DESC:TECHNICAL FIELD
The present disclosure relates to the field of fabrication methods of customized bioresorbable biliary stents and, more specifically, a method of fabrication of bioresorbable biliary stents using custom lattice structure of biodegradable thermoplastic polymer blends/composites (e.g., using an additive manufacturing and surface modification).
BACKGROUND
Stents, including biliary stents, have undergone significant evolution, revolutionizing their fabrication, base materials, deployment strategies, and clinical effectiveness over the years. In the historical context, plastic stents were extensively employed for sealing benign biliary strictures. However, their widespread use was hindered by inherent limitations, primarily frequent occlusions leading to “restrictures” (i.e., narrowing of the stent itself due to occlusions (blockages). The necessity for multiple plastic stents over time through revision procedures further compounded these challenges.
To address the aforementioned issues, self-expandable metallic stents were introduced, offering a reduction in the number of endoscopic procedures and demonstrating longer patency (i.e., a state of a body passage or duct being open and unobstructed) as compared to plastic stents. Despite these limited benefits, non-degradability posed a significant drawback, necessitating additional surgical interventions to replace the stent in the event of occlusion or other associated complications. Recognizing the limitations of both plastic and metallic stents, there exists a growing interest in bioresorbable stents. These stents hold promise as they eliminate the need for additional surgeries, providing a solution to the challenges posed by their non-degradable counterparts. Bioresorbable stents can undergo complete degradation into non-toxic products, marking a significant advancement in the field of biliary stent technology. However, the fabrication of such bioresorbable stents especially, the bioresorbable biliary stents remain a prominent technical challenge. In an example, the challenges in fabricating bioresorbable biliary stents are multifaceted. The technical challenges involve finding the right balance in material properties to ensure stent functionality and biocompatibility while also ensuring that the stent degrades at an appropriate rate without causing harm. Another aspect is the manufacturing process, which must produce stents with precise dimensions and structural integrity.
Therefore, in light of the foregoing discussion, there exists a need to overcome the aforementioned drawbacks.
SUMMARY
The present disclosure provides a method of fabrication of bioresorbable biliary stent using a custom lattice structure of a biodegradable thermoplastic polymer blend. The present disclosure provides a solution to the technical problem of the non-biodegradability of biliary stents and the specific requirement of fabrication of bioresorbable biliary stent with precise dimensions, structural integrity, and optimal mechanical properties, i.e. a combination of sufficient radial strength and flexibility to prevent restrictures and ensure longer patency. An aim of the present disclosure is to provide a solution that overcomes at least partially the problems encountered in the prior art and provide an improved method of manufacturing of bioresorbable biliary stents using custom lattice structure of biodegradable thermoplastic polymer. The improved manufacturing method results in a structurally improved biliary stent that are not only bioresorbable or biodegradable but also manifest improved structural integrity to prevent “restrictures.” In addition, the improved manufacturing method may ensure longer patency and ease of deployment. Moreover, the change of mechanical properties of the absorbable materials due to the use of the custom lattice structure in the method of fabrication significantly improves the flexibility of the produced bioresorbable biliary stent.
One or more objectives of the present disclosure is achieved by the solutions provided in the enclosed independent claims. Advantageous implementations of the present disclosure are further defined in the dependent claims.
In an aspect, the present disclosure provides a method of a fabrication of bioresorbable biliary stents using a custom lattice structure of a biodegradable thermoplastic polymer. The method comprises mixing one or more biodegradable thermoplastic polymers to form a polymer blend ; converting the polymer blend into a custom lattice structure; wrapping the custom lattice structure over a pre-heated mold having a tubular shape to form a hollow tube of the custom lattice structure; and forming a bioresorbable biliary stent in the form of a covered tubular construct by covering an outer side of the hollow tube of the custom lattice structure from deposition of nanofibers of the polymer blend.
Firstly, by converting the polymer blend into the custom lattice structure, the method allows for precise tailoring of the design of the bioresorbable biliary stent, enhancing its mechanical properties and structural integrity. The subsequent step of wrapping this custom lattice structure over a pre-heated mold to form a hollow tube is advantageous for achieving a tubular shape that aligns well with the anatomy and requirements of the biliary tract. Additionally, the use of the biodegradable thermoplastic polymers ensures the bioresorbability of the resulting stent, eliminating the need for additional removal procedures and contributing to improved patient outcomes. The incorporation of nanofiber deposition via electrospinning onto the outer side of the hollow tube further prevents bile leakage and introduces the potential for controlled drug release, fostering targeted therapeutic applications and improved tissue healing. The versatility and precision afforded by this approach in controlling the cubic lattice structure, tubular shape, and nanofiber deposition make it a promising avenue for developing bioresorbable biliary stents with enhanced performance and therapeutic with tunable properties.
It is to be appreciated that all the aforementioned implementation forms can be combined. All steps which are performed by the various entities described in the present application, as well as the functionalities described to be performed by the various entities are intended to mean that the respective entity is adapted to or configured to perform the respective steps and functionalities. It will be appreciated that features of the present disclosure are susceptible to being combined in various combinations without departing from the scope of the present disclosure as defined by the appended claims.
Additional aspects, advantages, features and objects of the present disclosure would be made apparent from the drawings and the detailed description of the illustrative implementations construed in conjunction with the appended claims that follow.
BRIEF DESCRIPTION OF THE DRAWINGS
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 present disclosure is not limited to specific methods and instrumentalities disclosed herein. Moreover, those skilled in the art will understand that the drawings are not to scale. Wherever possible, like elements have been indicated by identical numbers.
Embodiments of the present disclosure will now be described, by way of example only, with reference to the following diagrams wherein:
FIG. 1 is a flow chart of a method of fabrication of bioresorbable biliary stents using a custom lattice structure of biodegradable thermoplastic polymer blend, in accordance with an embodiment of the present disclosure;
FIG. 2 is a diagram illustrating a plurality of different unit cells corresponding to a plurality of planar lattice structures obtained by converting one or more biodegradable thermoplastic polymer pellets, in accordance with an embodiment of the present disclosure;
FIG. 3 is a diagram illustrating hollow tubes of different custom lattice structures of FIG. 2, in accordance with an embodiment of the present disclosure;
FIG. 4A is a diagram illustrating various planar lattice structures having different infill angles, in accordance with another embodiment of the present disclosure;
FIG. 4B is a diagram illustrating a graphical representation of a force required to displace various planar lattice structures versus a displacement of atoms of the various planar lattice structures having different infill angles, in accordance with another embodiment of the present disclosure;
FIG. 5 is a diagram illustrating scanning electron microscope (SEM) micrographs of electrospun nanofibers under different operating parameters, in accordance with an embodiment of the present disclosure;
FIG. 6 is a diagram illustrating a graphical representation of the degradation of different types of bioabsorbable biliary stents over a period of time, in accordance with an embodiment of the present disclosure;
FIG. 7A is a diagram illustrating a graphical representation of differential scanning calorimetry (DSC) thermograms of a 3D printed bioabsorbable biliary stent without nanofibers versus a bioabsorbable biliary stent covered with nanofibers, in accordance with an embodiment of the present disclosure;
FIG. 7B is a diagram illustrating a graphical representation of X-ray diffraction (XRD) profiles of a 3D printed bioabsorbable biliary stent without nanofibers versus a bioabsorbable biliary stent covered with nanofibers surface deposition, in accordance with an embodiment of the present disclosure;
FIG. 8 is a diagram illustrating a graphical representation of a comparison of a planar lattice structure obtained from different absorbable polymers, in accordance with an embodiment of the present disclosure;
FIGs. 9 and 10 are graphical representations illustrating Differential Scanning Calorimetry (DSC) of different polymer blends, in accordance with an embodiment of the present disclosure;
FIGs. 11 and 12 are graphical representations depicting an FTIR spectrum of the polymer blends, in accordance with an embodiment of the present disclosure;
FIGs. 13A and 13B are graphical representations depicting a relationship between stress and strain for tensile tests of the 3D-printed custom lattice structure of polymer blends, in accordance with an embodiment of the present disclosure;
FIG. 14 is a graphical representation representing the degradation pattern of bioresorbable biliary stents fabricated using different PDO and PCL blends, in accordance with an embodiment of the present disclosure;
FIG. 15 is a graphical representation of in-vitro degradation of different PDO blend bioresorbable biliary stents, in accordance with an embodiment of present disclosure;
FIG. 16 is a graphical representation of in-vitro degradation of the bioresorbable biliary stents, in accordance with an embodiment of the present disclosure; and
FIG. 17 is X-ray image of the PDO or PDO blend stents containing varying concentrations of radiopaque marker, in accordance with an embodiment of present disclosure.
