Published on

  • Be the first to comment

  • Be the first to like this

No Downloads
Total Views
On Slideshare
From Embeds
Number of Embeds
Embeds 0
No embeds

No notes for slide


  1. 1. The best place to find helping hand is at the end of your arm --- Swedish Proverb. BIOMECHANICS OF MECHANICAL HEART VALVE 1 Benjamín González, Humberto Benítez, Kenneth Rufino, Merisabeth Fernández and Waleska Echevarría 2Abstract - Heart valves all are prone to disease and The mitral valve, which lies between the two left chambersmalfunction, and can be replaced by prosthetic heart of the heart, consists of two triangular-shaped flaps ofvalves. The two main types of prosthetic heart valves are tissue called leaflets. The leaflets of the mitral valve aremechanical and bioprosthetic. The mechanical valve is connected to the heart muscle through a ring called theexcellent in terms of durability, but is hindered by its annulus, which acts like a hinge.tendency to coagulate the blood. Bioprosthetic valve isless durable and must be replaced periodically. All The mitral valve is anchored to the left ventricle byvalve types must be durable, because the body is an tendonlike cords, resembling the strings of a parachute,extremely hostile environment for a foreign object, called chordae tendineae cordis.including prosthetic heart valves. Today, engineers areresearching new designs of prosthetic heart valves. They When working properly, heart valves open and close fully.use the mechanical properties to make an artificial heart In mitral regurgitation, the mitral valve does not open orvalve design. An artificial mitral valve is an option for close properly. Some blood from the left ventricle flowshumans with irreparable valve disease. backward into the left atrium with each heartbeat. Regurgitation refers to the leakage (backflow) of bloodKey words -- Heart valve, Biocompatibility, Alumina, through a heart valve.Titanium, Biomaterial, Polyether urethane, Polyester,Pyrolitic carbon. INTRODUCTIONHeart valves prevent the backflow of blood, which ensuresthe proper direction of blood flow through the circulatorysystem. Without these valves, the heart would have to workmuch harder to push blood into adjacent chambers. Theheart is composed of 4 valves (Figure 1). The Tricuspidvalve is between the right atrium and right ventricle. ThePulmonary valve is between the right ventricle and thepulmonary artery. The Aortic valve is between ventricleand the aorta and the Mitral valve is between the leftatrium and left ventricle. It opens and closes to control Figure 1. Heart Valves [1].blood flowing into the left side of the heart. Heart Valve Problems [7] Heart valves open like a trapdoor. The leaflets of the mitralvalve open when the left atrium contracts, forcing blood There are numerous complications and diseases of the heartthrough the leaflets and into the left ventricle. When the valves that can prevent the proper flow of blood. Heartleft atrium relaxes between heart contractions, the flaps valve diseases fall into two categories: Stenosis andshut to prevent blood, that has just passed into the left Incompetence. The stenotic heart valve prevents the valveventricle, from flowing backward. from opening fully, due to stiffened valve tissue. Hence, there is more work required to push blood through the1 This review article was prepared on December 8, valve. Whereas, the incompetent valves cause inefficient 2003 for the course on Mechanics of Materials - I. blood circulation and cause backflow of blood in the heart, Course Instructor: Dr. Megh R. Goyal. Professor in called as regurgitation. Biomedical Engineering, General Engineering Department, PO BOX 5984, Mayagüez Puerto Rico Treatment Options [22] 00687-5984. For details contact: or visit at: On a large scale, medication is the best alternative, but in some cases defective valves have to be replaced with a prosthetic valve in order for the patient to live a normal2 The authors are in the alphabetical order. life. An enormous amount of research and development has proven to be most beneficial, as prosthetic heart valve technology has saved thousands of lives. Engineers andDecember 2003 Applications of Engineering Mechanics in Medicine, GED at University of Puerto Rico, Mayagüez 1
  2. 2. scientists have done much work to design a valve that can For a decade and a half, the caged ball valve was the bestwithstand millions, if not billions, of cardiac cycles. The artificial valve design. In the mid-1960s, new classes oftwo main prosthetic valve designs include mechanical and prosthetic valves were designed that used a tilting disc tobioprosthetic (tissue) Heart Valves. better mimic the natural patterns of blood flow. The tilting- disc valves have a polymer disc held in place by twoMitral Valve Replacement [22] welded struts. The disc floats between the two struts in such a way, as to close when the blood begins to travel Valve replacement is done when valve repair is not backward and then reopens when blood begins to travelpossible. Artificial Heart valve is the last solution for forward again. The tilting-disc valves are vastly superior topeople with a damage heart valve caused by any disease as the ball-cage design. The titling-disc valves open at anregurgitation, etc… In valve replacement surgery, an angle of 60° and close shut completely at a rate of 70artificial prosthetic valve replaces the damaged mitral times/minute. This tilting pattern provides improved centralvalve. The two types of artificial valves are mechanical and flow while still preventing backflow. The tilting-disc valvestissue. Mechanical valves, which are made of biomaterials, reduce mechanical damage to blood cells. This improvedmay last a long time. However the patient with a flow pattern reduced blood clotting and infection.mechanical valve must use an anticoagulant medication However, the only problem with this design was itssuch as warfarin (Coumadin, Panwarfin) for the rest of life tendency for the outlet struts to fracture as a result ofto prevent blood clots from forming on the valve. If a blood fatigue from the repeated ramming of the struts by the disc.clot forms on the valve, the valve won’t work properly. If aclot escapes the valve, it could lodge in an artery to the Bileaflet valves were introduced in 1979. The leafletsbrain, blocking blood flow to the brain and causing a swing open completely, parallel to the direction of thestroke. Tissue valves are made of biological tissue such as a blood flow. The bileaflet valves were not ideal valves.pig’s valve. These kinds of valves are called bioprostheses. The bileaflet valve constitutes the majority of modern valveThese may wear out over time and may need to be replaced designs. These valves are distinguished mainly forin another operation. However the tissue valve can avoid providing the closest approximation to central flowuse of long-term anticoagulation medication. achieved in a natural heart valve.Mitral valve repair or replacement involves open-heart Mechanical Heart Valvesurgery. Through an incision in the breastbone (sternum),the heart is exposed and connected to a heart-lung machine Prosthetic Heart Valves are fabricated of differentthat assumes the breathing and blood circulation during the biomaterials. Biomaterials are designed to fit the peculiarprocedure. The surgeon then replaces or repairs the valve. requirements of blood flow through the specific chambersAfter the operation, which lasts several hours, the patient of the heart, with emphasis on producing more central flowspends one or more days in an intensive care unit, where and reducing blood clots. Some of these biomaterials arethe general recovery is closely monitored. alumina, titanium, carbon, polyester, polyurethane etc…History and Advances of Artificial Heart Valves [1] The mechanical properties of these biomaterials involve how a material responds to the application of a force. TheThe first mechanical prosthetic heart valve was implanted three fundamental types of forces that can be applied arein 1952. Over the years, 30 different mechanical designs stretching (tension), bending, or twisting. Materialshave originated worldwide. These valves have progressed respond to the forces by deforming (changing shape). Anfrom simple caged ball valves, to modern bileaflet valves. elastic response is reversible, while an inelastic response isThe caged ball design is one of the early mechanical heart irreversible. In the elastic region, an elastic modulus relatesvalves that use a small ball that is held in place by a welded the relative deformation a material undergoes to the stressmetal cage. The ball in cage design was modeled after ball that is applied. The transition between elastic deformationvalves used in industry to avoid backflow. Natural heart and failure occurs at the yield point (or stress) of thevalves allow blood to flow straight through the center of material. In designing a component with the material, anthe valve. This property is known as central flow, which inelastic response is considered failure. Failure can bekeeps the amount of work done by the heart to a minimum. plastic deformation or ductile failure. It can also beWith non-central flow, the heart must work harder to breaking, including brittle failure or fracture. Mechanicalcompensate for the momentum lost due to the change of properties of a material in the range of elastic behaviordirection of the fluid. Caged-ball valves completely block include its elastic modulus under tension and shear stresses,central flow; therefore the blood requires more energy to its Poisson’s ratio, its resilience, and its flexural modulus.flow around the central ball. In addition, the ball may cause The transition to failure is denoted by the yield stress ordamage to blood cells due to collision. Damaged blood breaking strength of the material.cells release blood-clotting ingredients; hence the patientsare required to take lifelong prescriptions of anticoagulants.December 2003 Applications of Engineering Mechanics in Medicine, GED at University of Puerto Rico, Mayagüez 2
