GLOBUS MEDICAL, INC.
`EXHIBIT 1023
`IPR2015-to be assigned
`(Globus v. Bonutti)
`
`Page 1 of 8
`
`

`
`THE USE OF CERAMICS FOR BONE REPLACEMENT
`
`A COMPARATIVE STUDY OF THREE DIFFERENT POROUS CERAMICS
`
`ATSUMASA UCHIDA, SYDNEY M. L. NADE, ERIC R. MCCARTNEY, WILLIAM CHING
`
`From the University of Western Australia, and the University ofNew South Wales
`
`Ceramics have many properties which might make them suitable alternatives to bone grafts. This present
`study was done to find a suitable biodegradable porous ceramic for human bone replacement. Three different
`porous ceramics (calcium aluminate, calcium hydroxyapatite and tricalcium phosphate), with interlinked
`pores of two size ranges (150 to 210 um and 210 to 300 um), were implanted into the skulls of rats and rabbits
`for up to six months; the interaction with surrounding bone, which is virtually devoid of bone marrow, was
`then assessed. The ceramics caused no adverse biological response. Tissue ingrowth into pores throughout the
`implant was seen in all three types and in both pore sizes of ceramic, but the density of the penetrating tissue
`was far less for calcium aluminate than for calcium hydroxyapatite or tricalcium phosphate. For each type of
`ceramic, the soft-tissue ingrowth was more dense with the larger pore size, and with a longer period of
`implantation. Bone ingrowth was not usually seen within the pores of any ceramic. There were no differences
`in the histological findings between the rats and the rabbits. The results demonstrate that it is possible to
`produce ceramic materials with a porous structure which allows ingrowth of tissue and biological fluids.
`
`In recent years the use of ceramics in bone and joint
`surgery has received considerable attention, particularly
`as permanent implants for joint replacement. For the
`latter purpose the material most used is high-purity
`alumina, which is biologically inert. In contrast, biologi-
`cally active ceramics such as tricalcium phosphate or
`calcium hydroxyapatite have been considered for use as
`biodegradable bone replacements. The concept of bio-
`degradability implies that the material is replaced by
`bone as it degrades. There have been several studies of
`this type of bone ingrowth in animals, and its clinical
`applications have been described (Bhaskar er al. 1971;
`Hentrich et al. 1971; Heller et al. 1975; Frame 1975;
`Levin, Getter and Cutright 1975; Cameron, Macnab and
`Pilliar 1977; Ferraro 1979; de Groot 1980; Jarcho 1981).
`How to induce bone to form within porous ceramics,
`and how to manufacture such materials, are the questions
`to which we have directed our efforts.
`Injured and
`transplanted autologous bone marrow can stimulate the
`formation of bone (Burwell 1964; Boyne 1970; Nade and
`
`A. Uchida. MD. University Research Fellow
`National Defense Medical College. Saitama, Japan.
`S. M. L. Nade. MD. FRCS. FRACS. Professor ofOrthopaedic Surgery
`Department of Surgery (Orthopaedic). The Queen Elizabeth 11 Medical
`Centre (University ofwestern Australia). Nedlands. Western Australia
`6009.
`
`E. R. McCartney, BSC, PhD. ARACI. MlE(Aust). Fl Ceram, Associate
`Professor and Head
`W. Ching. BSC. MSC, ARACI. Research Fellow
`Department of Ceramic Engineering. University of New South Wales,
`Kensington. NSW 20.13. Australia.
`Requests for reprints should be sent to Professor S. M. L. Nade.
`
`© 1984 British Editorial Society
`0301 620X/84/206252.00
`
`of Bone and Joint Surgery
`
`VOL, 66-3. No. 2. MARCH 1984
`
`Burwell 1977; Nade 1979). This osteogenic potential of
`bone marrow in its natural site is probably stimulated
`when a defect occurs in bone, as in fracture repair. If
`such a defect could be filled with a porous ceramic
`material, newly-fonned bone might invade the ceramic.
`Eventually, if the appropriate ceramic were chosen, the
`implant might be slowly dissolved or resorbed, or both,
`and be replaced in part or whole by newly-forrned bone.
`Our previous studies have shown that four different
`ceramics—alumina, calcium aluminate, calcium hy-
`droxyapatite and tricalcium phosphate—are biocompa-
`tible, and the latter three biodegradable. When these
`ceramics were implanted in combination with bone
`marrow into abdominal muscle sites, newly-forrned bone
`was seen in and about the implants (Nade et al. 1983).
