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Effects of implantation on the mechanical properties of the Polyurethane diaphragm of left ventricular assist devices
Effectsof implantationon the mech~c~ prope~es of the polyurethanediaphragmof 1efIi ventricularassist devices Kozaburo Hayashi,TakehisaMatsuda, HisateruTakanoJvIitsuoUmezu, YoshiyukiTaenakaandTakaoNakamura Dep8~ments of Biomed~~ai Engineering and ~jB~jaf ~uj~shifod-ai 5, Suita, Osaka 565, Japan fReceived 28 December 1983: revised 1 August 1984)
Oq$8ns,
N~~~o~~i cafdjuv8scoiar
Center
Research
Institute,
Tensile properties of blood pump diaphmgms made from a segmented polyether polyum~ne (Toyobo TM5) were studied aft8r imp~nting in goats for variable periods of tima up to 72 days. The irnp~n~oR deemeted the tensile strength md ultimate elongation at breed, while the elastic modulus increaslsd very slightly. There changas in the strength and ductility were primarily caused by the contact of material with blood rather than by the mechanical fatigue of material. Mechanical stability was greatly improved by removing residual oligomers from the material by a refining pmcadure. Tha refinad polyurethane has characteristics fevoumble for blood pump applicstions. Keywords:
Potvmers, Segmented tensile properties -
.oO/vethe~oo/vo~thhan@, .,
left ventricuiarassist
Besides blood compatibility, mechanical ftexibility and strength are important requirements of elastomers used for the diaphragm of left ventricular assist devices and artificial heart pumps. Segmented polyether polyurethanes like Biomer” (Ethicon) and Avcothane@ 51 (Avco Corp.) have been widely used in these devices owing to current favourable experiences with themI.‘. In the devetopment of left ventricular assist devices (LVADs), the mechanical properties of several elastomers including the above two materiats have been studied*5. Our in vitro experiments indicate that Avcothane@ 51 has unstable mechanical properties under dynamic loading conditions. Biomer” however, showed very stable behaviour under cyclic deformation with high flexibility and toughness. Toyobo TM5 (Toyobo Co., Osaka), a polyether polyurethane similar to BiomeP, has higher strength and ductility than BiomeP, although its static and dynamic flexibility are slightly worse and less stable. Toyobo TM5 polyurethane was selected for the pump diaphragm because it has favourable mechanical properties. A series of polyurethanes with soft segment component of different molecular weights and with various characteristics is also available from the manufacture@. A permanently implantable LVAD pump of pusherplate-type was designed taking into consideration the mechanical properties of Toyobo TM5 polyurethane, and @ 1985 82
Butterworth Biomsterials
8 Co (Publishers) 1985,
Vol 6 March
Ltd. 0142-9612/85/02~82~7$03.00
device, implantations
in vitro fatigue test,
it was imptanted in the goat to study pump performance and durabili~6. The changes in the mechanical properties caused by implantation in goats of the polyurethane diaphragm (used as a LVAD pump) are presented in this paper. Effects of the refinement of the material on the tensile and fatigue properties were also studied by in viva and in vim tests.
EXPERIMENTAL
PROCEDURES
Materials A segmented polyether polyurethane designated Toyobo TM5 has been used for the LVAD diaphragm. Another polyurethane, designated Toyobo TM3, was very thinly coated on the blood contacting surface since it has excellent blood compatibility7. The soft segment of these polyurethanes is composed of polytetramethytene glycol and 4,4’-diphenylmethane diisocyanate (MDI). The molecular weights of soft segment components of Toyobo TM5 and TM3 are 2000 and 1350, respectively. The hard segment contains MDt and propylene diamine. These materials are usually prepared as a 15% by weight solution in dimethyl formamide (DMF). In the experimental studies carried out so far4*5, a regular grade of TM5 polyurethane containing around
Segmented
BackDlate HousIng Outflow valve and cannulo
, Diaphragm
\"
for ventilation
Port
transducer Yf
41 #Piston
Drive
pressure
rod \
polyurethane:
K. Hayashi
et al.
forward by about 10 mm. All pumps were driven pneumatically, and usually counterpulsated synchronously with the natural heart. After pumping for variable periods of time, the animals were sacrificed, the pumps were removed from the body during autopsies and rinsed with a saline solution. Immediately after the pump autopsies, 3-5 specimens [with the dumb-bell shape (gauge length: 16.0 mm; width: 5.0 mm)] were cut out from the unsupported section of the diaphragms, unless otherwise stated, and were stored in a saline solution until mechanical testing. All tensile tests were carried out on wet specimens within 2 h of the pump removal.
Pneumotlc cylinder and cannula Figure 1 Cross section of pusher-plate-type polyurethane diaphragm is incorporated.
LVAD pump into which a
5.7% by weight oligomers has been used. In the latter part of the study reported here, however, a refined grade of the polyurethane containing minimal amount of oligomers (less than 0.3%) was introduced. In the refining process oligomers are extracted with methyl alcohol for 24 h followed by filtration through two filters with mesh size No. 1250.
Fabrication
process
Diaphragm. The Toyobo TM series of polyurethanes cannot be cured by injection moulding nor by extrusion techniques. Pump components are successfully formed only by solution moulding, drying to remove the solvent and heat setting to stabilize the shape. Toyobo TM5 solution diluted to 8% by weight with DMF was used to fabricate the pump diaphragm. To form a 1 mm thick diaphragm, a disc mould of SUS 304 stainless steel was dipped in this solution about 25 times with 1 h drying time (70-80°C in heated clean air) between applications. The technique consisted of rotating the mould slowly in a vertical posture to retain a uniform thickness while heating in air. After curing, the mould was washed for 5 h in running water kept at 60°C prior to detaching the diaphragm. The diaphragm was then dried in a vacuum chamber at room temperature. After the pump was assembled, its inner surface was very thinly coated (around 50 p) with TM3 polyurethane to enhance the blood compatibility. Figure 1 shows the diaphragm incorporated into the pusher-plate-type LVAD pump. Design specifications, and in vitro and in vivo performance of the pump are described elsewhere6. Sample sheet. Sample sheets of 1 mm thickness were fabricated by pouring the 8% by weight TM5 solution into a stainless steel dish five times with a 5 h drying time (at 80°C) between applications. After curing, they were washed in running water at 60°C for 5 h, and then dried in a vacuum chamber at room temperature. These sample sheets were cut with a special punch to a standardized dumb-bell shape (gauge length: 16.0 mm; width: 5.0 mm) and used for in vitro tensile and fatigue tests.