  3. 3. BIOMATERIALS Alumina as biomaterialThe requirements for an artificial heart valve are Alumina is the most widely and versatile ceramic. Much ofstaggering. The valve must be easy to insert. It must last a the research on this ceramic was done during the 1950s andlong time. It must be able to open and close 35 million 1960s. Alumina is chemically stable against mosttimes a year for 20 to 50 years. It must allow high blood environments except hydrofluoric acid and some moltenflow with minimal turbulence and must not leak. The valve salts. These traditional ceramics set upon hydration ifalso should not cause blood clots and also: produced in the special form of re-hydratable alumina cement (more commonly in the form of calcium aluminate Collapse to 5 mm when crimped. cement). Also alumina is widely used for medical implants Top of stent expands to 25 mm. like mechanical heart valve. This type of ceramic is also Middle of stent expands to 30 mm. used in several medical fields as dentistry, orthopedical and Bottom of stent expands to 25 mm. cardiologist application. Deployed height is 25.4 mm. Collapse to 5 mm when crimped. It is a ceramic, non-metallic, and inorganic compound that Barrel shaped. displays great strength and stresses resistance to corrosion Top stent expands to 30 mm. wear and low density. Alumina is a highly bioinert No damage to leaflets. material and resistant to most corrosive environments, Length is 12.7 mm - 25.4 mm. including the highly dynamic environment of the human body.1. Alumina (Al2O3) : aluminium oxide [17] Compatibility between Bioceramics and the HumanAlumina (Al2O3) is a bioinert material. Bioinert materials Environment [17 and 26]do not chemically react with the local chemicals As aresult, cells can survive next to the material but do not The major problem on implants designs is the fairly limitedform a union with it. Often fibrous protective cells grow choice of materials, and consequently, determination of thenear the implant surface to protect local cells from compatibility of the material of choice with the tissue.mechanical damage. Bioinert materials were first used for There are no standard methods of compatibility testing andprosthetics. These materials can be very strong but have the number of variables involved is usually much largerthe disadvantage of not bonding to the local cells. than the typical engineering problem. For example, humanNumerous problems have been encountered in anchoring blood is 1/3 as salty as seawater, stays at a steady 37ºC, andthe bioinert implants to bone. In early implants, some contains active enzymes (the immune system).implants became deformed or displaced, causing seriousdamage to the surrounding tissue. Human body is one of the most corrosive environments that inorganic substances can encounter. Furthermore, as theAlumina is a traditional ceramics that offer many various metabolic processes occur in an organism theadvantages compared to other biomaterials. These are various complex molecules that may enclose a substanceharder and stiffer than steel; more heat and corrosion continually change in concentration and variety. Lactic acidresistant than metals or polymers; less dense than most produced from muscle cells during anaerobic cellularmetals and their alloys; and their raw materials are both respiration is a prime example. Additionally, the timeplentiful and inexpensive. Design requirements for alumina factor of the “compatibility reaction” is important; theas a biomaterial are: implant - tissue interaction is a sequential chain of reactions, characteristic for the material and the patient. High fluid resistance. Avoid hemorrhage. Beyond the chemical factors, the response of tissue Low incident of thromboembolism. depends additionally on geometric characteristics of the Be economic. implant, e.g. shape, size, surface/volume ratio. These High performance. factors will generally determine the state of stress at the Avoid stiffening of the leaflets. interface and thus could interfere with the interfacial Optimal designs. reactions. Porosity and its size distribution within an Good thermal conductivity. implant have been shown to affect the interactions. It has Ability to open and close 35 million times a year been generally established, that tissue will grow into pores for 20-50 years. larger than ~120 nm. Biocompatibility. Most polymers seem to be slowly “digested” by the human Avoid blood clots. body and metals are slowly corroded: high concentration of Available easily. metallic elements has been detected close to the (metallic) implant surface. Passive oxide film can significantly slowDecember 2003 Applications of Engineering Mechanics in Medicine, GED at University of Puerto Rico, Mayagüez 3
  4. 4. down the reactions with tissue, rendering titanium or more scratch resistant than metal or polyethylene; so it isstainless steel virtually neutral. However, polymeric and most durable than other valve materials.metallic implants are generally classified as “temporary”implants, with very low adhesive strength of attachment to b. Ion release: Since ceramics do not release ions, there arethe tissue. no long-term unknowns pertaining to systemic effects due to ion release with this hard bearing couple, unlike metal-Alumina is considered bioinert due to a thin layer of metal bearing couples.titanium ions on its surface, although some studies showthat the body can absorb alumina. Various researchers have c. Friction and wetability: A material that holdsfound alarmingly low levels of Al in rats’ nervous systems lubrication to its surface is considered wet able. Aluminaafter the 20-week postoperative period. ceramic is a more wet able material than metal. Lubrication helps to reduce friction between components. AluminaThe bioinert ceramics, like ZrO2, Al2O3, SiC, Si3N4 do not ceramic has improved since the 1974. Third generationdevelop strong interfaces, but also do not liberate ions into materials have nearly twice the strength as the originalthe internal environment. This is at the expense of lesser material because of enhancements in purity, density andmechanical performance and reliability of ceramics, as grain size.compared to metals. A compromise is ceramic-coatedmetal, although some additional liabilities are created (e.g. d. Fracture: This property continues to be the primaryadhesion of the coating; increased processing costs etc.). concern regarding ceramic components. Improper handling and implantation, poor implant design and material, orAlumina Mitral Valve [26] mismatched components caused fractures in early ceramic designs. When correctly implanted, the fracture rate hasCeramic materials are somewhat limited in applicability by been reported between one-tenth to one-twentieth of atheir mechanical properties, which in many respects are percent (0.001 - 0.0005) and it is projected thatinferior to those of metals. The principal disadvantage is a contemporary materials will be even lower. Aluminadisposition to catastrophic fracture in a brittle manner with should be use, only in compression.very little energy absorption. e. Strength: Though ceramics are brittle in nature, aluminaThe ceramic mitral valve is comprised of a single crystal ceramic inserts are extremely strong and exceed FDAalumina disc and titanium valve ring. Alumina consists of Guidance Document standard for ceramic heads of 46 kNaluminum and oxygen ions. These ions combine firmly by or 10,340 pounds burst strength. This exceeds the strengthionic bond and are arranged in hexagonal closed packed of the ceramic head as well as the neck of the femoral stem.structure. The single crystal alumina disk is 1.0 mm thick. As with any modular interface under load, there is aBoth mechanical and chemical polishing smoothed the potential for micro motion and associated fretting and/orsurfaces. The valve ring was milled from a single piece of corrosion. However, the alumina design minimizes thetitanium and was coated with Tin by reactive ion plating amount of motion at the taper interface, which should(See appendix IV). Alumina has a good blood reduce the corrosion potential.compatibility, excellent wear resistance, largely inert anddurability. Alumina mitral valve avoids thrombus Alumina mechanical properties are summarized as:formation and thromboembolism. • Good mechanical strength (Figure 3).Tensile strength of single alumina is more than three times • Good thermal conductivity.greater that LTI carbon. Alumina has hardness eight times • High electrical resistivity.greater than LTI carbon. Alumina is insoluble in water and • High hardness (Figure 2).has high corrosion. • Wear resistant.Properties of Alumina • Good chemical stability. • Largely inert.a. Scratch resistance: The extreme hardness of alumina is • Excellent tribological characteristics.second only to a diamond. Metal-on-metal articulations canbe scratched causing an abrasive surface. Foreign debris inthe joint may also accelerate implant wear. Alumina isDecember 2003 Applications of Engineering Mechanics in Medicine, GED at University of Puerto Rico, Mayagüez 4
