J. BIOMED. MATER. RES.
VOL. 11, PP. 373-394 (1977)
Porous Acrylic Cement* A. M. RIJKE and M. R. RIEGER, Department of Materials Science, School of Engineering and Applied Science, R. E. McLAUGHLIN, Department of Orthopedics and Rehabilitation, and S. McCOY, Department of Surgery, School of Medicine, University of Virginia, Charlottesville, Virginia 22901
Summary The use of acrylic bone cement has a number of shortcomings, viz., high curing temperatures that can cause thermal necrosis, release of toxic monomer, and a less than perfect cement-to-bone bond. However, by modifying the cement composition through the addition of a soluble, nontoxic filler such as sucrose or tricalcium phosphate which does not impair the workability of the material during surgery, a significant improvement in the performance of the cement can be achieved. Because the filler replaces part of the acrylic components, less heat is generated during curing while the filler itself acts as a heat sink. Also, less monomer, proportional t o the amount replaced by the filler, diffuses from the implant site. Upon elution of the filler, a porous cement will be obtained provided that a critical minimum percentage loading is exceeded so that the filler crystals will make physical contact with each other. The value of this percentage depends on both crystal modification and size. I n the 125-175 prn sucrose crystal size range, the critical minimum percentage lies in the range of 20-28 wt % loading. Above 30%, the interconnecting pore size increases sharply to a value which allows good tissue ingrowth into the pores. The introduction of filler and pores causes a drop in strength, but the diametral tensile strength of modified cement containing up to 40% pores and sucrose lies between .7 and 1.5 kg/mm*, respectively, which is still in the same range ELS that of bone.
INTRODUCTION Early attempts to mechanically implant artificial joints by impacting the prosthesis into bone frequently failed because the prostheses *Presented in part a t the 21st Annual Meeting of the Orthopedic Research Society, San Francisco, California, 1975.
373 @ 1977 by John Wiley & Sons, Inc.
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loosened. To reduce the number of failures, two methods have been developed. One of these is based on the finding that bone grows into the pores of inert materials such as sintered fibers, powdered metals, ceramics, and some Although porous materials and prostheses coated with a porous layer have been shown to improve the bonding to bone, their fabrication is a lengthy procedure and cannot be custom-fitted to insure mechanical stabilization a t the time of surgery. Such stabilization is an essential condition for tissue ingrowth into the pores. The second method has been the use of an acrylic seating cement. Charnley4 and others have pioneered its use in total hip replacement with outstanding results, and the material is now finding application in other areas of orthopedics. Despite its clinical attractiveness, however, there have been reports of disturbing complications during and after surgery, vie., high curing temperatures, release of toxic monomer into the blood, and loosening of the prosthesis. I n what follows we will show that these shortcomings can be overcome by modifying the composition of the cement by the admixture of an optimal amount of a suitable crystalline compound such as sucrose or tricalcium phosphate
High Curing Temperature and Thermal Necrosis The curing or setting temperature of the acrylic material is accompanied by the evolution of a considerable amount of heat. Temperatures as high as 83°C have been measured during tn vtvo curing a t the cement-tissue i n t e r f a ~ e ,and ~ necrosis has been observed in experimental animals as a result of th is6 High setting temperatures can be reduced by the introduction of a heat sink such as reported by Homsy,6 who mixed TiOz with the curing cement. A temperature decrease at the cement-tissue interface from 83°C to 54°C was observed when 1.5% TiO, was mixed with the cement, but the loss of strength of the material was significant. Of course, in hip arthroplasty the metal components of the prostheses act as effective heat sinks themselves.’ For the evaluation of a n optimum cement composition, it, is important to assess the otherwise obvious heat-sink effect in vivo because the amount of heat generated and the highest temperatures reached with the concomitant thermal necrosis is determined by the amount of cement used and the actual surface-tc-volume ratio of
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implanted cement. Curing temperatures should be lowered enough to prevent thermal damage to surrounding tissue, but not lowered enough to inhibit high monomer conversion and rapid curing which minimizes the life of free monomer.