DETAILED DESCRIPTION OF EMBODIMENTS
The following detailed description illustrates embodiments of the present disclosure and ways in which they can be implemented. Although some modes of carrying out the present disclosure have been disclosed, those skilled in the art would recognize that other embodiments for carrying out or practicing the present disclosure are also possible.
FIG. 1 is a flow chart of a method of fabrication of bioresorbable biliary stents using custom lattice structure of a polymer blend, in accordance with an embodiment of the present disclosure. With reference to FIG.1, there is shown a flow chart of a method 100 of fabrication of bioresorbable biliary stents using a custom lattice structure of a polymer blend.
At step 102, the method 100 includes mixing one or more biodegradable thermoplastic polymers to form a polymer blend. In an example, the polymer mixture comprises a first biodegradable polymer, i.e., polydioxanone (PDO) and a secondary biodegradable polymer selected from polycaprolactone (PCL) and polyethylene glycol (PEG). In another example, the polymer mixture comprises a first biodegradable polymer, i.e., polydioxanone (PDO) and a secondary biodegradable polymer selected from polycaprolactone (PCL) or polyethylene glycol (PEG). The first biodegradable polymer acts as a main component blended with the secondary biodegradable polymer. In some example, the PDO and the secondary polymer are mixed in 80:20 ratio. In some other examples, the PDO and the secondary polymer are in the 70:30 ratio. In yet another example, the PDO and the secondary biodegradable polymer are in 60:40 ratio. During blending of the PDO and the secondary biodegradable polymer temperature of the melt mixer is maintained at a temperature of 1250-135 degrees Celsius. The melt mixer is operated at a rotor speed of 60 rpm and the polymer mixture is circulated in the melt mixer for five to six minutes to ensure homogeneous mixing. Further, the polymer mixture is the collected and stored as polymer blend in a dry, cold location. The polymer blend is chopped into small pieces; and the small pieces of the polymer blend are fed into a 3D printer cartridge for subsequent processing.
At step 104, the method 100 comprises converting polymer blend into a custom lattice structure. The polymer is shaped into the planar lattice structure. In an example, the one or more biodegradable thermoplastic polymer pellets are polydioxanone (PDO) pellets. It is observed experimentally that polymer blends when used as a raw material for bioresorbable biliary stents manifest excellent biocompatibility and biodegradability, making it safe for use in the human body. The polymer blend further manifests enhance mechanical strength and flexibility as compared to other bioabsorbable materials, which contributes to maintaining shape and function of a biliary stent to be fabricated using the polymer blend material over time. The custom lattice structure refers to a custom-arranged configuration of a perforated planar sheet of biodegradable thermoplastic polymer, where perforations are in a specific pattern. This results in optimized material properties like structural strength and flexibility.
In another example, instead of the polymer blend, other polymer blends may be used without limiting the scope of the disclosure. For example, polycaprolactone (PCL), polyglycolide (PGA), polylactide (PLA), polylactide-co-tri-methylene carbonate (PLMC), and their copolymers may be alternatively used. However, based on experimentation, it was observed that compared to other biodegradable polymers, the polymer blend offers some advantages, such as good flexibility, appropriate degradation profile, and minimal inflammatory response.
In an example, the polymer blend is converted into the custom lattice structure by using an additive manufacturing, specifically design-guided additive manufacturing. The design-guided additive manufacturing refers to the use of computer-aided design (CAD) to precisely control the three-dimensional (3D) printing process. In the design-guided additive manufacturing approach, the biliary stent design is created in a CAD program, which is then converted into instructions for the 3D printer. The method allows for the creation of complex structures with specific mechanical properties tailored to their intended use.
In an implementation, the converting of the polymer into the custom lattice structure comprises performing three-dimensional (3D) printing of the polymer blend at a temperature range of 120-135 degrees Celsius, a speed range of 5-10 millimetres per second (mm/s) and a pressure range of 250-350 kilo Pascal (kPa). The custom lattice structure is a two-dimensional (2D) planar structure having a thickness ranging from 0.4-0.7 mm. Further details of converting polymer blend into the custom lattice structure are explained in the experimental part later in the disclosure.
At step 106, the method 100 comprises wrapping the custom lattice structure over a pre-heated mold having a tubular shape to form a hollow tube of the custom lattice structure. The custom lattice structure may be a planar structure, which may be heated first and then wrapped around the pre-heated mold (e.g., a hollow glass mold), where the custom lattice structure takes a tubular shape matching the shape of the tubular mold. The tubular mold is kept at a high temperature (e.g., in the range of 70-90 degrees Celsius in an implementation) to mold the custom lattice structure of the polymer blend into the tubular shape, followed by rapid cooling to lock the structure. The method 100 allows the creation of a hollow, tubular stent structure with precise dimensions (i.e., lengths, diameters, and wall thicknesses) and mechanical properties, leveraging the inherent flexibility of the heated polymer as well as additional flexibility rendered by the custom lattice structure and the rapid setting capability upon cooling.
In some implementations, a mold assembly process may be used for fabricating the biliary stent using thermoforming. In one implementation, the polymer blend is converted into a custom lattice structure, which undergoes thermoforming at a controlled temperature range of 80°C to 90°C. For example, the rhombus-patterned custom lattice structure is positioned within a mold assembly, where it is shaped into the final stent structure. Advantageously, the mold assembly incorporates a solid rod within the lumen of the structure to provide mechanical support and ensure uniform deformation during the thermoforming process. During thermoforming, the mold assembly ensures that the softened cubic lattice structure lattice conforms precisely to the intended stent geometry. The solid rod acts as an internal mandrel, preventing collapse and maintaining the cylindrical lumen integrity. The mold is configured to apply uniform heat distribution, ensuring that the polymer material undergoes consistent thermal expansion and molecular realignment to achieve the desired mechanical properties. The presence of the solid rod within the mold helps in maintaining the dimensional accuracy of the stent’s cross-section, ensuring structural stability after cooling and solidification.
Experimental results demonstrate the effect of the mold assembly configuration on the final stent morphology. Stents fabricated using a solid rod within the mold exhibit a well-defined, circular lumen with uniform wall thickness, indicating proper material distribution and retention of structural integrity. Conversely, when the stent is formed without the support of a solid rod, the lumen undergoes irregular deformation, leading to partial or complete collapse. The deformation suggests that the absence of internal structural support during thermoforming results in non-uniform stress distribution, affecting the mechanical reliability of the stent. The comparison highlights the role of the mold assembly, particularly the use of an internal support rod, in achieving precise lumen geometry and ensuring the functional efficacy of the stent. The mold design prevents defects, enhances reproducibility, and improves the mechanical performance of the fabricated stent, making it suitable for medical applications.
