Bioceramics consisting of Cecil phosphatesalts

K. Groot de
Department of Biomateriais, 1979 .&hook of Dentistry and Medicine, Free University, Amsterdam. Received 9 October

After a discussion of the chemical considerations involved in the production of calcium phosphate ceramics, animal and clinical studies are reviewed. Specific conclusions are that although these ceramics have high compressive strengths, they are not suitabie for joint replacements. Prevention of alveolar ridge resorption is a promising concept, and space-oiling and use of aids for jaw-bone enlargement are proposed for routine clinical application.

Since it was found characterized phosphate

that hard tissues, bones and teeth, phase in which role, medical calcium researchers

were brushite J/ \-

Ca + P in serum \ hydroxyapatite e octacalcium phosphate

by an inorganic

plays a dominant

have considered Already application However, form, practical tolerated interest

this salt as a means to influence in the early years of this century, phosphate in fracture

healing Albeet

processes of bony tissues. suggested and tested (in aminals and patients) of tricalcium since these salts were only available were limited eventually purpose. in calcium the possible healing. in powder A variety tricalcium well-known. [Cas(P04)2] of other well-known conditions, or (better) phosphate, According is unstable calcium phosphate salts cannot

exist in physiological

among which whitiockite,

so-called is the most whitlockite

applications

to slurries, which served no by new bone, kept those with a alive2-. sintering phosphate It is techsalts to

to various authors18-M, in water according

The fact that these slurries were well phosphate salts; especially

to the reaction:

and replaced

H20 +4Ca3(P04)2

Cato(P04)e(OH)2

+ 2Ca2+ + 2HPO$-

Ca/P ratio close to that of bone (1.5-1.671, obvious that, with the advent of advanced niques, attention in the form be machined ceramic was focussed to calcium

Thus, a powder with

with CaiP = 3/Z, and in equiirbrium as a whitlockite, example Another is calcium

with water,

should not be considered lattice defects. tetraphosphaie20:

but as an apatite

of solid blocks that had sufficient in the right shape, to be handled physiological based on calcium phosphates

strength

by the surgeon, with Ca/P applied to to such

and to withstand materials practice. ratios of 1.5-l in clinical an extent, review current

loads. At the moment,

.7 are on the verge of being widely knowledge and clinical applications

It is the purpose then of this article

Therefore, equilibria

we may conclude as described

that, due to mutual solution,

dynamical

that engineer

and surgeon alike might be stimulated

by Munzenberg from

and the instabilities surfaces of particles to 2 (tetrain differences diffence

to focus their interest

on this group of biomaterials.

of other salts in physiological with Ca/P ratios varying cal~iumphosphate) physiological fluid.

1 (brushite)

will be the same after incubating This means that no biological behaviour, by different Ca/P ratios. and that biological

will exist in interface

CHEMICAL
As already calcium brushite According

CONSIDERATIONS
mentioned, bonemineral is a salt in which the assumed that with phosphate role8-15. exists, .7. It is generally [~a,*(PO4)~(OH)~], octacalcium

cannot

be explained conclusion.

When we discuss implant important apatite ratio of Ca to P is 1.5-l hydroxyapatite (Ca HP04*2H20), CaiP = 7.67, is not stablelg,
CalO(p04)6(oH)2

studies, we will refer to this system, hydroxy-

In an anhydrous

due to the reaction:

+

is the main constituent,

while other salts as

ZCa3PO4)2

+ Ca4P209

H2.

[CaBH2(P04)6*5H20]

also play a dominant an equilibrium as:

@ 1980

to Munzenberg16,,

Crystallographically, apatite

the end product formed

may still seem to be initially keeps an

which can be simply written

0142-96121601010047-04 $02.00

because the Cas(PO4)2

IPC Business Press Biomaterials 1980. Voi 1 January 47

Calcium phosphate

ceramics:

K. de Groot

apatitic lattice (by inclusion of defects). Only prolonged heating, and high vacuum, accelerate the phase transition to whitlockite. Newesely*O found that temperatures of up to 1400C, and complete absence of water, are needed to decompose chemically pure hydroxyapatite, while apatite samples with higher P content (lower Ca/P ratio) are somewhat less stable, probably due to the lattice defects. They are turned into whitlockite at IOOOC, again when no water is present. As a rule of thumb, presence of water favours formation of structure with apatite lattice when Ca/P ratio is between 1.5 and 1.7, at temperatures up to 1200-1300C. while prolonged absence of water leads to whitlockite structures (a socalled o-form at temperatures above 1400C. and a fi form at temperatures below 14OOC). In practice, this means that all materials with a Ca/P ratio of 1.5-l .7 sintered at temperature of 1000-1300C, with no explicit exclusion of water, will be apatitic.

explanation for these empirical findings seems obvious: cells can digest isolated particles, and since the ease of isolating particles decreases from slurries to materials without micropores, it can be readily explained that degradation rates decrease accordingly.

CLINICAL

APPLICATIONS

Calcium phosphate ceramics can be made with properties imitating hard tissues to a large extent: compressive strengths up to 5000 kg/cm* (enamel 3500 kg/cm*), macroporosities with value varying from almost zero (enamel) to more than 50% (cancellous bone), degradation rates from l-2% per year as for cortical bone, to 300% for cancellous bone. It is not surprising then that a replacement for almost any hard tissue has been suggested in the literature. This review is limited to published human studies.

ANIMAL

STUDIES

Tooth replacement
The presence of roots prevents further resorption of jawbones, and the presence of teeth is not only aesthetically but also functionally superior to a prosthesis. The tight bond between calcium phosphate ceramics and bony tissues, suggeststhe use of this material as artificial toothroot. Denissen*43 and Riess44n45used a form with negligible degradation and appreciable degradation respectively. Denissen submerged about 100 apatite roots in fresh extraction wounds, and found alveolar bone growing onto the (conical) root within two months. A two year follow up showed no failures; roots stayed in place, the bulk of
the alveolar ridge was retained alveolar and dentures ridges. with implantable was reopened below the gingival surface could be worn on the implanted teeth:

Before sintered materials could be prepared, slurries of calciumphosphate were investigated. All studies ranging from the first report of Albee to more recent data of Ray5, Getter et aL6 and Cutright et a/.7, lead to the conclusion that the powders are resorbed and replaced by bone, when implanted in bony tissues. Bhaskar et a/.* reported on degradability of tricalcium phosphate (Ca/P = 3/2) and found that cells of mesenchymal origin were clearly implicated, thus suggesting at least partially a cellular mechanism. Further studies showed macrophages and giant cells with ceramic particles in their cytoplasm, again showing that not only passive dissolution but intracellular digestion plays an important role in this biodegradation process22-29. In contrast with these findings are results published by a group led by Jarcho30-35 who obtained materials in which no individual powder particles were identifiable anymore. He found no biodegradation at times up to a year, and made the claim that pure apatite could not be resorbed in bony tissues. This claim was disproven however by findings of others, like Rejda et a/.36*37 and, more recently, Holmes38, who did find resorbtion of apatite implants, in agreement with our above mentioned conclusion that differences in biological behaviour, like degradation, cannot be explained by chemical differences in properties of calcium phosphate implants. Since the difference between Jarchos materials and those of Rejda and Holmes, is not their apatitic structure, but their density, a relation between density and degradation is obvious. Studies of Peelen et a/.3g showed that an important property is the porosity. Peelen distinguished microporosity (pores with the size of powder particles, that are left when the particles are not completely fused during the sinterprocess) and macroporosity (pores of several hundred microns). Microporosity determines degradation rates, among other factors as species and age of animal and site of implantation, and macropores allow bony ingrowth. We may conclude that all calcium phosphate ceramics are degradable, but the rate is determined by microporosity. A porous material may contain both types of pores (and thus be biodegradable and allowing ingrowth) or only micropores, (being biodegradable) or only macropores (allowing ingrowth but being almost biostable). Dense materials are almost without pores of either type, and do therefore hardly show degradation. A cellular

Riess has implanted while a few months to construct a crown

30 patients

roots were first implanted

later the healed wound

on this root. A one year study showed that to have a

the teeth to be immobilized. In assessing these results, we must consider Cranin50 failure showed any (metallic) lO%/year. rate of about endosseous implant be considered