Animal implantation LVAD pumps were implanted in 4 goats with body weights between 34 and 57 kg. They were placed on the thoracic wall outside the body. Approximately3 I min-’ of blood flow from the left atrium to the descending aorta was bypassed by the pump. To obtain this amount of bypass flow, the pusher-plate was moved backward and
Tensile test. Tensile tests were carried out in air at room temperature by a servo-hydraulic testing machine (Tokyo Koki Seizosho, Tokyo) at the piston speed of 15 mm/min or by a conventional tensile tester (Tensilon STM50, Toyo Baldwin Co., Tokyo) at a crosshead speed of 10 mm/min. In both cases, a Vidicon displacement analyser was used forthe non-contact measurement of deformation developed in the parallel part of a specimen over which the stress is uniformly distributed3. Tensile strength at break, a,, ultimate elongation, @a, and secant modulus at 30% elongation, E3c, were determined from the stress-strain relationship obtained by the tensile test. The secant modulus is defined by the ratio of stress to corresponding strain at any specified point on the stress-strain curve. In this study, flexibility of a material was expressed by the secant modulus at 30% elongation. In vitro fatigue test. Fatigue tests were carried out on specimens which were obtained from the sample sheets of the regular and refined grades of Toyobo TM5 polyurethanes. The testing was performed by the servo-hydraulic tester for about 1 month under conditions of 50% of mean strain, E,, 10% of strain amplitude, E,, and 2 Hz of cyclic rate, f, in sine waveform. Test specimens were immersed into a cholesterol-lipid solution or a saline solution kept at 37°C during the fatigue test. The composition of the cholesterol-lipid solution, shown in Table 7, is rather similar to that used by Carmen and Mutha for the in vitro testing of silicone rubber heart-valve poppets*. Mean stress, a,, stress amplitude, a,, and the ratio of stress amplitude to strain amplitude, uJE,. were obtained, where the stress/strain ratio, ad&, was used to express the flexibility of a material under dynamic loading conditions.
RESULTS Effects of implantation Figures 2 and3 show typical examples of the stress-strain curves of diaphragms implanted in goats as LVADs and Table 1
Composition
of cholesterol-lipid
solution
Constituent
Concentration
NaCl Glucose Urea Alanine Glutamine Glyclne Tnoleln Cholesterol Cholesterol paimitate Lecithin Sodturn azide
9.00 1 .oo 0.25 0.1 5 0.15 0.15 4.50 1 .oo 1.50 2.50 0.20
Biomaterials
1985,
(gl-‘)
Vol 6 March
83
Segmented
polyurethane:
Toyobo
K. Hayashi
et al.
TM5 diaohram (Regular
4
grade)
I(321
^o
n
5
3
0
100
50 Strain
(Xl
E
Figufe 2 Smss-smh cunw in the low sfmin renge obteined regukr grade diephregms implanted in goets as 1 VADs.
for
50 Toyobo TM5 dioPhrogm (Regular&Yodel
-0
500 strain
Figure 3 impknted
Whole stress-strain in goats as LVADs.
1000 (X1
E
curves
crf regufer
1500 grade
diaphragms Toyobo TN5 dlaohragm
that of non-implanted, virgin diaphragm which was soaked in a saline solution at room temperature for2 h. As can be seen in Figure 2 the im~lantat~u~ has an influence on the stress-strain relationship jn the low strain range below 50% elongation: the flow stress increases with the increase in the period of implantation if compared at the same strain, This result indicates that the diaphragm flexibility decreases very gradually by the implantation and pumping. In these curves, the irregular distortion observed in fatigue-tested specimens of Toyobo TM5 poiyurethane4,s does nut appear, which implies that the strain developed in the convoluted section of diaphragm during pumping is minimal because of the optimal design of the diaphragm6. Table 2
Comparison
of tensile properties
of convoluted
Convoluted Secant
modulus
E,
Tensile
strength
me (MPa)
Elongation
Biomateriais
r985,
#fe j%)
Voi 6 March
(MPa)
d-
ok
00 0
2
of imolantotion
grade)
50 T
(days)
Figure 4 Tensile properties of regular grade diaphragms versus period implantatiun. Represented are mean values and error ranges.
of
fT5yobo
Implanted
‘as cast’
Convoluted
Flat
TM%
Fewfar
Pde)
fOr 72 cl Flat
5.2
5.2
5.6
5.5
38.9
37.1
24.4
22.7
1449.0
(Regular
10
5
Period
and fiat sections of pump diaphragms Non-implanted,
84
In Figure 3 the influence of the implantation on the stress-strain characteristics of the diaphragm is seen, In particdar, the tensile strength decreases dropping to about 60% of that of the non-implanted virgin diaphragm at only 6 d implantation. Since the tensile strength of a material generally corresponds to its fatigue strength and durability, the endurance might be decreased significantly by the implantation. The ultimate elongation at break is also decreased by implantations although the decrease in elongation is relativefy less than that of the tensile strength. The ultimate elongation of the diaphragm implanted for 6 d decreased to about 85% of that of the non-implanted, virgin material. The tensile strengths of the diaphragms implanted for more than 6 d are similar to those of the diaph~gms implanted for 6 d, but the elongation continuously decreased the longer the implantation period reaching approximately 70% of the virgin diaphragm after implantation for 72 d. The tensile strength, ultimate elongation and secant modulus versus the duration of impfantation are shown in Figure 4. Each point is represented by the mean value and error range of the data obtained with 3-5 specimens from a diaphragm, The diaphragm material hardens very gradually and it is considerably weakened and made brittle by implantation as the LVAD. To know whether the change mentioned above in the mechanical properties of the diaphragm is caused by contact of the material with blood or by the exposure to cyclic deformation, tensile tests were carried out on specimens taken from the flat section of the diaphragm which underwent little deformation during pumping due to the constraint of the attached pusher-plate. Table 2 summarizes the results obtained from the convoluted and flat sections of the non-im~tanted, virgin diaphragm and the diaphragm implanted for 72 d. The flat section uf the diaphragm has almost the same tensile properties as the unsupported, convoluted section in each case. These results indicate that the change in the mechanical charac-
1419.0
f 089.0
1043.0
11
Segmented
TOYOCG Tfl5 (Regular grader
!(lU)
f
I:721
F
somoie sheet
Dlaahra4m V: Non-lmalanted, virgin
Key
I(n): lmolonted for n davr L: Non-fatigued, lmnersed tn cholesterol-Ilold solution for 1 mOnth FA: Fatlgued In air for 1 mOnth FL: Foflgued in ChOleSterOi-lIDId solutton for 1 month Figure
5 Comparison of in viva change in diapbra~m characteristics with in vitm change in tensile pmpetiies of sample sheets (regular grade).
4
0 % _[
Toyobo TM5 mole sheet f = 2HZ, Em = 50x, Cd = 10%
3
Refined -----
Regular -----
Saline so!ution ChOleSterOl-liDid
0 Reuetitizn
SOlIJtiOn
4
2 number
Figure 6 Change in the mean deformation.
Fi x 10m6
stress of sample
5
(cycles)
sheet during cyclic
teristics of the diaphragm induced by implantation primarily caused by the contact with blood.
Comparison
between
K. Hayashi
et al.
while the reduction in the ductility is caused by the cyclic deformation or material fatigue. Secant moduli of the nonimplanted materials remain unchanged or decrease either by immersing in the cholesterol-lipid solution, or by fatigue-testing in the solution. This behaviour is different from the phenomenon observed in the implanted diaphragm, in which the secant modulus increases very gradually with increase in the period of implantation as shown in Figures 4 and 5. The reason for the contrast in the change of the secant modulus between the implanted and nonimplanted specimens is not known at present.
