Claims:We Claim:

1. A tubular neurovascular flow diverter implant device having microporous structure for use in the treatment of intracranial aneurism, comprising plurality of bioresorbable polymer microfilaments of 20-50 micron diameter braided in one over two pattern with a braiding angle in the range of 30-200 degrees, said microfilaments being subjected to annealing treatment and being coated with bioresorbable elastomeric coating.

2. The flow diverter as claimed in claim 1, wherein said microfilaments are selected from filaments of poly L-lactic acid (PLLA), poly L-lactide-co-glycolide (PLGA) or a combination thereof.

3. The flow diverter as claimed in claim 1 or 2, wherein the diameter of the said microfilaments is in the range of 25-45 micron.

4. The flow diverter as claimed in claim 1, wherein the number of microfilament is in the range of 24-120 and more preferably 32-96 depending on the diameter of the device.

5. The flow diverter as claimed in claim 1, wherein braiding angle is in the range of 120-160 degree and more preferably 130-150 degree.

6. The flow diverter as claimed in any preceding claim, wherein it comprises 12-30 pores/mm2 and more preferably 15-25 pores/mm2.

7. The flow diverter as claimed in any preceding claim, wherein the braiding pattern is open ended, close ended or a combination thereof.

8. The flow diverter as claimed in any preceding claim, wherein the monofilaments are provided with radiopaque marker.

9. The flow diverter as claimed in any preceding claim, wherein platinum tungsten radiopaque wire of 20-50 micron diameter, are braided along with said polymer microfilaments.

10. The flow diverter as claimed in any preceding claim, wherein the bioresorbable elastomer comprises of poly L-lactide-co caprolactone, polycaprolactone and 1, 6 hexa methylene diisocyanate cross linker.

11. The flow diverter as claimed in any preceding claim, wherein bioresorbable elastomer coating thickness is in range of 1 µm to 10 µm and more preferably 2-5 micron.

12. The flow diverter as claimed in any preceding claim, wherein the radial strength of the device in in the range of 20-30 N.

13. The flow diverter as claimed in any preceding claim, wherein bioresorbable implant is coated with anti-thrombogenic, anti-inflammatory or any specific hormonal drug.

14. A method for manufacturing tubular neurovascular flow diverter device having microporous structure for use in the treatment of intracranial aneurism, comprising the steps of
- providing plurality of bioresorbable polymer microfilaments of 20-50 micron diameter;
- braiding the said plurality of microfilaments under controlled braiding parameters, in one over two pattern with a braiding angle of 30-200 degrees and forming a tubular braided scaffold;
- annealing the braided tubular scaffold at a temperature range of 90-130 degrees depending on the glass transition temperature and melting point of the polymer of the microfilaments.
- coating the so braided tubular structures with bioresorbable polymer; and
- curing the so coated tubular structure scaffold.

15. The method as claimed in claim 14, wherein the braiding is carried out in a braiding machine with the following braiding parameters:
Parameter Range
Nominal Ratchet Spring (mm) 0.5±0.1
Nominal Spring Tension (mm) 0.4±0.1
Career Speed (volts/Hz) 12±3
Take-Up Speed (volts/Hz) 20-25
Height (cm) 34±1

16. The method as claimed in claim 14, wherein annealing is carried out in stages and wherein primary annealing is perform between 90°C to 130°C temperature for duration of 8 hours to 24 hours and secondary annealing is done near to melting point i.e. between 90°C and 110°C temperature for duration of 1 hours to 5 hours.

17. The method as claimed in claim 14, wherein the said braided scaffold is heat cured at temperature between 70°C to 140°C for duration of 14 hours to 24 hours.

18. The method as claimed in any preceding claim, wherein pluralities of radiopaque markers are incorporated in the braided scaffold before annealing.

19. The method as claimed in claim 18, wherein the radiopaque markers are in the form of marker attached to the polymer monofilaments or in the form of wire braided along with the monofilaments.

20. The method as claimed in any preceding claim, wherein a coating of anti-thrombogenic, anti-inflammatory or any specific hormonal drug is provided in the braided implant.