In an implementation, the forming of the hollow tube of the custom lattice structure comprises providing a temperature shock by transferring the hollow tube of the custom lattice structure from a first temperature range of 80-90 degrees Celsius to a second temperature range of 0 to 4 degrees Celsius in gradual manner to lock the shape of the hollow tube of the custom lattice structure. Further details of the forming of the hollow tube of the custom lattice structure, taking an example of polymer blend as raw material, are explained in the experimental part later in the disclosure.
At step 108, the method 100 comprises forming a bioresorbable biliary stent in the form of a covered tubular construct by covering an outer side of the hollow tube of the custom lattice structure from the deposition of nanofibers of the pure polymer or polymer blend. The covering of the outer side of the hollow tube of the custom lattice structure with nanofibers is achieved through electrospinning. In this process, a solution of the pure polymer or polymer blend (i.e., the same material used previously for the custom lattice structure or a different material depending on the degradation rate of the different material) may be spun into nanofibers and deposited onto the outer side of the hollow tube of the custom lattice structure. In some other implementations, the covered tubular construct may be formed by covering the outer side of the hollow tube of the custom lattice structure from the deposition of nanofibers of diverse types of thermoplastic polymers in order to obtain different properties. In some examples, degradation rates of the covered biliary stent may be tuned by choosing different thermoplastic polymers for the printed core and the coating.
In an example, the hollow tube of the custom lattice structure may be transferred to a rotating stainless-steel mandrel for the surface modification process. The electrospinning operation may utilize specific parameters like flow rate, voltage, and spinning distance for the fabrication of a fine coating of the biodegradable thermoplastic polymer nanofibers on the stent surface. Further, the electrospinning operation enhances the properties of the surface of the biliary stent, improving biocompatibility and enabling the controlled release of therapeutic molecules and controlled release of drugs. The therapeutic molecules are released for various purposes, such as anti-cancer/anti-bacterial treatments. In some examples, during the electrospinning operation, growth factors are incorporated into the coating applied to the biliary stent's surface. The incorporation of growth factors into the biliary stent's surface coating aims to promote better neo-tissue healing. In some other examples, the electrospinning operation may enable a release of the radiopaque markers. The inclusion of radiopaque markers may allow healthcare professionals to accurately visualize and monitor the placement and performance of the stent within the body. The method 100 thus manifests several technical effects as compared to the conventional fabrication method of conventional biliary stents. For instance, the method 100 combines design-guided additive manufacturing combined with surface coating operation of electrospinning to obtain covered biliary stents having increased flexibility due to custom lattice structures and multi-functional abilities, such as drug-eluting feature, growth-factor loaded for better neo-tissue healing, etc. It was possible to achieve fine bioresorbable biliary stent structures of narrow diameters (sub 3-4 mm outer diameter) and long lengths (40-60 mm) with good radial and bending compliance and suitable degradation rates.
In an implementation, the deposition of nanofibers of the pure polymer or polymer blend is caused by an electrospinning operation, where the electrospinning operation is performed at a flow rate ranging from 1 and 1.5 millilitres per hour (mL/hr) and an accelerating voltage ranging from 15-20 kilovolt (kV). It is observed that performing electrospinning at the flow rate of 1 to 1.5 mL/hr and the accelerating voltage of 15-20 kV allows for precise control over the deposition of nanofibers. This controlled environment facilitates the creation of a uniform, thin coating on the bioresorbable biliary stent structures so as to achieve very fine bioresorbable biliary stent structures of narrow diameters (sub 3-4 mm outer diameter) and long lengths (40-60 mm) with good radial and bending compliance, and suitable degradation rates. The precise control over fibre thickness and density also contributes to the overall effectiveness and safety of the stent in medical applications.
EXPERIMENTAL PART
I. Materials Used
Medical-grade Polydioxanone (PDO) was obtained in the form of pellets and was directly used as the raw material for melt-based extrusion three-dimensional (3D) printing in a 3D printer (e.g., a BioX, Cellink printer). Along with PDO, polycaprolactone (PCL) and polyethylene glycol (PEG) of appropriate molecular weight were also acquired. 3D models were designed in an application (e.g., SolidWorks), and customized geometric codes (G-codes) were made by slicing the Stereolithography (Stl) files generated using RepetierHost software.
II. EXAMPLES OF FABRICATION
Example 1: Fabrication method of bioresorbable biliary stent using custom lattice structure of PDO.
a. Fabrication of PDO lattice planar structure
The PDO pellets were fed into the cartridge of the 3D printer (BioX, Cellink). Melt-extrusion 3D printing was employed to print the polymer into customized lattice planar structures. Optimized printing parameters were as follows:
i. printing temperature of 125-135°C;
ii. speed of 1 to 3 milli meters per second (mm/s); and
iii. pressure of 250-350 kilo pascal(kPa)
Different designs of three-dimensional (3D) models were prepared using SolidWorks and sliced using Repetier Host tool. Two different designs of unit cells, namely rhombus cell and Z and a cell size of 2 mm and 3.5 mm for each design were designed.
b. Fabrication of PDO hollow tubes of lattice planar structures with cellular walls
The printed lattice planar structures were kept inside a furnace at 80°C and then wrapped inside a hollow glass mold, pre-heated at the same temperature. The glass mold with the tubular lattice structure inside was kept for some time to set the polymer into that shape, after which it was transferred to 0 to 4 degrees Celsius in gradual manner to allow the polymer to lock into that shape.
c. Electrospinning of PDO nanofibers
The hollow tube of lattice structure of cellular walls was wrapped around a rotating stainless-steel mandrel, which acted as the collector. PDO solution (12% w/v) in 2,2,2-trifluoroethanol (TFE) was used as the solution, and the electrospinning parameters were varied as: flow rate of 1 and 1.5 mL/ h, accelerating voltage of 15 and 20 kV and needle to collector distance is set at 21 cm. The spinning time is roughly about 10 minutes to obtain a very thin coating over the stent surface.
d. Characterization
PDO in the form of 3D printed filament of lattice structure and electrospun into nanofibers was characterized for its thermal properties via differential scanning calorimetry (DSC). Differential scanning calorimetry (DSC) was performed on around 5-10 mg of PDO at a scanning rate of 10°C/min from -50°C to 200°C under a nitrogen atmosphere at a flow rate of 50 mL/min. Different thermal transition parameters, including glass transition temperature, cold crystallization temperature, enthalpy of melting and cold crystallization, and percentage of crystallinity, were estimated. X-ray diffraction (XRD) was performed for structural characterization of polydioxanone (PDO) as three-dimensional (3D) printed filament and electrospun nanofibers, using a Rigaku X-ray diffractometer with Cu -K? radiation at a scan speed of 0.025°/s. Scanning electron microscopy (SEM) was performed on the electrospun polydioxanone (PDO) nanofibers to evaluate the morphology of the fibers. Mechanical characterization was performed using dynamic mechanical analysis (DMA) in the controlled force mode, with a loading rate of 0.1 N/min at 37°C. In vitro degradation was performed using Sorenson’s buffer (pH=8) at 37°C.
e) X-ray Imaging:
Iohexol, a clinical contrast agent was incorporated in to fabricated stents to induce radiopacity. Methods such as electrospinning and dip coating were used for coating iohexol on the fabricated stents. TFE was used to prepare solutions containing 10 and 20 w/w % iohexol in PDO/PCL 70:30. The stent was carefully dipped in the solution for 1 minute to ensure uniform coating, then removed. Then they are dried in a hot air oven. This was done on both ends. For electrospinning of Iohexol-polymer solution, the following parameters were used: flow rate of 1 and 1.5 mL/h, accelerating voltage of 15 and 20 kV, and needle to collector distance of 21 cm. The spinning duration was set to 5 minutes in order to achieve a very thin layer on the stent surface. The stents were inserted into a spinning mandrel to ensure uniform fibre deposition across the surface. The dried samples were checked under X-ray to check the radiopacity.