Effects of material I(6)
polyurethane:
is
in vivo and in vitro results
In Figure 6, the in vivo change of the diaphragm characteristics is compared with the in vitro change in the tensile properties of sample sheets caused by cyclic deformation and/or by immersion in the cholesterol-lipid solution. Soaking in the solution (L in Figure 5) decreases the tensile strength and secant modulus, while increasing the elongation very slightly. On the other hand, the cyclic deformation in air (FA) decreases the ductility, but increases the tensiie strength. When fatigue-tested in the cholesterol-lipid solution (FL), both the tensile strength and elongation decrease significantly. This phenomenon is quite similar to that observed in a diaphragm implanted in the goat as a component of the LVAD pump. From these results it might be considered that the decrease in the tensile strength observed in the implanted diaphragm is due to some constituents of the cholesterol-lipid solution,
refinement
Figure 6 shows change in the mean stress of the regular and refined grades of Toyobo TM5 polyurethane during fatigue tests in saline or cholesterol-lipid solution kept at 37°C. Rapid decrease in the mean stress is observed in the early stage of cyclic deformation, and stress relaxation appears in all cases. The stress relaxation in the regular grade of material is larger in the cholesterol-lipid solution than in the saline solution. In the case of the refined material, the stress relaxation behaviour observed in the cholesterol-lipid solution is very similar to that in the saline solution: there appears to be no effect of cholesterol-lipids on the stress relaxation characteristics in the refined grade of material. In all cases, the stress relaxation continues gradually even after several million cycles of deformation. As shown in Figure 7, the ratio of stress amplitude to strain amplitude decreases in the early stage of fatigue test in the same manner as the mean stress. In a few million cycles, however, the ratio reaches a constant value in each case. Again in the refined grade of material, there is no difference between the stress/strain ratios observed in saline solution or in cholesterol-lipid solution, while there is a significant difference in the regular material. Figure 8 shows stress-strain curves of the regular and refined materials in a low strain range. They were obtained after cyclical deformation forca 1 month (5 X 1 O6 cycles) in cholesterol-lipid solution or in saline solution both kept at 37”C, or after immersion in each solution at 37°C for the same period under no load. Stress-strain curves of materials in this’as cast’ condition are also included in this figure. The ‘as cast’, virgin material of the refined grade has significantly higher flow stress in this strain range than the regular grade. The flow stress in the refined
10 ^o P -
Toyobo TN5 male sheet f = 2tlz.Em = SO%, E* = 10%
8
m
0
Reeuior _---_-
Refined -w--w
-
-
Saline solution Cholesterol-lipid solution
6
4
2 Reoetition near
N x 1Clm6(cycles1
Figure 7 Change in the ratio of stress emplifude sample sheet during cyclic deformetion.
Biomaterials
1985,
?o strain amplitude
Vol6
March
of
85
Segmented
polyurethane:
K. Hayashi
et al.
ToyObO TN5 somale sheet 6 r
Regular ------
Refined -----
._____._.__-----------
Cholesterol-lipid Saline
Virgin
_____-
~~-~
significantly decreased the secant modulus and ultimate elongation, but only diminished the tensile strength very slightly. These changes are very similar to those observed with the regular grade of sheet material. However, the reduction of elastic modulus caused by the cyclic deformation in the cholesterol-lipid solution was considerably larger in the refined material than in the regular one as shown by comparing the results in Figure 9 with those in Figure 5. Like the diaphragm, non-implanted, virgin specimens obtained from the refined grade of sample sheet had higher secant moduli and tensile strength, but lower elongation than those of the regular grade.
DISCUSSION
I
OV
I
50
0 Strain
E
100 (X)
Figure 8 Stress-strain curves in the low strain range obtained regular and refined grades of sample sheets.
for
material is slightly decreased by immersion in saline or cholesterol-lipid solution, but it is still slightly higher than that observed for the regular grade of material. The cyclic deformation applied in the saline solution or in the cholesterol-lipid solution reduces the flow stress of the refined material in the strain range below 100% elongation. This phenomenon is quite different from that observed with the regular grade of material in which the flow stress in the strain range between 5&100% increases significantly with cyclic deformation in these solutions. In the refined material either fatigued or nonfatigued, the stress-strain curves obtained after immersion in cholesterol-lipid solution are very similar to those observed after immersion in saline solution. For fatigued material of the refined grade, the irregular distortion in the stress-strain curve observed in the fatigued, regular material does not occur. Figure 9 summarizes the in vivo change in the tensile properties of the diaphragm fabricated from the refined grade of TM5 polyurethane caused by the implantation as well as the in vitro change appearing in the sample sheet of the same material following the cyclic deformation and immersion into the cholesterol-lipid solution. Comparing these results with those shown in Figure 5, it can be seen that the change in the tensile properties of the refined grade of material caused by animal implantation is slightly less than that of the regular diaphragm: also there appears almost no change in the ultimate elongation. Even in the refined grade, however, the tensile strength drops to about 75% of that of the non-implanted, virgin diaphragm after 10 d implantation, although this reduction is much less than those observed in the regular grade of diaphragms. The elastic modulus and tensile strength of the refined grade of diaphragm were higher than those of the regular diaphragm whether it was implanted or not. In the case of the refined grade of sample sheet, the in vitro cyclic deformation in the cholesterol-lipid solution
86
Biomaterials
1985,
Vol 6 March
Boretos et al.’ studied the mechanical properties of Biomer@ used as the blood contacting surface in heart assist devices implanted in calves. They reported that the flow stress at 100% elongation increased from 4.1 1 to 4.35 MPa in 11 wk, and subsequently to 4.52 MPa in 35 wk. i.e. the implantation increased the secant modulus gradually. The implantation up to 35 wk decreased the tensile strength and elongation at failure, although the reduction in the tensile strength was very slight. These changes in the tensile properties of Biomer” by implantation are essentially similar to our results with Toyobo TM5 polyurethane. Recently Phillips et aL2 have carried out a similar study on the tensile properties of Biomer” implanted in calves as blood sacs for total artificial hearts and left ventricular assist devices. Their results show no statistically significant reduction in the tensile strength and flexibility after long-term use in the blood contacting environment, although there is a large variation in individual samples. Based on their test results, they concluded that a carefully fabricated sac is reliable from a mechanical fatigue Toyobo TM5 (Refined grade)
I(10) Diaphragm Key
V
L
FL
Sawle sheet
V: Non-imolonted,virgin l(10): Implanted for 10 days L: Non-fotlgued, imwrsed in cholesterol-lioidsolution FL: Fatigued in cholesterol-lioldsolution for 1 month
Figure 9 Comparison of in vivo change in diaphragm characteristics with in vitro change in tensile properties of sample sheets (refined grade). Represented are mean values and error renges.
