Claims:We claim,

1. A craniotomy plug implant having a plurality of porous horizontal layers of lay down filaments sequentially adhered to the adjacent layer to form a layered scaffolding structure with an interconnected porous network, longitudinally extending from a proximal end having a lesser surface area to a distal end having a greater surface area, said proximal end having a lesser lay down filament width than that of the distal end and the said porous network has at least two different pore size and/or shape.

2. The implant as claimed in claim 1, wherein the porosity of the scaffolding is in the range of 30%-80% and more preferably 60%-70%.

3. The craniotomy plug implant as claimed in claim 1, wherein the said surface area increases from the proximal to the distal end in a staged or continuous manner.

4. The implant as claimed in any of claims 1-3, wherein the shape of the implant is conical, truncated-conical, a pentahedron, a truncated-pentahedron or a button mushroom shape.

5. The implant as claimed in claim 1, wherein the proximal end of the implant is adapted to be inserted in the burr hole of the skull.

6. The implant as claimed in claim 1, wherein the distal end of the implant is adapted to act as a cap.

7. The implant as claimed in claim 1, wherein shape of the pores are square, triangular, polygonal or a combination thereof.

8. The implant as claimed in any preceding claims, wherein the larger pore size is in the range of 1400µm to 1800µm and smaller pore size is in the range of 450µm to 650µm.

9. The implant as claimed in any preceding claim, wherein the lay down filament width range from 0.2.mm to 0.41 mm.

10. The implant as claimed in claim 9, wherein the lay down filament width of the distal end is 0.39-0.41mm.

11. The implant as claimed in claim 9, wherein the lay down filament width of the proximal end is 0.2 mm.

12. The implant as claimed in any preceding claim, wherein the shape of the pores is determined through lay down filament patterns.

13. The implant as claimed in claim 12, wherein 0°/90°/180°/270° lay-down pattern is used to form square pores while 0°/60°/120° and 0°/72°/144°/36°/108° is used to for a combination of triangular and polygonal pores.

14. The implant as claimed in claim 12, wherein of 0°/90°/180°/270° is used for different size of pores.

15. A method for craniotomy implant made of polycaprolactone (PCL) having different layers by 3D printing, comprising
- providing a CAD model suitable for 3D printing of an implant scaffolding with required design of interconnected highly porous network of filaments;
- converting the CAD model into machine readable format for 3D printing;
- providing polycaprolactone filament of suitable filament diameter;
- 3D printing the implant at extrusion temperature of 75 degree centigrade, extrusion multiplier of 115%, printing speed at 4mm/sec and bed temperature of 30 degree centigrade; and
- optionally curing the 3D printed implant for pertaining additional strength to the implant.

16. The method as claimed in claim 15, wherein the curing is carried out at a temperature range of 5-70°C, preferably at 20-57°C and a curing time range of 5 minutes to 5 hours preferably between 30 minutes to 3 hours.

17. The method as claimed in claim 15, wherein the design parameters are set for fabricating different layers of the printed plug having different lay down filament width for better flexibility.

18. The method as claimed in claim 15, wherein the design parameters are set for fabricating the interconnected porous network having plurality of pore sizes for better cell penetration, cell proliferation, and nutrient and oxygen exchange.

19. The method as claimed in claim 18, wherein the larger pore size is in the range of 1400µm to 1800µm and smaller pore size is in the range of 450µm to 650µm.

20. The method as claimed in claim 15, wherein the lay down filament width is 0.2 mm to 0.41 mm.

21. The method as claimed in claim 15, wherein the lay down filament width is 0.39 mm to 0.41 mm.

22. The method as claimed in any preceding claim, wherein the process further comprising coating the plug with suitable therapeutic agent for prevention of post craniotomy consequences such as infection or inflammation.

23. The method as claimed in claim 21, wherein therapeutic coating is carried out by spray coating, dip coating, roll to roll coating, vapor deposition or electrospinning.

24. The method as claimed in any of claims 14-22, wherein built platform of the 3D machine is heated to 30°C causing the plug implant to stick firmly to the bed.

25. The method as claimed in any of claims 15-24, wherein the polycaprolactone (PCL) filament is heated at 75°C temperature to converting it into a printable form.

