SENSOR-STENTS

Abstract

Stents adapted to allow for monitoring an environment into which they have been inserted in a body, as well as methods of making and using such stents and systems involving such stents. Such stents allow for the detection and treatment of side effects and deleterious results of stent insertion. These stent are makeable by processes and methods involving three dimensional printing.

Claims

1.-38. (canceled)

39. A stent adapted to allow for monitoring an environment into which it has been inserted in a body.

40. The stent of claim 39, further defined as comprised of a resistive material and a conductive material.

41. The stent of claim 40, wherein the resistive material comprises a plastic, metal, ceramic, or composite.

42. The stent of claim 40, wherein the conductive material comprises a plastic, metal, ceramic, or composite.

43. The stent of claim 40, wherein at least one of the restive material and the conductive material are materials that can be formed by a three dimensional printing process.

44. The stent of claim 40, wherein the three dimensional printing process comprises fused deposition modeling, selective laser sintering, selective laser annealing, selective heat sintering, stereolithography, digital light processing, electron beam melting, electron beam freeform fabrication, and/or direct metal laser sintering.

45. The stent of claim 40, further comprising an electo-insulative covering.

46. The stent of claim 39, further defined as adapted to monitor the environment by measuring electrical resistance if the stent is deformed during use.

47. The stent of claim 46, wherein the stent is adapted to wirelessly transmit data about the electrical resistance of the stent to a receiver outside of the body during use.

48. The stent of claim 46, further defined as adapted to generate energy for measuring resistance and/or transmitting data from physical movements of or in the body.

49. The stent of claim 46, further defined as adapted to determine a physiological change at a location of insertion in the body during use.

50. The stent of claim 49, wherein the physiological change is restenosis, stent thrombosis, aneurysm, or an aortal tear or a symptom of any of these.

51. The stent of claim 39, further defined as being comprised of a material that will dissolve at a desired time after insertion in the body.

52. The stent of claim 39, further defined as configured to be placed in a human artery or vein.

53. A method comprising: obtaining a stent of claim 39; inserting the stent into a subject's body; and monitoring an environment in the body into which the stent has been inserted.

54. The method of claim 53, wherein the stent is placed in a human artery or vein.

55. The method of claim 53, wherein monitoring the environment comprises monitoring electrical resistance in the stent.

56. The method of claim 55, wherein the monitoring is via wireless transmission of information from the stent to a receiver outside of the body.

57. The method of claim 53, further defined as a method of detecting a physiological change at a location of insertion in the body.

58. The method of claim 57, wherein the physiological change is indicative of restenosis, stent thrombosis, aneurysm, or an aortal tear or a symptom of either of these.

59. The method of claim 57, further comprising treating the subject in response to a detected physiological change.

60. The method of claim 21, wherein the treatment comprises angioplasty, stent implantation, brachytherapy, intracoronary radiation, and/or aspiration thrombectomy.

61. The method of claim 53, further comprising producing the stent using a three dimensional printing process according to dimensions of the location in the body into which the stent is to be inserted.

62. The method of claim 53, where the stent is rolled prior to insertion.

63. The method of claim 53, wherein the stent is substantially cylindrical prior to insertion.

64. The method of claim 53, wherein the stent is adapted to expand after insertion.

65. A method of producing a stent of claim 39, comprising: obtaining a resistive material; and using a process comprising three dimensional printing to form a stent comprising the resistive material.

66. The method of claim 65, wherein the resistive material is a plastic, metal, ceramic, or composite.

67. The method of claim 65, further comprising obtaining a conductive material; and using a process comprising three dimensional printing to form a stent comprising the conductive material.

68. The method of claim 67, wherein the conductive material is a plastic, metal, ceramic, or composite.

69. The method of claim 65, wherein the three dimensional printing process comprises fused deposition modeling, selective laser sintering, selective heat sintering, stereolithography, digital light processing, electron beam melting, electron beam freeform fabrication, and/or direct metal laser sintering.

70. The method of claim 65, further comprising forming an electo-insulative covering on the stent.

71. The method of claim 65, further comprising connecting the stent to a wireless transmitter adapted to wirelessly transmit data about the electrical resistance of the stent to a receiver outside of the body during use.

72. The method of claim 65, wherein the three dimensional printing produces a substantially flat structure.

73. The method of claim 72, further comprising rolling the flat structure into a cylinder or spiral prior to insertion.

74. The method of claim 73, further comprising fusing edges of the flat structure to form a cylinder during insertion.

75. The method of claim 65, wherein the three dimensional printing process produces a structure that is not substantially flat.

76. A system comprising a stent of claim 39 and a wireless receiver.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0028] The following drawings form part of the present specification and are included to further demonstrate certain aspects of the present invention. The invention may be better understood by reference to one or more of these drawings in combination with the detailed description of specific embodiments presented herein.