Segmented
point of view when subjected to 100% elongation or less for long-term use. Tensile properties of blood bags made from a DuPont T-l 27 based segmented polyether polyurethane (Toray Ind., Tokyo) as well as those made from a poly(vinyl chloride) paste (PVC) and then very thinly coated with Avcothane” 52 were studied by lmachi et a/.‘* after implanting in goats as artificial hearts. After 288 d implantation the tensile strength of the polyurethane decreased from 36.4 to 30.3 MPa, while its elongation increased from 865 to 920%. The rate of decrease in the tensile strength of the polyurethane (?7%) was less than that observed for the regular and refined grades of Toyobo TM5 polyurethanes (40% and 26%, respectively). In the case of the PVC sac, the tensile strength and elongation dropped 82% and 76%, respectively, for those of the nonimplanted, virgin material after implantation for longer than 6 months. These data except for the results obtained by Phillips et a/. * indicate that the tensile strength of polyurethanes and PVC decrease when these materials are used as the blood contacting surfaces for pumps. However, the tensile strength of polyurethanes observed after implantation for less than 7 yr are still higher than the stress level estimated to develop in a pump diaphragm. For example, the stress in the 1 mm thick diaphragm of a pusher-plate-type blood pump is estimated at about 3.14 MPa when the regular grade of Toyobo TM5 polyurethane is used? Forthe long-term application, however, it might be required to increase the tensile strength while keeping the elastic modulus low and elongation high since the tensile strength of a material generally corresponds to its fatigue strength and durability. Stokes and Cobian” reported that polyether poly urethanes with brand names of Pellethane” 2363-80A and Pellethane@ 2363~55D (Upjohn) showed significant reduction in tensile strength and elongation in the first months after subcutaneous implantation in rats. However, they observed that vacuum desiccation of specimens obtained from implants after 1 and 2 yr showed considerable recovery towards the original tensile strength and elongation. They ascribed the reduction of strength and elongation to the absorption of water. We also observed decrease in the tensile strength of Toyobo TM5 poly urethane and Biomer@ after they were soaked in a saline solution or cholesterol-lipid solution for approximately 1 mnth under no load condition4,5. One of the reasons for the reduction in strength might be the absorption of water. As shown in Figure 5, however, the degree of decrease in the tensile strength is much more remarkable in the implanted material than in the specimens immersed in the cholesterol-lipid solution. Significant reduction of the mechanical strength of polyurethane caused by contact with blood might be primarily attributable to the microcracks originating from lipids or some blood constituents absorbed into the microvoids formed by the elution of oligomers5, 12. In fact, for a refined grade of polyurethane which contains the minimal amount of oligomers, the mechanical stability was greatly improved as shown in Figures 6, 7 and 9. The tensile strength of the refined diaphragm implanted for 10 d is more than 50% higher than that of the diaphragm made from the regular grade of polyurethane and implanted in a goat for 6 d. Change in the mechanical properties within the first 6 d after implantation were not studied in these experiments. Very early changes in the mean stress and stress/strain ratio during the in vitro fatigue tests (Figures
polyurethane:
K. Hayashi
et al.
6and 7) suggest that the in vivo change in the mechanical properties might appear in the very early period of implantation. Differences in fabrication processes between the diaphragm and sample sheet yielded fairly large variation of their mechanical properties as can be seen from Figures 5 and 9. The sample sheet gives higher elastic modulus and lower ductility than the diaphragm, although their tensile strength is similar. These differences might be attributable to the different rates of solvent evaporation. Even though there are some influences of fabrication process on the mechanical properties, change in the tensile properties of the diaphragm caused by the animal implantation is essentially similar to that developed in the sample sheet by the cyclic deformation in the cholesterollipid solution except for the change in the secant modulus of the regular grade of diaphragm. These results indicate that the change in the tensile properties of implant materials can be predicted to some extent by the in vitro fatigue tests on standardized specimens in the cholesterollipid solution. As can be seen comparing Figures 5 and 9, the tensile
strength
Although
is improved
the tensile
decreased
by
strength
test in the cholesterol-lipid one,
refining
procedures. diaphragm
is
as well as by the in vitro fatigue
by implantation
that of the regular
the
of the refined
solution the degree
in a similarfashion of decrease
to
is less in
refined material than in the regular one. The tensile strength and ultimate elongation of the refined grade of the material are maintained at higher levels than those of the regular material even after the 10 d implantation. The secant modulus of the diaphragm is increased slightly by the refining procedures. The refined grade of Toyobo TM5
the
polyurethane Biomerm. improve
has almost
Based the
similar
on these
material
and
mechanical
results,
we
will
properties
to
continue
to
to use it in our blood pumps.
ACKNOWLEDGEMENT This research work was supported financially in part by: Grant-in-Aid for Scientific Research from the Ministry of Education (No. 557322 and No. 57570520); Research Grant for Cardiovascular Diseases and Grant for Scientific Research Expenses for Health and Welfare Program from the Ministry of Health and Welfare; and Japan Heart Foundation Research Grant for 1981 (ali with Dr Kozaburo Hayashi as the principal investigator). The authors wish to thank Messrs K. Murayama and M. Tanaka of Toyobo Co. and DrT. Tsunetsugu of Sumitomo Bakelite Co. for providing materials used in this study.
REFERENCES Kolff, J.. Hershgotd, E.J., Hadfield. C., Olsen, D.B.. Lawson, J. and Kolff. W.J., The improving hematologic picture in long-term survlvmg calves with total artifxial hearts,Altif. Organs 1979, 3, 97-103 Phillips, W.M.,
Pierce, W.S., Rosenberg, G. and Donachy, J.H., The use of segmented polyurethane in ventricular assist devices and artificial hearts, in Synthetic Biomedical Polymers Concepts and Applications, (Eds M. Srycher and W.J. Robinson), Technomic Pub., Z 980, pp 39-57 Hayashi, K. and Nakamura, T., Material test system for the evaluation of mechanical properties of biomaterials, J. ffiomed. Mater. Res. (In press)
Biomaterials
1985,
Vof 6 March
87
Segmented
4
5
6
7
8
BB
polyurethane:
K. Hayashi
et al.
Hayashi, K., Takano, H., Matsuda, T. and Umezu, M., Mechanical stability of elastomeric polymers for blood pump applications, J. Biomed. Mater. Res. (in press) Hayashi, K., Matsuda, T., Takano, H. and Umezu, M., Effects of immersion in cholesterol-lipid solution on the tensile andfatigue properties of elastomeric polymers for blood pump applications, J. Biomed. Mater. Res. 1984. 18, 939-951 Hayashi, K., Nakamura, T., Takano, H., Umezu, M., Taenaka, Y. and Matsuda, T., Design of pusher-plate-type left ventricular assist device based on mechanical analyses,Artif. Organs 1984, 8, 204-2 14 Hayashi, K., Matsuda,T., Iwata, H., Nakamura,T.,Takano, H. and Akutsu, T., Mechanical and ESCA studies on new segmented polyether polyurethanes for blood pump applications, Abstr. 30th Ann. Mtg. Amer. Sot. Art. Intern. Organs 1984. 20 Carmen, R. and Mutha, SC., Lipid absorption by silicone rubber
Biomateriats
1985.
