1. BIOMATERIALS ENT 311/4 Lecture 9 Blood Contacting Implants or Devices Prepared by: Nur Farahiyah Binti Mohammad Date: 26 th August 2008 Email : farahiyah@unimap.edu.my

2. 2 Teaching Plan COURSE CONTENT Define and identify blood contacting implant. Describe and recommend primary requirements for biomaterials for blood contacting implant. Discuss the development of biomaterials for long term implant Identify common problems for heart valve prosthesis, total artificial hearts and pace makers DELIVERY MODE Lecture Supplement LEVEL OF COMPLEXITY Knowledge Repetition Application Analysis Evaluation COURSE OUTCOME COVERED Ability to describe the concept of biocompatibility & basic concepts of materials used in medical application Ability to select biomaterials that can be used for different medical applications and explain the criteria that will lead to a successful implants

3. 3 Blood contacting implants or devices have a direct contact with the blood. Blood comes in contact with foreign materials either for a short term or long term. 1.0 Introduction

4. 4 Short term extracorporeal devices (outside the body): Dialyzers Blood oxygenator Tubes and catheters for transport the blood

5. 5 1.0 Introduction Long term blood contacting implant: Heart valves prostheses Vascular grafts Cardiac pacemakers Implantable artificial organs

6. 6 2.0 Primary requirement The primary requirement for biomaterials for long-term implants are: Blood compatibility (blood compatible) Non-toxicity Durability Non-irritating to tissue Resistant to platelet and thrombus deposition Nondegradable in physiological enviroment Do not absorb blood element Do not release foreign substance

7. 7 3.0 Design consideration The implant should mimic the function of organ that it replace without interfering with the surrounding anatomical structures. Must be suitable size and weight Biomaterial chosen must be easily available, inexpensive, easily machinable and sterilizable.

8. 8 3.0 Design consideration As an example: artificial heart valve is required to open and close on an average once every second (valves open and close 30 million times per year). The biomaterial chosen must be such that the valve is durable and will not fail under fatigue stress after implantation in patient.

9. 9 Revision “ Biocompatibility is the ability of a material to perform with an appropriate host response in a specific application” (William, 1987).

10. 10 Revision In vivo test for tissue compatibility 1. Sensitization 2. Irritation 3. Intracutaneous reactivity 4. Systemic toxicity (acute toxicity) 5. Subcronic toxicity (subacute toxicity) 6. Genotoxicity 7. Implantation 8. Hemocompatibility (Blood compatibility)

11. 11 4.0 Blood compatibility Blood compatibility can be defined as the property of material or device that permits it to function in contact with blood without inducing adverse reactions. Implant should not Induce coagulation (blood clotting) Damage blood cells Should not induce Hemolysis (the breaking open of red blood cells and the release of hemoglobin into the surrounding fluid)

12. 12 4.0 Blood compatibility 4.1 Blood Coagulation Coagulation is a complex process by which blood forms clots. 4.1.1 Mechanism: Intrinsic Initiated by blood contact with either a damaged portion of the blood vessel wall or another thrombogenic (clot causing) surface. Takes 7-12 minutes to form a soft clot

13. 13 4.0 Blood compatibility Extrinsic Result of the presence of a foreign body or tissue damage (other than blood vessel) Takes 5-12 seconds to form a soft clot

14. 14 4.0 Blood compatibility 4.1.2 Factor affect the blood compatibility of a material i. Surface roughness Rough surface have a greater surface area and contact surface with blood compared to smooth surfaces Result in faster coagulation

15. 15 4.0 Blood compatibility ii. Surface Charge The tunica intima (the innermost layer of artery or vein) of a normal blood vessel has a negative surface charge due to proteins at surface of the cell membrane. Formed blood element (red cells, white cells, and platelets) also have a negative charge. Natural repulsive force between intima and cells minimizes cell damage and coagulation iii. Low surface tension Blood cells less likely to adhere to a surface with a low surface tension

16. 16 4.0 Blood compatibility iv. Heparinized surfaces Heparin is a polysaccharide with negative charge. Heparin is a naturally-occurring anticoagulant produced by basophils and mast cells. Heparin acts as an anticoagulant, preventing the formation of clots and extension of existing clots within the blood. it allows the body's natural clot lysis mechanisms to work normally to break down clots that have already formed Attempt made to attach heparin chemically to the surface of the implant to prevent blood clot.