26. The method as claimed in any preceding claim, wherein the 3D printing technique is Fused Deposition Modelling technique.

27. The implant as claimed in any preceding claim, wherein it is coated with suitable therapeutic agent for prevention of post craniotomy consequences such as infection or inflammation.

28. The implant as claimed in claim 26, wherein the therapeutic agent is selected from the group of anti-bacterial agents, analgesic agents, steroidal or non-steroidal anti-inflammatory agents, opioids, anti-proliferative agents, anti-cholinergics, antifungal agents, anti-parasitic agents, antiviral agents, blood thinner and anti-clotting agents.

Dated this 1st day of August 2019.

, Description:BIORESORBABLE CRANIOTOMY PLUG IMPLANT AND METHOD OF MANUFACTURING THEREOF

Field of Invention:

The present invention relates to a bioresorbable craniotomy plug implant and method of manufacturing thereof. Particularly, this invention is related to a bioresorbable craniotomy plug with different pore sizes and lay down filament width for covering trephination burr holes in neurosurgery and which can be coated with therapeutic agent for preventing infection or inflammation. The invention is further related to additive manufacturing particularly 3D printing of bioresorbable implant using bioresorbable polymer poly- caprolactone (PCL) by means of Fused Deposition Modeling technology (FDM).

Background of the Invention:

The sudden blow on the head due to head injury tears blood vessels that run along the surface of the brain. This is referred as an acute subdural hematoma. In a subdural hematoma, blood gets collected between the layers of tissue of brain. Due to accumulation of blood, pressure on the brain increases. Therefore, burr hole is made to relieve pressure on the brain when blood builds up and starts to compress brain tissue. Burr hole is nothing but the surgically placed hole in the skull also known as cranium. Burr hole is commonly utilized in neurosurgery. After the surgery, this burr hole is covered using various types of bone grafts which include allograft, xenograft and autograft.

A wide variety of bone grafts and bone substitute materials are used in neurosurgery. Burr holes often result in small but undesirable skin depressions. Bone grafts or substitute materials are used to fill those defects. Titanium is extensively used in neurosurgery due to its excellent biocompatibility, high mechanical strength and easy handling. Silastic and alumina ceramic are also used to fabricate various implants to reconstruct burr holes and to prevent postoperative indentations in the skin. Ceramic implants based on hydroxyapatite are increasingly used because of their mechanical property, osteoinductive property and integrative characteristics.

Apart from xenografts, autologous bone is also used for osseous reconstruction because of its superior biocompatibility and osteoinductivity. This technique represents an inexpensive and straight forward approach but the primary incision needs to be extended to harvest the graft from the surrounding bone. In addition, the use of patient’s own bone is associated with donor-site morbidity and graft resorption. Implantation of allograft, autograft, metal and ceramics has their own disadvantages and complications. For instance, these implants are widely accepted but they cannot be degraded or reabsorbed by the host tissue. Thereby, they cannot be used as the potential replacement of host tissue. Clinically, foreign body reactions are also observed with these implants such as surgical site infection (SSI), bone flap resorption (BFR) and long-term problems like minimal potential for new bone growth and poor remodeling of reconstructed area.

Synthetic materials implanted in the body as temporary or permanent structures do not allow growing natural tissue and remodeling of treatment site through own body cells. On the other hand, polymer material based scaffold or implant act as a template that allows the body's own cells to grow and form new tissues while the scaffold gets gradually absorbed.

Bioresorbable craniotomy implant such as plug made up of polycaprolactone is (PCL) getting attention due to excellent biocompatibility, mechanical strength and osteoinductivty. Additionally, such implants are suitable for tissue bone regeneration, bone restoration and easy to use which does not require any type of attachment to the bone. PCL expanded when in contact with hydrophilic solution, hydrophilic liquid and/or cerebrospinal fluid.

However, there is a need of manufacturing implants which are biocompatible and bioresorbable with controllable degradation and resorption rates to substantially match tissue replacement. The implant should have a tailored surface chemistry for cell attachment, proliferation and differentiation and promotes vascular integration. The implant should have suitable mechanical properties to match those of the tissues at the site of implantation.
Objects of the Invention:

It is the primary object of the invention to provide a bioresorbable craniotomy plug implant which is flexible and can be press fitted in the burr hole after neurosurgery.