`The ceramic materials used in that study did not have
`regular pore sizes, nor did the pores show regular
`interlinkage. It was determined that a pore size greater
`than 100 pm was necessary to allow ingrowth of bone.
`The size and regularity of the pores is a critical
`factor in the design of ceramic implants for potential
`clinical use, not only for tissue penetration and bone
`ingrowth, but also for physical strength. In order to allow
`tissue penetration and bone formation within the cer-
`amic,
`large pores are needed;
`to retain compressive
`strength, the pores must be small—between these two a
`balance must be established.
`
`The purpose of this study was to find a suitable
`biodegradable ceramic that combined the properties of
`strength with porosity, and also to find a way of
`stimulating bone growth within its pores. In this paper
`we examine the histological effects of implanting cer-
`
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`
`270
`
`A. UCHIDA, S. M. L. NADE, E. R. MCCARTNEY, W. Cl-IING
`
`ranges were added to the plastic mixtures. A weight ratio
`of two parts of ceramic material to one part of polymer
`beads was used. The polymer beads were either polysty-
`rene (Monsanto) or polymethyl methacrylate (Imperial
`Chemical Industries). Both of these produced a uniform
`structure of interconnecting pores. The morphology of
`these pore structures was more suitable than that
`produced by the inclusion of spheres of polyvinyl chloride
`which we had used previously (Nade et al. 1983). The
`granulated materials containing the beads were pressed
`in a steel die.
`The discs were first fired in an electric furnace at
`
`100°C for one hour and 200°C for three hours, before the
`temperature was raised to 400°C for five hours. The
`temperature was then raised slowly to lO00°C for one
`hour. The slow increase in temperature allowed the
`polymer beads to melt and vaporise,
`resulting in
`interconnecting pores. The porosity of the finished discs
`was approximately 50%.
`The preparation and implantation of ceramics. The
`recipients were Sprague-Dawley rats, weighing 500 to
`800 g, and New Zealand white rabbits, weighing 2.5 to
`4.5 kg. The ceramic discs were implanted in pairs, one of
`each pore size being implanted into the parietal bone of
`the skull. Rats were implanted with one of these ceramic
`
`Table I. Number and type of ceramic discs and period of implantation
`
`amics with different chemical and physical properties
`into the skull—a site containing little or no bone marrow.
`This has pennitted an assessment of the histocompatibil-
`ity of the materials with bone, and the contribution of
`the surrounding bone to osteogenesis.
`
`MATERIALS AND METHODS
`
`Ceramic materials. The three ceramic materials used
`
`were calcium aluminate [CaO.Al203], calcium hydroxy-
`apatite [Ca,0(PO,,)2(OH),«,] and tricalcium phosphate
`[Ca3(PO4)2]. The materials were prepared in the Biocer-
`amics Laboratory, University of New South Wales. The
`implants were produced in the form of porous discs,
`3 mm in diameter and 1 mm thick. For each ceramic two
`
`types of discs were prepared: those with pore diameters
`measuring 150 to 210 um; and those measuring 210 to
`300 um.
`While calcium is a natural constituent of bone,
`calcium aluminate does not occur in living organisms.
`However,
`it has been shown to be biodegradable
`(Klawitter 1970).
`It was prepared from Alcoa A14
`alumina and analytical reagent grade calcium hydroxide.
`The mixture was milled in glass jars for one-and-a-half
`hours, using polypropylene rods as the milling medium.
`Distilled water was added to make a paste. After drying
`at 110°C and grinding, it was calcined at lO00°C for one
`houn
`
`The other two materials contain only elements
`present in bone. The calcium hydroxyapatite that we
`used was of the same chemical composition and crystal
`structure as that in the principal mineral phase of bone.
`It was prepared by milling together 28% by weight of
`calcium hydroxide and 72% by weight of calcium
`hydrogen phosphate [CaHPO4.2H2O]. The mixture was
`calcined at 800°C for two hours and finished at lO00°C
`
`for three hours. The product was crushed and the x-ray
`diffraction pattern was determined.
`Tricalcium phosphate [Ca_~,(PO4)2] was prepared by
`milling calcium hydroxide and calcium hydrogen ortho-
`phosphate in distilled water for three hours. Compared
`with the preparation of calcium hydroxyapatite, a lower
`ratio of calcium hydroxide was required to form tri-
`calcium phosphate. The weight ratio used was 18% of
`calcium hydroxide and 82% of calcium hydrogen phos-
`phate. After drying, the mixture was ground to a fine
`powder, mixed with distilled water to fomi a paste, and
`then calcined at
`lO00°C for 15 minutes. The calcined
`
`material was ground and boiled in distilled water to
`remove excess lime. It was finally calcined at lO00°C for
`15 minutes. The x-ray diffraction pattern was determined
`after each calcination. The final product was required to
`be free of hydroxide and soluble phosphate.