17. 17 4.0 Blood compatibility 4.2 HEMOLYSIS Motion at a blood-surface interface may damage red and white blood cell resulting in cell death. Damage of cell occurs with shear stresses on the cells of less than 500dyn/cm 2. Chronic and accumulated damage of red blood cells and leakage of the cellular contents can result in: Anemia Kidney Failure Toxemia

18. 18 Blood contacting implant or devices BLOOD IN CONTACT Long termShort term Heart valve prostheses Vascular grafts Cardiac pacemakers Blood oxygenator of heart lung machine Dialyzer of hemodialysis machine Tubes and catheters for transport the blood

19. 19 5.0 Heart valve prostheses Why we need heart valve prosthesis? To replace disease natural human valve or, To replace malfunction natural valve Left ventricular valves (mitral and aortic) become incompetent more frequently than right ventricular valves (tricuspid and pulmonary). Why?

20. 20 5.0 Heart valve prostheses HEART VALVES Heart valves are very important, as they prevent the backflow of blood, which ensures the proper direction of blood flow through the circulatory system. Without these valves, the heart would have to work much harder to push blood into adjacent chambers. The heart is composed of 4 valves: tricuspid, pulmonary, mitral, and aortic.

21. 21 5.0 Heart valve prostheses HEART VALVE PROBLEMS There are numerous complications and diseases of the heart valves that prevent the proper flow of blood. Heart valve diseases fall into two categories, Stenosis The stenotic heart valve prevents the valve from opening fully, due to stiffened valve tissue. Hence, there is more work required to push blood through the valve Incompetence. the incompetent valves cause inefficient blood circulation by permitting backflow of blood in the heart

22. 22 StenosisIncompetence

23. 23 5.0 Heart valve prostheses TREATMENT OPTIONS On a large scale, medication is the best alternative, although in some cases defective valves have to be replaced with a prosthetic valve in order for the patient to live a normal life

24. 24 5.0 Heart valve prostheses MAIN PROSTHETIC HEART VALVE Heart valve prostheses can be classified into two type: 1. Mechanical prostheses : made of non-biological materials. 2. Biological heart valve: made of biological tissue Heart valves are designed to fit the peculiar requirements of blood flow through the specific chambers of the heart, with emphasis on producing more central flow and reducing blood clots.

25. 25 5.0 Heart valve prostheses 1. MECHANICAL PROSTHESIS a) Caged ball This valve uses a small ball that is held in place by a welded metal cage. The ball in cage design was modeled after ball valves used in industry to limit the flow of fluids to a single direction

26. 26 5.0 Heart valve prostheses b. Tilting disc Have a polymer disc held in place by two welded strut The disc floats between the two struts in such a way, as to close when the blood begin to travel backward and then reopen when blood begin to travel again. The titling-disc valves open at an angle of 60 ° and close shut at rate of 70 times/minute

27. 27 5.0 Heart valve prostheses Advantages: Provide improved central flowwhile still preventing backflow Reduce mechanical damage to blood cells Reduce blood clotting and infection Problem: Have a tendency for the outlet strut to fracture as a result of fatigue from the repeated ramming (smash into) of the struts by the disc.

28. 28 5.0 Heart valve prostheses c. Bileaflet valves Consist of two semicircular leaflets that pivot on hinges Advantages: Provide the closest approximation to centarl flow achieved in natural heart valve. Disadvantages: They do not close completely, which allows some backflow. Since backflow is one of the properties of defective valves, the bileaflet valves are still not ideal valves.

29. 29 5.0 Heart valve prostheses d. Trileaflet heart valve Afford true central flow characteristic with reduced back flow Good wear characteristic. Significantly improve patient’s quality of life. This will be achieved due to reduced consumption of anticoagulants by the patients, reduced noise, low blood hemolysis, and the elimination of the need for repeated implantations because of high reliability of the mechanical design.