Release of Monomer During Curing in situ At the time of insertion of the dough, only part of the monomer is polymerized. Consequently, it is inevitable that some monomer will be released before the curing process has been completed, as indeed has been found by several workers.*-1° Homsy has shown the presence of monomer in the circulation and the lung gases5 of several patients. Several toxic effects have been demonstrated. I n dogs, pulmonary infarcts and hemorrhagic lesions in the lungs have been observed after injecting the monomer intravenously. 5.10 There have been many reports of transient hypotcnsion and even of sudden death. Although the amount of monomer released during total hip replacement is usually clinically insignificant, it is clearly desirable t o reduce even this small amount. Considerably smaller quantities of monomer continue to be released long after the cessation of the polymerization reaction. This has been interpreted by some" as an indication of metabolic breakdown of the polymer, but such a degradation is difficult to conceive and there have been no adequate studies addressed to this point. On the other hand, it is likely that a large percentage of monomer, up t o 15%, will remain unconverted under these polymerization conditions.'** This is a result of the fact that the reaction mixture becomes increasingly viscous and subsequently a glass, the further the reaction proceeds and ultimately stops completely well before all monomer has been consumed. It is interesting to note that the addition of a solvent, such as benzene, which will decrease the viscosity of the mixture, increases the conversion to near The unconverted monomer will slowly diffuse from the implant and its concentration will decrease exponentially with time, the actual concentration being dependent on amount and surface-to-volume ratio of the implanted cement. *The 95% conversion reported in the Polymer HandbookL6refers only to the controlled laboratory conditions used for the manufacture of bulk poly(methy1 methacrylate) and does not apply to acrylic bone cement products or surgical conditions.
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It should be pointed out that for the purpose of tracing monomer, Oppenheimer et 511.” and also subsequent workers have used methyl14C-methacrylate exclusively. As the labeled carbon is in the ester methyl position, it does not necessarily follow that the 14Cactively reflects the kinetics of methyl methacrylate. Eggert and co-workersl4 reported that the 14C levels in the circulation of six patients were significantly higher than the methyl methacrylate concentrations as measured by gas chromatography. Simulating the arthroplasty in vitro, they could show that this discrepancy was due to the presence of radioactive oligomers in addition to methyl methacrylate. A further discrepancy may be expected with time as methyl methacrylate is rapidly degraded into as yet unknown products.15
The Bone-Cement Bond Acrylic cement itself possesses no adherent qualities. It acts as a cement and depends on the conformation of both the implant and the substrate to hold it in place. It is not surprising, therefore, that a number of reports have appeared in the literature which show that even in the absence of infection, the bond between the bone and cement can become loose. With the use of certain types of prostheses loosening has occurred in as many as 10% of the case~.1~-~0 The area of weakness exists usually at the cement-to-bone interface and not a t the cement-to-implant interface. As has been mentioned above, it has been known for some time that the use of porous, inert materials can greatly strengthen the bond between implant and bone. This improved bond is achieved by the ingrowth of fibrous tissue and bone. Recent investigations have indicated that rapid bone formation into the implant material with the concomitant stable bonding between prosthesis and bone can be realizcd after a 4 week period.21*22I n actual practice, the time required for initial ingrowth depends mainly on porosity, pore size, pore distribution, and nature of the implant material, but not on the location in the skeletal system. Complete penetration of bone into all voids obviously depends on the size of the porous portion of the implant. For implants in the femur of dogs and rabbits, a period of 3-6 months was required for complete ingrowth into all pores. It is the purpose of this study t o show that the surgically attractive qualities of the cement can be combined with the advantages of
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porous implants. Sucrose or tricalcium phosphate crystals mixed with the cement in the desired crystal size and quantity act as a n effective heat sink during the curing step, preventing thermal necrosis and leach out following implantation, leaving continuous, interconnecting pores for tissue ingrowth. I n addition, the added crystals contribute to the bulk of the fixating material. Therefore, the amount of cement required for each surgical procedure is reduced, and the release of monomer during curing into the central circulation is proportionally decreased.
METHODS AND MATERIALS Acrylic Cement Two cement systems were used interchangeably to show that the principles discussed above are valid for cement other than the most commonly used. Simplex-P is a product of North Hill Plastics Ltd., London. It consists of two components: a liquid containing methyl methacrylate monomer, N,N-dimethyl-p-toluidine (DMT) for accelerator, and a small amount of hydroquinone for inhibitor and a solid containing methyl methacrylate-styrene copolymer and benzoyl peroxide (BPO) for initiator. The second cement, supplied by Esschem Co., Essington, Pennsylvania, substituted 20/80 ethyl methacrylatemethyl methacrylate copolymer in the solid component but was otherwise the same as Simplex-P. For the in vitro studies, outdated Simplex-P was used after the solid component was heated a t 80°C for 24 hr to destroy all BPO present. Before mixing with the liquid component, a 1% (by wt) amount of fresh BPO was added to the solids. This procedure was found necessary to insure consistent curing times amoung different batches.