21. A tubular neurovascular flow diverter implant device having microporous structure for use in the treatment of intracranial aneurism as claimed in any of clams 1-13, wherein the device is capable of being implanted at the body lumen with help of a catheter.
22. The tubular neurovascular flow diverter implant device having microporous structure for use in the treatment of intracranial aneurism manufactured by the method as claimed in any of claims 14-20.

Dated this 24th day of April, 2019.

(SOUMEN MUKHERJEE)
IN/PA - 214
Applicants’ Agent
for seenergi IPR

, Description:BIORESORBABLE NEUROVASCULAR FLOW DIVERTER AND METHOD OF MANUFACTURE THEREOF

Field of the Invention:
The present invention relates to a bioresorbable neurovascular flow diverter and method of manufacture thereof. More particularly the present invention relates to an implantable self-expanding ultrathin bioresorbable neurovascular device that is intended for the treatment of intracranial aneurysm. Also, this invention is related to a method of manufacturing a braided microporous tube from bioresorbable material for neurovascular implant.
The invention specifically comprises of a bioresorbable flow diverter in the form of microporous polymeric braided mesh. The invention more specifically relates to the method to manufacture a bioresorbable flow diverter with high strength, excellent flexibility and reduced pore size.

Background of the Invention:
Intracranial aneurysms occur in the neurovasculature and typically developed at vessel branch points. Aneurysms of the anterior neurovasculature can include cavernous ICA (Internal Carotid Artery) aneurysms, superior hypophyseal artery aneurysms, ophthalmic artery aneurysms, anterior choroidal aneurysms, posterior communicating artery (PcomA) aneurysms, anterior communicating artery (AcomA) aneurysms, ICA termination aneurysms, anterior cerebral artery (ACA) aneurysms and middle cerebral artery (MCA) aneurysms. Aneurysms of the posterior neurovasculature can include anterior inferior cerebella artery (AICA) aneurysms, posterior inferior cerebella artery (PICA) aneurysms, superior cerebella artery (SCA) aneurysms, posterior cerebral artery (PCA) aneurysms and basilar apex aneurysms. Aneurysms can be treated prior to its un-ruptured state and ruptured state. Size of the aneurysm is a critical parameter for treatment. Rupturing of the aneurysm is mainly related to its size and outcomes showed that small sized aneurysms having size of less than 7 mm have a less risk of rupture and will grow in size slowly.
The prognosis for a ruptured cerebral aneurysm depends on the extent and location of the aneurysm, the person's age, general health and neurological condition. Some individuals with a ruptured cerebral aneurysm die from the initial bleeding. Other individuals with cerebral aneurysm recover with little or no neurological deficit. Generally, about two-third of patients have a poor outcome, death, or permanent disability. The prevalence of intracranial aneurysm is about 1%-5% (10 million to 12 million persons in the United States) and the incidence is 1 per 10,000 persons per year in the United States (approximately 27,000), with 30 to 60 year-olds being the age group most affected. Intracranial aneurysms occur more in women by a ratio of 3 to 2 and are rarely seen in pediatric populations.
Widely used method for prevention of aneurysm rupture is flow diversion. It is an endovascular technique which involves inserting a microcatheter in the femoral artery and its advancement to the aneurysm site where the flow diverter is placed over the aneurysm neck which result in diverting blood flow and shrinkage of aneurysm over a period of time. The method of flow diversion is safe in comparison to other techniques, as it does not involve placement of implant within the aneurysm sac and when placed along with coil, the method avoid the risks associated with coil protudence to the parent artery. Therefore, flow diversion technique reduces rupture of the aneurysm during surgery.
Self-expanding flow diverter is currently generally made up from non-bioresorbable metal filament which includes stainless steel, cobalt-chromium alloy, and superelastic Nitinol. Self-expanding metallic material is the most common due to their high tensile strength. However, the use of metallic self-expanding flow diverter in current treatment has disadvantages like corrosion & toxicity in the body. Implantation of metallic stent may lead to long-term mechanical stress which may cause low-grade injury and persistent inflammation. On the other hand, biodegradable implant may overcome short-term need for a diseased aneurysm region and eliminate the potential long-term complications due to metallic implant. So, to minimize or eliminate the disadvantages associated with metallic flow diverter, implants with fully bioresorbable materials are considered safer and more biocompatible.
However, it is difficult to manufacture such bioresorbable microporous flow diverter with optimum radial stiffness and flexibility. Hence there is a need of providing bioresorbable flow diverter with high strength, excellent flexibility and reduced pore size, which is suitable as an implant in the treatment of intracranial aneurysm.