  5. 5. Biomaterials and implant research will continue to concentrate on serving the needs of medical device manufacturers and recipients, as well as medical professionals, and on developing technologies to meet TitaniumNitride those needs. Future biomaterials like alumina will incorporate biological factors directly into an implant’s Titanium surface to improve biocompatibility and bioactivity. New Series1 projects will be directed at materials development for LT C I arbon improved mechanical integrity, corrosion resistance, and Series2 Alumina biocompatibility. Institute engineers will also apply statistical finite element analysis, stereo imaging strain 0 5 10 15 20 analysis, and composite materials to the biomaterials program. Therefore, alumina is one of these experimental materials for the future. Figure 3. Tensile Strength (MPa) of biomaterials [26].Figure 2. Hardness of different biomaterials [26]. 1000Valve Problems with Alumina 800 600a. It is a hard material so that machining is difficult. 400Therefore, some molding process must be developed which 200can produce a finished valve with the accurate internal 0 Titanium Alumina Carbon Stainlessshape required to achieve good homodynamic performance. LTI Steelb. The tissue covering requires a porous, textured aluminasurface on which to anchor itself firmly, but the main bodyof the conduit valve must be in the most dense form ofalumina, with virtually no porosity, in order to maintainstructural strength. The molding process must therefore 2. Polyesteraccommodate variable porosity in some way. What is polyester? [27]c. Alumina cannot avoid thromboembolism totally. Polyester is a synthetic resin formed by the condensation of polyhydric alcohols with diabasic acids. Polyesters areAlumina Future thermosetting plastics used in making sythentic fibres and constructional plastics. It is an extremely resilient fibre thatResearch is being done to combine alumina with other is smooth, crisp and particularly springy. Its shape ismaterials for better heart valve implants. These determined by heat and it is insensitive to moisture. It isexperiments try to avoid tromboembolism, which is the lightweight, strong and resistant to creasing, shrinking,major problem on heart valve implants. Today, there are no stretching, mildew and abrasion. It is readily washable andmaterials to avoid totally thrombosis. Alumina is a is not damaged by sunlight or weather and is resistant tomaterial with good mechanical properties, but mechanical moths and mildew. The following requirements must beheart valve manufactures didn’t use for this purpose. satisfied to use polyester as a biomaterial in heart valvesInstead alumina is utilized in dental implants. implants:Lawsuits against medical device manufacturers, • The body’s immune system must not attack therestructuring of FDA approval procedures, patient biomaterial.expectations, and the health care reform movement are • Compatible with body tissues and fluidschanging the future of the medical device community and • Must have strength, flexibility and hardnessshaping the direction of biomaterials research. As a result, • Must be nontoxic, nonreactive or biodegradablenew materials and manufacturers will be required to meet • The replacement valve must be smooth to preventFDA standards. Another important issue not often the destruction of blood vessels.discussed is that implant recipients expect an implant to • The valve must also be anchored to the inside offunction and to last forever. the heart. • Must be an elastomer so it can be flexible during the pumping cycle.December 2003 Applications of Engineering Mechanics in Medicine, GED at University of Puerto Rico, Mayagüez 5
  6. 6. • The material must not exhibit mechanical fatigue well as prosthetic dilatation and failure caused this concept over the device’s lifetime. to be abandoned in the late 1970s. Surprisingly enough, the • The material’s surface must have an acceptable ideal values for the porosity and water permeability of a low propensity for thrombus formation, as well as vascular prosthesis are defined poorly. the best possible blood compatibility • Must not be prone to calcification. In spite of the success of expanded PTFE grafts that remain • The material must be easily formed into complex patent for many years without any tissue encapsulation, it is shapes. still believed that complete healing of the luminal surface is a critically important requirement for long-term patency.Structure and Physical Properties of Polyester One approach to achieve this was proposed by DeBakey and to improve the anchoring of fibrous tissue, increase • Polyester chains tend to be flexible and are easily cellular adhesion, and hence promote the formation entangled or folded. neointima by the use of the velour design. This involves • Degree of crystallinity is the amount of ordering weaving or knitting rather than straight fibers to give a in a polymer. rougher, randomized, and more open appearance to the • Stretching or extruding a polymer can increase external and/or internal surface of the graft. External velour crystallinity. enables better incorporation of the graft within the host tissue, whereas internal velour encourages the formation of • Degree of crystallinity is also determined by thicker neointima. This may be less important in clinical average molecular mass. practice since complete endothelialization is never • Bonds formed between polyester chains make the accomplished in humans. Even so, internal external and polyester stiffer. double velour grafts are widely available.Development of Polyester in Vascular Surgery As a result of the complications such as dilatation associated with the light-weight weft-knitted design,Vascular prostheses fabricated as polyester textile tubes are manufacturers have taken steps to increase the strength ofmost frequently used devices in peripheral vascular surgery grafts by using thicker polyester yarns and tighter, morefor the replacement of large and medium sized vessels. compact woven constructions. The more open wovenLong term results representing a period of follow-up over velour constructions should be anastomosed with a larger15 – 20 years have shown satisfactory results when Dacron than normal bite or cut with a hot cautery in order to reducegrafts are installed in the aortic and iliac sites. Technical the risk of fraying at the suture line. The regular woven anddevelopments to improve the device over the years have low porosity woven design are used widely for thepassed through different generations of concepts. The replacement of the thoracic aorta and for interventionsrelative merits of these different designs are still a matter of involving a cardiopulmonary bypass with heparinization.intensive research. For those surgeons who prefer the ease of handling and suturing of the knitted construction, most major modelsWoven or Knitted Design with the more dimensionally stable warp knitted prosthesis have now replaced former weft knitted models, thusWeslowski was the first to recognize the importance of the ensuring the same good anchorage of the neointima butporosity within the graft wall for the healing process of the avoiding the complications associated with dilatation andgraft. By using a more open textile structure with large raveling of the textile structure in vivo. The importance ofpores between the polyester fibers it was predicted that maintaining the initial strength of vascular prostheses at ancellular elements and fibrous tissue would be able to acceptable level is now widely accepted.penetrate the interstices of the graft wall and generate