III. Results
With reference to FIG.2, there is shown a plurality of different unit cells corresponding to a plurality of planar lattice structures obtained by converting one or more biodegradable thermoplastic polymer pellets as discussed in example 1. In the FIG. 2, there is shown a first planar lattice structure 202, which has a rhombus shape pattern 202A with a cell size of about 3.5 mm. A second planar lattice structure 204 has a Z-shaped shape pattern 204A with a cell size of about 3.5 mm. A third planar lattice structure 206 a rhombus shape pattern 206A with a cell size of about 2 mm, whereas a fourth planar lattice structure 208 has a Z-shaped shape pattern 208A with a cell size of about 2 mm. The plurality of planar lattice structures was successfully 3D printed, and mechanical testing was performed on each of these cells (i.e., the custom planar lattice structures) to understand the influence of design on the final properties. In the uniaxial testing routine, the 2 mm rhombus unit cell (i.e., the planar lattice structure with rhombus-shape pattern) exhibited the highest Young’s modulus but also lowest strain at failure, while the 3.5 mm rhombus unit cell had the highest strain at failure. These differences can be called shape and design-driven, as the base material is PDO in all cases. This gives sufficient freedom in customising the design according to patient-specific requirements of mechanical properties of bioabsorbable biliary stents.
With reference to FIG. 3, there is shown hollow tubes of the custom lattice structure that were obtained from custom lattice structure of FIG. 2. In this embodiment, the hollow tubes of custom lattice structure have outer diameters of about 3-4 mm. A first hollow tube of custom lattice structure 302 is obtained from the first planar lattice structure 202 (the rhombus shape pattern 202A with the cell size of about 3.5 mm). A second hollow tube of custom lattice structure 304 is obtained from the second planar lattice structure 204 (the Z-shaped pattern 204A with the cell size of about 3.5 mm). A third hollow tube of custom lattice structure 306 is obtained from the third planar lattice structure 206 (the rhombus shape pattern 206A with a cll size of about 2 mm). A fourth hollow tube of custom lattice structure 308 is obtained from the third planar lattice structure 206 (the Z-shape pattern 208A with the cell size of about 2 mm). These hollow tubes of custom lattice structure are obtained when the planar lattice structures were rolled into hollow tubes over a mold and resulted in small diameters (sub 3-4 mm) and lengths as long as 50-60 mm. These dimensions are very advantageous for use as biliary stents and also difficult to be achieved by conventional 3D printing, injection moulding and the like.
With reference to FIG. 4A, there is shown an effect of one or more infill angles on the planar lattice structure, which has a rhombus shape pattern. In the illustrated embodiment of FIG. 4A, there is shown a plurality of planer lattice structures 400A obtained at different infill angles. The term “infill angles” refers to an orientation at which a material is deposited or filled within the lattice structure. The infill angle is described in terms of angles (e.g., 30 degrees, 60 degrees, 90 degrees). The infill angle impacts the strength and characteristics of the final printed part. The plurality of planar lattice structures 400A includes a fifth planar lattice structure 402, a sixth planar lattice structure 404, and a seventh planar lattice structure 406. The fifth planar lattice structure 402 has a rhombus shape pattern 402A that is obtained at a first infill angle of 30 degrees. The sixth planar lattice structure 404 has a rhombus shape pattern 404A obtained at a second infill angle of 60 degrees. The seventh planar lattice structure 406 has a rhombus shape pattern 406A obtained at a third infill angle of 90 degrees. The fifth planar lattice structure 402 has a denser pattern than the sixth planar lattice structure 404 and the seventh planar lattice structure 406. In some examples, the denser pattern offers a balance between strength and material efficiency. In other words, the fifth planar lattice structure 402 has a more tightly packed planar lattice structure with increased crisscrossing than the sixth planar lattice structure 404 and the seventh planar lattice structure 406.
With reference to FIG. 4B, there is shown a graphical representation 400B of a force required to displace various planar lattice structures versus a displacement of atoms of the various planar lattice structures having different infill angles, in accordance with another embodiment of the present disclosure. The graphical representation 400B includes X-axis representing the displacement of the planar lattice structure and Y-axis representing force required to displace the planar lattice structure. The graphical representation 400B includes a first curve 408, a second curve 410, and a third curve 412. The first curve 408 corresponds to the fifth planar lattice structure 402 which has the rhombus shape pattern 402A. At the first infill angle of 30 degrees, a variation between displacement of the fifth planar lattice structure 402 and a force applied to move the fifth planar lattice structure 402 is non-linear. The second curve 410 corresponds to the sixth planar lattice structure 404, which has a rhombus shape pattern 404A. The second curve 410 corresponds to the sixth planar lattice structure 404 is more stable and resistant to force. The third curve 412 corresponds to the seventh planar lattice structure 406 which has the rhombus shape pattern 406A. From the third curve 412 is clear that the planar structure becomes more brittle and unstable at the third infill angle of 90 degrees. The seventh planar lattice structure 406 is stronger and stiffer than the fifth planar lattice structure 402.
The infill angle for a particular planar lattice structure may depend on its intended application. For example, a material that needs to be strong and stiff might benefit from a high infill angle, while a material that needs to be conductive might benefit from a lower infill angle.
With reference to FIG. 5, there is a diagram illustrating scanning electron microscope (SEM) micrographs 500 of electrospun nanofibers 502 under different operating parameters. As a means to achieve covered bioabsorbable biliary stents to minimize bile leaks, electrospinning was employed as a surface-coating technique. In the FIG. 3, defect-free nanofibers 40 were achieved at a flow rate of 1 mL/h and 20 kV electric voltage. A thickness of roughly 0.5-0.8mm was achieved after 10 minutes of electrospinning, which was optimal for the use case of coated bioabsorbable biliary stents. Additionally, only nanofibrous stent (without the 3D printed core) was achieved by spinning over a rotating mandrel, which was used as a control.
With reference to FIG. 6, there is shown a graphical representation 600 of the degradation of different types of bioabsorbable biliary stents over a period of time. In the graphical representation 600, X-axis 602 represents a number of days and Y-axis 604 represents an extent of degradation in terms of weight percent values. The bioabsorbable biliary stents including an uncovered bioabsorbable biliary stent, a covered bioabsorbable biliary stents, and a bioabsorbable biliary stent with nanofibrous surface coating, were subjected to degradation at 37°C in Sorenson’s buffer (pH=8) which physiologically mimics human bile. Interestingly, the fibrous stent, i.e., bioabsorbable biliary stent with nanofibrous surface coating was the most stable with slow degradation profile as depicted in FIG. 6, while the uncovered bioabsorbable biliary stent (represented as “Bare”) degraded faster than the covered ones, i.e., the covered bioabsorbable biliary stents 608, 610, and 612. The bioabsorbable biliary stent with nanofibrous surface coating is also referred to as the bioresorbable biliary stent that is in the form of the covered tubular construct by covering the outer side of the hollow tube of the custom lattice structure from deposition of nanofibers of the biodegradable thermoplastic polymer (e.g., PDO).