Sucrose and Tricalcium Phosphate (TCP) Crystals These crystals were obtained in several size ranges by sifting analytical-grade sucrose and TCP through standard mesh sieves. The sizes were selected a t random, but all were above the pore size reported to be the minimum for bone ingrowth.22 No attempt was made t o sterilize these crystals.
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Measurement of Curing Temperature Spherical samples of curing cement were wrapped in wet cotton and contained in a small glass beaker in a 37°C circulating water bath. The temperature of the curing cement was read directly from a small thermometer, the bulb of which was wrapped with thin aluminum foil and placed in the center of the sample. Identical results were obtained when using a thermocouple and recorder.
Monomer Release from Curing Sample I n order to study the effect of sucrose and T C P loading on the reduction of monomer release, it is important to control the surfaceto-volume ratio of the curing samples throughout the experimental procedure. To this end, the polymer was mixed with 1% (by wt) BPO and the desired amount of sucrose or TCP. At t = 0, monomer containing 0.5% D M T was added to the mixture to the amount of 0.5 ml/gram of polymer and stirred for 1 min. At t = 5 min, the mixture was extruded onto fluorocarbon-coated stainless steel wire gauze t o form cylindrical rods. At t = 6 min, these rods were placed in 75 ml distilled water. The temperature of the water was 25OC which rose to not more than 28°C for a 14 g sample of plain cement. At t = 20 min, the water was poured off, beaker and cement washed with water, and the concentration of methyl methacrylate in the combined solutions was measured spectrophotometrically a t 215 nm. This experiment was repeated using outdated human blood ; in this case, the blood samples were extracted three times with cyclohexane. I n another set of experiments, the rods were exposed to a nitrogen atmosphere which was bubbled a t constant rate through three consecutive cyclohexane traps.
Pore Continuity On completion of the curing step, the crystals of the additive will leach out and leave pores in the implanted cement. To assure continuous porosity, however, the crystals must touch each other and, therefore, a critical percentage minimum must be exceeded. Although it is possible, in principle, to calculate this critical percentage from crystal shape, size distribution, and percentage, the number of uncertain parameters in the final expression renders this method unfeasible. Instead, the pore continuity was determined experi-
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mentally by extracting cement in the shape of 6 X 5 mm cylindrical plugs with water in a Sohxlet apparatus followed by drying to constant weight. This procedure was repeated until all extractables were removed.
Porosity and Interconnecting Pore Size (i.p.s.) The minimum percentage of crystals in the cement required for interconnection of the pores can be estimated from the studies mentioned in the previous section, but for obtaining tissue ingrowth, the interconnections between the voids left by the soluble crystals must exceed a minimum size of approximately 10-20 pm.’ These “bottle necks” are presumably located where the crystals touched each other and their actual dimensions are determined by both crystal size, shape, and percentage. It has been estimated that these i.p.s. are about 5-10 times smaller than the added crystals. An experimental estimate of the i.p.s. can be obtained from mercury intrusion porosimetry. To this end, the porous samples as described above were exposed to mercury pressures up to 55 MN/m2 (8000 psi) and the cumulative pore volume registered as a function of pressure.23
Porosity, Pore Size and Strength of Acrylic Cement The introduction of pores, particularly during the early stage when little or no ingrowth has yet occurred, will cause a significant drop in strength of the acrylic implant. This reduction can be minimized by matching the rate of dissolution of the additive with the rate of tissue ingrowth. Candidate additives less soluble than sucrose, such as tricalcium phosphate, may therefore be more suitable. We have measured the change in strength of acrylic cement as a result of the addition of sucrose and TCP, before and after elution with water, on an Instron tensile-testing machine. The diametral tensile strength (DTS) was directly calculated from the load a t collapse applied perpendicularly to the axis of the cylindrical plugs at a crosshead speed of 2 mm/min, and the dimensions of the samples.
Implantation and Sectioning The actual elution of sucrose additive from the modified acrylic cement and the concomitant ingrowth of tissue into the newly
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formed pores were investigated in vivo in a preliminary implantation study. A 0.6 cm hole was made with an electrical drill through the cortices of the ilia of New Zealand white rabbits. Cement inserted in the hole formed a mushrooming plug on either side of the ilium. On sacrificing the animals after 1-270 days, the entire plug and surrounding 1-2 cm of bone was removed, and embedded in poly(methy1 m e t h a ~ r y l a t e ) . ~Sections ~ 150 p thick were cut with a diamond-blade saw and stained with Van Gieson collagen stain.