It is another object of the invention is to provide a bioresorbable craniotomy plug implant which has a greater lay down filament width at the distal end side of the plug than the proximal end side.

It is another object of the invention is to provide a bioresorbable craniotomy plug implant having a filament scaffolding with at least two pore shape and/or size.

It is a further object of the present invention to provide a bioresorbable craniotomy plug implant coted with therapeutic agents.

It is yet another object of the invention to provide a process for 3D printing of the bioresorbable craniotomy plug implant of the present invention.

It is yet another object of the invention to provide the optimum required parameters for 3D printing process of the bioresorbable craniotomy plug implant of the present invention.

The above and the other objects of the invention would be clear from the description herein below.

Summary of the Invention:

Accordingly the present invention provides a craniotomy plug implant having a plurality of porous horizontal layers of lay down filaments sequentially adhered to the adjacent layer to form a layered scaffolding structure with an interconnected porous network, longitudinally extending from a proximal end having a lesser surface area to a distal end having a greater surface area, said proximal end having a lesser lay down filament width than that of the distal end and the said porous network has at least two different pore size and/or shape. The surface area of the implant increases from the proximal to the distal end in a staged or continuous manner.

The shape of the implant may be conical, truncated-conical, a pentahedron, a truncated-pentahedron or a button mushroom shape, wherein the proximal end of the implant is adapted to be inserted in the burr hole of the skull and the distal end of the implant is adapted to act as a cap.

Preferably the shape of the pores are square, triangular, polygonal or a combination thereof.

The larger pore size of the implant is in the range of 1400µm to 1800µm and smaller pore size is in the range of 450µm to 650µm.

The lay down filament width ranges from 0.2.mm to 0.41 mm.

Preferably, the lay down filament width of the distal end is 0.39-0.41mm and the lay down filament width of the proximal end is 0.2 mm.

The shape of the pores is determined through lay down filament patterns such as 0°/90°/180°/270° lay-down pattern is used to form square pores while 0°/60°/120° and 0°/72°/144°/36°/108° is used to for a combination of triangular and polygonal pores.

The invention also provides a method for craniotomy implant made of polycaprolactone (PCL) having different layers by 3D printing, comprising providing a CAD model suitable for 3D printing of an implant scaffolding with required design of interconnected highly porous network of filaments, converting the CAD model into machine readable format for 3D printing, providing polycaprolactone filament of suitable filament diameter;3D printing the implant at extrusion temperature of 75 degree centigrade, extrusion multiplier of 115%, printing speed at 4mm/sec and bed temperature of 30 degree centigrade, and optionally curing the 3D printed implant for pertaining additional strength to the implant.

Preferably, the curing is carried out at a temperature range of 5-70°C, preferably at 20-57°C and a curing time range of 5 minutes to 5 hours preferably between 30 minutes to 3 hours.
The design parameters are set for fabricating different layers of the printed plug having different lay down filament width for better flexibility, such the design parameters are set for fabricating the interconnected porous network having plurality of pore sizes for better cell penetration, cell proliferation, and nutrient and oxygen exchange.

The method as claimed in any preceding claim, wherein the process further comprising coating plug with suitable therapeutic agent for prevention of post craniotomy consequences such as infection or inflammation.

Preferably, the therapeutic coating is carried out by spray coating, dip coating, roll to roll coating, vapor deposition or electrospinning.

Preferably, the built platform of the 3D machine is heated to 30°C causing the plug implant to stick firmly to the bed the polycaprolactone (PCL) filament is heated at 75°C temperature to converting it into a printable form.

The 3D printing technique is Fused Deposition Modelling technique.

Preferably, the therapeutic agent is selected from the group of anti-bacterial agents, analgesic agents, steroidal or non-steroidal anti-inflammatory agents, opioids, anti-proliferative agents, anti-cholinergics, antifungal agents, anti-parasitic agents, antiviral agents, blood thinner and anti-clotting agents.

Brief Description of the Drawings:

Figure 1a is a schematic representation of porous design of the implant according to one embodiment, when seen from the bottom.