30. 30 5.0 Heart valve prostheses BIOMATERIAL USED IN MECHANICAL HEART VALVE Heart valve typeComponentBiomaterial Caged ballBall/occluder Cage Suture ring Silicone rubber (Silastic) Cobalt-chromium alloy (Stellite 21®) or titanium Silicone rubber inser under knitted composite Teflon and polypropylene cloth Tilting discLeaflet Housing/strut Suture ring Polyacetal (Delrin®),pyrolytic carbon, ultra height molecular polyethylene (UHMWPE) Cobalt-chromium alloy (Haynes 25®) or titanium Teflon® or Dacron®

31. 31 5.0 Heart valve prostheses Heart valve typeComponentBiomaterial BileafletLeafleat Housing Suture ring Pyrolytic carbon Double velour Dacron® tricot knit polyester TrileafletLeaflet Ring Pyrolytic carbon Titanium alloy coated with high-density turbostratic carbon

32. 32 5.0 Heart valve prostheses Advantages of mechanical heart valve Disadvantages of mechanical heart valve High durability- typically last for the lifetime of the patient 1. The increased risk of blood clotting 2. When blood clots of any kind occur in the heart, there is a high probability of a heart attack or stroke. 3. Patient need to take anti-coagulant drug 4. Anti-coagulant caused birth defects in the first trimester of fetal development

33. 33 5.0 Heart valve prostheses 2. BIOLOGICAL/ PROSTHETIC TISSUE HEART VALVE i. Human tissue valves ii. Animal tissue valve Advantages: Design of valve are closer to the design of the natural valve. Do not require long term anticoagulant Do not cause damage to blood cells Do not suffer from many of structural problems experienced by the mechanical heart valve

34. 34 Human Tissue valve Homograft: valves that are transplanted from another human being Autograft: valves that are transplanted from one position to another within the same person. Dysfunctional aortic valve (exit of the left ventricle) is removed, patient’s pulmonic valve is then transplanted to the aortic position. A homograft pulmonic valve is usually used to replace the patient’s pulmonic valve.

35. 35 Human Tissue valve

36. 36 Animal tissue valve Refereed as heterograft or xenograft valves. The two common prosthesis valve from animal tissue are: PORCINE VALVES BOVINE PERICARDIAL VALVE

37. 37 Animal tissue valve  PORCINE VALVES  Valve tissue from pig  Valve tissue is sewn to a metal wire stent made of cobalt-nickel alloy.  The wire is bent to form three U-shaped prongs.  A Dacron cloth sewing skirt is attached to the base of the wire stent, and then the stents themselves are also covered with cloth.  Porcine valves have good durability and usually last for ten to fifteen years.

38. 38 Animal tissue valve BOVINE PERICARDIAL VALVE  Bovine pericardial valves are similar to porcine valves in design.  The major difference is the location of the small metal cylinder which joins the ends of the wire stents together.  In the case of pericardial valves, the metal cylinder is located in the middle of one of the stent post loops.  Pericardial valves have excellent hemodynamics and have durability equal to that of standard porcine valves after 10 years.

39. 39 Porcine valve Leafleat Stent

40. 40 Pericardial valve Leafleat Suture ring Stent

41. 41 Biological tissue valves Heart valve typeComponentBiomaterial Porcine bioprosthesis Leaflets Stent Suture ring Porcine aortic valve fixed by stabilized gluteraldehyde Polypropylene stent covered with Dacron, Elgiloy wire covered with porous knitted Teflon cloth Dacron, soft silicone rubber insert covered with porous Teflon cloth Pericardial bioprosthesis Leaflets Stent Suture ring Bovine pericardial tissue fixed by stabilized gluteraldehyde Polypropylene stent covered with Dacron, Elgiloy wire covered with porous knitted Teflon cloth PTFE fabric over silicone rubber filter

42. 42 Biological tissue valves Advantages of biological heart valve Disadvantages of biological heart valve 1. Design of valve are closer to the design of the natural valve. 2. Do not require long term anticoagulant 3. Do not cause damage to blood cells 4. Do not suffer from many of structural problems experienced by the mechanical heart valve 1. Stiffening of the tissue due to the build up calcium. 2. Calcification can cause a restriction of blood flow through the valve (stenosis) or cause tears in the valve leaflets.