RESULTS AND DISCUSSION Curing Temperature Exotherms were collected for cement containing various percentages and crystal sizes of sucrose and TCP. The effect of weight of sample on peak temperature is very pronounced and increases steadily with sample weight. Also, the time during which a high temperature is maintained increases markedly with sample weight. The effect of crystal size on the peak temperature is negligible for the size range investigated (53-297 pm). The effect of percentage loading on the peak temperatures is illustrated in Figure 1. The heat-sink effect of the additives is marked, the more so for T C P because of its larger specific heat. As was pointed out in the Introduction, the actual temperature measured a t the cement-tissue interface, the time that this temperature is maintained, and the concomitant thermal damage to the tissue is very much dependent on mass and surface-to-volume ratio of the cement sample in vivo. The actual values reported in the Figure 1, therefore, merely show thc: relative effect of sucrose and T C P as a heat sink.
Monomer Release During Curing It is seen from Figure 2 that the monomer release is proportional to sample weight as a result of the cylindrical shape of the samples. The lines extrapolate to about 8 mg of monomer for zero sample weight; this can be interpreted as that released by the two end surfaces of the cylindrical samples. For the samples containing 25% and particularly 37.5% T C P the relationship is no longer linear, indicating that factors other than mere replacement of cement by
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Peak temperature of curing cement (28 g) holding different percentages of (0)sucrose (mesh 120/140) and (+) TCP (mesh 60/80).
additive come into play. The inset in Figure 2 shows th a t the reduction of monomer release from a 10 g sample is somewhat smaller than the precentage additive on a per weight basis, but larger than on a per volume basis. Corresponding results were obtained when trapping monomer vapor in cyclohexane. The experiments in aqueous environment have been repeated with cement holding sucrose crystals instead of TCP. Here, the monomer release was also found to increase with sample weight, but the reduction of monomer release was about 25% irrespective of the precentage sucrose. It is presumed that the readily soluble sucrose a t the cement-water interface leaves behind an irregular, pitted surface on dissolution, thereby increasing the effective surface area from which monomer can diffuse into the environment. This would partly offset the reducing effect of the added sucrose. This assumption has been supported by our observation that when the same samples were cured in nitrogen atmosphere, the expected reduction of monomer release was found again. A sample of polymer holding 12.5 wt yo 120/140 mesh sucrose crystals was cured in outdated human blood following the same experimental procedure as described above, except that the blood was
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&0 100 v)
W E I G H T S A M P L E I N GRAMS Fig. 2. Amount of monomer released from 6.35 mm diameter cylindrical cement samples containing different percentages TCP: ( 0 )0 wt %; (+) 12.5 25 wt %; (A)37.5 wt %. In water at 2Ti°C. Inset: Reduction of wt %; monomer released from 10 g cylindrical sample as a function of percentage T C P additive. From interpolation in above graph.
extracted with cyclohexane three times. Possibly as a result of the extraction step required for the blood samples, less monomer is collected from blood than from water, i.e., 4.12 mg/g of sample versus 10.2 mg/g for pure cement. However, the monomer released as a result of 12.5% added sucrose was reduced to 3.22 mg/g, ( 2 2 7 3 , which compares well with the 25% observed from the same sample when cured in water.
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Some indication of the effect of sucrose and TCP crystals on the reduction of monomer released in vivo has been obtained from a single experiment using two dogs. I n one dog, about 15 ml of cement holding 45 wt yo 60/80 mesh TCP was worked through a hole in the ilium, and 5 ml blood samples were taken every minute following implantat,ion from the inferior vena cava proximal to the caval bifurcation, cathetered through the opposite femoral vein. The procedure was repeated on the opposite ilium with the same volume of plain cement. Using the second dog, the experiments were repeated with cement filled with 25 wt % 120/140 mesh sucrose. For cement holding &Yo TCP, a monomer reduction of 80% was recorded. For cement holding 25% sucrose, a reduction of 56y0 was recorded. These values are considerably larger than expected on the basis of our in vitro experiments, and have not been explained.