Objects of the Invention:
It is the primary object of the invention is to provide a bioresorbable neurovascular flow diverter.
It is another object of the invention is to provide a bioresorbable polymer microfilament based braided flow diverter.
It is another object of the invention is to provide a bioresorbable polymer microfilament based braided flow diverter, the radial strength and flexibility whereof is comparable to similar metallic flow diverters.
It is yet another object of the invention is to provide a bioresorbable ultrathin polymer microfilament based braided flow diverter.
It is another object of the invention to provide a bioresorbable polymer microfilament based braided flow diverter, which is radiopaque.
It is a further object of the present invention is to provide a bioresorbable elastomer coated polymer microfilament based braided flow diverter.
It is another object of the invention to provide a bioresorbable polymer microfilament based braided flow diverter coated with specific drugs.
It is a further object of the invention is to provide a method for manufacturing bioresorbable polymer microfilament based braided flow diverter.
How the above objects are fulfilled is described in the detailed description below with the help of the appended drawings.

Summary of the Invention:
Accordingly the present invention provides, a tubular neurovascular flow diverter implant device having microporous structure for use in the treatment of intracranial aneurism, comprising plurality of bioresorbable polymer microfilaments of 20-50 micron diameter braided in one over two pattern with a braiding angle in the range of 30-200 degrees, said microfilaments being subjected to annealing treatment and being coated with bioresorbable elastomeric coating.
Preferably, the microfilaments are selected from filaments of poly L-lactic acid (PLLA), poly L-lactide-co-glycolide (PLGA) or a combination thereof, and wherein the diameter of the said microfilaments is in the range of 25-45 micron. Preferably, the number of microfilament is in the range of 24-120 and more preferably 32-96 depending on the diameter of the device.
Preferably the braiding angle is in the range of 120-160 degree and more preferably 130-150 degree and the braided structure comprises 12-30 pores/mm2 and more preferably 15-25 pores/mm2.
Preferably, the braiding pattern is open ended, close ended or a combination thereof.
In the flow diverter, the monofilaments may be provided with radiopaque mark and also platinum tungsten radiopaque wire of 20-50 micron diameter, may be braided along with said polymer microfilaments.
Preferably said bioresorbable elastomer comprises of poly L-lactide-co caprolactone, polycaprolactone and 1, 6 hexa methylene diisocyanate cross linker and the bioresorbable elastomer coating thickness is in range of 1 µm to 10 µm and more preferably 2-5 micron.
The flow diverter has a radial strength of the device in the range of 20-30 N.
Preferably, the bioresorbable implant is coated with anti-thrombogenic, anti-inflammatory or any specific hormonal drug.
The present invention also provides a method for manufacturing tubular neurovascular flow diverter device having microporous structure for use in the treatment of intracranial aneurism, comprising the steps of
- providing plurality of bioresorbable polymer microfilaments of 20-50 micron diameter;
- braiding the said plurality of microfilaments under controlled braiding parameters, in one over two pattern with a braiding angle of 30-200 degrees and forming a tubular braided scaffold;
- annealing the braided tubular scaffold at a temperature range of 90-130 degrees depending on the glass transition temperature and melting point of the polymer of the microfilaments.
- coating the so braided tubular structures with bioresorbable polymer; and
- curing the so coated tubular structure scaffold.
Preferably, the braiding is carried out in a braiding machine with the following braiding parameters:
Parameter Range
Nominal Ratchet Spring (mm) 0.5±0.1
Nominal Spring Tension (mm) 0.4±0.1
Career Speed (volts/Hz) 12±3
Take-Up Speed (volts/Hz) 20-25
Height (cm) 34±1

Preferably, the primary annealing is perform between 90°C to 130°C temperature for duration of 8 hours to 24 hours and secondary annealing is done near to melting point i.e. between 90°C and 110°C temperature for duration of 1 hours to 5 hours and also the said braided scaffold is heat cured at temperature between 70°C to 140°C for duration of 14 hours to 24 hours.

Preferably, plurality of radiopaque markers are incorporated in the braided scaffold before annealing, wherein the radiopaque markers are in the form of marker attached to the polymer monofilaments or in the form of wire braided along with the monofilaments.