`In order to form the three types of ceramic into
`porous discs, pregelatinised starch and distilled water
`were added and mixed with each. Beads of an organic
`polymer which had been graded into the specified size
`
`
`
`Type ofceramie
`Calcium
`aluminate
`
`Calcium
`hydroxyapatite
`
`Tricalcium
`phosphate
`
`Duration of implantation (days)
`In rabbits
`In rats
`
`I4 56 71 91 182
`
`14 56 91 182
`
`I50-2l0
`
`2l0-300
`
`150-210
`
`210-300
`
`150-210
`
`2 l 0-300
`
`pairs; whereas rabbits were implanted with two, one pair
`cranially and one pair caudally. Each implant site was a
`small burr hole in the parietal bone, made with an electric
`dental drill and a round-ended diamond burr. The burr
`
`holes did not pass through the thickness of the skull
`across their whole diameter, but were large enough to
`accommodate the ceramic implants easily, but snugly.
`To ensure that the implant remained in place, the thin
`layer of muscle stripped from the skull was apposed over
`the implant site before closing the skin incision. The
`duration of implantation and the number of implants
`used in each species are shown in Table 1.
`Microscopic examination. After killing the animals by an
`overdose of anaesthetic, the implant sites in the skull
`were clearly exposed. Approximately square pieces of
`
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`THE USE OF CERAMICS FOR BONE REPLACEMENT
`
`271
`
`skull containing the ceramic implants were then removed,
`and fixed with 10% buffered formol saline. After fixation,
`they were decalcified in 10% formic acid. The decalcifi-
`cation
`process
`dissolved
`the
`ceramic
`and
`de-
`mineralised the bone, leaving only the soft tissues and
`bone matrix. This was done to ensure that thin sections
`
`could be examined histologically. Our previous study
`(Nade et al. 1983) had indicated that attempts to saw or
`grind thick sections containing both soft
`tissues and
`ceramic were unsatisfactory for detailed analysis of
`cellular changes.
`Thin sections embedded in paraffin wax were cut
`and stained with haematoxylin and eosin. All
`the
`specimens were reduced in size, then washed in distilled
`water, followed by 70‘’/,,, 90% and 100% ethyl alcohol
`solutions for 24 hours each. After placing them in acetone
`for 24 hours to remove fats and oils, they were then
`immersed in liquid methyl methacrylate. The monomer,
`which is colourless, was freshly distilled before use. The
`specimens were then transferred to glass capsules for
`embedding. A syrup-like methyl methacrylate, which
`had been previously partially polymerised, was intro-
`duced into the capsules. To ensure that no air bubbles
`were trapped inside the specimens, the capsules were
`placed in a vacuum desiccator for about 15 minutes.
`Polymerisation took place in an oven at 60°C for 24
`hours. The embedded specimens were removed from the
`glass capsule and sliced into thinner sections in a Metals
`Research Microslice equipped with an annular saw. The
`face of the cross-section showing the relation between
`the bone and ceramic was studied under the scanning
`electron microscope. This instrument not only makes it
`possible to observe the specimen at magnifications much
`higher than those available using the optical microscope,
`but the depth of focus is also much greater.
`A relatively recent advance in scanning electron
`microscopy, which has taken place at the University of
`New South Wales, has been of considerable assistance in
`
`the study of the samples. Dr V. Robinson, of the Faculty
`Scanning Electron Microscope Unit, has perfected a
`technique which permits samples to be viewed without
`prior coating with a conducting medium, such as carbon
`or gold. What is more important for our samples is that
`the specimen chamber can be operated at selected
`pressures of air or water vapour. Dehydration of the
`biological tissue is thus avoided.
`
`RESULTS
`
`Light microscopy. Around all the ceramic implants, a
`connective tissue capsule was formed, mainly fibrous,
`but in some instances (particularly in the rabbits) also
`including some fat. The pattern of this connective tissue
`varied with the duration of implantation, being less
`cellular, less vascular and more regularly arranged the
`longer the implant was in place (Figs 1 and 2). Foreign
`body or inflammatory cellular response to the implants
`was minimal. A few scattered giant cells were sometimes
`seen within the ceramic pores or surrounding connective
`tissue.