Pore Continuity Pore continuity and percentage extractables in the various samples were tested by extracting sucrose-loaded cylindrical plugs as described above. The results are given in Figure 3. It is seen that for low percentage loading, the percentage extractables, probably mainly superficial sucrose, increases only slowly with increasing original percentage loading, indicating that most crystals are separately embedded in that concentration range. Beyond a critical percentage, however, the crystals begin to make physical contact with each other and the percentage extractable sucrose increases sharply, the more so for the narrower crystal size ranges. This critical percentage occurs for the smallest crystals at a lower percentage loading.26 The curves in Figure 3 level off for a little less than 30 wt %, loading at well over 100% sucrose lost. This indicates that the acrylic cement holds water-soluble materials other than sucrose, such as unconverted monomer and by-products of catalyst and accelerator.
Interconnecting Pore Size The results of mercury intrusion porosimetry studies are usually given in terms of cumulative pore volume expressed as a function of pore size. The relation between the pressure required to force the
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WEIGHT PERCENTAGE SUCROSE
Plot of percentage sucrose extracted from cement vs. weight percentage sucrose in the original samples.
mercury through the pores into the plug and interconnecting pore size is given by 4y cos e P= d
where P is the pressure, y is the surface tension of mercury, d is thc interconnecting pore diameter, and e is the advancing contact angle between mercury and acrylic cement, here taken to bc 130 degrees. The midpoint of the steep part of the curve is taken as the i.p.s. The cumulative pore volume at which the curve levels off in the high pressure range provides an estimate of pore volume accessible to the
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mercury and therefore an estimate of percentage extractable sucrose. This latter can also be calculated from the data in Figure 3. Interconnecting pore sizes are plotted against weight percentages loading with three different sizes of sucrose crystals in Figure 4. It is seen that the i.p.s. increases rapidly in the loading range between 30 and SO%, but values of only a few microns, too small for tissue ingrowth but large enough for elution of a t least part of the sucrose, are recorded for samples which held slightly less than 30% before extraction. The extractability of all sucrose as indicated in Figure 3 corresponds well with the sudden drastic increase in i.p.s., as shown 00 -
50 0 0 S O 200250 300 CRYSTAL S I Z E . ern
- 50/60 - 120/14o
A - 230~70 s3-63
Fig. 4. Graph of interconnective pore sizes in extracted cement versus weight percentage sucrose before extraction. Inset: i.p.s. as function of average sucrose crystal sizes used.
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in Figure 4. For the smallest crystal size this valuc reads about 22%. Inset in Figure 4 is a plot of i.p.s. versus the averaged size of the crystals mixed in with cement. Although the data are scarce, the expected features are well borne out by our experiments26:for low percentage loading (30%), the i.p.s. is small (3 pm) and decreases slowly with crystal size due to the looser packing of the larger crystals. However, a t higher percentage loading (4OY0), the i.p.s. is large (23 pm) and initially increases with crystal size because large crystals, when packed sufficiently close, will touch with larger interfaces than small crystals, thereby increasing the i.p.s., but as crystal size increases, loose packing becomes predominant and the i.p.s. will again decrease. This explains the maximum in the 4oy0 curve. Also shown is the curve for 35% loading derived from I;igure 4 by interpolation. The most marked feature of these results is the rapid increase in i.p.s. within a relatively narrow percentage loading range. For instance, if we tentatively assume an i.p.s. of 20 pm for tissue ingrowth, we can interpolate from the graphs with a great deal of accuracy that this i.p.s. is realized with 150 pm sucrose crystals for 37y0 loading. Above 37y0, an i.p.s. of 20 pm or larger is realized by two crystal sizes, a small one and a large one. Below 37% there is no crystal size that can realize an i.p.s. of 20 pm or larger. A similar set of values will apply to TCP crystals. From the results, it is clear that an optimal choice of crystal size and prrcentage can be madr only when an i.p.8. large enough to allow for satisfactory tissur ingrowth is established first. A valuc of approximately 10-20 pm, based on ingrowth studies of other workers, is probably a valid rstimatr. I t is interesting to note hrre that, when using 150 pm crystal size, approximately 3% mow or less than 37% loading will increase or drcreasr the i.p.s. from 20 to 30 pm or 10 pm, respectively. It is therefore possiblr to arrive a t a narrowly defined formula in terms of crystal size and percrntagr in ordrr to secure acceptable ingrowth as cxpressed by i.p.s. Inasmuch as the optimal conditions of our surgical crment are determined by a variety of parameters, it can be rnvisaged that the rrlation between i.p.s. and crystal sizr as outlined abovr will enter our computations so as to accommodate other desirablr properties of the acrylic crment most effectively.