Brief Description of the Accompanying Drawings:
Figure 1 shows the bioresorbable neurovascular flow diverter of the present invention.
Figures 2a-2d show the different braiding angles of the bioresorbable neurovascular flow diverter of the present invention.
Figures 3a-3c show the open ended braided tubular scaffold of the bioresorbable neurovascular flow diverter of the present invention.
Figure 4 shows an one side open ended and one side close ended braided tubular scaffold of the bioresorbable neurovascular flow diverter of the present invention.
Figure 5 shows a both side close ended braided tubular scaffold of the bioresorbable neurovascular flow diverter of the present invention.
Figures 6a-6b show the braiding pattern after elastomeric coating of the braided tubular scaffold of the bioresorbable neurovascular flow diverter of the present invention.
Figure 7a-7b show the marker design and position over flow diverter.
Figure 8 shows bioresorbable neurovascular flow diverter of the present invention containing two braided radiopaque wires.
Figure 9 shows a coated flow diverter implant device of the present invention.
Figure 10 are bar graphs showing polymer properties of the bioresorbable neurovascular flow diverter of the present invention.
Figure 11 are bar graphs showing the various degradation pattern of the bioresorbable neurovascular flow diverter of the present invention.

Detailed Description of the Invention:
Present invention relates to the field of micro porous bioresorbable braided device made-up of one or more types of plurality of biresorbable polymer filaments. In one embodiment the braided tube can also be fabricated from combination of bioresorbable and non-bioresorbable filaments. In a preferred embodiment, poly (L-lactic acid) (PLLA) and/or poly (L-lactide-co-glycolide) (PLGA) monofilament is/are used to create braided cylindrical structure in combination with platinum radiopaque markers.
Present invention is aimed at achieving micro porous bioresorbable braided tube having open or closed ends with closed angle, high strength and with more flexibility and reduced pore size. The braiding process is done by using ultrathin oriented PLGA or PLLA monofilaments having uniform diameter in the range from 10 micron to 100 micron, more preferably 30 micron to 60 micron which is extruded from PLGA or PLLA granules. The extruded monofilament is annealed to enhance its mechanical properties of monofilament which can withstand high tension braiding which ensures stronger crossing points after braiding process. Braided structure is stabilized by heat treatment under vacuum conditions to form tubular implant.
Further, the implant is coated with bioresorbable elastomer to gain self-expanding properties of the device. In one aspects of invention, bioresorbable elastomer is combination of PLC, PCL and cross-linker. In another aspect of the invention, elastomer coated flow diverter device is additionally coated with anti-thrombogenic, anti-inflammatory or any specific hormonal drug. Anti-thrombogenic coating helps in prevention of thrombus in blood vessel and hormonal coating enhances wound healing of blood vessel, prevents blood vessel occlusion at treatment site and helps in vessel reconstruction.
The present invention discloses self-expanding micro-porous bioresorbable braided implant from shape memory bioresorbable PLGA or PLLA material for the treatment of intracranial aneurysm by redirects and reroutes the arterial blood flow and create gate-way which avoids blood to enter inside an aneurysm sac. Flow diverter implant having a diameter in the range of 2mm to 5mm and length in the range of 10mm to 40mm. The device can be fabricated from several shape memory polymers such as poly-L-lactide-co-caprolactone (PLC), 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. Particularly, polymer blends from poly (L-lactide-co-caprolactone) (PLC) and poly (L-lactide-co-glycolide) (PLGA) show good performance of shape fixity and recovery at physiological body temperature i.e. 37°C and found to be most suitable material for self-expanding stent/ scaffold.
In the present invention, the flow diverter implant has greater braiding angle leading to smaller pore size and greater pore density which in turn results in high scaffold coverage area at the aneurysm neck side, which enhances endothelial layer formation across the aneurysm neck. The microporous braided implant contains small pores of bioresorbable material with specific braiding construction results in sufficient radial strength, foreshortening and other self-expanding stent property as compared to conventional products.
In one embodiment, the bioresorbable flow diverter comprises a PLLA monofilament extruded from the PLLA granules. The initial molecular weight (Mw) of poly-l-lactide resin raw material ranges from 500000-600000 g/mol, Mn (number average molecular weight) of resin ranges from 300000 g/mol to 400000 g/mol and PDI (polydispersity index) to resin is in the range of 1.4-2.0. These PLLA granules will convert into a monofilament with diameter of 20-50µm having higher peak load in between 0.160 lbf -0.190 lbf, peak stress in between 80000 psi-99000 psi, elongation in between 35%-45%, modulus in between 700 ksi-900 ksi, elongation at break in between 2 inch- 3 inch, break load in between 0.150 lbf-0.190 lbf. The PLLA monofilament molecular weight (Mw) ranges from 200000 gm/mole – 400000 gm/mole, Mn (number average molecular weight) range from 50000 gm/mole – 200000 gm/mole and PDI (polydispersity index) in range of 2.0 – 3.0.