awell-attached, more completely healed surrounding Externally Supported Designcapsule. Unfortunately, measurements of waterpermeability were mistakenly assumed to measure the The problem of flattening and occlusion of a vascular graftporosity of the graft wall, and as a result manufacturers at the point where it crosses a knee or hip joint is wellproduced thinner and thinner textile structures using finer known. External reinforcement of the graft by means of aand finer polyester yarns with a view to improve the rigid spiral support has proven to be effective in alleviatinghealing performance of the prostheses. The creation of the this problem and has found merit in the axillofemoralultra-light-weight design provided the surgeon with a more position as well. The performance observed during animalflexible graft that was easier to handle and suture. But too trials as well as clinical observations of explanted deviceshigh water permeability posed difficulties in preclothing suggest that high levels of friction and fatigue can occur tothe graft so as to achieve hemostasis. Problems of the textile structure underneath the rigid external support.hemorrhage at the time of implantations and complications This is particularly problematic with those models whereassociated with secondary hematomas around the grafts as the external support is not well attached to the outer surfaceDecember 2003 Applications of Engineering Mechanics in Medicine, GED at University of Puerto Rico, Mayagüez 6
  7. 7. of the prosthesis. As a result, perhaps the most valuable of polyester have gained in popularity due to the similarapplication for this type of design is in the axillofemoral rates of occlusion and ease of use. Despite thesebypass where compression of the graft may occur, when the advantages, there is continuing concern over thepatient is lying on the relevant side. nevertheless high rates of occlusion, for both native and synthetic grafts which significantly contributes to theComposite Design greater than 30% failure rate experienced within one year. As these failures often lead to limb loss and other seriousIn order to improve the biocompatibility of porous complications, the availability of a non-thrombogenic graftsynthetic grafts, it has been proposed that the polyester or one with reduced thrombo-genicity would havetextile structure be impregnated or coated with a significant clinical impact and could serve to reduce thecrosslinked protein. A number of different proteins have incidence of thrombosis related complications. Polymericbeen studied, including albumin, collagen, gelatin, elastin, biomaterial surfaces such as polyester and PTFE areand chitosan. Observations from comparative in vivo intrinsically thrombogenic. Grafts composed of thesestudies as well as from our explant retrieval program materials can be surface modified in order to reduce thisindicate that the healing process is virtually identical with inherent thrombogenicity. Heparin treatment of the surfacesthe coated and uncoated grafts. The only difference, if any, of a number of medical devices such as catheters, heartresides in the rate of the healing process, wich is slowed by valves, stents and bypass circuitry has successfully beenthe addition of the protein coating. Because the prosthesis used as a means of reducing surface already nonpermeable to blood and ready to implant themoment it is removed from is sterile packaging, the need In 1991, InterVascular developed the concept of addingfor blood transfusion and preoperative manipulation is unfractionated high molecular weight heparin to the innerreduced. In addition, since the coating is resorbed slowly, it lumen of a graft through a stable bonding process. It washas been proposed that antibiotics and growth promoting believed that this modification of the graft surface couldfactors be added to the protein in order to reduce the risk of significantly reduce its thrombogenicity and potentiallyinfection and enhance the healing of the neointima. improve graft performance and clinical outcome. Heparin is coupled to the InterGard Heparin surface using tri-The cellular seeding of vascular prostheses with endothelial dodecylammonium chloride (TDMAC) which forms ancells appears to be a very promising technique. The insoluble complex with heparin and in turn binds with highexperimental research to date has improved our affinity to the polyester flow surface through its longunderstanding of the different functions of the endothelial hydrophobic tails. The heparinized graft is then coated withcell and its interactions with blood. However, the efficiency collagen which acts as a barrier to prevent rapid release ofof the cell seeding procedure leaves much to be desired, the heparin from the graft surface. A series of studies wasand, while the technique has proven useful in a few human performed to evaluate the safety and efficacy of thetrials, it is not yet ready for routine clinical use. In the long InterGard heparin coated graft. Animal studies wereterm, there it do appear to be beneficial in using this performed to confirm that no bleeding complications andtechnology, particulary in femoropopliteal and distal sites good healing characteristics were associated with the use ofwhere the rate of flow is limited and in reducing the the heparin bonded graft.incidence of infection. In addition, complete ISO 10993 biocompatibility testsAnother type of surface coating proposed for vascular were performed to assure that safety and biocompatibilitygrafts involves the use of the plasma graft polymerization requirements were met. Bench studies were conducted toprocess. This technique can modify the surface chemistry evaluate the retention of heparin on the InterGard heparinand hence the biocompatibility of a synthetic material. graft in a simulated model of circulation usingTypically, plasma of fluorethylene gas is generated in a physiological flow rates and pressures. In these studies,evacuated chamber containing the prosthesis by means of a heparin levels remained constant for 7 days in thehigh-frequency magnetic field. The free radicals so InterGard heparin collagen coated graft but declinedproduced react rapidly with each other and with any surface dramatically in the non-collagen coated graft demonstratingthey encounter, depositing a thin layer of a fluorocarbon that the stable bonding process of ionic coupling topolymer on the polyester fibers of the vascular graft. The TDMAC followed by hydrophobic interaction withflow surface is thus likely to be more hydrophobic and polyester immobilizes the heparin to the graft. Furthermore,biocompatible. Preliminary results in animals have so far the collagen coating helps retain the heparin complexbeen promising, but they have not been confirmed in preventing its premature release. Additional studies werehumans. performed which demonstrated that the heparin-collagen coating dramatically reduces the deposition of fibrin (aBiocompatibility measure of thrombogenicity) relative to uncoated polyester Although saphenous vein remains the material of choice grafts. These studies coupled with on going promisingfor vascular reconstruction, fem-popliteal grafts composed clinical data continue to support the safety, utility andDecember 2003 Applications of Engineering Mechanics in Medicine, GED at University of Puerto Rico, Mayagüez 7
  8. 8. clinical benefits associated with the InterGard Heparin lenses, removable dental prostheses, renal dialyzers), andgraft. transient applications (e. g. cardiopulmonary bypass, over- the-needle catheters, diagnostic and therapeutic catheters).Polyesters Chemical Properties [20] The polymers used most often in these applications are the silicone elastomers, the acrylics, polyvinyl chloride, fluorinated ethylene propylene and polycarbonates.Polyesters are formed either by a reaction between a dibasicacid and a dihydroxy alcohol or by the polymerization of a In the past ten years, research work on the artificial hearthydroxy carboxylic acid. The chemical structure of a has stimulated interest in this new family of polymers, thepolyester is shown in figure 4. Polyesters are naturally clear segmented polyurethane elastomers. Originally developedand colorless; however they can be colored and made for commercial applications, these polymers exhibit highaccording to specifications. Polyesters do not show wear flexure endurance, high strength, and inherentwith exposure to poor weather conditions. They are highly nonthrombogenic characteristics, and are expected to haveresistant to chemical deterioration, withstanding most a positive effect on future medical applications. Segmentedsolvents, acids, and salts. They are also resistant to heat polyurethane polymers are widely used as artificial heart,damage and can be made to be self-extinguishing. vascular grafts, catheter, diaphragm of blood pump, pacemakers wire insulation, heart valves, cardiac-assistNot to be