Vol 6 March
9
10
11 12
heart valve poppets-in vivo and in vitro results, J. Biomed. Mater. Res. 1972. 6. 327-346 Boretos, J.W., Pierce, W.S., Baier, R.E., Leroy, A.F. and Donachy, J.H., Surface and bulk characteristics of a polyether urethane for artificial hearts, J. Biomed. Mater. Res. 1975. 9, 327-340 Imachi, K., Fujimasa, I., Takido, N., Nakajima, M., Motomura, K., Kohno, A., Ono, T. and Atsumi. K., ln viw evaluation of the materials of artificial heart pumps- thromboresistance, biocompatibility and durability during long-term implantation, Proc. 3rd Ann. Conf. Jpn Sot. Biomat. 1981, 6%72 Stokes, K. and Cobian, K., Polyether polyurethanes for implantable pacemaker leads, Biomatetieb 1982, 3, 225-231 Takahara, A., Tashita, J., Kajiyama, T. and Takayanagi, M., Blood compatibility and change in fatigue strength by absorption of blood components in thermoplastic elastomers, Proc. 3rdAnn. Conf. Jpn Sot. Biomat. 1981, 61-64
Oq$8ns,
N~~~o~~i cafdjuv8scoiar
Center
Research
Institute,
Tensile properties of blood pump diaphmgms made from a segmented polyether polyum~ne (Toyobo TM5) were studied aft8r imp~nting in goats for variable periods of tima up to 72 days. The irnp~n~oR deemeted the tensile strength md ultimate elongation at breed, while the elastic modulus increaslsd very slightly. There changas in the strength and ductility were primarily caused by the contact of material with blood rather than by the mechanical fatigue of material. Mechanical stability was greatly improved by removing residual oligomers from the material by a refining pmcadure. Tha refinad polyurethane has characteristics fevoumble for blood pump applicstions. Keywords:
Potvmers, Segmented tensile properties -
.oO/vethe~oo/vo~thhan@, .,
left ventricuiarassist
Besides blood compatibility, mechanical ftexibility and strength are important requirements of elastomers used for the diaphragm of left ventricular assist devices and artificial heart pumps. Segmented polyether polyurethanes like Biomer” (Ethicon) and Avcothane@ 51 (Avco Corp.) have been widely used in these devices owing to current favourable experiences with themI.‘. In the devetopment of left ventricular assist devices (LVADs), the mechanical properties of several elastomers including the above two materiats have been studied*5. Our in vitro experiments indicate that Avcothane@ 51 has unstable mechanical properties under dynamic loading conditions. Biomer” however, showed very stable behaviour under cyclic deformation with high flexibility and toughness. Toyobo TM5 (Toyobo Co., Osaka), a polyether polyurethane similar to BiomeP, has higher strength and ductility than BiomeP, although its static and dynamic flexibility are slightly worse and less stable. Toyobo TM5 polyurethane was selected for the pump diaphragm because it has favourable mechanical properties. A series of polyurethanes with soft segment component of different molecular weights and with various characteristics is also available from the manufacture@. A permanently implantable LVAD pump of pusherplate-type was designed taking into consideration the mechanical properties of Toyobo TM5 polyurethane, and @ 1985 82
Butterworth Biomsterials
8 Co (Publishers) 1985,
Vol 6 March
Ltd. 0142-9612/85/02~82~7$03.00
device, implantations
in vitro fatigue test,
it was imptanted in the goat to study pump performance and durabili~6. The changes in the mechanical properties caused by implantation in goats of the polyurethane diaphragm (used as a LVAD pump) are presented in this paper. Effects of the refinement of the material on the tensile and fatigue properties were also studied by in viva and in vim tests.
EXPERIMENTAL
PROCEDURES
Materials A segmented polyether polyurethane designated Toyobo TM5 has been used for the LVAD diaphragm. Another polyurethane, designated Toyobo TM3, was very thinly coated on the blood contacting surface since it has excellent blood compatibility7. The soft segment of these polyurethanes is composed of polytetramethytene glycol and 4,4’-diphenylmethane diisocyanate (MDI). The molecular weights of soft segment components of Toyobo TM5 and TM3 are 2000 and 1350, respectively. The hard segment contains MDt and propylene diamine. These materials are usually prepared as a 15% by weight solution in dimethyl formamide (DMF). In the experimental studies carried out so far4*5, a regular grade of TM5 polyurethane containing around
Segmented
BackDlate HousIng Outflow valve and cannulo
, Diaphragm
\"
for ventilation
Port
transducer Yf
41 #Piston
Drive
pressure
rod \
polyurethane:
K. Hayashi
et al.
forward by about 10 mm. All pumps were driven pneumatically, and usually counterpulsated synchronously with the natural heart. After pumping for variable periods of time, the animals were sacrificed, the pumps were removed from the body during autopsies and rinsed with a saline solution. Immediately after the pump autopsies, 3-5 specimens [with the dumb-bell shape (gauge length: 16.0 mm; width: 5.0 mm)] were cut out from the unsupported section of the diaphragms, unless otherwise stated, and were stored in a saline solution until mechanical testing. All tensile tests were carried out on wet specimens within 2 h of the pump removal.
Pneumotlc cylinder and cannula Figure 1 Cross section of pusher-plate-type polyurethane diaphragm is incorporated.
LVAD pump into which a
5.7% by weight oligomers has been used. In the latter part of the study reported here, however, a refined grade of the polyurethane containing minimal amount of oligomers (less than 0.3%) was introduced. In the refining process oligomers are extracted with methyl alcohol for 24 h followed by filtration through two filters with mesh size No. 1250.
Fabrication
process
Diaphragm. The Toyobo TM series of polyurethanes cannot be cured by injection moulding nor by extrusion techniques. Pump components are successfully formed only by solution moulding, drying to remove the solvent and heat setting to stabilize the shape. Toyobo TM5 solution diluted to 8% by weight with DMF was used to fabricate the pump diaphragm. To form a 1 mm thick diaphragm, a disc mould of SUS 304 stainless steel was dipped in this solution about 25 times with 1 h drying time (70-80°C in heated clean air) between applications. The technique consisted of rotating the mould slowly in a vertical posture to retain a uniform thickness while heating in air. After curing, the mould was washed for 5 h in running water kept at 60°C prior to detaching the diaphragm. The diaphragm was then dried in a vacuum chamber at room temperature. After the pump was assembled, its inner surface was very thinly coated (around 50 p) with TM3 polyurethane to enhance the blood compatibility. Figure 1 shows the diaphragm incorporated into the pusher-plate-type LVAD pump. Design specifications, and in vitro and in vivo performance of the pump are described elsewhere6. Sample sheet. Sample sheets of 1 mm thickness were fabricated by pouring the 8% by weight TM5 solution into a stainless steel dish five times with a 5 h drying time (at 80°C) between applications. After curing, they were washed in running water at 60°C for 5 h, and then dried in a vacuum chamber at room temperature. These sample sheets were cut with a special punch to a standardized dumb-bell shape (gauge length: 16.0 mm; width: 5.0 mm) and used for in vitro tensile and fatigue tests.
Animal implantation LVAD pumps were implanted in 4 goats with body weights between 34 and 57 kg. They were placed on the thoracic wall outside the body. Approximately3 I min-’ of blood flow from the left atrium to the descending aorta was bypassed by the pump. To obtain this amount of bypass flow, the pusher-plate was moved backward and
Tensile test. Tensile tests were carried out in air at room temperature by a servo-hydraulic testing machine (Tokyo Koki Seizosho, Tokyo) at the piston speed of 15 mm/min or by a conventional tensile tester (Tensilon STM50, Toyo Baldwin Co., Tokyo) at a crosshead speed of 10 mm/min. In both cases, a Vidicon displacement analyser was used forthe non-contact measurement of deformation developed in the parallel part of a specimen over which the stress is uniformly distributed3. Tensile strength at break, a,, ultimate elongation, @a, and secant modulus at 30% elongation, E3c, were determined from the stress-strain relationship obtained by the tensile test. The secant modulus is defined by the ratio of stress to corresponding strain at any specified point on the stress-strain curve. In this study, flexibility of a material was expressed by the secant modulus at 30% elongation. In vitro fatigue test. Fatigue tests were carried out on specimens which were obtained from the sample sheets of the regular and refined grades of Toyobo TM5 polyurethanes. The testing was performed by the servo-hydraulic tester for about 1 month under conditions of 50% of mean strain, E,, 10% of strain amplitude, E,, and 2 Hz of cyclic rate, f, in sine waveform. Test specimens were immersed into a cholesterol-lipid solution or a saline solution kept at 37°C during the fatigue test. The composition of the cholesterol-lipid solution, shown in Table 7, is rather similar to that used by Carmen and Mutha for the in vitro testing of silicone rubber heart-valve poppets*. Mean stress, a,, stress amplitude, a,, and the ratio of stress amplitude to strain amplitude, uJE,. were obtained, where the stress/strain ratio, ad&, was used to express the flexibility of a material under dynamic loading conditions.