[0029] FIG. 1 shows various prototype designs for the stents of the invention.

[0030] FIG. 2 is a 3D model of finalized stent design with photograph of actual stent; the stent has a 0.3 mm thickness and a 0.25 diameter.

[0031] FIGS. 3A and 3B shows the result of a study in which stents were compressed and their resistances measured.

[0032] FIGS. 4A and 4B show graphs of pressure over time and voltage over time from the compressed stents.

[0033] FIG. 5 is a calibration curve for the stent maps voltage to pressure.

DESCRIPTION OF ILLUSTRATIVE EMBODIMENTS

[0034] The invention and the various features and advantageous details are explained more fully with reference to the non-limiting embodiments that are illustrated in the accompanying drawings and detailed in the following description. Descriptions of well-known starting materials, processing techniques, components, and equipment are omitted so as not to unnecessarily obscure the invention in detail. It should be understood, however, that the detailed description and the specific examples, while indicating embodiments of the invention, are given by way of illustration only and not by way of limitation. Various substitutions, modifications, additions, and/or rearrangements within the spirit and/or scope of the underlying inventive concept will become apparent to those skilled in the art from this disclosure.

[0035] The following examples are included to demonstrate preferred embodiments of the invention. It should be appreciated by those of skill in the art that the techniques disclosed in the examples which follow represent techniques discovered by the inventor to function well in the practice of the invention, and thus can be considered to constitute preferred modes for its practice. However, those of skill in the art should, in light of the present disclosure, appreciate that many changes can be made in the specific embodiments which are disclosed and still obtain a like or similar result without departing from the spirit and scope of the invention.

[0036] Cardiac stents of the invention were designed such that the stents and the surrounding tissue can be continuously monitored for any sign of restenosis or thrombosis. These problems associated with stents can be characterized by a constricting of blood-flow in the affected vessel. Using the basic fluid mechanics definition of mass flow rate,

{dot over (m)}=vA

where is the density of the fluid, v is the velocity, and A is the cross-sectional area, and assuming constant flow rate and density, equation 1 relates cross-sectional area to velocity.
As the area is reduced, the velocity must increase. Bernoulli's equation,

[00002]$\frac{p_1}{}+\frac{v_1^2}{2.Math..Math.g}+h_1=\frac{p_2}{}+\frac{v_2^2}{2.Math..Math.g}+h_2+.Math..Math.h_1$

assuming gravity, energy, density, and height are constant simplifies to

[00003]$\frac{p_1}{}+\frac{v_1^2}{2.Math..Math.g}=\frac{p_2}{}+\frac{v_2^2}{2.Math..Math.g}$

which relates velocity of a flow to pressure. The assumptions of constant mass flow rate, zero energy input, and constant height are all valid along a small length of blood vessel. Therefore, a constriction in area under these conditions will result in an increase in velocity and a decrease in pressure. In order to measure the local pressure decrease along a stent, the inventors designed a stent that is itself a sensor by making the sensor that could provide data in the same manner as a strain gauge.

[0037] Using a conductive 3D-printer filament in conjunction with a Makerbot Replicator Dual 3D-printer and white ABS plastic filament, enabled preliminary studies to prove that strain gauges could be produced via three dimensional printing (data not shown). A conductive plastic filament was used as well in some studies.

Example 1

[0038] Stents were printed as a flat mesh. Because 3D-printing progresses by layers, each layer can be a continuous extrusion of plastic, but in between layers the strength is diminished as the first layer cools. Testing of a variety of prototype stents optimized a stent of strength, flexibility, and size.

[0039] FIG. 1 shows a variety of stent designs that were created using Solidworks with white ABS. Stent designs 1-4 were focused on achieving maximum flexibility. While their flexibility was high, their stability was poor. When folded into a cylindrical shape, the diameter was inconsistent. Stent 5 sacrificed some of that flexibility and complexity to achieve simplicity and good stability. Stent designs 6-11 experimented with varying sizes of diamond, thickness of the struts, and vertical thickness of the horizontal stent. These tests were all focused on optimizing flexibility and strength. Bonding the stents into cylindrical form involved using acetone to fuse the ends to one another.

[0040] The final design, stent 12, is capable of folding to an effective diameter of 0.25. FIG. 2 shows the design, the flat printed stent, and the stent after bonding into a cylindrical form. The stent is three layers thick, with layer height 0.1 mm each. The stents were printed at 230 C. with a heated printing platform at 110 C., which encourages strong bonding between layers. Three layers was determined to be the best for a blend of flexibility and strength with regard to the particular application. The design is on the same order of magnitude as stents currently used.

Example 2

[0041] To confirm that the stents produced in Example 1 would operate as strain gauges, they were subjected to the same type of stress to which they would be subjected to when implanted.