With reference to FIG. 7A, there is shown a graphical representation 700A of differential scanning calorimetry (DSC) thermograms of a 3D printed bioabsorbable biliary stent (represented as “3DP”) without nanofibers versus a bioabsorbable biliary stent covered with nanofibers surface deposition (represented as “NFs”), in accordance with an embodiment of the present disclosure. In the FIG. 7A, the X-axis represents temperature in degrees Celsius, whereas Y-axis represents heat flow per unit mass (mW/g). The “mW/g" describes the rate of heat transfer (in milliwatts) per gram of the 3D printed bioabsorbable biliary stent (represented as “3DP” and a graphical line 704) without nanofibers versus a bioabsorbable biliary stent covered with nanofibers surface deposition (represented as “NFs” and a graphical line 702). The DSC thermograms show two endothermic peaks, one at around -40°C and the other at around 100°C. In the graphical line 702, related to the bioabsorbable biliary stent covered with nanofibers surface deposition, there are two endothermic peaks 702A, whereas in the graphical line 704, related to the 3D printed bioabsorbable biliary stent (represented as “3DP”) without nanofibers there are two to three endothermic peaks 704A at different positions and different heat flow rate, as shown. The two endothermic peaks 702A of the graphical line 702 related to the bioabsorbable biliary stent covered with nanofibers indicate the nanofibers surface deposition increases the amount of energy that the bioabsorbable biliary stent of PDO polymer can absorb, as compared to the 3D printed bioabsorbable biliary stent (represented as “3DP”) without nanofibers. In other words, the 3D printed part (i.e., 3D printed bioabsorbable biliary stent (represented as “3DP”) without nanofibers) had a higher percentage crystallinity (48%) (not desirable) than the bioabsorbable biliary stent covered with nanofibers (36%).
With reference to FIG. 7B, there is shown a graphical representation 700B of X-ray diffraction (XRD) profiles of a 3D printed bioabsorbable biliary stent (represented as “3DP”) without nanofibers versus a bioabsorbable biliary stent covered with nanofibers surface deposition (represented as “NFs”), in accordance with an embodiment of the present disclosure. In the FIG. 7B, the X-axis represents temperature in degrees Celsius, whereas the Y-axis represents intensity in the XRD study. In a graphical line 706, related to the bioabsorbable biliary stent covered with nanofibers, there is observed a broader peak at around 20°, which indicates that it is less crystalline as compared to the two sharper peaks 710 at different positions along a graphical line 708 related to the 3D printed bioabsorbable biliary stent without nanofibers.
With reference to FIG. 8, there is shown a graphical representation 800 of a comparison of planar lattice structures obtained from different absorbable polymers. The X-axis represents displacement in micrometres (µm), whereas Y-axis represents force in Newtons (N). The displacement here is of a planar lattice structure due to the application of the force. The graphical representation 800 includes a first curve 802, a second curve 804, and a third curve 806. The first curve 802 corresponds to a planar lattice structure manufactured using PDO polymer. The second curve 804 corresponds to a planar lattice structure manufactured using PLA (Polylactic acid) polymer. The third curve 806 corresponds to a planar lattice structure manufactured using PCL (polycaprolactone) polymer. The planar lattice structure obtained from PLA polymer exhibits the highest force peak, indicating its superior strength compared to PCL polymer and PDO polymer. However, the sharp drop in force after the peak shows the brittle behaviour of the planar lattice structure manufactured using PLA polymer. The planar lattice structure obtained from PCL polymer has a lower force peak than PLA polymer but a broader peak, indicating the ability of PCL polymer to deform slightly before failure. This demonstrates higher ductility of the planar lattice structure obtained from PCL polymer ductility compared to PLA polymer. The planar lattice structure obtained from PDO polymer has the lowest force peak and the broadest peak among the three polymers (i.e. PCL, PLA, PDO), indicating the lowest strength and highest ductility of PDO polymer. The ductility property makes the PDO polymer more suitable for application in the manufacturing of biliary stents. The highest ductility of PDO polymer occurs when the polymer chains are allowed to maintain a more linear and flexible structure. The flexibility is advantageous for the biliary stents as it enables them to navigate through intricate and tortuous anatomical structures within the body without compromising their structural integrity. The PDO polymer further manifests enhanced mechanical strength and flexibility as compared to other bioabsorbable materials, which contributes to maintaining the shape and function of a biliary stent to be fabricated using the PDO material over time.
Both uncovered and covered bioabsorbable biliary stents hold promise for various applications. Uncovered stents, with their sub-4mm diameters, could excel as intrahepatic stents where bile leaks are less of a concern. Covered stents especially with nanofibers deposition, on the other hand, would be well-suited for the extrahepatic biliary tract due to their added protection against bile leaks.
Thus, the bioresorbable biliary stent with nanofiber surface coating has several significant advantages, such as a) large market potential for biliary stents by offering a fully absorbable option in human body (i.e., a fully bioresorbable biliary stent); b) enhanced easy of deployment, where if a shape memory polymer is used, the biliary stent can be pre-compressed for easy deployment within the body; c) the bioresorbable biliary stent readily allows for the integration of drug-eluting features, enhancing its therapeutic capabilities due to surface coating and the custom lattice structures; d) the disclosed fabrication method offers precise control over the mechanical properties of the absorbable material, allowing for customization based on specific needs; and lastly, e) the disclosed bioresorbable biliary stent’s shape, size, and position can be adjusted after deployment, further enhancing its versatility and efficacy.
Example 2: Fabrication method of bioresorbable biliary stent using custom lattice structure of a polymer blend.
a. Melt blending
A Haake melt mixer was employed for preparing polymer blends, the PDO served as the primary component and was systematically blended with secondary polymers (PCL and PEG). The blending process was executed at three specific compositional ratios (80:20, 70:30, and 60:40), with PDO maintaining the majority composition. The procedure commenced with the introduction of precisely pre-weighed polymer mixtures through the mixer's hopper system. Processing parameters were optimized at 130°C temperature and 60 rpm rotor speed to ensure effective melting and mixing. The polymer mixture underwent continuous circulation within the Haake mixer for a predetermined duration of five to six minutes, facilitating homogeneous blend formation. Upon completion of the mixing cycle, the homogeneously blended polymer samples were carefully collected and transferred to a controlled storage environment characterized by dry and cold conditions to maintain their structural and chemical integrity.
b. Fabrication of the polymer blend lattice planar structure
The polymer blend was fed into the cartridge of the 3D printer (BioX, Cellink). Melt-extrusion 3D printing was employed to print the polymer into customized lattice planar structures. One gram of the polymer blend was fed into the cartridge of the 3D printer ((BioX, Cellink) after the filaments were chopped into tiny pieces. The material was printed into unique forms using melt-extrusion 3D printing.
Optimized printing parameters were as follows:
i. printing temperature of 125-135°C;
ii. speed of 6-10milli meter per second (mm/s); and
iii. pressure of 250-350 kilo pascal(kPa)
Different designs of three-dimensional (3D) models were prepared using SolidWorks and sliced using Repetier Host tool. Two different designs of unit cells, namely rhombus cell and Z and a cell size of 2 mm and 3.5 mm for each design were designed.
c. Fabrication of the polymer blends hollow tubes of lattice planar structures with cellular walls.