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Diametrical Tensile Strength of Acrylic Cement The mechanical properties of bone have been the topic of investigations by many worker^.^^^^ Values ranging from 7.7 to 12.4 kg/mm2 (11,00CF17,000 psi) have been reported for the tensile strength, whereas compressive strengths have been found to range between 9.8 and 19.7 kg/mm2 (14,000-28,OOO psi). These wide ranges are the result of differences between test specimens and between methods of loading. Heat-cured poly(methy1 methacrylate) has a tensile strength of about 6.5 kg/mm* and a compressive strength of about 10 kg/mm2.16 I n arthroplasty, the forces applied to bone by the implant are compressive and mostly perpendicular to the long axis of the bone. When the load was applied perpendicularly to the long axis, we measured values between 0.62 and 1.5 kg/mm2 for the diametral tensile strengths of cylindrical test specimens of fresh, adult femoral cortex in agreement with Evans’ finding^.^' For the roots of dry teeth, 1 2 - 2 0 kg/mm2 was found. The DTS of pure acrylic bone cement was measured to be 2.3-2.5 kg/mm2, which compares well with the values reported by Lautenschlager et a1.28 Diametral tension is formulated for homogeneous, isotropic bodies and cannot be applied to porous acrylic without restriction. The absolute tensile values for porous samples are therefore questionable, but serve well to demonstrate the reduction in strength as a result of the induced porosity on a relative basis. The results of our DTS experiments on loaded and porous cement are shown in Figure 5. Here, log u is plotted against weight percentage sucrose, both before and after extraction in water. u=-
Here u is the DTS (kg/mm2), 1 is the length, and d is the diameter of the cylindrical plugs. For the unextracted samples, log u initially decreases slowly, but more rapidly beyond the 40% loading range and the more SO for the smaller crystal sizes. For the extracted samples, therc is a linear decrease of log u with percentage loading for each of the three sucrose crystal sizes for less than approximately 30yo loading. This corresponds with the range
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E E 1.0
I I0 2
5 0.1 I-J
1 0 5 - 125
5 3 - 63
WEIGHT PERCENT SUCROSE
Fig. 5. Diametral tensile strength (kg/mmZ) of cement before and after extraction of sucrose plotted as a function of weight percentage sucrose in the unextracted samples.
of Figure 3 in which less than 1 0 0 ~ o sucrose has been extracted. Above 30%, where all sucrose has been extracted, the weight percent sucrose is the same as percent porosity. The linearity is here continued but with a new proportionality factor. The onset of this second linear part of the graph occurs a t a smaller percentage loading for the smaller crystal sizes. This again is in agreement with the results of our extraction studies as shown in Figure 3. The diametral tensile strength of an extracted, 4oa/, porous sample is approximately 2-2.5 times less than that of unextracted cement, about 3 times less than that of pure cement, and therefore about the same strength as bone. As was pointed out above, the elution of sucrose or T C P from the cement and the ingrowth of tissue are two overlapping processes, and the in vivo tensile strengths of the implants will therefore remain well above those of the extracted samples during any stage of the implant’s history. Even during the early
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stage when no ingrowth has as yet occurred, the tensile strength will vary only between the values for unextracted and extracted cement. The elution of sucrose or TCP from the cement causes surfaces defects in addition to porosity, and it may therefore be informative to measure mechanical strength in some surface sensitive mode, such as by bending or impact. These studies are presently in progress.
Implantation Studies Early results of implantation studies confirm that sucrose crystals are eluted from acrylic cement in vivo and that tissue ingrowth ensues. The tissue ingrowth seen in the stained sections was rated on an arbitrarily chosen 0-4+ scale. No tissue growth was noted in the plugs from the control rabbits which had plain cement or in those plugs which were removed a t 1-4 days. No or little ( I f ) tissue ingrowth was noted in plugs from rabbits sacrificed at 15 days or in the plugs with less than 20% sucrose at any time. Much more (3f to 4+) tissue ingrowth was noted in animals sacrificed after 30 or more days at sucrose concentrations of 3&60%. In these preliminary studies, crystal size and percent porosity appeared to make little differences in the amount of tissue ingrowth in these rabbits. Some of these results are averaged in Figure 6. The extend of ingrowth, here averaged over E
tX X W
A 2 1
PERCENTAGE SUCROSE LOADING
Fig. 6. Extent of tissue ingrowth in porous cement rated on an arbitrary scale of 0-4 as a function of weight percentage sucrose loading in implanted material. Plugs were implanted in the ilia of New Zealand rabbits for 30-270 days. Numbers in parenthesis are number of sections investigated. The results include six narrow crystal size ranges between 44 and 500 pm.