outdone, DuPont was also at the forefront of devices, components of hemodialysis units, skin grafts andpolyurethane technology in the U.S., receiving patents in blood filters. Since the segmented polyurethane exhibit1942 covering the reactions of diisocyanates with glycols, high strength, nonthrombogenic characteristics, the mostdiamines, polyesters and certain other active important applications appear to be in the cardiovascularhydrogencontaining chemicals. From these humble area. Because of higher hydrolytic resistance and betterbeginnings emerged the polyurethanes, the most versatile properties at low temperatures, the structures ofpolymers in the biomaterials armamentarium. polyurethanes prepared from lactones can be used as medical, solvent-activated, pressure-sensitive adhesives. Future scope of polyurethane A material used in the leaflet heart valves, mechanical heart valve coatings and total artificial heart is polyether-basedFigure 4. Chemical Structure of polyester [20]. polyurethane. However, one drawback of this material is the absorption of the proteins and thus, the onset of3. Polyurethanes [25 and 27] thrombosis and bacterial infection. The right materials have the good mechanical properties of polyurethane whilePolymers are considered some of the most promising class eliminating the risk of thrombosis and bacterial infection.of biomaterial. They can be selected according to certain Unfortunately, scientists have been unable to find a suitablecharacteristics such as mechanical resistance, degradability, substitute with such mechanical properties as well aspermeability, solubility, as well as transparency. relative biocompatibility. Therefore, scientists have begunPolyurethanes are the polymers most widely used in the searching for possible improvements to polyurethane in anconstruction of blood-contacting products and devices. attempt to increase its biocompatibility.History of polyurethane One possible solution to the compatibility problem is to synthesize a polymer alloy consisting of polyurethane alongNineteen eighty-seven marked the 50th anniversary of the with a phospholipid polymer. A current polymer alloy thatintroduction of polyurethanes. Professor Otto Bayer was has shown promise in combating the onset of thrombosis assynthesizing polymer fibers to complete with nylon when well as bacterial infection is 2-methacryloyloxethylhe developed the first fiber-forming polyurethane in 1937. phosphorylcholine (PMEH) with segmented polyurethane. Research on this alloy has shown a significant decrease inPolyurethanes technology the amount of proteins absorbed at the blood-suface interface. In fact, when protein adsorption data wasCurrent activities of suppliers, designers, manufacturers recorded, the amount of the protein adsorbed on the 2-and physicians clearly indicate that devices manufactured methacryloyloxethyl phosphorycholine segmentedfrom synthetic polymers have become an integral part of polyurethane tubing was only 17% of that adsorbed byhealth-care technology. Initially focused on life-threatening segmented polyurethane tubing alone. In similar attempt,situations, their clinical uses now include permanent scientists synthesized an alloy of polyurethane with theimplantation (e. g. artificial hearts, hip prostheses, addition of poly (tetramethylammonium) oxide andintraocular lenses), intermediate applications (e. g. contact methylene diphenylene diisocyanate along with chainDecember 2003 Applications of Engineering Mechanics in Medicine, GED at University of Puerto Rico, Mayagüez 8
  9. 9. extenders of 3-trinethylammonium-1,2-propanedioliodide demonstrates an impressive combination of mechanical(TMPI) and 3-dimethylamino-1,2-propanedioliodide properties and biological compatibility. The Polymer(DMP). This alloy had been previously found to restrict the Technology Group developed Elasthane in response toonset of thrombosis. In an experiment conducted to Dows decision to limit Pellethanes use in chronicallydetermine the protein attachment rate constant of three implanted medical devices. In developing Elasthane, PTGpolyurethane alloys as well as pure polyurethane. This invested in the same continuous reactor technology to offerpolyurethane, labeled PEU-N, was found to have a higher the only Pellethane substitute with the same high molecularattachment constant (.00059 cm/min) than either of the weight and reduced thermal history as Pellethane. PTG hasother polyurethane alloys including a phospholipids rigorous quality control and documentation of thepolymer alloy (PEU-G). However, PEU-N did have a lower manufacturing procedures, formula optimization, andadhesion constant than pure polyurethane (PEU-B). precision feed pumps. Formal validation of Elasthane was accomplished through rigorous short- and long-term testingNot all polyurethanes are equally effective in their in conjunction with a major academic institution and abiocompatibility properties. Polyurethanes comprise a large medical device company that has since received approval tofamily of materials, with urethane linkage being the only implant the material. A comprehensive FDA Masterfile alsocommon characteristic. They have been found to vary in backs Elasthane.clinical applications. When implanted in the human body,polyester-based polyurethanes tend to undergo a rapid Elasthane™ polyether urethane is a thermoplastichydrolysis and should be avoided in medical applications. elastomer formed as the reaction product of a polyol, anDue to their quick crystallization, polycaprolactone-based aromatic diisocyanate and a low molecular weight glycolpolyurethanes can be used as medical applications, but only used as a chain extender. Polytetramethylene oxideas pressure-sensitive adhesives. Polybutadiene-based (PTMO) is reacted in the bulk with aromatic isocyanate,polyurethanes have been investigated, yet no medical 4,4-methylene bisphenyl diisocyanate (MDI), and chainapplication has been found to date. Castor oil-based extended with 1,4-butanediol.polyurethanes can be used, but due to their poor tearresistance, have a very limited use in medical applications Application of Elasthane™ polyether urethanesince they are virtually insensitive to hydrolysis, andtherefore are very stable in the physiological environment. Numerous medical devices and technologies have benefited from the combination of exceptionally smooth surfaces, excellent mechanical properties, stability, and good4. Polyether urethane biocompatibility of Elasthane™ polyether urethane.In the preparation of this type of polymers, polyether-based Pellethane is currently the polyurethane used for theglycols are used. If they are cured with aromatic diamines tricuspid semilunar valves. Due to its high molecularthen their structure-property relationships will be very weight, valves fabricated from Elasthane have shown tosimilar to those of polyester urethanes. At high NCO/NH2 reduce the degree of calcification. Furthermore, Elasthaneratios the excess isocyanate forms biuret branch points. that has been chemically modified with polyethylene oxideThus, an increase in cross-linking causes a reduction in (P) and sulfonate (SO) SMEs showed lower surface plateletmodulus, elongation, compression set, and tears strength. adhesion and thrombus formation, suggesting improved blood compatibility.The secondary reactions occur to a much less extent thanthe primary reactions but their importance must not be Hydrodynamic evaluation of Pellethane valves showedunderestimated. Formation of allophanates or biurets is minimum pressure drop and very low energy lossesresponsible for some of the cross-linking and branching compared with other commercially available valves. It wasand therefore has an important influence on the properties also found that in durability tests, prototypes have lastedof the polyurethane product. for 17 years.Elasthane™ polyether urethane [19] Mechanical Properties of Polyether urethane [10]Elasthane™ polyether urethane is a high-strength, aromatic At lower hardness levels, practically all elastomericthermoplastic with a chemical structure and properties very materials, including polyurethane elastomers, merely bendsimilar to Pellethane® 2363 polyetherurethane series, which under impact. As conventional elastomers are compoundedhas been used to fabricate a large number of implantable up to higher hardness they tend to lose elasticity and crackdevices, including pacemaker leads and cardiac prosthesis under impact. On the other hand, polyurethane elastomersdevices such as artificial hearts, heart valves, intraaortic when at their highest hardness levels have significantlyballoons, and ventricular assist devices. PTGs Elasthane is better impact resistance than almost all plastics.designed for chronically-implanted medical devices andDecember 2003 Applications of Engineering Mechanics in Medicine, GED at University of Puerto Rico, Mayagüez 9