RESULTS Effects of implantation Figures 2 and3 show typical examples of the stress-strain curves of diaphragms implanted in goats as LVADs and Table 1
Composition
of cholesterol-lipid
solution
Constituent
Concentration
NaCl Glucose Urea Alanine Glutamine Glyclne Tnoleln Cholesterol Cholesterol paimitate Lecithin Sodturn azide
9.00 1 .oo 0.25 0.1 5 0.15 0.15 4.50 1 .oo 1.50 2.50 0.20
Biomaterials
1985,
(gl-‘)
Vol 6 March
83
Segmented
polyurethane:
Toyobo
K. Hayashi
et al.
TM5 diaohram (Regular
4
grade)
I(321
^o
n
5
3
0
100
50 Strain
(Xl
E
Figufe 2 Smss-smh cunw in the low sfmin renge obteined regukr grade diephregms implanted in goets as 1 VADs.
for
50 Toyobo TM5 dioPhrogm (Regular&Yodel
-0
500 strain
Figure 3 impknted
Whole stress-strain in goats as LVADs.
1000 (X1
E
curves
crf regufer
1500 grade
diaphragms Toyobo TN5 dlaohragm
that of non-implanted, virgin diaphragm which was soaked in a saline solution at room temperature for2 h. As can be seen in Figure 2 the im~lantat~u~ has an influence on the stress-strain relationship jn the low strain range below 50% elongation: the flow stress increases with the increase in the period of implantation if compared at the same strain, This result indicates that the diaphragm flexibility decreases very gradually by the implantation and pumping. In these curves, the irregular distortion observed in fatigue-tested specimens of Toyobo TM5 poiyurethane4,s does nut appear, which implies that the strain developed in the convoluted section of diaphragm during pumping is minimal because of the optimal design of the diaphragm6. Table 2
Comparison
of tensile properties
of convoluted
Convoluted Secant
modulus
E,
Tensile
strength
me (MPa)
Elongation
Biomateriais
r985,
#fe j%)
Voi 6 March
(MPa)
d-
ok
00 0
2
of imolantotion
grade)
50 T
(days)
Figure 4 Tensile properties of regular grade diaphragms versus period implantatiun. Represented are mean values and error ranges.
of
fT5yobo
Implanted
‘as cast’
Convoluted
Flat
TM%
Fewfar
Pde)
fOr 72 cl Flat
5.2
5.2
5.6
5.5
38.9
37.1
24.4
22.7
1449.0
(Regular
10
5
Period
and fiat sections of pump diaphragms Non-implanted,
84
In Figure 3 the influence of the implantation on the stress-strain characteristics of the diaphragm is seen, In particdar, the tensile strength decreases dropping to about 60% of that of the non-implanted virgin diaphragm at only 6 d implantation. Since the tensile strength of a material generally corresponds to its fatigue strength and durability, the endurance might be decreased significantly by the implantation. The ultimate elongation at break is also decreased by implantations although the decrease in elongation is relativefy less than that of the tensile strength. The ultimate elongation of the diaphragm implanted for 6 d decreased to about 85% of that of the non-implanted, virgin material. The tensile strengths of the diaphragms implanted for more than 6 d are similar to those of the diaph~gms implanted for 6 d, but the elongation continuously decreased the longer the implantation period reaching approximately 70% of the virgin diaphragm after implantation for 72 d. The tensile strength, ultimate elongation and secant modulus versus the duration of impfantation are shown in Figure 4. Each point is represented by the mean value and error range of the data obtained with 3-5 specimens from a diaphragm, The diaphragm material hardens very gradually and it is considerably weakened and made brittle by implantation as the LVAD. To know whether the change mentioned above in the mechanical properties of the diaphragm is caused by contact of the material with blood or by the exposure to cyclic deformation, tensile tests were carried out on specimens taken from the flat section of the diaphragm which underwent little deformation during pumping due to the constraint of the attached pusher-plate. Table 2 summarizes the results obtained from the convoluted and flat sections of the non-im~tanted, virgin diaphragm and the diaphragm implanted for 72 d. The flat section uf the diaphragm has almost the same tensile properties as the unsupported, convoluted section in each case. These results indicate that the change in the mechanical charac-
1419.0
f 089.0
1043.0
11
Segmented
TOYOCG Tfl5 (Regular grader
!(lU)
f
I:721
F
somoie sheet
Dlaahra4m V: Non-lmalanted, virgin
Key
I(n): lmolonted for n davr L: Non-fatigued, lmnersed tn cholesterol-Ilold solution for 1 mOnth FA: Fatlgued In air for 1 mOnth FL: Foflgued in ChOleSterOi-lIDId solutton for 1 month Figure
5 Comparison of in viva change in diapbra~m characteristics with in vitm change in tensile pmpetiies of sample sheets (regular grade).
4
0 % _[
Toyobo TM5 mole sheet f = 2HZ, Em = 50x, Cd = 10%
3
Refined -----
Regular -----
Saline so!ution ChOleSterOl-liDid
0 Reuetitizn
SOlIJtiOn
4
2 number
Figure 6 Change in the mean deformation.
Fi x 10m6
stress of sample
5
(cycles)
sheet during cyclic
teristics of the diaphragm induced by implantation primarily caused by the contact with blood.
Comparison
between
K. Hayashi
et al.
while the reduction in the ductility is caused by the cyclic deformation or material fatigue. Secant moduli of the nonimplanted materials remain unchanged or decrease either by immersing in the cholesterol-lipid solution, or by fatigue-testing in the solution. This behaviour is different from the phenomenon observed in the implanted diaphragm, in which the secant modulus increases very gradually with increase in the period of implantation as shown in Figures 4 and 5. The reason for the contrast in the change of the secant modulus between the implanted and nonimplanted specimens is not known at present.