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(4 Fig. 7. (a) Light photomicrograph of a 150 pm thick section from a plug of cement embedded in a rabbit ilium for 30 days. When implanted, the cement contained 60 wt % sucrose as crystals ranging in size from 250 to 297 pm. Note presence of noneluted sucrose crystals. 120 X. (b) High-power magnification (565 X ) of a tissue seam growing into the acrylic cement. Note lamellar patterns and cellular detail. 40% sucrose crystal loading, embedded for 30 days. Sucrose crystal size, 105-149 urn.
all periods of implantation, is essentially proportional with percentage original sucrose loading. A histologic section is shown in the Figure 7. The tissue appeared to be fibrous and fairly cellular. Charnley has noted that the bony surface in contact with the cement probably dies from chemical and thermal trauma and is replaced by fibr~cartilage.~Some areas of our sections show direct contact between bone and cement, but a fibrous tissue much like that Charnley4 and Laing et al.29 have described was observed only occasionally. It is tissue of this nature, however, that appears to invade the porous cement. It occurs in a lamellar arrangement and polarizes light, indicating organized fibrous collagenous tissue. The occurrence of birefringence is in
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(b) Pig. 7. (continued)
agreement with Charnley’s findings of fibrous tissue surrounding implant material^.^ I n some tissue sections, we suspected the presence of bony ingrowth b u t this observation has not as yet been confirmed by microradiography. A more detailed, quantitative evaluation of tissue ingrowth into implants with narrowly controlled interconnecting pore sizes is presently in p r e p a r a t i ~ n . ~ ~
CONCLUSIONS Our experimental studies have shown that the addition to acrylic cement of soluble, physiologically acceptable crystals which will elute following the curing of the cement and leave behind continuous pores of appropriate size, can successfully reduce curing temperatures below damaging limits, reduce the release of toxic monomer, and allow the ingrowth of fibrous and, possibly, bony tissue. It is obvious that crystalline additives other than sucrose and TCP can bring about the same effects, provided that they meet the same
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surgical and physiological requirements as do sucrose and TCP, such as a) solubility in tissue fluids, b) insolubility in methyl methacrylate, c) nontoxicity, d) nondeformability, e) melting point above the peak curing temperature of the cement, and f) nonpolymeric nature t o prevent the buildup of swelling pressures which will break the acrylic implant.* There appears to be no reason why the modification of acrylic cement by the admixture of a crystalline component should not be compatible with the incorporation of antibiotic^.^^ I n fact, it is expected that porosity and vascular ingrowth throughout a large part of the implant will prove advantageous to fighting infection. We have paid special attention to the handleability of the cement a t the time of mixing and insertion. If a ratio of 20 g of polymer solids t o 10 ml of monomer liquid is maintained, we found that the addition of up to 40 wt % sucrose did not alter the consistency significantly except when using a very fine grade of sucrose. The appearance of the dough immediately after mixing is somewhat drier compared with pure cement, b u t this difference disappears after about 2 min. Within the composition range likely to be of use in orthopedic applications, we do not expect that the addition of crystals will cause problems to the surgeon. The reported data have provided the groundwork for the computation of the optimal parameters that describe the composition formulas of acrylic cement as required by specific surgical applications. Such formulas will also be applied for the use of acrylic cement in periodontal applications, the internal fixation of external prostheses, and possibly the bridging of bone gaps and spinal fusion. The results of a few preliminary studies have so far revealed a measure of success. I n view of the clinical success of the unmodified acrylic cement during the past decade, it is believed that the addition of crystalline additives such as sucrose and T C P constitute a major improvement in its remaining undesirable qualities : the relatively high curing temperature, the toxicity of the monomer, and the less than perfect bonding of the cement to tissue. Thanks are due to Dr. Joe Sipe of S-K Surgical Specialties, Philadelphia, Pa., for valuable suggestions and for performing the mercury intrusion porosimetry experiments. This work was supported in part by USPHS Grant AMI52403. *Patents are pending.
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Received April 1, 1976 Revised July 30, 1976