Figure 1b is a schematic representation of porous design of the implant according to another embodiment, when seen from the bottom.

Figure 1c is a perspective schematic representation of porous design of the implant of the present invention.

Figure 1d is a side view of schematic representation of porous design of the implant of figure 1c the present invention.
Figure 2 is a schematic representation of implant design with different layout pattern of the lay down filaments for producing different pore shape and size.

Figure 3 shows an exemplary implant of the present invention with two pore sizes.

Figure 4 shows slanted or press-fit design of implant.

Figure 5 is a schematic representation of 3D printing process.

Detailed Description of the Invention:

Bioresorbable implant made up of polycaprolactone has excellent biocompatibility, mechanical strength and osteoinductivty. Therefore polycaprolactone is a suitable material for manufacturing the plug implant of the present invention. It reabsorbed by host tissue and allowing new host tissue generation due to porous structure of implant. Further, such implants degrade slowly over a period of 18 to 22 months allowing cells to attach, proliferate and deposit mineralized matrix.

The craniotomy implant of the present invention is made of polycaprolactone (PCL) having a layered scaffolding with an interconnected highly porous network of filaments.

The implant has a plurality of porous horizontal layers of lay down filaments sequentially adhered to the adjacent layer to form a layered scaffolding structure with an interconnected porous network. The implant longitudinally extends from a proximal end to a distal end. The proximal end surface has a lesser surface area in comparison to that at the distal end. The proximal end of the implant has a lesser lay down filament width than that of the distal end. Further the porous network of the implant has at least two different pore sizes and/or shape.

The surface area from the proximal to the distal end may increase gradually or in staged manner.

Shape of implant of the present invention includes but not limited to button mushroom shape, cone, truncated-cone, a pentahedron and /or a truncated-pentahedron.

The implant may have single filament width or has two or more than two different filamentous size in implant. In the present invention, the width of filament is either same throughout the implant or may have 2 to 3 different width of filament in various layers. The varying filament width provides extra flexibility which allows use of single size implant to cover minor deviated sized hole. Thereby, allowing doctor to perform surgery procedure using small or minimum required hole instead of hole as per the available implant size.

The lay down filament width varies in the range of 0.2- 0.41mm.

Porosity of any structure depends on the solid part either in form of filament, rod or any other and its dimension (length, width, etc.). Further, in interconnected structure sufficient strength can be achieved due to interconnected architecture even at low filament width. 0.2 - 0.41mm width provides sufficient mechanical strength against biomechnical forces applied at treatment site. Furthermore, more than 60% of porosity is achieved at 0.2 – 0.41mm which allows easy tissue growth.

The implant of the embodiments of the present invention is shown in figure 1. As shown in figure 1 a-d, in an embodiment, the implant of the present invention has a shape of a button mushroom comprising an integrated structure of a stem at the bottom portion (at the proximal part i.e. nearer to the brain) adapted to be inserted in the burr hole and a substantially planar top surface at the distal (nearer to the skull/hair) part. The stem portion is press fitted in the burr hole of the skull while the top surface acts as the cover. In this embodiment, the diameter of the stem section is substantially less than the top portion. Therefore, the surface area at the stem area is less than the top and it increases in a single stage.

In the description, the term ‘proximal /proximal end’ is used to describe the implant end nearer to the brain and the term ‘distal/distal end’ is used to describe the end towards the top of the skull and nearer to hair.

In one embodiment, as shown in Fig. 4, the implant has slanted periphery to enable it to be press-fitted in the burr hole.

In some embodiment, the implant can take a shape of an inverted cone wherein the diameter of the implant progressively increases from the bottom (proximal) portion to the top (distal) portion and so is the surface area.

In some embodiment, the implant can have a pentahedron shape, where the proximal end portion with the least surface area is press fitted in the burr hole near the brain and the distal end portion with the highest surface area acts as the top cover while the slanted area is positioned in between the proximal and distal end to cover the thickness of the skull.