[0042] A set of analog calipers were coated with an insulating tape and used to compress the stent to precise diameters. A digital multi-meter was used to directly measure resistance, not voltage. The diameter and resistance value were recorded and graphed. The voltage across the stent was measured periodically, both while diameter was increasing and decreasing in order to detect any permanent damage as evidenced by a baseline shift.

[0043] FIGS. 3A and 3B show the results of this test. As the cylindrical stents compressed into an oval, the relationship between displacement and resistance was positive, and the resistance of the sensor at the end of the experiment is extremely close to what it was at the beginning. This indicates that the stents can be used to collect information about pressures in the stent, because conditions that stop the flow of blood through the passageway by narrowing the vessel, decrease the area. Therefore, any pressure decrease relates to an area decrease, indicating a problem such as restenosis or thrombosis. This enables one to monitor for such directly in real time and in vivo.

Example 3

[0044] To confirm that the stents could detect changes in pulsatile flow, like those found in the blood stream, a further study was conducted with a stent employing actual fluid flow, driven by a peristaltic pump to simulate blood flow conditions.

[0045] A 40 M test stent was connected in series with an 18 M control stent. The peristaltic pump created a sinusoidal pressure that was measured using two sensors connected to an Iworx 214 station, and a data-logging digital multi-meter measured the voltage drop across the test stent resulting from the applied 1V DC.

[0046] Specifically, two diameters of blood vessel mimicking vascular graft were combined with one stent to create a test sample. The untreated stent was rolled up and placed inside the larger diameter graft. The thinner diameter was able to slide into the center of the stent with minimal friction. The outer graft material was used to make sure the stent made contact with the inner tube, ensuring it would experience the same pressure changes. However, unlike a normal stent, this stent was actually mounted outside the vessel that would receive the flow. This was necessary because otherwise the experiment would require an insulating coating to keep water out of the electrical circuit. The test sample was connected to a system powered by a peristaltic pump. This pump creates a pulsatile flow similar to the way a heart does, rather than a traditional pump with constant flow. As a result of the placement of the stent and the tightness of the fit, the sensor only experiences the peaks of the pressure and not the valleys.

[0047] To take measurements, both a data-logging digital multi-meter and an Iworx 214 station were used. As before, the stent test specimen was connected in series with another stent to create a voltage divider. A potential of 1V was supplied, and the resistances of the test stent and the series stent was 40 M and 18 M, respectively. The digital multi-meter measured the voltage drop across the test specimen twice every second, and the Iworx station was connected to two pressure sensors on either side of the specimen. FIGS. 4A and 4B show the data for one such test.

[0048] FIG. 5 displays the graphs of the pressure versus time data as well as stent voltage versus time. Because the pressure graph is sinusoidal, the root mean square of the pressure was taken over the sections corresponding to the various pump settings. These values were correlated to the average voltage readings from the stent in order to create a sensor calibration curve. According to the calibration curve, the sensor output in this current configuration is 3.2*10-6 volts per RMS gauge pressure in pascals. This graph exemplifies that the output of the sensor changes with the input (pressure) on the sensor. From the equation discussed above, one can deduce that pressure output is directly related to the flow speed of blood, which is related to the area of the passage way. Problems that stop the flow of blood through the passageway by narrowing the vessel, decreasing the area. So a pressure decrease relates to an area decrease, indicating a problem such as restenosis or thrombosis.

[0049] All of the embodiments disclosed and claimed herein can be made and executed without undue experimentation in light of the present disclosure. While the stents and methods of this invention have been described in terms of preferred embodiments, it will be apparent to those of skill in the art that variations may be applied to the them and in the steps or in the sequence of steps of the method described herein without departing from the concept, spirit and scope of the invention. More specifically, it will be apparent that certain agents which are both chemically and physiologically related may be substituted for the agents described herein while the same or similar results would be achieved. All such similar substitutes and modifications apparent to those skilled in the art are deemed to be within the spirit, scope and concept of the invention as defined by the appended claims.

REFERENCES

[0050] The following references, to the extent that they provide exemplary procedural or other details supplementary to those set forth herein, are specifically incorporated herein by reference. [0051] Grove E. C. L and Kristensen S. D., Stent thrombosis: definitions, mechanisms and prevention. European Society of Cardiology, 8 May 2007. www.escardio.org/communities/councils/ccp/e-journal/volume5/Pages/vol5n32.aspx#.Up5FW8S1xcY. 3 Dec. 2013. [0052] Huda Hamid and John Coltart, Miracle stentsa future without restensosis. McGill Journal of Medicine. National Center for Biotechnology Information, July 2007. www.ncbi.nlm.nih.gov/pmc/articles/PMC2323487/. 3 Dec. 2013. [0053] What Is Coronary Angioplasty? National Heart, Lung, and Blood Institute, 1 Feb. 2012. http://www.nhlbi.nih.gov/health/health-topics/topics/angioplasty/. 3 Dec. 2013.