Effects of material I(6)
polyurethane:
is
in vivo and in vitro results
In Figure 6, the in vivo change of the diaphragm characteristics is compared with the in vitro change in the tensile properties of sample sheets caused by cyclic deformation and/or by immersion in the cholesterol-lipid solution. Soaking in the solution (L in Figure 5) decreases the tensile strength and secant modulus, while increasing the elongation very slightly. On the other hand, the cyclic deformation in air (FA) decreases the ductility, but increases the tensiie strength. When fatigue-tested in the cholesterol-lipid solution (FL), both the tensile strength and elongation decrease significantly. This phenomenon is quite similar to that observed in a diaphragm implanted in the goat as a component of the LVAD pump. From these results it might be considered that the decrease in the tensile strength observed in the implanted diaphragm is due to some constituents of the cholesterol-lipid solution,
refinement
Figure 6 shows change in the mean stress of the regular and refined grades of Toyobo TM5 polyurethane during fatigue tests in saline or cholesterol-lipid solution kept at 37°C. Rapid decrease in the mean stress is observed in the early stage of cyclic deformation, and stress relaxation appears in all cases. The stress relaxation in the regular grade of material is larger in the cholesterol-lipid solution than in the saline solution. In the case of the refined material, the stress relaxation behaviour observed in the cholesterol-lipid solution is very similar to that in the saline solution: there appears to be no effect of cholesterol-lipids on the stress relaxation characteristics in the refined grade of material. In all cases, the stress relaxation continues gradually even after several million cycles of deformation. As shown in Figure 7, the ratio of stress amplitude to strain amplitude decreases in the early stage of fatigue test in the same manner as the mean stress. In a few million cycles, however, the ratio reaches a constant value in each case. Again in the refined grade of material, there is no difference between the stress/strain ratios observed in saline solution or in cholesterol-lipid solution, while there is a significant difference in the regular material. Figure 8 shows stress-strain curves of the regular and refined materials in a low strain range. They were obtained after cyclical deformation forca 1 month (5 X 1 O6 cycles) in cholesterol-lipid solution or in saline solution both kept at 37”C, or after immersion in each solution at 37°C for the same period under no load. Stress-strain curves of materials in this’as cast’ condition are also included in this figure. The ‘as cast’, virgin material of the refined grade has significantly higher flow stress in this strain range than the regular grade. The flow stress in the refined
10 ^o P -
Toyobo TN5 male sheet f = 2tlz.Em = SO%, E* = 10%
8
m
0
Reeuior _---_-
Refined -w--w
-
-
Saline solution Cholesterol-lipid solution
6
4
2 Reoetition near
N x 1Clm6(cycles1
Figure 7 Change in the ratio of stress emplifude sample sheet during cyclic deformetion.
Biomaterials
1985,
?o strain amplitude
Vol6
March
of
85
Segmented
polyurethane:
K. Hayashi
et al.
ToyObO TN5 somale sheet 6 r
Regular ------
Refined -----
._____._.__-----------
Cholesterol-lipid Saline
Virgin
_____-
~~-~
significantly decreased the secant modulus and ultimate elongation, but only diminished the tensile strength very slightly. These changes are very similar to those observed with the regular grade of sheet material. However, the reduction of elastic modulus caused by the cyclic deformation in the cholesterol-lipid solution was considerably larger in the refined material than in the regular one as shown by comparing the results in Figure 9 with those in Figure 5. Like the diaphragm, non-implanted, virgin specimens obtained from the refined grade of sample sheet had higher secant moduli and tensile strength, but lower elongation than those of the regular grade.
DISCUSSION
I
OV
I
50
0 Strain
E
100 (X)
Figure 8 Stress-strain curves in the low strain range obtained regular and refined grades of sample sheets.
for
material is slightly decreased by immersion in saline or cholesterol-lipid solution, but it is still slightly higher than that observed for the regular grade of material. The cyclic deformation applied in the saline solution or in the cholesterol-lipid solution reduces the flow stress of the refined material in the strain range below 100% elongation. This phenomenon is quite different from that observed with the regular grade of material in which the flow stress in the strain range between 5&100% increases significantly with cyclic deformation in these solutions. In the refined material either fatigued or nonfatigued, the stress-strain curves obtained after immersion in cholesterol-lipid solution are very similar to those observed after immersion in saline solution. For fatigued material of the refined grade, the irregular distortion in the stress-strain curve observed in the fatigued, regular material does not occur. Figure 9 summarizes the in vivo change in the tensile properties of the diaphragm fabricated from the refined grade of TM5 polyurethane caused by the implantation as well as the in vitro change appearing in the sample sheet of the same material following the cyclic deformation and immersion into the cholesterol-lipid solution. Comparing these results with those shown in Figure 5, it can be seen that the change in the tensile properties of the refined grade of material caused by animal implantation is slightly less than that of the regular diaphragm: also there appears almost no change in the ultimate elongation. Even in the refined grade, however, the tensile strength drops to about 75% of that of the non-implanted, virgin diaphragm after 10 d implantation, although this reduction is much less than those observed in the regular grade of diaphragms. The elastic modulus and tensile strength of the refined grade of diaphragm were higher than those of the regular diaphragm whether it was implanted or not. In the case of the refined grade of sample sheet, the in vitro cyclic deformation in the cholesterol-lipid solution
86
Biomaterials
1985,
Vol 6 March
Boretos et al.’ studied the mechanical properties of Biomer@ used as the blood contacting surface in heart assist devices implanted in calves. They reported that the flow stress at 100% elongation increased from 4.1 1 to 4.35 MPa in 11 wk, and subsequently to 4.52 MPa in 35 wk. i.e. the implantation increased the secant modulus gradually. The implantation up to 35 wk decreased the tensile strength and elongation at failure, although the reduction in the tensile strength was very slight. These changes in the tensile properties of Biomer” by implantation are essentially similar to our results with Toyobo TM5 polyurethane. Recently Phillips et aL2 have carried out a similar study on the tensile properties of Biomer” implanted in calves as blood sacs for total artificial hearts and left ventricular assist devices. Their results show no statistically significant reduction in the tensile strength and flexibility after long-term use in the blood contacting environment, although there is a large variation in individual samples. Based on their test results, they concluded that a carefully fabricated sac is reliable from a mechanical fatigue Toyobo TM5 (Refined grade)
I(10) Diaphragm Key
V
L
FL
Sawle sheet
V: Non-imolonted,virgin l(10): Implanted for 10 days L: Non-fotlgued, imwrsed in cholesterol-lioidsolution FL: Fatigued in cholesterol-lioldsolution for 1 month
Figure 9 Comparison of in vivo change in diaphragm characteristics with in vitro change in tensile properties of sample sheets (refined grade). Represented are mean values and error renges.