The printed lattice planar structures were kept inside a furnace at 80°C and then wrapped inside a hollow glass mold, pre-heated at the same temperature. The mold with the tubular lattice structure inside was kept for some time to set the polymer into that shape, after which it was suddenly transferred to 0°C to allow the polymer to lock into that shape.
d. Electrospinning of PDO nanofibers
The hollow tube of the lattice structure of cellular walls was wrapped around a rotating stainless-steel mandrel, which acted as the collector. PDO solution (12% w/v) in 2,2,2-trifluoroethanol (TFE) was used as the solution, and the electrospinning parameters were varied as: flow rate of 1 and 1.5 mL/ h, accelerating voltage of 15 and 20 kV and needle to collector distance is set at 21 cm. The spinning time is roughly about 10 minutes to obtain a very thin coating over the stent surface.
e. Characterization:
The PDO blends were characterized for its thermal properties via DSC (Differential scanning calorimetry). DSC was performed on around 3 to 5 mg of PDO (or its blend) at a scanning rate of 10°C/min from -50°C to 200°C under a nitrogen flow rate of 50 mL/min. The PDO blends were characterised using Fourier Transform Infrared Spectroscopy (FTIR) in order to check the presence of functional groups. Mechanical characterization was performed using Dynamic mechanical analysis (DMA) in the controlled force mode, with a loading rate of 0.1 N/min at 37°C. The in vitro degradation of the blends was investigated by immersing the samples in Sorenson's buffer (pH=8) at 37°C and tracking the weight loss over a predetermined period. The weight loss of stents was investigated using human bile as a medium.
Results:
FIGs. 9 and 10 are graphical representations illustrating Differential Scanning Calorimetry (DSC) of different polymer blends, in accordance with an embodiment of the present disclosure. FIGs. 9 and 10 are explained in conjunction with FIGs. 1 to 8. With reference to FIG. 9, there is shown a graphical representation 900 depicting Differential Scanning Calorimetry (DSC) obtained after the characterisation of polymer blend containing PDO and PCL in different ratios, as explained in example 2.
The graphical representation 900 shows the relationship between temperature and heat flow. The temperature is expressed in degrees Celsius in an abscissa axis. Heat flow is expressed in Joule per gram in an ordinate axis. The graphical representation 900 includes a first region depicting positive heat flow and a second region depicting negative heat flow. The first region includes a first curve 902A, a second curve 904A and a third curve 906A. The second region includes a fourth curve 902B, a fifth curve 904B and a sixth curve 906B. The first curve 902A represents a polymer blend of PDO and PCL present in 60:40 ratio, the second curve 904A represent polymer blend of PDO and PCL present in 70:30 ratio and the third curve 906A represent polymer blend of PDO and PCL present in 80:20 ratio. Similarly, the fourth curve 902B represents polymer blend of PDO and PCL present in 60:40 ratio, the fifth curve 904B represent polymer blend of PDO and PCL present in 70:30 ratio, and the sixth curve 906B represent polymer blend of PDO and PCL present in 80:20 ratio.
In the first region (i.e., positive heat flow region), the first curve 902A, the second curve 904A, and the third curve 906A represent the crystallization behaviour of PDO and PCL blends. Each curve demonstrates characteristic exothermic peaks, with varying intensities corresponding to their blend compositions. At approximately 25-30 degrees Celsius, the second curve 904A shows the highest intensity crystallization peak with a sharp, well-defined exotherm, indicating optimal crystallization behaviour at blend composition (PDO and PCL in 70:30 ratio). The 906A curve (PDO and PCL in 80:20 ratio) displays a moderately intense peak, demonstrating how the increased PDO content influences the crystallization process. Meanwhile, the first curve 902A (PDO and PCL in 60:40 ratio) exhibits a broader, less intense peak, suggesting that higher PCL content leads to more gradual crystallization. After the initial crystallization peaks, all three curves (the first curve 902A, the second curve 904A and the third curve 906A) show a gradual stabilization and flatten out as the temperature increases beyond 50 degrees Celsius, indicating complete crystallization of both polymer components (i.e., PDO and PCL). The second curve 904A (PDO and PCL in a 70:30 ratio) demonstrates the most favourable crystallization characteristics, suggesting that the polymer blend in which PDO and PCL are in a 70:30 ratio might be the optimal blend ratio for achieving desired material properties in the bioresorbable biliary stent.
The second region (i.e., negative heat flow region) displays corresponding endothermic melting behaviour the fourth curve 902B, the fifth curve 904B, and the sixth curve 906B for the different blend ratios. The fourth curve 902B, the fifth curve 904B, and the sixth curve 906B, exhibit two distinct melting peaks the first peak occurring at approximately 55 degrees Celsius (corresponding to PCL melting) and the second peak at around 105 degrees Celsius (indicating PDO melting). The intensity and depth of endothermic peaks (indicated by the fourth curve 902B, the fifth curve 904B, and the sixth curve 906B) correlate directly with the blend compositions. Further, the fourth curve 902B (the PDO and PCL blend having higher PCL content) shows more pronounced lower-temperature peaks, while the sixth curve 906B (the PDO and PCL blend with higher PDO content) displays more prominent higher-temperature peaks. Further, the fifth curve 904B, demonstrates balanced peak intensities, implying optimal blend characteristics. The clear separation of melting peaks across all compositions indicates successful blending while maintaining the distinct thermal properties of each component, confirming both the immiscibility of the polymers and the stability of the blends. The thermal behaviour profile provides insights for processing parameter optimization, particularly in establishing appropriate temperature windows for subsequent melt processing operations.
With reference to FIG. 10, there is shown a graphical representation 1000 depicting Differential Scanning Calorimetry (DSC) obtained after characterisation of polymer blend containing PDO and PEG in different ratios. The graphical representation 1000 includes a first region depicting positive heat flow and a second region depicting negative heat flow. The first region includes a first curve 1002A, a second curve 1004A and a third curve 1006A. The second region includes a fourth curve 1002B, a fifth curve 1004B and a sixth curve 1006B. The first curve 1002A represents polymer blend of PDO and PEG present in 60:40 ratio, the second curve 904A represents polymer blend of PDO and PEG present in 70:30 ratio and the third curve 906A represents polymer blend of PDO and PEG present in 80:20 ratio. Similarly, the fourth curve 902B represents polymer blend of PDO and PEG present in 60:40 ratio, the fifth curve 904B represents polymer blend of PDO and PEG present in 70:30 ratio and the sixth curve 906B represents the polymer blend of PDO and PEG present in 80:20 ratio.
In the first region (positive heat flow region), the first curve 1002A, the second curve 1004A, and the third curve 1006A represent the crystallization behaviour of different blend compositions. The second curve 1004A shows a distinctive pattern with higher initial heat flow around 0.5-0.7 Joule per gram, demonstrating optimal crystallization characteristics. The third curve 1006A exhibits a gradual decline in heat flow as temperature increases, while 1002A shows intermediate behavior, consistent with varying blend compositions.
In the second region (i.e., negative heat flow region), the fourth curve 1002B, the fifth curve 1004B, and the sixth curve 1006B, display characteristic endothermic melting behaviour. Each curve (the fourth curve 1002B, the fifth curve 1004B, and the sixth curve 1006B) exhibits two distinct melting peaks, the first at approximately 50 degrees Celsius and the second around 100° degrees Celsius, corresponding to the melting points of the constituent polymers (PDO and PEG). The fifth curve 1004B, shows the most pronounced endothermic valley at around 100 degrees Celsius, reaching approximately “-2.0 watts per gram”, indicating a strong melting transition. The depth and sharpness of the endothermic peaks vary among the curves, with the fifth curve 1004B, demonstrating the most defined transitions. The clear separation between the melting peaks across all compositions confirms successful polymer blending while maintaining the distinct thermal characteristics of each component.
On comparing FIG. 9 with FIG. 10, similar thermal behaviour patterns are observed, though with slightly different peak intensities and positions, indicating the universal applicability of the thermal characterization method across different polymer blends. The consistency in thermal behaviour patterns across both thermograms validates the reliability of the characterization and confirms the reproducibility of the blend properties. Based on the characterisation, the nozzle temperature of the printing head was decided.