The implant has varying proximal and distal layer lay down filament width. Variation of lay down width of the proximal and distal layer of implant allow easy fitting of implant in the burr hole as more flexibility is achieved when distal layers have higher lay down filament width hence have reduced flexibility than bottom (proximal – layer toward brain) layers with lesser filament width hence imparted with enhanced flexibility. Thus, implant has varying flexibility from distal to proximal end which allows easy fitting of implant in slightly reduced size burr hole. Also, variation of lay down thickness in layers allow easy fitting in slightly smaller holes thereby reducing size of operative area.

In another embodiment, in inverted conical shape of the implant, bottom (proximal) surface has lesser lay down filament width and the top (distal) has a greater lay down filament width which provide better fitting in slightly smaller burr hole. Further, in an embodiment, the implant may have difference in width of lay down filament which may be distributed in 2, 3 or 5 layers.

Due to variable flexibility in different layers, a single size implant can be used for wide and slightly deviated size of hole thereby reducing requirement of less sizes of implant. Further, distal to proximal layer filament width variation provides better sealing effect in slightly deviated (smaller than implant) burr hole due to comparatively more flexibility at proximal portion thereby providing much firm sealing effect.

In another embodiment, the implant has pores with different porosity e.g. two or more types of pores of different pour size. This provides better cell penetration, cell proliferation, and nutrient and oxygen exchange (An example of different size of pore is shown in Figure 3). Smaller pores filled slowly and partly thereby preventing cell death. Large pore helps for better exchange of nutrient and oxygen. Whereas, smaller pore limit the formation of large cell aggregates and reduced cell differentiation while the larger pores allow higher degree of differentiation and aggregation.

Preferably the smaller pores are in the range of 450µm to 650µm and the larger pores are in the range of 1400µm to 1800µm. Figure 3 shows different lay down filament width and pore sizes.

The lay down pattern of the filament results in different types of pore. For example, 0°/90° lay-down pattern results in square pores. Lay down patterns of 0°/60°/120°, 0°/90°/180°/270° and 0°/72°/144°/36°/108° are used to give a combination pattern of triangular, square and polygonal pores respectively. Further, in present invention lay down pattern of 0°/90°/180°/270° is used to make implant containing two different size of pores. The different lay out patterns are shown in figure 2.

The present invention also discloses a method of manufacturing bioresorbable craniotomy implant (plug) using FDM based 3D printing and 1.75 mm polycaprolactone filament where plug have porosity of more than 50%. The porosity of implant is achieved by the design of implant, more preferably by lay filament width. The control of filament width is achieved through optimization of process parameters e.g. extruder temperature, extrusion multiplier percentage, printing speed, bed temperature etc. The, above described parameters are controlled in such a way that width of filament remains same in all layers or can vary in different layers.

The present invention relates to optimization of process parameter for manufacturing of polycaprolactone based craniotomy implant by FDM technology. In FDM, implant is made through layer by layer method. The design and thickness of width play the major role in characteristic of implant such as mechanical and porosity. The different layers of the implant have different orientation such 0 degree, 90 degree, 180 degree 270 degree etc with shifted pattern. In present invention, extruder temperature, extrusion multiplier percentage, printing speed and bed temperature are optimized to have lay filament width range from 0.2 mm to 0.41mm.

Wrapping, filament retraction and layer adhesion is most influencing characteristic of printing process which directly affects product features. In the present invention, process parameters are set to prevent wrapping, filament retraction or layer adhesion issue.

The Bioresorbable craniotomy plug’s scaffold is fabricated as per process flow shown in Fig.5 The unique ability of rapid prototyping or 3D printing technology is to provide a customized implant to suit individual patient needs. To manufacture patient specific implant, site of reconstruction is scanned using Computed Tomography (CT). Then, scan data is converted to a 3D CAD file which can be rectified to achieve the desired scaffold shape. Rectified CAD model is further interpolated into a series of 2D layers using computer software and then transferred to the 3D printing. 3D printing allows high degree of control and reproducibility of scaffold or implant porosity, pore size and geometry. 3D printing also offers the ease and flexibility of varying the scaffold/implant characteristics to meet specific structural and functional requirements of tissue. Further, Conventional 2D scaffolds are satisfactory for multiplying cells, but are less satisfactory when it comes to generating functional tissues. Therefore, 3D printed bioresorbable scaffold system is preferred for the generation and maintenance of highly differentiated tissues.