  10. 10. Such great toughness, combined with the many other useful to improve blood compatibility of implantableoutstanding properties associated with the high hardness polyurethanes, and may also be advantageous as regardspolyurethane leads to many applications in engineering. fatigue durability of flexing materials in long term(Appendix I gives properties of different kinds of applications.Polyurethanes). Polyurethane heart valves: Fatigue failure, Calcification and Polyurethane StructureBiocompatibility of Polyether Urethane Six flexible-leaflet prosthetic heart valves, fabricated fromThe blood contacting surface of some leaflets hearts valves a polyether urethane urea (PEUE), underwent long-termare made of polyether urethane (PEU, n = 22). This fatigue and calcification testing by Dernacca GM,polyurethane can be resistant to thrombus formation when Guldransen NJ; Wikinson R; and Wheatley DJ. Theyprocessed into an ultra smooth contacting surface. discovered that three valves exceeded 800 million cyclesElastomeric polyurethanes are inherently thromboresistant. without failure. Three valves failed at 775, 460, and 544Although blood compatibility and nonthrombogenicity are million cycles, respectively. Calcification was observedsubject to many complex factors, such as polymer surface with and without associated failure in regions of highcomposition, device configuration, and blood-flow strain. Comparison with similar valves fabricated from acharacteristics, they tend to perform well in numerous polyether urethane (PEU) suggested that the PUE is likelydevice configurations. Their apparent thromboresistance is to fail sooner as a valve leaflet. Localized calcification wasthought to reside in polyurethane’s ability to preferentially developed in PEUE leaflets at the primary failure site ofabsorb serum albumin. PEU leaflets, close to the coaptation region of three leaflets. The failure mode in PEU valves had theWhen the biomaterial surface comes into contact with appearance of abrasion wear associated with calcification.blood, a protein layer of fibrin results from the High strains in the same area may render the PEUE leafletspolymerization of fibrinogen. When bacteria interacts with vulnerable to calcification. Intrinsic calcification of thisthe surface of a blood-contacting biomaterials it does so tape, however, is a long-term phenomenon unlikely tothrough this adsorbed protein layer. Therefore, bacteria can cause early valve failure. Both polymers performedeasily attach itself to the material surface and cause similarly during static in vitro and in vivo calcificationinfection. testing and demonstrated a much lesser degree of calcification than bioprosthetic types of valve materials.When choosing a material to combat bacterial adhesion, it Polyurethane valves can achieve the durabilities required ofis essential that the material limits protein adsorption. an implantable prosthetic valve, equaling the fatigue life ofProteins tend to be negatively polarized and thus currently available bioprosthetic valves.hydrophobic in nature. With this in mind, it is beneficial toselect a material that is similarly polarized, thus likely to Polyurethane heart valve durability: Effects of leafletsrepel the proteins from the biomaterial’s surface, hindering thickness and materialthe protein-surface interaction and protein adsorption bythe surface. By disrupting this adsorption of proteins, the The durability of a flexible trileaflet polyurethane valve ismaterial is less likely to develop a protein layer and less determined by the thickness of its leaflets. Leaflet thicknesslikely to promote the development of bacterial growth and is also a major determinant of hydrodynamic function. Theinfection. study was conducted by Dernacca GM; Guldransen NJ; Wikinson R; and Wheatley DJ examined valves (n = 31)Surface modification of polyurethane heart valves: with leaflets made of polyether urethane (PEU, n = 22) or aeffects on fatigue life and calcification polyether urethane urea (PEUE, n = 9), of varying thickness distributions. The valves were subjected toPolyurethane heart valves can be functionally durable with accelerated fatigue test at 37ºC and failure was monitored.minimal calcification, in vitro. In vivo, these characteristics Leaflet thickness ranged from 60 to 200µm. PEU leafletwill depend on the resistance of the polyurethane to thickness bore no relationship to durability, which was lessthrombogenesis and biodegradation. Surface modification than 400 million cycles. PEUE valves, in contrast,may improve the polyurethane in these respects, but may exceeded 800 million cycles. Durability in PEUE valvesadversely affect calcification and durability. This study was directly related to leaflet thickness ( r = .93, p 0.001),investigates the effects of surface modifications of two with good durability achieve with median leafletpolyurethane heart valves (PEU and PEUE) on vitro fatigue thicknesses of approximately 150 µm. Thus polyurethanesand calcification behavior. Modifications included heparin, valves can made with good hydrodynamic properties andtaurine or aminosilane. Aminosilane modification of PEUE with sufficient durability to consider potential clinical use.valves increased durability compared with PEOmodification. Appropiate surface modification may beDecember 2003 Applications of Engineering Mechanics in Medicine, GED at University of Puerto Rico, Mayagüez 10
  11. 11. New polyurethane heart valve prosthesis: Design, being used in more than 4 million implants in more than 25manufacture and evaluation different valve designs for a clinical experience on the order of 18 million patient-years.In light of the thrombogenicity of mechanical valves andthe limited durability of bioprosthetic valves, alternative Pyrolytic carbon (PyC) belongs to the family of turbostraticdesigns and materials are being considered for prosthetic carbons, which have a similar structure of graphite, butheart valves. A new tri-leaflet valve, made entirely from subtly different. In graphite, the carbon atoms arepolyurethane, has been developed. The valve comprises covalently bonded in planar hexagonal arrays that arethree thin polyurethane leaflets (approximately 100µm stacked and held together by weak interlayer bonding. Forthick suspended from the inside of a flexible polyurethane turbostratic carbons, the stacking sequence is disordered,frame. The closed leaflet geometry is elliptical in the radial resulting in wrinkles or distortions within layers. Thisdirection and hyperbolic in the circumferential direction. structural distortion provides the superior ductility andValve leaflets are formed and integrated with their support durability of pyrolytic carbon, compared to other carbonframe I a single dip coating operation. The dipping process structures such as graphite.consistently gives rise to tolerably uniform leaflet thicknessdistributions. In hydrodynamic test, the polyurethane valveexhibits pressure gradients similar to those for abioprosthetic valve (St Jude Bioimplant), and levels ofregurgitation and leakage are considerably less than thosefor either a bileaflet mechanical valve (St Jude Medical) orthe bioprosthetic valve. Six out of six consecutivelymanufactured polyurethane valves have exceeded theequivalent of 10 years function without failure inaccelerated fatigue tests. The only failure to date occurredafter the equivalent of approximately 12 years cycling, andthree valves have reached 527 million cycles(approximately 13 years equivalent).5. Pyrolytic CarbonBackgroundDr. Jack Bokros and Dr. Vincent Gott [11] discoveredpyrolytic carbon, the premier material for artificial heartvalves at General Atomics (GA). In 1966, Dr. Bokros wasworking on pyrolytic carbon coatings for nuclear fuelparticles for the GA gas-cooled nuclear power reactors. Hestumbled upon its potential for medical uses through whathas been called “a lesson in serendipity”. He read an articleby Dr. Vincent Gott, who has been testing carbon-basedpaint as a blood compatible coating for artificial heart Figure 5. Crystal structure of graphite [23].components. Bokros contacted Gott who initiated thecollaboration. Mechanical properties [23]Dr. Gott was searching for a material to use in artificialheart valves that did not provoke blood clots and had the The Pyrolytic carbon, with its inherently dense, glassymechanical durability to endure for a recipient’s lifetime. structure and its ability to be highly polished, has become aPyrolytic carbon, from GA, met both of his need. GA popular choice. Furthermore its electrical conductivity isinitiated a development project headed by Dr. Brokros to useful in allowing it to become electrostatically charged soadd the needed durability to the material. This endeavor that it can repel the blood cells. This unique material is onewas successful and the biomedical grade of pyrolytic of the most blood-compatible of all man-made materials, ascarbon was rapidly incorporated into the existing heart opposed to metals. The human body recognizes implantedvalve designs. metal as a foreign material, and protects itself from the object by coating it with layers of blood. But, pyrolyticToday, pyrolytic carbon (Figures 5 and 6) remains a carbon and other so-called blood-compatible coatings arepopular material available for mechanical heart valves, unrecognized by the body and are accepted.December 2003 Applications of Engineering Mechanics in Medicine, GED at University of Puerto Rico, Mayagüez 11