`A zone of bone necrosis was seen around each
`
`implant site. This could have been due to ischaemia, or a
`result of the heat generated during drilling of the implant
`site, or both.
`Ingrowth of soft connective tissues into the pores
`was seen with all the ceramics used. For each of the three
`
`types (calcium aluminate, calcium hydroxyapatite and
`tricalcium phosphate), the connective tissue tended to be
`more dense in the discs with larger pores (210 to 300 um)
`than in those with smaller pores (150 to 210 um) (Figs 3
`and 4); the connective tissue also became more dense the
`longer the implant was in place.
`With very few exceptions, newly-formed bone was
`not seen within, and adjacent to, the ceramics. In a few
`sections new bone growth was seen in small, discrete
`areas along the edges of bone immediately adjacent to
`the implant.
`
`
`
`The pattern of connective tissue surrounding calcium hydrox apatite. Figure |—At 14 days. Figure 2—At 9] days. Note the development of an
`organised capsule and the lack of oreign-body response. (Haematoxylin and eosin, x 320.)
`
`VOL. 66-3. No. 2. MARCH I984
`
`Page 4 of 8
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`

`
`272
`
`A.UC}-IIDA,
`
`s. M. L. NADE, E. R. MCCARTNEY, W.CHlNG
`
`
`
`Fig. 4
`Tissue ingrowth at 91 days into discs of calcium hydroxyapatite with two different pore sizes. Figure 3~Pores 150 to 210 pm in diameter. Figure
`4~—Pores 210 to 300 um in diameter. The ceramic has been dissolved out. The organisation of the connective tissue shows the regularity of the
`pores and their interlinkage. (Haematoxylin and eosin. x 320.)
`
`Each of the three materials had distinctive features
`
`of response, and even though the ceramic had been
`dissolved out of the sections, the type used could be
`predicted, with experience, from examination of the
`pattern of tissue response. There was no difference in
`histological response between the rats and the rabbits.
`Calcium aluminate. The response to this ceramic was
`quite distinctive. The tissue growing into the pores was
`very fine and predominantly acellular, even with the
`larger pore size and the longer period of implantation
`(Fig. 5). A little bone was seen in a few peripheral pores
`of one 182-day implant in a rat.
`Calcium hydroxyapatite. There was a strong and quite
`dense ingrowth of connective tissue into the pore structure
`of the calcium hydroxyapatite implants, which delineated
`quite clearly its structure of well-rounded pores inter-
`linked by a network of fine connecting tunnels (Fig. 6).
`_
`,
`The connective tissues became denser and more regularly
`
`
`
`Tissues within the pores of calcium aluminate at 9l days. The tissue is
`_
`I
`.
`y
`.
`.
`.
`acellular and non-organised compared to the tissue ingrowth ofcalcium
`hydroxyapatite (Figs 3 and 4). (Haematoxylin and eosin, x 130.)
`
`Figure 6 Tissue ingrowth into the pores of calcium hydroxyapatite at 9| days. Note the regularity of pores and their interlinkage. (Haematoxylin
`and eosin. x 400.) Figure 7 ——Tissue ingrowth into the pores of tricalcium phosphate at 91 days. The clear spaces were occupied by ceramic before
`being dissolved. The pores are less regular and aspherical. (Haematoxylin and eosin, X I30.)
`
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`THE USE OF CERAMICS FOR BONE REPLACEMENT
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`273
`
`arranged the longer the period of implantation.
`In contrast to the usual appearance, one 140-day
`implant in a rabbit had large amounts of bone in many
`pores throughout the ceramic. It was interesting to note
`that this particular implant was seen to be closely apposed
`to a fairly extensive zone of bone marrow, with some of
`the bone marrow being included in a few of the pores.
`Tricalcium phosphate. There was a strong and dense
`ingrowth of connective tissue into the pore structure,
`very similar to that seen in the calcium hydroxyapatite
`discs. However, the two ceramics were generally easily
`distinguished:
`tricalcium phosphate had less clearly-
`rounded pores and the interpore tunnels had a much
`wider diameter than those of calcium hydroxyapatite
`(Fig. 7). This tendency became more apparent with
`increasing times of implantation, suggesting a time-
`dependent process of biodegradation. No bone growth
`was observed in any of the tricalcium phosphate implants.
`
`Scanning electron microscopy. The correlation between
`the pore structure of the ceramic and the newly-formed
`connective tissue was detected accurately using the
`scanning electron microscope.