In case of scaffold or implant, implanted as bone or cartilage, it is necessary to protect them from overloading for a sufficient period of time to allow proliferation of cells and their extracellular matrix. This can be achieved by controlling the porosity of implant. Present invention discloses a bioresorbable plug suitable for bone tissue regeneration, wherein the implant comprises number of layers in such a fashion that provide desired porosity.

In 3D printing, process parameter such as extruder temperature, extrusion multiplier percentage, printing speed and bed temperature are critical for manufacturing of implant without layer adhesion and (filament) wrapping which affect the product quality and performance. Extrusion multiplier control amount of filament comes out from the nozzle for adjusting extrusion flow rates. Further, extrusion multiplier ratio depends on material. On the other hand, minor changes in extrusion ratio affect the temperature such as increase in extrusion multiplier from 1.00 to 1.05, leads to extrusion of 5% more filament. Subsequently, leads to increase in temperature, so that filament can still melt before being extruded. Also, an optimized FDM process involves complex interactions among the hardware, software and material properties. The extruder temperature and the filament feed rate have the most direct influence on the material flow for the fabrication of porous models. To obtain a specific extruded diameter for a constant volumetric flow, the minimum roller speed is determined by using a low FDM printing speed (4-8 mm/s) for steady material deposition in a minimum fabrication time. The optimum values of extruder temperature and filament feed rate are obtained through iterative modification to achieve a target length width. The porosity is controllable both by varying the channel size during the design process and also by modifying the flow conditions through the FDM head during processing. Porosity of the scaffolds ranges from 30% to 80%, more preferably 60% to 70%. Further, interconnecting porous matrix architecture of plug implant provides appropriate pore size, porosity and comparable mechanical properties to scaffold. Polycaprolactone’s strength and fracture-resistant properties enable the implant to be firmly anchored in the surrounding calvarium, leading to stable reconstruction.

The optimization of process parameter can be further understood by following example.

Table 1: Optimization of 3D printing process parameter
Trial Extrusion
Temperature
(°C) Extrusion
Multiplier
Percentage (%) Printing Speed
(mm/s) Bed
Temperature
(°C)
1. 90 110 04 26
2. 75 110 04 26
3. 75 115 04 30

Example 1
For lay down filament of 0.4mm is achieved by optimization process parameter. Extrusion temperature, extrusion multiplier percentage, printing speed and bed temperature are 90°, 110%, 04mm/sec and 26°C respectively. At this parameter lay down filament width is uniform but variation is larger than ±0.01mm. Lay down filament width ranges from 0.380 to 0.410mm. However, threading (retraction) and improper printing at the edges of layers is observed. Desired porosity is not achieved due to improper retraction of filament during printing.

Example 2
For lay down filament of 0.4mm is achieved by optimization process parameter. Extrusion temperature, extrusion multiplier percentage, printing speed and bed temperature are 75°, 110%, 04mm/sec and 26°C respectively. At this parameter lay down filament width is uniform. Lay down filament width ranges from 0.347 to 0.353mm which is smaller than required. However, minor threading (retraction) and improvement in printing at the edges of layers observed. Due to un-optimized combination of extrusion multiplier percentage and extrusion temperature filament retraction is not well and filament does not stick at defined parameter. However, better printing quality is achieved with overall good porosity.

Example 3
For lay down filament of 0.4mm is achieved by optimization process parameter. Extrusion temperature, extrusion multiplier percentage, printing speed and bed temperature are 75°, 115%, 04mm/sec and 30°C respectively. At this parameter lay down filament width is uniform. Lay down filament width ranges from 0.395 to 0.410mm (0.39mm ± 0.006mm). No threading (retraction) and improvement in printing at the edges of layers is observed. Plug also sticks to the bed properly. Optimized combination of extrusion multiplier percentage, bed temperature and extrusion temperature led to printing of uniform and well printed plug. Angels between two adjacent layers are also in well defined range. No filament retraction is observed which improved overall porosity of plug.

The other lay over filament width such as 0.2-0.3mm may also be achieved by suitably modifying the process parameters disclosed above.