  12. 12. Figure 6. Acoustic emission amplitude versus frequencyfor crack extensionsg. This plot shows an emission peak at90kHz, indicating a normal mode crack extension in a Figure 7. Fracture stress versus density for unalloyed LTIpyrolytic carbon test sample [23]. pyrolytic carbons [26].In its processed form, pyrolytic carbon is a microscopicallysmooth, hard, black ceramic-like material. Like ceramic, itis subjected to brittleness.Fortunately, pyrolytic carbon possesses a mechanicalproperty that mitigates this fragility in the presence offlaws, making it inherently difficult to accidentallyintroduce cracks of significant size into the material. Inparticular, unlike true ceramics, pyrolytic carbon is highlyductile. Thus, if a sharp, hard object is pressed intopyrolytic carbon, it can respond by deforming locally toaccommodate the object elastically. When the object iswithdrawn, there may be no residual depression, and littleor no microcracking surrounding the site. It is this intrinsic,atomic microstructure-derived resistance to externallyimposed crack nucleation that permits such an otherwisebrittle material to be used in the human body.The mechanical properties of pyrolytic carbon are largelydependent on the density as shown in Figures 8 and 9. Theincreased mechanical properties are directly related to the Figure 8. Elastic modulus versus density for unalloyed LTIincreased density, which indicates that the properties pyrolytic carbons [25].depend mainly on the aggregate structure of the material.Graphite and glassy carbon have lower mechanical strength Deposition of pyrolytic carbon coatings for heart valvesthan pyrolytic carbon as given in table 1. However, theaverage modulus of elasticity is almost the same for all For heart valves, a silicon-alloyed pyrolytic carbon is usedcarbons. The strength and toughness of pyrolytic carbon are in the form of a thick coating on a polycrystalline graphitequite high compared to graphite and glassy carbon. This is substrate. Silicon is added to improve mechanicaldue to the smaller number of flaws and unassociated properties such as stiffness, hardness, and wear resistance,carbons in the aggregate. without significant loss in biocompatibility. Components are made by co-depositing carbon and silicon carbide on the graphite substrate by a chemical vapor-deposition, fluidized bed process that uses a gaseous mixture of silicon-containing carrier gas with a hydrocarbon.December 2003 Applications of Engineering Mechanics in Medicine, GED at University of Puerto Rico, Mayagüez 12
  13. 13. Table 1. Properties of various types of carbon [25]. Type Graphite Glassy Pyrolytic carbon Density, g/ml 1.5 -1.9 1.5 1.5 -2.0 Elastic 24 24 28 modulus, MPa Toughness, 138 172 517 m-N/ cm3 (525a) Compressive strength 6.3 0.6 4.8 a 1.0 w /o Si – alloyed pyrolytic carbon, Pyrolite (Carbomedics, Austin, Tex). Figure 8. OmnicarbonTH mechanical heart valve [17].Pyrolytic Carbon Mechanical Valves in the Market Adverse Events potentially associated with the use ofa. OmnicarbonTM mechanical cardiac valves include:The Omnicarbon mechanical heart valve is manufactured, • Angina.marketed and sold, by Medical CV. Blair Mowery,president and chief executive officer of Medical CV, noted • Cardiac arrhythmia.that the results from at least 10 clinical studies, including • Clinically significant transvalvular regurgitation.over 10,000 patient years of use, have consistently • Disc impingement/ entrapment.demonstrated one-third to one-half fewer complications • Endocarditis .with the Omnicarbon valve, such as blood clots and stroke, • Heart failure.compared to other mechanical valves. The Omnicarbon • Hemolysis or hemolytic anemia.heart valve is a monoleaflet valve; a valve with a single • Hemorrhage.hingeless pivoting disc to employ pyrolytic carbon in both • Myocardial infarction.its housing and disc for improved blood compatibility. Also • Nonstructural dysfunction.Omnicarbon valve does not have fixed pivot recesses that • Perivalvular leak.are characteristic of bileaflet designs and that are • Stroke.demonstrated to be the primary location for blood clot • Structural dysfunction.formation. • Thromboembolism. • Tissue interference with valve function.The disc is slightly curved and retained within the housing • Valve thrombosis.ring, located 1800 from each other on the other side of thehousing ring. The disc closes on the housing ring at a 120 Precautions and Warnings: In order to avoid harmfulangle relative to the plane of the housing ring, and can damages to the health of the patient, the followingopen to a maximum angle of 800. The disc rotates freely precautions and warnings must be taken into account:within the housing ring because there are no fixed hingeswithin the housing ring. Because there are no struts • Do not use the valve if the use-before-date on theprotruding across the flow orifice, the open disc separates package has expired.the flow channel into two orifices. • If the disc disengages undetected handling damage or extreme pressure on the disc mayIndications for Use: cause this. Should disengagement occur, do not attempt to re-engage the disc into the valveThe OmnicarbonTM is indicated for the replacement of housing; the valve should not be implanted.dysfunction, native or prosthetic, aortic or mitral valves. • If the valve came in contact with blood, do nor attempt to clean and resterilize such a valve forContra indications:The OmnicarbonTM is contraindicated for patients unable to use in another person. Foreign protein transfertolerate anticoagulation therapy. and/ or residue from cleaning agents may cause a tissue reaction.December 2003 Applications of Engineering Mechanics in Medicine, GED at University of Puerto Rico, Mayagüez 13
  14. 14. • Passing a catheter, surgical instrument, or immune system. It must minimize blood clotting and pacemaker lead through the OmnicarbonTM valve damage to the blood with minimum amount of effort. may cause serious valvular insufficiency, damage the valve, and/ or cause catheter entrapment. ON-X and common safety problems • Over sizing occurs when too large a valve is forced into the tissue annulus. This may cause Thrombosis is a problem that causes blood clots on the adjacent tissue to inhibit the free movement and working surface of a valve, which impairs valve function. full travel of the valve disc. As a thrombus gets bigger, it will eventually block the moving parts so that the valve can no longer open and / or • No hard, sharp instruments should come in close fully. By using extremely smooth ON-X carbon and contact with the disc or valve housing ring may by designing the valve to induce smooth flow and thorough cause scratches or other surface imperfections self-cleaning, ON-X reduces the risk of thrombosis. which may result in blood injury, thrombus formation and/ or structural damage. In the case of tissue encroachment, the body’s healing process can also impair valve function. As the body heals • A valve soiled by fingerprints or foreign around the mechanical heart valve, tissue builds up around materials may cause clotting or blood damage. the valve. This becomes a problem if the tissue grows over the valve and begins to block it or restrict the moving parts. The ON-X valve was designed with leaflet guards and optimized length to ensure that tissue doesn’t interfere withb. ON-X Carbon [17] valve function.Dr. Vincent Gott compared the clotting tendencies of In the blood damage problem, turbulence and rapidsilicon carbide, pyrolytic carbon alloyed with silicon changes in pressure can affect the blood flow. The longercarbide and pure pyrolytic carbon. Pure carbon was shown flared body of the ON-X smoothes flow. The leaflets areto be least thrombogenic. MCRI overcame the need for free to open completely to align with the flow and onlysilicon carbide by applying new technologies to the move a short distance to close, which reduces turbulencepyrolytic carbon manufacturing processes. Without silicon and buffers. The ON-X valve minimizes damage to bloodcarbide, the pure carbon’s surface finish is unmatched in cells.purity and smoothness. There was an additional reward inpurifying carbon. ON-X carbon is 50% stronger than Typical mechanical properties of ON-X Carbon are givenprevious carbons. Its added flexural strength is essential to in table 2.the manufacturability of the ON-X valve’s sophisticateddesign.How does ON-X work?Like natural valves, mechanical heart valves are one-wayvalves that are opened and closed by the action of the bloodpushing on flaps known as leaflets. The ON-X valve’sleaflets (Figure 9) are somewhat like double doors thatopen and close but never latch. In the case of doors, if thewind blows from one direction, the doors will be blownopen. If blown from the other direction, the doors will beclose. This analogy is an over simplification as thedemands of the body can be both rigorous and subtle.Safety and efficiency of ON-X Two measures of a good mechanical heart valve are safetyand efficiency. To be safe, a valve must not wear out, break Figure 9. ON-X mechanical heart valve [17].or malfunction. It must not be ejected by the body’sDecember 2003 Applications of Engineering Mechanics in Medicine, GED at University of Puerto Rico, Mayagüez 14