In one embodiment, to maintain outer profile of implant and to make implant delivery via microcatheter, monofilament diameter should be less than 100 micron. In a preferred embodiment, monofilaments are circular and having diameter of 20-50 micron; more preferably monofilaments have a diameter of 25-45 micron.
The extruded PLLA monofilament is annealed between 100°C and 130°C temperature for duration of 30 minutes to 4 hours to enhance the monofilament strength. The PLLA monofilament contain specific mechanical properties i.e. tensile strength, % elongation, etc. which is given below in Table 1.
Table-1: Tensile Properties of PLLA Monofilament
Characteristics Values
Tensile Strength (psi) 4-8
Elongation at Break (%) 10-15
Maximum Load (N) 0.2-1.0

In another embodiment, PLGA granules comprises of 85% mol L-Lactide and 15% mol Glycolide with IV (inherent viscosity) ranges of 1.80dl/g to 2.5dl/g and melting point ranges from 126°C to 145°C temperature and glass transition temperature ranges from 40°C to 45°C. The PLGA oriented monofilaments are extruded which has a tensile strength values 8-10 fold higher than the strength of non-oriented polymer monofilament. The extruded PLGA monofilament is annealed between 100°C and 130°C temperature for duration of 30 minutes to 1 hour to enhance the monofilament strength. The annealed PLGA monofilament can withstand high yarn tension braiding which enhance the strength of braided configuration. Mechanical properties include break load, elongation and modulus to determine properties of monofilament which in turn provide desired characteristic of braided scaffold. The break load of PLGA monofilament with diameter between 20 µm and 50 µm ranges from 0.070 lbf to 0.090 lbf, elongation ranges from 10 % to 20 %.
The extruded monofilament is annealed to enhance its mechanical properties of monofilament which can withstand high tension braiding which ensure stronger crossing points after braiding process. In one aspect of invention, braided structure is mainly fabricated from shape memory polymers and glass transition temperature selection of polymer is of great importance for self-expansion properties. Braiding angles can be optimized that leads to formation of braided mesh with reduced pore size which enhance implant radial stiffness and device integrity.

Braiding Process
Figure 1 shows a tubular microporous bioresorbable braided tube of the present invention, the braiding whereof is carried out in a circular braiding machine. The braiding of thin monofilaments to form tubular shape requires special spindle designing for the braiding machine. Here, the spindle is designed to roll monofilament in such a way that it reduces extra pressure on monofilament and avoid breakage of material during braiding process. The microporous bioresorbable braided tube of the present invention is braided on specific stainless steel Teflon coated mandrel which holds the braid structure during braiding process.
In preferred embodiment, to achieve microporous structure of implant 24 to 120 monofilaments are used to create tubular bioresorbable braided implant for the treatment of intracranial aneurysm, this number is selected on the basis of the porosity and implant location i.e. aneurysm neck, aneurysm size. More specifically 32 to 96 monofilaments are used to create the microporous braided tube form circular braiding.
In the present embodiment, to braid ultra-thin bioresorbable monofilament special braiding carrier has been designed. This modified braiding carrier contains specific roller to pull the bioresorbable filaments while machine is operating. This modified braiding carrier contains specific ratchet spring and carrier spring.
For example in order to braid 20-50 micron monofilaments, braided carrier needs ratchet spring and carrier spring of 0.2-0.6 mm. The spring tensions depend on the basis of selection of polymer material and its mechanical properties like tensile strength of the filaments. In preferred embodiment, in order to run ultrathin bioresorbable filament, the braiding carrier needs low tension spring which will reduce extra pressure during the braiding.
In a preferred embodiment, microporous braided bioresorbable implant is manufactured using 20-50 micron monofilaments by 32-96 carriers braiding machine and braided at specific braiding parameters given below.
Parameter Range
Nominal Ratchet Spring (mm) 0.5±0.1
Nominal Spring Tension (mm) 0.4±0.1
Career Speed (volts/Hz) 12±3
Take-Up Speed (volts/Hz) 20-25
Height (cm) 34±1