FIGs. 11 and 12 are graphical representations depicting the FTIR spectrum of the polymer blends, in accordance with an embodiment of the present disclosure. FIGs. 11 and 12 are described in conjunction with elements from FIGs. 1 to 10. With reference to FIG. 11, there is shown a graphical representation 1100 depicting exemplary FTIR spectra of polymer blends. Specifically, the graphical representation 1100 depicts the absorption of infrared light by a polymer blend of PDO and PCL at different wavelengths, typically measured in wavenumbers. Wavenumber is expressed in centimeters inverse (cm-1) in an abscissa axis. Transmittance is expressed in percentage in an ordinate axis.
The graphical representation 1100 includes a curve 1102, a curve 1104, and a curve 1106, representing different blend compositions, showing characteristic absorption peaks. The most significant feature across all spectra is the prominent carbonyl (C=O) peak, visible at approximately a first peak 1108, a second peak 1110, and a third peak 1112. The peaks demonstrate the preservation of the carbonyl functional group despite the high-temperature processing during melt mixing and extrusion printing. Similarly, FIG. 12 includes a graphical representation 1200, including a curve 1202, a curve 1204, and a curve 1206 correspond to PDO and PCL blends present in ratios of 80:20, 70:30, and 60:40, respectively, each showing the characteristic carbonyl absorption at peaks a first peak 1208, a second peak 1210, and a third peak 1212. The maintenance of the carbonyl peaks across all blend compositions is significant as it confirms that no thermal degradation occurred during the processing steps. The consistency of the carbonyl peak intensities and positions across different blend ratios indicates successful blend formation while maintaining the chemical integrity of the constituent polymers. The presence and stability of the carbonyl groups are important for the controlled degradation behaviour of the final product, as these functional groups play a vital role in the hydrolytic degradation mechanism of the bioresorbable biliary stents.
FIGs. 13A and 13B are graphical representations depicting a relationship between stress and strain for tensile tests of the 3D-printed custom lattice structure of polymer blends, in accordance with an embodiment of the present disclosure. FIGs. 13A and 13B are described in conjunction with elements from FIGs. 1 to 12. With reference to FIG. 13A, there is shown a graphical representation 1300A including a curve 1302A, a curve 1304A and a curve 1306A. The curve 1302A represents the 3D custom lattice structure of the polymer blend composed of PDO and PCL in a 60:40 ratio. The curve 1304A represents the 3D custom lattice structure of the polymer blend composed of PDO and PCL in a 70:30 ratio. The curve 1306A represents the 3D custom lattice structure of the polymer blend composed of PDO and PCL in an 80:20 ratio. Strain is expressed in percentage in an abscissa axis. Stress is expressed in kilopascal (kPa) in an ordinate axis. The curve 1306A, representing the highest PDO content, shows the steepest initial slope and reaches maximum stress more quickly, indicating higher stiffness but lower flexibility.
In contrast, the curve 1302A exhibits a more gradual slope, reaching about 1.4 MPa at 2.5% strain, demonstrating greater flexibility due to higher PCL content. The intermediate composition represented by the curve 1304A shows balanced mechanical properties between the two extremes. The trend of the graphical representation 1300A clearly illustrates how increasing PCL content reduces the modulus of the polymer blend, resulting in enhanced flexibility, which is important for the deployment of stents.
With reference to FIG. 13B, there is shown a graphical representation 1300B, including a curve 1302B, a curve 1304AB and a curve 1306B. The curve 1302B represents the 3D custom lattice structure of the polymer blend composed of PDO and PEG in a 60:40 ratio. The curve 1304B represents the 3D custom lattice structure of the polymer blend composed of PDO and PEG in a 70:30 ratio. The curve 1306B represents the 3D custom lattice structure of the polymer blend composed of PDO and PEG in 80:20 ratio.
The mechanical behaviour of PDO and PEG blends, shown in graphical representation 1300B, reveals significantly different characteristics compared to PDO and PCL blends as explained in FIG. 13A. The curve 1302B, the curve 1304B, and the curve 1306B demonstrate much higher strain percentages, extending to 35 percent. Specifically, the curve 1302B (highest PEG content) exhibits classic ductile behaviour with a large plastic deformation region, reaching strains up to 35% before failure. The curve 1306B shows the highest initial stress response but lower ultimate strain, typical of materials with higher PDO content. The intermediate composition (represented by the curve 1304B) displays balanced properties between strength and ductility. The graphical representation 1300B shows that increasing PEG content leads to more ductile behaviour, with higher strain capabilities but lower initial stiffness, while higher PDO content results in more brittle behaviour with higher initial stiffness but lower strain capabilities.
FIG. 14 is a graphical representation representing the degradation pattern of a biliary stent fabricated using different PDO and PCL blends, in accordance with an embodiment of the present disclosure. FIG. 14 is explained in conjunction with elements of FIGs. 1 to 13B. With reference to FIG. 14, there is shown a graphical representation 1400 including a plurality of curves representing different polymer blend compositions. The graphical representation 1400 shows the relationship between the number of days and weight loss of stents. Time is expressed in number of days in an abscissa axis. Weight loss is expressed in percentage in an ordinate axis. The graphical representation 1400 illustrates the degradation profiles of PDO and polymer blend in human bile. The graphical representation 1400 includes a curve 1402 representing pure PDO, a curve 1404 representing polymer blend of PDO and PCL in 80:20 ratio, a curve 1406 representing polymer blend of PDO and PCL in 70:30 ratio, and a curve 1408 representing polymer blend of PDO and PCL in 60:40 ratio. In the initial 15 days (shown in the lower portion of the curve 1402, the curve 1404, the curve 1406, and the curve 1408), all compositions show relatively similar degradation behaviour with minimal weight loss. However, after the mark of the 15th day, the curve 1402 (pure PDO) shows a dramatic increase in weight loss, leading to complete degradation by the 40th day.
In contrast, the blended compositions (represented by the curve 1404, the curve 1406, and the curve 1408) maintain better structural integrity even beyond fifty-fifth days. The curve 1406 (representing PDO and PCL in 70:30 ratio), demonstrates the most favourable degradation profile with the lowest weight loss percentage among all blend compositions. The divergence in degradation behaviour becomes particularly pronounced in the 25–40-day period, where the curve 1402 (pure PDO) shows accelerated degradation while the blends maintain their structural integrity, confirming the stabilizing effect of PCL incorporation in the stent composition.
FIG. 15 is a graphical representation of in-vitro degradation of different PDO blend stents, in accordance with an embodiment of present disclosure. FIG. 15 is explained in conjunction with elements from FIGs. 1 to 14. With reference to FIG. 15, there is shown a graphical representation 1500 including a curve 1502 and a curve 1504. The graphical representation 1500 illustrates the comparative degradation behaviour of the curve 1502 (covered PDO stents) and the curve 1504 (representing covered biliary stents fabricated using PDO and PCL in 70:30 ratio ) over 80 days. The curve 1502 shows an initial gradual weight loss up to 10 days, followed by a steeper degradation profile between 10 days to 40 days, reaching approximately 35% weight loss by 40th day. The curve 1504 demonstrates significantly different degradation kinetics. The curve 1504 exhibits a more controlled and gradual weight loss pattern throughout the study period, with an initial slow degradation phase up to 50 days, followed by a moderate increase in degradation rate between 50-70 days, ultimately reaching about 55% weight loss by 70th day. The stark difference in degradation profiles between the two compositions, particularly the extended stability of the curve 1504 as compared to the curve 1502, validates the superior performance of the blend for biliary stent applications. The extended degradation profile of the PDO and PCL present in 70:30 ratio, maintaining structural integrity even after 70 days, makes it particularly suitable for clinical applications where longer stent residence times are required, especially in extrahepatic biliary tract applications where controlled degradation is crucial.