In other embodiment, implant may be cured for additional strength. The curing time and temperature depends on the polymer and its properties. In present invention curing temperature ranges from 5° C to 70° C, more preferably 20° C to 57°C. Curing time ranges from 5 minutes to 5 hours, more preferably 30 minutes to 3 hours.

In other embodiment, implant may be coated with therapeutic agent. The post operative consequences include pain, infection, haematoma, wound healing complications etc (Kurland, David B., et al. Neurocritical care 23.2 (2015): 292-304). Therapeutic agent includes but not limited anti-bacterial agent, analgesic agent, steroidal or non-steroidal anti-inflammatory agents, opioids, anti-proliferative agent, anticholinergics, antifungal agents, antiparasitic agents, antiviral agents, blood thinner, anti-clotting agents, biostatic compositions, vasoconstrictors, and combinations thereof. In the present invention, preferable therapeutic agent is anti-bacterial, anti-inflammatory or anti-clotting agents. Anti-bacterial agent includes but not limited to neomycin, tobramycin, kanamycin, gentamicin, rifamycin, streptomycin, ansamycins, cephaloridine, Cephalosporins or their derivatives, cephalexin, methicillin, cefazolin, cephalothin, cephapirin, oxacillin, floxacillin, erythromycin, oleandomycin, or spiramycin; penicillins, such as penicillin G and V, amoxicillin, tyrothricin, bacitracin, vancomycin, polymyxins and likewise. Anti-inflammatory drug includes but not limited to paracetamol, naproxen sodium, ibuprofen, diclofenac sodium, rofecoxib, indomethacin, codeine phosphate, tramadol hydrochloride, dextropropoxyphe hydrochloride, triamcinolone, mometasone, betamethasone, amcinonide, lumiracoxib, ketamine, duloxetine, tapentadol and their combination thereof.

The amount of therapeutic agents ranges from 0.001mg to 10mg, preferably 0.01mg to 5mg more preferably 1mg to 2mg. Release period of drug may ranges from days to hours. However, release profile of therapeutic agent can be tuned using different release regulator or excipients. Drug release regulator or excipient include but not limited to poly-L-lactide (PLLA), poly-DL-lactide-co-glycolide(PLG), poly-D-lactide(PDLA), poly-DL-lactic (PDLA), poly-L-lactide-co-e-caprolactone(PLCL), polyglycolide, Poly (ethylene-co-vinyl acetate), Poly (ethylene glycol), Poly (methacrylic acid), glycerol, polyethylene glycol or their derivatives, poly vinyl alcohol or their derivatives, polyvinylpyrrolidone or their derivatives, poly(vinyl acetate), cellulose, sodium citrate and their combination thereof.

The ratio of excipient and drug ranges from 90:10 to 90:10 more preferably 30:70 to 50:50. The coating composition comprises of drug and excipient and a solvent. The example of solvent can include, but not limited to, water, dimethyl sulfoxide (DMSO), ?,?'- dimethylformamide (DMF), ?,?'-dimethylacetamide (DMAC), N-methyl-2-pyrrolidone (NMPO), 1,3-dimethyl-2-imidazolidinone (DMEU), 1,3-dimethyl-3,4,5,6-tetrahydro-2-(1H)-pyrimidinone (DMPU), methanol, ethanol, 1-propanol, isopropanol, acetone, diethyl ether, methyl acetate, ethyl acetate, xylene, and mixtures of thereof.

In other embodiment, deposition of therapeutic agent on implant surface can be achieved by vapor deposition, chemical and electrochemical techniques, spraying, roll to roll coating, physical coating etc. Coating method includes but not limited to dip coating, spin coating, kiss coating, thermal or plasma spraying, electroplating etc. In the present invention, method of coating is spray coating or dip coating.

In another embodiment, the implant may be coated partially of fully.

In other embodiment, drug coated implant can be directly printed by mixing drug and filament in liquifying chamber (e.g. extrusion chamber) and printed by same parameter mentioned above will omit the need of coating later on. In other embodiment of present invention, filament containing drug can be directly used to make drug eluting/coated implant.

The invention is described with the help of some preferred embodiments but various modifications may be made without departing from the scope of the description and the appended claims.