In an embodiment, a first monofilament is overlapped to two adjacent monofilaments and make quadrangle/rhombus shape which give specific braiding angles ranging from 30°-200°. Many filaments are formed over a mandrel to create a hollow lumen with a specific cross-sectional shape and size; this cross sectional shape having braiding angles in range of 30°-200° which gives microporous structure of hollow braided lumen. As illustrated in Figures 2a-2d, the angle can be directly measured, as it is the angle between two intersecting filaments in the braided structure. The axial density of the braid can be changed by altering the braid angle, further it enhances strength and flexibility by changing braided configuration. In the present embodiments, angle is defined in range of 30°-200°. In preferred embodiment, braiding angle generated ranges from 120°-160°, more preferably from 130°-150°. The braiding angle of the flow diverter braided mesh directly affects its pore size and ultimately radial stiffness, which is an important parameter affecting the flow diverter’s ability to maintain its integrity and structure after placement into the body lumen. In present embodiments, pores generated due to braiding pattern are in the ranges of 12-30 pores/mm2 and more preferably from 15-25 pores/mm2.
It is found that subsequent increase in the braiding angle with increased diameter of braided mesh tube leads to increase in the radial stiffness and integrity of the implant along with the mechanical properties. As the diameter of the flow diverter increases, the quadrangular cells in the braided mesh structure dilates and it leads to decrease in the braiding angles of the flow diverter. The braiding angle of the flow diverter is inversely proportional to the pore size i.e. as the braiding angles of the flow diverter decreases, the pore size of the quadragular cell increases which in turn, reduces the radial stiffness, integrity and mechanical properties of flow diverter. As the braiding angle of the flow diverter braided mesh increased with the increasing braided tube diameter, the quadrangular cells are compressed leading to decrease in the pore size of the cells, resulting into improvement in the radial stiffness and integrity of the braided mesh.
In an embodiment, braided ultrathin bioresorbable filament has free ends at both the sides as shown in Figure 3a-3c.
In another embodiment, the braided configuration has close cell design at one side and open end at other sides as shown in Figure 4. The braiding pattern facilitates better expansion and provides strength at distal portion which helps to make easy delivery of the device from microcatheter lumen.
In another embodiment, the braiding configuration has closed braiding as illustrated in Figure 5; which reduces the chance of puncture during implantation. Closed end braiding also facilitates improving the radial properties and reducing implant foreshortening. The closed ends further prevent migration of flow diverter from the site of implantation.