43. 43 Common problem with implanted heart valve Mechanical valveBiological tissue valve 1. Thrombo-embolism 2. Structural failure 3. Red blood cell and platelet destruction 4. Tissue overgrowth 5. Damage to endothelial lining 6. Tearing of sutures 7. Paravalvular leakage 8. Infection 1. Tissue calcification (build up of calcium around the tissue 2. Leaflet rupture 3. Paravalvular leakage 4. Infection

44. 44 Prosthetic heart valve type

45. 45 Conclusion The future for replacement heart valves lies in tissue engineering. The most ideal replacement would be formed from the patient's tissue, and tailored to the right shape and dimensions. This would improve the biocompatibily factor, and increase the life expectancy of the heart valve.

46. 46

47. 47 6.0 VASCULAR GRAFT BLOOD VESSELS Blood vessel are the channels through which blood is distributed to body tissue. Blood vessel are classified as either: Arteries (carry blood away from the heart) Capillaries Veins (carry blood to the heart)

48. 48 6.0 VASCULAR GRAFT BLOOD VESSELS PROBLEMS Vascular graft is needed to replace diseased blood vessel such as atherosclerosis blood vessel and aortic aneurysm. Atherosclerosis is a disease in which plaque (plak) builds up on the insides of your arteries. Aneurysm is blood-filled dilation (balloon- like bulge) of a blood vessel caused by disease or weakening of the vessel wall.

49. 49 Blood vessel problem Atherosclerosis Aneurysm

50. 50 6.0 VASCULAR GRAFT TREATMENT OPTIONS The main treatment for atherosclerosis is lifestyle changes. You also may need medicines and medical procedures. For aortic aneurysms or aneurysms that happen in the vessels that supply blood to the arms, legs, and head (the peripheral vessels), surgery involves replacing the weakened section of the vessel with an artificial tube.

51. 51 6.0 VASCULAR GRAFT TypeDescription BIOLOGICAL GRAFT AutograftGraft transplanted from part of a patient’s body to another. Example: saphenous vein graft for pheripheral bypass AllograftHomograft. Transplanted vascular graft tissue derived from the same species as recipient. XenograftHeterograft. Surgical graft of vascular tissue derived from animal. Example: moddified bovine heterograft SYNTHETIC GRAFT Dacron PTFE (polytetrafluoroethylene) Other Woven, knitted Expanded, knitted Nylon, polyurethane

52. 52 6.0 VASCULAR GRAFT Polyurethane vascular graft photographed in situ in carotid artery

53. 53 Synthetic graft - Dacron Dacron grafts are manufactured in either a woven or knitted form. woven knitted

54. 54 Synthetic graft - Dacron Woven grafts have smaller pores and do not leak as much blood. To reduce the blood loss knitted grafts should be pre-clotted prior to insertion. They are less frequently used than woven grafts. Dacron grafts have recently been manufactured coated with protein (collagen/albumin) to reduced the blood loss and antibiotics to prevent graft infection. Dacron grafts are frequently used in aortic and aorto-iliac surgery.

55. 55 Synthetic graft - PTFE Polytetrafluoroethylene (PTFE) is a knitted graft. Its smooth surface is less thrombogenic than Dacron. Its smooth wall is prone to kinking as it passes around joints necessitating it to be externally supported.

56. 56 Synthetic graft-stent graft A stent graft is a tubular device, which is composed of special fabric supported by a rigid structure, usually metal. The rigid structure is called a stent. An average stent on its own has no covering, and therefore is usually just a metal mesh. Although there are many types of stent, these stents are used mainly for vascular intervention.

57. 57 Synthetic graft-stent graft The device is used primarily in endovascular surgery. Stent grafts are used to support weak points in arteries, commonly known as an aneurysm. Stent grafts are most commonly used in the repair of an abdominal aortic aneurysm, in a procedure called an EVAR (Endovascular Aneurysm Repair ). The theory behind the procedure is that once in place inside the aorta, the stent graft acts as a false lumen for blood travel through, instead of into the aneurysm sack.

58. 58

59. 59 Problem The commonest complications associated with the use of vascular grafts are: Graft occlusion (blockage) Graft infection (Graft infection is thankfully rare (1-2%)) True and false aneurysms at the site of anastomosis Distal embolisation (blocking of a graft) Erosion in to adjacent structures

60. 60 Conclusion Most of the vascular graft are stiffer compared to the host artery. Development with more compliant grafts and in modifying the surface interaction of the graft with blood may result in reducing the problems with loss of patency. Recent advance is to engineered vascular graft from recipients own tissue. This will provide better biocompatibility and performance.