  15. 15. Table 2. Typical surface and mechanical properties of On- Table 3. Biocompatibility Tests Results [9].X Carbon [9]. Tests Results Cytotoxicity L-929 non-cytotoxic Property Units On-X Membrane Elution Sensitization ISO 0% sensitization: Wear Resistance mm3/km, 10-6 1.23 Kligman Grade I sensitization Coefficient of Friction ------ 0.15 rate, not significant Irritation Saline CSO negligible irritant Youngs Modulus GPa 26 Acute Systemic negative Toxicity Saline CSO Flexural Strength MPa 490 Rabbit Pyrogen non-pyrogenic USP Physical / Chemical passes USP Density gm/cm3 1.9 Screening Tests standards Mutagenicity Ames non-mutagenic Strain to Failure % 1.6 Hemolysis Direct Contact non-hemolytic Rabbit Blood Strain Energy MPa-mm/mm 7.7 Complement Activation non-activating Residual Stress MPa 18.2 The titanium alloy Ti-6Al-4V is used as the carrier structure for replacement heart valves. The titanium is ring Fracture Toughness MPa m1/2 1.67 shaped and supports the moving mechanisms of the replacement valve. It also carries the polyester structure that binds the valve to the tissue. Fatigue Threshold m/cycle 1.11 (DK70.3) Medical grade titanium alloys have a significantly higher Fatigue Crack Velocity m/cycle, 10-15 3.98 strength to weight ratio than competing stainless steels. The range of available titanium alloys enables medical Critical Surface Tension dynes(cm) 42 specialists’ designers to select materials and forms closely tailored to the needs of the application. The full range of Surface Roughness Ra(nm) 33.9 alloys reaches from high ductility commercially pure titanium used where extreme formability is essential, to Surface Chemistry Atomic % ~85 fully heat treatable alloys with strength above 1300 MPa Carbon (190 ksi). Shape–memory alloys based on titanium further extend the range of useful properties and applications. A Surface Chemistry Atomic % 0 combination of forging or casting, machining and Silicon fabrication are the process routes used for medical products. Surface Chemistry Atomic % ~15 Oxygen Functional Requirements The following requirements must be satisfy to use titanium as a biomaterial in heart valves implants: • The body’s immune system must not attack the6. Titanium (Ti) [24 and 27] biomaterial. • Compatible with body tissues and fluidsThe high strength, low weight, outstanding corrosion • Must has strength, flexibility and hardnessresistance possessed by titanium and titanium alloys have • Must be nontoxic, nonreactive or biodegradableled to a wide and diversified range of successful • The valve must also be anchored to the inside ofapplications which demand high levels of reliable the heart.performance in surgery and medicine. More than 1000 • The material must not exhibit mechanical fatiguetones (2.2 million pounds) of titanium devices of every over the device’s lifetime.description and function are implanted in patients • The material’s surface must have an acceptableworldwide every year. low propensity for thrombus formation, as well as the best possible blood compatibility • Must not be prone to calcification.December 2003 Applications of Engineering Mechanics in Medicine, GED at University of Puerto Rico, Mayagüez 15
  16. 16. Titanium Performance in Medical Applications Advancements: TitaniumThe titanium alloy Ti-6Al-4V is classified as biologically Material selection for implantable medical devices hasinert biomaterial or bioinert. Titanium is judged to be improved with the availability of nitinol, or “NiTi”, acompletely inert and immune to corrosion by all body nickel-titanium alloy that has proved to be biocompatible,fluids and tissue, and is thus wholly biocompatible. As durable and non-thrombogenic.such, it remains essentially unchanged when implanted intohuman bodies because of its excellent corrosion resistance. Researchers at University of California, Los AngelesThe human body is able to recognize bioinert materials as (UCLA) have designed thin-film NiTi semi-lunar heartforeign, and tries to isolate them by encasing them in valve for use in both surgical and non-surgicalfibrous tissues. However, they do not illicit any adverse (transcatheter) human heart valve replacements:reactions and are tolerated well by the human body.Furthermore, they do not induce allergic reactions such as • Surgically implantable thin-film NiTi valves arehas been observed on occasion with some stainless steels, undergoing in vitro testing to determine theirwhich have induced nickel hypersensitivity in surrounding functionality, durability and corrosive properties;tissues. • Designs and prototypes of percutaneously inserted catheter-based thin-film NiTi valves areThe favorable characteristics of titanium including under continuing development.immunity to corrosion, biocompatibility, strength, low • Use of thin-film nitinol as a novel material for themodulus and density. The lower modulus of titanium alloys development of improved human prosthetic heartcompared to steel is a positive factor. Two usefulness valves for surgical implantation and forparameters of the implantable alloy are the notch percutaneous insertion.sensitivity. The ratio of tensile strength in the notchedversus un-notched condition and the resistance to crackpropagation, or fracture toughness. Titanium scores well in 7. Biomaterials versus stainless steel (Table 4)both cases. Typical NS/TS ratios for titanium and its alloysare 1.4 - 1.7 (1.1 is a minimum for an acceptable implantmaterial). Fracture toughness of all high strength Alumina is a versatile material with applications inimplantable alloys is above 50 MPam-1/2 with critical crack medicine, because it has good compatibility with humanlengths well above the minimum for detection by standard environment. Compared to stainless steel, mechanicalmethods of non-destructive testing. The two most common properties of Alumina are worst in modulus of elasticity,types of Ti-6Al-4V used for the implants are Ti-6Al-4V shear modulus, thermal expansion coefficient. Alumina isGrade 5 and Grade 23. better in stress, strain and safety factor. Stainless steel is more resistant but it is not utilized on heart valve implants,Ti-6Al-4V (Grade 5) because it doen not have good biocompatibility with humanThis alpha-beta alloy is the workhorse alloy of the titanium blood. Alumina is a bioceramic while stainless steel is aindustry. The alloy is fully heat treatable in section sizes up biometal with different 15 mm and is used up to approximately 400°C (750°F).Since it is the most commonly used alloy – over 70% of all Stainless steel is stiffer than the titanium alloy Ti6Al4V.alloy grades melted are a sub-grade of Ti6Al4V. This is explained by the steel’s higher modulus of elasticity (196 GPa vs. 120 GPa). Steel is more rigid than titaniumThe addition of 0.05% palladium (grade 24), 0.1% (steel’s higher shear modulus: 80 GPa vs. 44 GPa).ruthenium (grade 29) and 0.5% nickel (grade 25) Stainless steel is more fracture resistant than titanium (steelsignificantly increases corrosion resistance in reducing has more tensile strength: 875 MPa vs. 616 MPa). Titaniumacid, chloride and sour environments, raising the threshold is more resistant to yielding that stainless steel (Ti has atemperature for attack to well over 200°C (392°F). higher yield stress: 950 MPa vs. 700 MPa). See appendix VI.Ti-6Al-4V (Grade 23)The essential difference between Ti6Al4V ELI (grade 23) Pyrolytic carbon is less stiffer than stainless steel. This isand Ti6Al4V (grade 5) is the reduction of oxygen content explained by the steel’s higher modulus of elasticity (196to 0.13% (maximum) in grade 23. This offers improved GPa vs. 17-28 GPa). Stainless steel is more resistant thanductility and fracture toughness, with some reduction in pyrolytic carbon because of its tensile strength is biggeststrength. Grade 29 also having lowered level of oxygen will compared to pyrolytic carbon (875 MPa vs. 200 MPa) .deliver similar levels of mechanical properties to grade 23according to processing.December 2003 Applications of Engineering Mechanics in Medicine, GED at University of Puerto Rico, Mayagüez 16