Annealing Process
In the present invention, polymer braided tube is secured at its both end on mandrel and subjected to annealing process to stabilize the braided structures. The annealing temperature is selected based on the bioresorbable polymer properties mainly glass transition temperature and the melting temperature.
In one embodiment, braided mandrels are kept under vacuum oven in a controlled condition of 500-800 mmHg pressure. The annealing process is preferably conducted at specific temperature e.g. 90°C to 130°C for specific time e.g. 14 to 20 hrs. Temperature and time of annealing process is selected as per polymer material.
In one embodiment braid structure is annealed at multiple stages i.e. initial annealing treatment and terminal annealing treatment. Initial annealing treatment ranges from 90°C to 130°C for duration of 8 hours to 24 hours and terminal annealing treatment ranges from 90°C to 120°C for duration of 1 hour to 5 hours. This is more near to melting temperature of polymer material. The initial annealing treatment helps to release internal stress in braided monofilament and removal of monomer. The terminal annealing treatment helps to partially join braided cross wires which enhance the mechanical strength of braided configuration and also helps to get proper braiding angles after device deployment in arterial lumen.
For example, in the present invention bioresorbable monofilaments after braiding on Teflon coated mandrel are subjected to annealing in vacuum oven at two stapes, initial annealing is carried on 90°C to 130°C temperature for 12 to 20 hrs; more preferably 110°C to 120°C temperature for 14 to 18 hrs; more specifically 115 °C temperature for 16 hrs and terminal annealing is carried on 90°C to 110°C temperature for 1 to 05 hrs; more preferably 95°C to 105°C temperature for 2 to 4 hrs; more specifically 100 °C temperature for 3 hrs. Braided tube surface shows uniform braiding pattern after annealing treatment as shown in Figures 6a-6b.
Marker Attachment
In an embodiment of the present invention, microporous braided implant may be provided with radiopaque markers or radiopacity so that the implant is visible under fluoroscopy during invasive procedure. In one embodiment, radiopaque markers may be designed in the form of tube, coil, sheet or any other design. The radiopaque marker made up from biocompatible material such as platinum, Iridium, tantalum, gold or their combination. In preferred embodiment, tube marker made up from platinum tungsten material, is attached on the ultrathin braided structure. Preferably, the marker has internal diameter of 35-45 micron and wall thickness is 2-5 micron. In an embodiment the markers are secured in eight locations at each end of the tube to provide maximum radiopacity. This is shown in Figure-7b. Each marker preferably has length of 0.1-0.2 mm or as per the braided structure depicted in Figure 7a.
Also in another embodiment, one or more radiopaque monofilament may be braided with bioresorbable monofilaments to provide radiopacity to the implant as illustrated in Figure 8. Radiopaque monofilament along with the radiopacity provides extra radial strength to the implant. In preferred embodiment, two 20-50 micron platinum tungsten monofilaments are used along with the other forty six bioresorbable monofilaments.