FIG. 16 is a graphical representation in-vitro degradation of biliary stents as explained in tested in Sorenson’s buffer, in accordance with an embodiment of the present disclosure. FIG. 16 is explained in conjunction with elements of FIGs. 1 to 15. With reference to FIG. 16, there is shown a graphical representation including a curve 1602, a curve 1604, a curve 1606 a curve 1608, a curve 1610, a curve 1612, a curve 1614, and a curve 1616. The graphical representation 1600 illustrates the degradation profiles of various PDO and PCL blend compositions over 75 days, showing percentage weight loss over time. Time is expressed in number of days in an abscissa axis. Weight loss is expressed in percentage in an ordinate axis. The curve 1602 represents pure PDO uncovered stent, the curve 1604 pure PDO covered stent, the curve 1606 represents an uncovered biliary stent fabricated using PDO and PCL blend in a 60:40 ratio, the curve 1608 represents a covered biliary stent fabricated using a PDO and PCL blend in a 60:40 ratio. The curve 1610 represents an uncovered biliary stent fabricated using PDO and PCL blend in a 70:30 ratio, the curve 1612 represents covered biliary stent fabricated using a PDO and PCL blend in a 70:30 ratio. The curve 1614 represents an uncovered biliary stent fabricated using PDO and PCL blend in 80:20 ratio, the curve 1616 represents a covered biliary stent fabricated using a PDO and PCL blend in an 80:20 ratio.
The graphical representation 1600 compares covered (represented by the curve 1604, the curve 1608, the curve 1612 and the curve 1616) and uncovered biliary stents (represented by the curve 1602, the curve 1606, the curve 1610, and the curve 1614) in different blend ratios, tested in Sorenson's buffer under physiological conditions (37°C, pH 8). Pure PDO covered stent and pure PDO uncovered stent, exhibit rapid degradation, with complete collapse occurring within 40 days and a higher initial degradation rate compared to blends. Covered stents consistently demonstrate lower degradation rates, with each blend ratio showing better stability in the covered version. By day 75, uncovered stents experience approximately 10-15% more weight loss than their covered counterparts. The effect of PCL content is significant, as higher PCL content improves stability. The PDO and PCL blend present in 60:40 ratio shows the lowest weight loss (around 35% at 75 days), while the PDO and PCL blend present in 80:20 ratio exhibits higher weight loss (about 55%), and the PCO and PCL blend in 70:30 ratio demonstrates intermediate behaviour. Degradation behaviour over time reveals three distinct phases: gradual weight loss in the first 15 days, an increased rate from 15 to 45 days, and a steeper decline from 45 to 75 days, especially in blends with lower PCL content. All PDO and PCL blends maintain structural integrity beyond 70 days. The graphical representation 1600 highlights how blending PDO with PCL effectively modifies the degradation rate, offering better control over the lifetime of the biliary stent in physiological conditions. The combination of blending and surface coverage provides tunable degradation characteristics, making it suitable for various clinical applications.
FIG. 17 is X-ray image of the PDO or PDO blend stents containing varying concentrations of radiopaque marker, in accordance with an embodiment of present disclosure. FIG. 17 is explained in conjunction with elements from FIGs. 1 to 16. With reference to FIG. 17 there is shown an X-ray image illustrating the radiopaque properties of poly-dioxanone (PDO) stents containing varying concentrations of iohexol as a radiopaque marker. The X ray image displays three stent samples a first sample 1702 with "0%" concentration of iohexol, a second sample 1704 with "10%" concentration of iohexol and a third sample 1706 with "20%", concentration of iohexol. The first sample 1702 represents a baseline PDO stent without iohexol and exhibits minimal X-ray visibility. The second sample 1704, contains a low concentration of iohexol and demonstrates moderate radiopacity, showing enhanced visibility compared to the control. The third sample 1706, incorporates a high concentration of iohexol, exhibiting the highest radiopacity and the greatest visibility under X-ray imaging. Thie increasing brightness from left to right directly correlates with higher concentrations of iohexol, confirming the successful incorporation of the radiopaque marker through electrospinning. The findings validate the tunable X-ray visibility of these stents based on iohexol concentration and the efficacy of the manufacturing process in creating traceable bioresorbable stents. Clinically, these radiopaque properties enable non-invasive visualization of stent position, monitoring of stent integrity over time, and precise placement during surgical procedures. Furthermore, the adjustable visibility offers flexibility to tailor stent radiopacity based on specific anatomical or procedural requirements, enhancing their utility in medical applications.
Modifications to embodiments of the present disclosure described in the foregoing are possible without departing from the scope of the present disclosure as defined by the accompanying claims. Expressions such as "including", "comprising", "incorporating", "have", "is" used to describe and claim the present disclosure are intended to be construed in a non-exclusive manner, namely allowing for items, components or elements not explicitly described also to be present. Reference to the singular is also to be construed to relate to the plural. The word "exemplary" is used herein to mean "serving as an example, instance or illustration". Any embodiment described as “exemplary” is not necessarily to be construed as preferred or advantageous over other embodiments and/or to exclude the incorporation of features from other embodiments. The word "optionally" is used herein to mean "is provided in some embodiments and not provided in other embodiments". It is appreciated that certain features of the present disclosure, which are, for clarity, described in the context of separate embodiments, may also be provided in combination in a single embodiment. Conversely, various features of the present disclosure, which are, for brevity, described in the context of a single embodiment, may also be provided separately or in any suitable combination or as suitable in any other described embodiment of the disclosure.
,CLAIMS:CLAIMS
We Claim:
1. A method (100) of fabrication of bioresorbable biliary stents, the method (100) comprising:
mixing one or more biodegradable thermoplastic polymers to form a polymer blend;
converting the polymer blend into a custom lattice structure;
wrapping the custom lattice structure over a pre-heated mold having a tubular shape to form a hollow tube of the custom lattice structure; and
forming a bioresorbable biliary stent in form of a covered tubular construct by covering an outer side of the hollow tube of the custom lattice structure from deposition of nanofibers of the polymer blend.
2. The method (100) as claimed in claim 1, wherein the polymer blend comprises a first biodegradable polymer and a second biodegradable polymer.
3. The method (100) as claimed in claim 2, wherein the first biodegradable polymer is polydioxanone; and the second biodegradable polymer is selected from a group consisting of polycaprolactone and polyethylene glycol.
4. The method (100) as claimed in claim 1, wherein the converting of the polymer blend into the custom lattice structure comprises performing three-dimensional (3D) printing at a temperature range of 125-135 degree Celsius, a speed range of 5-10 millimetres per second (mm/s) and a pressure ranging from 250-350 kilo Pascal (kPa).
5. The method (100) as claimed in claim 4, wherein the custom lattice structure is a two-dimensional (2D) planar structure having a thickness ranging from 0.4-0.7 mm.
6. The method (100) as claimed in claim 1, wherein the forming of the hollow tube of the custom lattice structure comprises providing a temperature shock by transferring the hollow tube of the custom lattice structure from a first temperature range of 70-90 degree Celsius to a second temperature range of 0 to 4 degree Celsius to lock the shape of the hollow tube of the custom lattice structure.
7. The method (100) as claimed in claim 1, wherein the deposition of nanofibers of the biodegradable thermoplastic polymer is caused by an electrospinning operation.
8. The method (100) as claimed in claim 7, wherein the electrospinning operation is performed at a flow rate ranging from 1 and 1.5 millilitres per hour (mL/hr) and an accelerating voltage ranging from 15-20 kilovolt (kV).