Segmented
point of view when subjected to 100% elongation or less for long-term use. Tensile properties of blood bags made from a DuPont T-l 27 based segmented polyether polyurethane (Toray Ind., Tokyo) as well as those made from a poly(vinyl chloride) paste (PVC) and then very thinly coated with Avcothane” 52 were studied by lmachi et a/.‘* after implanting in goats as artificial hearts. After 288 d implantation the tensile strength of the polyurethane decreased from 36.4 to 30.3 MPa, while its elongation increased from 865 to 920%. The rate of decrease in the tensile strength of the polyurethane (?7%) was less than that observed for the regular and refined grades of Toyobo TM5 polyurethanes (40% and 26%, respectively). In the case of the PVC sac, the tensile strength and elongation dropped 82% and 76%, respectively, for those of the nonimplanted, virgin material after implantation for longer than 6 months. These data except for the results obtained by Phillips et a/. * indicate that the tensile strength of polyurethanes and PVC decrease when these materials are used as the blood contacting surfaces for pumps. However, the tensile strength of polyurethanes observed after implantation for less than 7 yr are still higher than the stress level estimated to develop in a pump diaphragm. For example, the stress in the 1 mm thick diaphragm of a pusher-plate-type blood pump is estimated at about 3.14 MPa when the regular grade of Toyobo TM5 polyurethane is used? Forthe long-term application, however, it might be required to increase the tensile strength while keeping the elastic modulus low and elongation high since the tensile strength of a material generally corresponds to its fatigue strength and durability. Stokes and Cobian” reported that polyether poly urethanes with brand names of Pellethane” 2363-80A and Pellethane@ 2363~55D (Upjohn) showed significant reduction in tensile strength and elongation in the first months after subcutaneous implantation in rats. However, they observed that vacuum desiccation of specimens obtained from implants after 1 and 2 yr showed considerable recovery towards the original tensile strength and elongation. They ascribed the reduction of strength and elongation to the absorption of water. We also observed decrease in the tensile strength of Toyobo TM5 poly urethane and Biomer@ after they were soaked in a saline solution or cholesterol-lipid solution for approximately 1 mnth under no load condition4,5. One of the reasons for the reduction in strength might be the absorption of water. As shown in Figure 5, however, the degree of decrease in the tensile strength is much more remarkable in the implanted material than in the specimens immersed in the cholesterol-lipid solution. Significant reduction of the mechanical strength of polyurethane caused by contact with blood might be primarily attributable to the microcracks originating from lipids or some blood constituents absorbed into the microvoids formed by the elution of oligomers5, 12. In fact, for a refined grade of polyurethane which contains the minimal amount of oligomers, the mechanical stability was greatly improved as shown in Figures 6, 7 and 9. The tensile strength of the refined diaphragm implanted for 10 d is more than 50% higher than that of the diaphragm made from the regular grade of polyurethane and implanted in a goat for 6 d. Change in the mechanical properties within the first 6 d after implantation were not studied in these experiments. Very early changes in the mean stress and stress/strain ratio during the in vitro fatigue tests (Figures
polyurethane:
K. Hayashi
et al.
6and 7) suggest that the in vivo change in the mechanical properties might appear in the very early period of implantation. Differences in fabrication processes between the diaphragm and sample sheet yielded fairly large variation of their mechanical properties as can be seen from Figures 5 and 9. The sample sheet gives higher elastic modulus and lower ductility than the diaphragm, although their tensile strength is similar. These differences might be attributable to the different rates of solvent evaporation. Even though there are some influences of fabrication process on the mechanical properties, change in the tensile properties of the diaphragm caused by the animal implantation is essentially similar to that developed in the sample sheet by the cyclic deformation in the cholesterollipid solution except for the change in the secant modulus of the regular grade of diaphragm. These results indicate that the change in the tensile properties of implant materials can be predicted to some extent by the in vitro fatigue tests on standardized specimens in the cholesterollipid solution. As can be seen comparing Figures 5 and 9, the tensile
strength
Although
is improved
the tensile
decreased
by
strength
test in the cholesterol-lipid one,
refining
procedures. diaphragm
is
as well as by the in vitro fatigue
by implantation
that of the regular
the
of the refined
solution the degree
in a similarfashion of decrease
to
is less in
refined material than in the regular one. The tensile strength and ultimate elongation of the refined grade of the material are maintained at higher levels than those of the regular material even after the 10 d implantation. The secant modulus of the diaphragm is increased slightly by the refining procedures. The refined grade of Toyobo TM5
the
polyurethane Biomerm. improve
has almost
Based the
similar
on these
material
and
mechanical
results,
we
will
properties
to
continue
to
to use it in our blood pumps.
ACKNOWLEDGEMENT This research work was supported financially in part by: Grant-in-Aid for Scientific Research from the Ministry of Education (No. 557322 and No. 57570520); Research Grant for Cardiovascular Diseases and Grant for Scientific Research Expenses for Health and Welfare Program from the Ministry of Health and Welfare; and Japan Heart Foundation Research Grant for 1981 (ali with Dr Kozaburo Hayashi as the principal investigator). The authors wish to thank Messrs K. Murayama and M. Tanaka of Toyobo Co. and DrT. Tsunetsugu of Sumitomo Bakelite Co. for providing materials used in this study.
REFERENCES Kolff, J.. Hershgotd, E.J., Hadfield. C., Olsen, D.B.. Lawson, J. and Kolff. W.J., The improving hematologic picture in long-term survlvmg calves with total artifxial hearts,Altif. Organs 1979, 3, 97-103 Phillips, W.M.,
Pierce, W.S., Rosenberg, G. and Donachy, J.H., The use of segmented polyurethane in ventricular assist devices and artificial hearts, in Synthetic Biomedical Polymers Concepts and Applications, (Eds M. Srycher and W.J. Robinson), Technomic Pub., Z 980, pp 39-57 Hayashi, K. and Nakamura, T., Material test system for the evaluation of mechanical properties of biomaterials, J. ffiomed. Mater. Res. (In press)
Biomaterials
1985,
Vof 6 March
87
Segmented
4
5
6
7
8
BB
polyurethane:
K. Hayashi
et al.
Hayashi, K., Takano, H., Matsuda, T. and Umezu, M., Mechanical stability of elastomeric polymers for blood pump applications, J. Biomed. Mater. Res. (in press) Hayashi, K., Matsuda, T., Takano, H. and Umezu, M., Effects of immersion in cholesterol-lipid solution on the tensile andfatigue properties of elastomeric polymers for blood pump applications, J. Biomed. Mater. Res. 1984. 18, 939-951 Hayashi, K., Nakamura, T., Takano, H., Umezu, M., Taenaka, Y. and Matsuda, T., Design of pusher-plate-type left ventricular assist device based on mechanical analyses,Artif. Organs 1984, 8, 204-2 14 Hayashi, K., Matsuda,T., Iwata, H., Nakamura,T.,Takano, H. and Akutsu, T., Mechanical and ESCA studies on new segmented polyether polyurethanes for blood pump applications, Abstr. 30th Ann. Mtg. Amer. Sot. Art. Intern. Organs 1984. 20 Carmen, R. and Mutha, SC., Lipid absorption by silicone rubber
Biomateriats
1985.
Vol 6 March
9
10
11 12
heart valve poppets-in vivo and in vitro results, J. Biomed. Mater. Res. 1972. 6. 327-346 Boretos, J.W., Pierce, W.S., Baier, R.E., Leroy, A.F. and Donachy, J.H., Surface and bulk characteristics of a polyether urethane for artificial hearts, J. Biomed. Mater. Res. 1975. 9, 327-340 Imachi, K., Fujimasa, I., Takido, N., Nakajima, M., Motomura, K., Kohno, A., Ono, T. and Atsumi. K., ln viw evaluation of the materials of artificial heart pumps- thromboresistance, biocompatibility and durability during long-term implantation, Proc. 3rd Ann. Conf. Jpn Sot. Biomat. 1981, 6%72 Stokes, K. and Cobian, K., Polyether polyurethanes for implantable pacemaker leads, Biomatetieb 1982, 3, 225-231 Takahara, A., Tashita, J., Kajiyama, T. and Takayanagi, M., Blood compatibility and change in fatigue strength by absorption of blood components in thermoplastic elastomers, Proc. 3rdAnn. Conf. Jpn Sot. Biomat. 1981, 61-64