Coating on Flow Diverter
After annealing and optional marker attachment, the braided scaffold is subjected to a polymer coating. Such polymer coating is a biresorbable elastomer formulation. In the present invention, a single polymer or two polymers or blends of polymers or cross-linkers are used to form a bioresorbable elastomer coating on braided scaffold. The polymers which can be used for bioresorbable elastomer includes but not limited to poly-L-lactide-co-caprolactone (PLC), polycaprolactone (PCL), poly-dl-lactic acid (PDLLA), polyglycerol sebacate (PGS), Poly L - lactide (PLLA), Poly(glycolic acid) (PGA), Polydioxane (PDO), Poly L-lactide co-glycolic acid (PLGA) or a mixture thereof. Cross-linkers like polyurethanes derived from diisocynates includes butane diisocyanate (BDI), hexamethylene diisocyanate (HDI), Isophorone diisocyanate (IPD), Lysine diisocyanate (LDI) and the like. The use of cross-linker enhances the mechanical strength and elasticity of the braided structure.
In an embodiment, a combination of PLC (70:30 ratio), PCL and a hexamethylene diisocyanate cross linker is used to formulate elastomer coating formulation. PLC polymer has a molecular weight of between 1,47,000 dl/g and 2,61,000 dl/g with I.V. ranging from 1.2 to 1.8 dl/g and glass transition temperature is between 18°C to 25°C. PCL polymer has molecular weight between 1,15,000 g/mol and 2,44,660 g/mol with I.V. ranging from 1.0 dl/g to 1.3 dl/g and glass transition temperature is between -58°C to -60°C. The solvent is a mixture of methylene chloride and acetone in a ratio of 1:19. The concentration of elastomer polymer in coating formulation is approximately between 0.4 % to 1.0 % to achieve high radial strength, high regaining ability or self-expansion properties.
In another embodiment, PLCL and a hexamethylene diisocyanate cross linker is used to formulate elastomer coating formulation. PLCL is a co-polymer of L-lactide and ?-caprolactone available with co-polymer molar ratio ranging from 90:10 to 60:40 and an inherent viscosity range of 0.2 to 2.0 dl/g. More preferably in this embodiment 50:50 ratio was selected for making elastomeric coating solution. Due to the vastly different properties of PLA and PCL, careful selection of the copolymer ratios allows for tailored material properties such as high degree of elasticity.
In this present embodiment, the marker attached flow diverter is coated with bioresorbable elastomeric coating formulation which enhances flexibility and self-expand properties of the implant as shown in Figure 9. Coating process is performed using spray coating technique, in which nitrogen air pressure use to get uniform, smooth coating surface and desired thickness after coating. However, other known coating processes may also be used. Elastomer coating thickness preferably ranges from 1 µm to 10 µm and more preferably between 2 µm to 5 µm to obtain high elasticity and self expansion properties. The elastomer coating parameters depends on accurately holding of flow diverter through collets, distance between spray gun and braided flow diverter, rotation of flow diverter, nitrogen gas pressure and solution flow rate. The distance between braided flow diverter is kept between 2 cm to 4 cm from the spray gun and flow diverter rotation ranges from 20 rpm to 30 rpm. This parameter helps in achieving smooth and uniform coating.
The elastomer coated braided flow diverter need to go through curing treatment to achieve desired elastic properties and imparts high strength to braided implant. In present embodiment, braided structure is preferably subjected to two treatment cycles. First elastomeric coating braided flow diverter is packed in vacuum desiccators for 8-20 hrs at room temperature. After that, braided flow diverter is thermally cured between 70°C-140°C temperature i.e. above glass transition temperature and below melting temperature of polymer. Thermal treatment was given for 8-20 hrs period time. Higher the temperature, shorter the treatment period and whole process is conducted in vacuum oven. Further, thermally treated braided structure is cooled to either ambient temperature or below ambient temperature i.e. 10°C to 25°C to stabilize the braid structure. The number of cycles helps to stabilized braid structure, remove residual stress, and enhance elasticity and mechanical strength of braid structure and avoid deformation of the strands during loading and deployment process.
For example, in one embodiment flow diverter is secured between collate and mandrel as implant is very soft and cannot withstand nitrogen air pressure to allow the proper rotation of the flow diverter. The elastomer coating solution flow rate is maintained between 0.15 to 0.30 ml/min and pressurized nitrogen or other inert gas is keep between 2 kg/cm2 to 4 kg/cm2 which helps in good adhesion and immediate drying on elastomeric coating formulation on braided scaffold. Elastomer coated scaffold, as shown in Figure 9 is kept in vacuum chamber under vacuum for 24 hours for drying to evaporate solvent from the coated scaffold and to remove residual solvent from scaffold. Further implants are cured/ heat cured at 70 °C to 140°C for 14 hrs to 24 hrs in vacuum oven, more preferably 110 °C temperature for 16 hrs in vacuum oven.
The elastomeric coating on flow diverter provides more flexibility and elasticity to the braided structure as compared to the uncoated braided structure. Also, braided structure radial stiffness increases compared to the non-elastomeric coating braided tube. The radial strength of non-elastomeric coated braided tube was in between 05 N to 20 N which increases above 20 N to 30 N when the braided tube was elastomeric coated.

Analytical properties of Braided Tube
In a preferred embodiment, PLLA material has been studied for the specific polymer property. Accompanying Figure 10 shows the different polymer property patterns of bioresorbable flow diverter initially after braiding, after annealing, after elastomeric coating and after sterilization process. It is evident from the graphical representations that the properties of polymer viz. molecular weight, number of molecular weight, polydispersity index (PDI), glass transition temperature, melting temperature and % crystallinity do not change when polymer is subjected to different process parameters i.e. temperature and time.

Degradation Pattern of Braided Tube
In the present invention, polymer can be selected based on the specific properties of the material which provide sufficient degradation of the implant material. The preferred embodiment, PLLA material is selected to braid the flow diverter implant which is reabsorb within 24-36 months in-vitro. The degradation of polymer has been studied at accelerated condition i.e. 70°C. The flow diverter starts to degrade after 5 weeks of interval. The flow diverter has been observed visually to analyze its structural integrity. It is observed that the flow diverter maintains its structural integrity for a period of 3-4 weeks and eventually loses its braided configuration and strength at 5 weeks interval. Figure 11 shows the degradation pattern of bioresorbable flow diverter initially, at 4 weeks and at 5 weeks. It is evident from the graphical representations that the properties of polymer viz. glass transition temperature, melting temperature and % crystallinity gradually decrease with time when flow diverter is subjected to accelerated degradation.
The present invention has been described with some preferred embodiments which is not in anyway limiting. Various modifications and variations are possible without departing from the scope of the invention as described above and as defined in the appended claims.