`The connective tissue in the pores of 14-day implants
`was homogeneous and smooth in structure on the cut
`surface (Fig. 8). The surface structure of the connective
`tissue gradually became more complex with time. The
`connective tissue in the pores also became more organised
`with time; (Fig. 9).
`Only limited biodegradation of the ceramics was
`seen with the scanning electron microscope, but criteria
`for biodegradation using this technique have not been
`adequately determined.
`With few exceptions, bone was not seen within the
`pores of the implants. In those exceptional cases, the
`newly-formed bone was separated from the ceramic by
`soft connective tissue (Fig. 10).
`
`Fig. 8
`
`
`
`
`Scanning electron micrograph of calcium hydroxyapatite at 9l days.
`(‘lose contact between ncwly-formed bone (B) and porous ceramic (PC)
`is not seen in this section; connective tissue (F) can be seen within the
`pores ofthe ceramic ( X 160).
`
`VOL. 66-3. No. 2. MARCH 1984
`
`Scanning electron micrographs of sawn sections of calcium hydroxyapatite. Figure 8—At I4 days: connective tissue (F) fills up the cavities of the
`porous ceramics (PC). ( x 400). Figure 9—At 182 days: the surface of connective tissue (F) is irregular ( x 400).
`
`
`
`DISCUSSION
`
`Since Smith (1963) suggested the use of ceramics for
`hard-tissue replacement, much hope has rested on these
`materials. Alumina is certainly being used increasingly
`for joint replacement. However, there have been only a
`few reports of comparative studies of biodegradable
`ceramics (Hulbert, Morrison and Klawitter 1972; Nelson,
`Stanford and Cutright 1977; Winter et al. 1981). Those
`having the most appropriate physical and chemical
`properties for clinical use should be selected initially
`after comparative studies in animals.
`reported that a
`Klawitter and Hulbert
`(1971)
`minimal pore size of approximately 100 um was the
`optimum for bone growth into porous ceramic. Our
`previous studies have confirmed this finding (Nade et al.
`1983). However, it is necessary to know more precisely
`the range of pore size for effective bone ingrowth, that at
`
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`274
`
`A. UCHIDA, S. M. L. NADE, E. R. MCCARTNEY, W. CHING
`
`the same time maintains physical strength. Therefore,
`we attempted to prepare porous ceramics with a uniform
`distribution of interconnected pores; we managed to
`produce ceramics with two different ranges of pore size
`(150 to 210 um and 210 to 300 um), having even
`distribution and uniform shape of pores.
`When these were implanted into the skull, soft
`(fibrous) connective-tissue ingrowth was observed in
`both pore types, although it was more dense in implants
`with larger pores. However, it will be necessary in the
`future to measure the extent of tissue ingrowth to augment
`the histological estimations and observations of this
`study.
`As there is little or no bone marrow in the skull of
`
`the rat or the rabbit, the fact that new bone growth was
`only seen in very few of the implants supports the
`postulate that bone formation is not facilitated in the
`absence of bone marrow (Nade 1977; Nade and Burwell
`1977). However, it was also observed that small amounts
`of newly-formed bone within and around the necrotic
`bone surrounding the ceramic seemed to be unrelated to
`the presence or absence of bone marrow in adjacent
`areas. The frequency with which this was observed and
`the -sparsity of the bone marrow in the skull questions the
`possibility that there may have been bone marrow near
`the area of the new bone growth but in another plane and
`not seen in the particular histological section being
`examined. This suggests that, although bone marrow
`may facilitate new bone growth,
`it
`is not absolutely
`necessary for its occurrence, a view put forward by Urist
`(1965), Urist and Dowell (1968), and Gray and Elves
`(1979).
`Tissue penetration into calcium aluminate was
`markedly less than into calcium hydroxyapatite and
`tricalcium phosphate. This indicated that calcium alu-
`minate could inhibit tissue ingrowth into its pores, even
`though it did not produce an overt, adverse tissue
`reaction. It
`is possible that aluminium released from
`calcium aluminate may play a significant role in inhibi-
`tion of tissue ingrowth, and this requires further study.
`In contrast, calcium hydroxyapatite and tricalcium
`phosphate contain only elements found in normal bone.
`There is much debate about the rate of biodegrada-
`tion of porous ceramics. This has arisen partly because
`investigators have not been able to take into account the
`different characteristics arising from chemical composi-
`tion (including stoichiometry), crystal structure, micro-
`structure and macroporosity. Even when these features
`have been assessed,
`their relations to the biological
`mechanisms of degradation are not fully understood.
