has a reduced profile in the range of 1.6-2.4mm for peripheral application. The scaffold graft 100 is loaded without any strut overlap and damage to the graft 3.

[0058] In an embodiment, the expansion or deployment of the scaffold graft 100 is performed at a temperature of 37°C in distilled water to stimulate the physiological condition. In an embodiment, seam less expansion of the scaffold graft 100 is performed which helps in maintaining the integrity of the graft 3. The loaded scaffold graft 100 is then sterilization using EtO, gamma or e-beam radiation sterilization.

[0059] The present invention will be further understood by reference to the following non-limiting examples.

Table 1: Coating formulations for covered nitinol scaffold formation [0060] Various process parameters of the present invention are listed in tables 2 and 3.

Table 2: Polymer coating parameter

Table 3: Scaffold loading parameters

[0061] The following invention is understood by various examples:

Example 1 (Prior art): 100 mg of PLCL is dissolved in 2ml dichloromethane (DCM) and final volume is made up to 10ml using acetone (Formulation 1-F1). The solution is kept in ultra-sonication bath for 10-15 minutes for homogenization of solution. The coating parameters are as mentioned in table 2. 7ml of coating solution is sprayed on the scaffold 1 to form the graft 3. The graft 3 is formed incompletely over the scaffold 1 and the graft 3 is not uniform. Holes are observed in the graft 3.

[0062] Example 2(Prior art): 100 mg of PLCL is dissolved in 2ml dichloromethane (DCM) and final volume is made up to 10ml using acetone (Formulation 2-F2). The solution is kept in ultra- sonication bath for 10-15 minutes for homogenization of solution. The coating parameters are as mentioned in table 2. 10ml of coating solution is sprayed on the scaffold 1 to form the graft 3. The graft 3 formed over the scaffold 1 is uniform however minor holes are observed when the scaffold graft 100 is inspected under microscope.

[0063] Example 3 (Present Invention): 70 mg of PLCL is dissolved in 10ml dichloromethane (DCM). The solution is kept in ultra-sonication bath for 10-15 minutes for homogenization of solution (Formulation 3-F3). The coating parameters are as mentioned in table 2. 12ml of coating solution is sprayed on the scaffold 1 to form the graft 3. The graft 3 formed over the scaffold 1 is uniform and transparent and no holes were observed in the graft 3.

[0064] Example 4 (Present Invention): 750mg of PLCL is dissolved in 05ml dichloromethane (DCM) and final volume is made up to 10ml using chloroform (Formulation 4-F4). The solution is kept in ultra-sonication bath for 10-15 minutes for homogenization of solution. The coating parameters are as mentioned in table 2. 1.5 ml of coating solution is sprayed on the scaffold 1 to form the graft 3. The graft 3 formed was uniform and no holes were observed. The cover strength of the graft 3 was improved from 40% to 50% than other solvent. However, combination of chloroform and DCM resulted into improved strength of the graft 3 but lead to increase in the thickness (lOOpm to 300pm) of the graft 3. Also, an opaque graft 3 was obtained.

[0065] While embodiments described are suitable for sealing of the peripheral blood vessel perforation. Additionally, the particular embodiments shown and described by reference to figures and examples should not be considered limiting to the invention, and obvious modification and combinations of features.

[0066] The scope of the invention is only limited by the appended patent claims. More generally, those skilled in the art will readily appreciate that all parameters, dimensions, materials, and configurations described herein are meant to be exemplary and that the actual parameters, dimensions, materials, and/or configurations will depend upon the specific application or applications for which the teachings of the present invention is/are used.

Claims

WE CLAIM

1. A scaffold graft comprising: a self-expandable scaffold, the self-expandable scaffold including an inner surface and an outer surface ; and characterized in that a first layer coated on at least the outer surface of the self-expandable scaffold resulting in a scaffold graft , the first layer including at least one polymer dissolved in at least one solvent in the concentration in the range of 0.6%-0.8% (w/v); and wherein the thickness of the first layer ranges from 30 to 60 microns; wherein reduced profile of the scaffold graft ranges from 1.6 mm to 2.4 mm.

2. The scaffold graft as claimed in claim 1 wherein the self-expandable scaffold is made of nitinol.

3. The scaffold graft as claimed in claim 1 wherein the polymer is made of at least one of poly-L-lactide-co-caprolactone (PLCL), polycaprolactone (PCL), poly-dl-lactic acid, (PDLLA), polyglycerol sebacate (PGS), poly L - lactide (PLLA), poly(glycolic acid) (PGA), poly L-lactide co- glycolic acid (PLGA) or a mixture thereof.

4. The scaffold graft as claimed in claim 1 wherein the at least one solvent includes one or more of dichloromethane in the concentration ranging from 20%-100% (v/v), chloroform in the concentration ranging up to 50% (v/v) and acetone in the concentration ranging up to 80% (v/v).

5. The scaffold graft as claimed in claim 1 wherein the at least one solvent includes

dichloromethane and acetone in the ratio ranging from 2:8 to 1:9.

6. The scaffold graft as claimed in claim 1 wherein the at least one solvent includes

dichloromethane and chloroform in the ratio ranging from 5:5 to 7:3.

7. The scaffold graft as claimed in claim 1 wherein the scaffold graft has a radial strength of at least 30N.

8. The scaffold graft as claimed in claim 1 wherein the first layer is coated with a drug formulation of Sirolimus and poly-DL-lactide (PDLLA) in the ratio of 50:50.

9. A method for manufacturing of the scaffold graft , the method comprising: fabricating a self-expandable scaffold, the self-expandable scaffold including an inner surface and an outer surface; coating a first layer on the outer surface of the self-expandable scaffold to form a covered scaffold, the first layer including a biodegradable graft; and annealing the covered scaffold at an annealing temperature and an annealing time to form a scaffold graft having a reduced profile in the range of 1.6 mm to 2.4 mm.

11. The method for manufacturing of the scaffold graft as claimed in claim 9 wherein, the fabricating the self-expandable scaffold includes one of braiding or laser cutting.

10. The method for manufacturing of the scaffold graft as claimed in claim 9 wherein, the coating of the first layer includes coating the self-expandable scaffold via a spray coating technique.

11. The method for manufacturing of the scaffold graft as claimed in claim 9 wherein, the covered scaffold is coated with a drug formulation of Sirolimus and poly-DL-lactide (PDLLA) in the ratio of 50:50.

12. The method for manufacturing of the scaffold graft as claimed in claim 9 wherein, the

annealing temperature is between 45-135°C.

13. The method for manufacturing of the scaffold graft as claimed in claim 9 wherein, the

annealing time is between 14-18 hours.

14. The method for manufacturing of the scaffold graft as claimed in claim 9 wherein, the first layer is made of at least one of poly-L-lactide-co-caprolactone (PLCL), polycaprolactone (PCL), poly-dl-lactic acid (PDLLA), polyglycerol sebacate (PGS), poly L - lactide (PLLA), poly(glycolic acid) (PGA), poly L-lactide co-glycolic acid (PLGA) or a mixture thereof dissolved in at least one solvent.

15. The scaffold graft as claimed in claim 14 wherein the at least one solvent includes one or more of dichloromethane in the concentration ranging from 20%-100% (v/v), chloroform in the concentration ranging up to 50% (v/v) and acetone in the concentration ranging up to 80% (v/v).

16. The scaffold graft as claimed in claim 15 wherein the at least one solvent includes

dichloromethane and acetone in the ratio ranging from 2:8 to 1:9.

17. The scaffold graft as claimed in claim 15 wherein the at least one solvent includes dichloromethane and chloroform in the ratio ranging from 5:5 to 7:3.