`Jarcho (1981) found no biodegradation at various times
`up to one year. In contrast, Levin et a1. (1975) reported
`that complete resorption of tricalcium phosphate oc-
`curred when it was implanted into canine bone. Based
`on the correlation between the available literature and
`
`his results, de Groot (1980) concluded that the rate of
`
`biodegradation is determined by microporosity. This he
`
`defined as pores with the size of powder particles that are
`left when the particles are not completely fused during
`the sintering process.
`In the case of calcium hydroxyapatite, porosity and
`degree of crystallisation have been shown to have a major
`effect. The durapatite form prepared by Jarcho et al.
`(1976) by a process of precipitation followed by firing at
`1100°C is solid, whereas samples formed by sintering
`pressed powders contain micropores. The samples we
`used were prepared with large and well-controlled pore
`structures. Durapatite has been shown to degrade at a
`negligible rate and to be significantly stronger than the
`sintered material.
`
`the ceramics were still obviously
`In this study,
`present in significant quantities, although a little resorp-
`tion had occurred. There was no obvious difference in
`
`the rate of biodegradation between the three different
`porous ceramics, or between the two different pore sizes.
`These results suggest that the rate of degradation may
`not be related either to the macroporosity (pore size) or
`to the chemical composition. Indeed, partially dissolved
`materials could allow for the sequestration of individual
`crystals or fragments that are sufficiently small to allow
`for aggressive cell-mediated removal such as occurs in
`phagocytosis. We have previously observed such a
`phenomenon in relation to soft-tissue implants of alu-
`mina, a ceramic not used in this study.
`The results indicate that the rate of biodegradation
`is not influenced by the difference in the diameters of the
`macropores. No conclusions can be drawn about the
`effect of micropores (less than 5 pm diameter) because
`the population of these would be similar in all implants.
`It is postulated that biodegradation occurs in materials
`of these chemical compositions at nearly equal rates,
`unaffected by the macroporosity but controlled by the
`specific volume of microporosity. The micropores were
`small and similar in the three types of ceramic implants
`used in this investigation. Quantitative methods for
`determining biodegradation are needed.
`
`CONCLUSION
`
`When placed into a bone defect prepared in the skull the
`three ceramic materials used in this study were well
`accepted by the host animals, causing no ill effects nor
`inflammation in the surrounding tissues. The calcium
`phosphate and calcium aluminate exhibited no toxicity,
`nor foreign-body response on histological assessment.
`Although the ceramics fitted the defect in the skull,
`bone ingrowth was slight and did not provide a useful
`basis for a comparison between the ceramics. Significant
`new—bone growth occurred only in association with
`isolated regions of bone marrow. Exceptions to this were
`detected in the necrotic bone surrounding the ceramic,
`where the occurrence of some newly-formed bone
`appeared to be unrelated to the presence of bone marrow.
`It must therefore be concluded that the presence of bone
`
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`THE USE OF CERAMICS FOR BONE REPLACEMENT
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`275
`
`marrow is not absolutely necessary for bone growth under
`all conditions.
`
`While the chemical differences between the phos-
`phates on the one hand, and the calcium aluminate on
`the other, do not appear to have influenced the rate of
`biodegradation,
`tissue growth in the vicinity of the
`aluminate was slowed. Further investigation is needed to
`establish whether the tissue growth is retarded by more
`alkaline conditions or aluminium ions leached from the
`aluminate.
`
`There are obviously many factors which must be
`considered in determining whether it is feasible to replace
`bone by ceramics. If the ideal of eventual replacement of
`a porous biodegradable ceramic used to fill a bone defect
`is to be achieved, means of stimulating the growth of
`bone into its pores needs further development. The extent
`of bone ingrowth in the ceramics we developed was
`insuflicient for them to have a clinical application, if
`implanted alone into a defect in a bone which does not
`contain a significant amount of marrow.
`
`This work was supported by grants from the National Health and Medical Research Council of Australia, The University of Western Australia.
`and the Australian Orthopaedic Association Research Fund. Technical assistance was given by Ms Lee Armstrong, Mr Peter Burrows, and Ms
`Yvonne Wallman. Mrs A. V. Wakelam cared for the animals and Mrs V. B. Graham-Smith typed the manuscript. We acknowledge with gratitude
`all this assistance.
`
`REFERENCES
`
`Bliaskar SN, Brady JM, Getter L, Grower MF, Driskell T. Biodegradable ceramic implants in bone: electron and light microscopic analysis. Oral
`Surg [971 ;32:336—46.
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