This means that a one year as positive, of

survival rate of, say, 90% cannot and that, generally, to make a definite Denissen are found years reported, preventing significant problem, essentially concept worthwhile our opinion conclusion

periods of at least three years are needed possible. If the experiments to be successful, i.e. with a failure might be available alveolar ridges. A this encountering rate of for

much less than 10% per year, after longer times than the two a very useful method of edentulous of denture resorption number

wearers,

may then benefit. of an implantable contribution

The one year study of Riess is artificial tooth will be a very but no reason is seen ceramics; Ultimately, in phosphate resorption.

too short to make an assessment. A durable to dentistry calcium

for the use of resorbable dense ceramics,

the experiments

of Riess should be done with

in order to limit

his use of resorbable

ceramics as coatings will result in a

metal implant, to which the findings of Cranin apply.

Orofacial reconstructions
Swart46 and Kent47 have recently phosphate small started clinical implants apatitic studies samples on the use of calcium lower jawbones. Swart (20%) with a relatively such that degradation apatites to enlarge resorbed of micropores, < 1 mm) as

uses macroporous amount

(10%)

rate is rather low. Kent applies dense (diameter

in the form of small particles

48

Biomaterials

1980,

Vol 1 January

Calcium phosphate

ceramics:

K. de Groot

a bone extender. Swart uses a sandwich technique to insert an implant in a horizontally split lower jawbone, He compared the fate of calcium phosphate implants with (classical) autologous (riblbone implants and concluded that calcium phosphate had two advantages: not only was no secondary operation needed, but, due to the selection of slow degrading calcium phosphate, the lower jawbones thus enlarged showed less resorption than was the case with rib implants. A disadvantage found after one year was however that pressure points between implants and denture could develop into dehiscencies. Dentures with soft linings however relieved this problem. it was considered very positive that skin could grow over exposed areas of the calcium phosphate implants without causing infection and subsequent exfoliation. To date Swarts implants have been followed for two years. According to Kent the use of small particles as bone extender yielded favourable results, but no detailed data are yet available. In assessingSwarts findings it may be concluded that sandwich type implantations may not be always necessary, but that a more simple approach of inserting an implant subperiosteally, may suffice as well. Soft lined dentures are necessary to avoid excessive pressures leading to unwanted dehiscencies. Snijde@ placed microporous (hence degradable) tricalcium phosphate into periodontal defects in 50 patients, and reported encouraging regeneration of lost periodontium. Similar experiments have been reported by Ferraro4g with @-whitlockite. In our opinion however, the fact that these periodontal studies are conducted with surgically created defects, and not with defects caused by inflammation (true periodontal disease), makes an assessment impossible. Studies should be conducted with pathological defects, not with surgical defects in healthy tissue. FeenstraM selected calcium hydroxyapatite for filling spaces, left after mastoidectomy, in 15 patients, No reactions differing from those encountered with autologous bone were found after times up to one year, and his conclusion is that, due to the shortened operation time (no secondary operation is needed), calcium phosphate implants should be preferred over the use of autologous bone from the iliac crest. PonssenlUi used macroporous (20%). and rather dense (10% micropores) apatitic tricalcium phosphate implants (20 x 10 x 10 mm) to join vertebrae in seventeen patients, and he also found the material to behave similarly to autologous bone from the iliac crest. The implants were immobile after eight weeks, and r~ntgenographically bone ingrowth was clearly visible. After one year the implant seemed to be resorbed and replaced partially by bone; the implant height was about 1 mm shorter (from IO to 9 mm).

biomaterials can compete favourably with autologous bone, especially in implant sites, where compression is the main mechanical load. Specific conclusions are: Preventing alveolar ridge resorbtion with non-degradable calcium phosphate root implants is a promising concept. Implantable tooth of a metal core, covered with degradable calcium phosphate will result in metallic implants that eventually fail. Filling space where bone originally belongs, should occur with degradable- calcium phosphates. The work of Feenstra and Ponssen shows that these materials can be routinely used for this purpose. Filling spaces where bone does not belong (enlargement of jawbones is an example) should be done with nondegradable calcium phosphate ceramics. Again, routine use in the clinic can be advised. In case of jawbone enlargement, one should use soft lined dentures. Calcium phosphate ceramics can withstand high compressive strength, but are intrinsically weak in tensile and bending properties. We forsee no use of calcium phosphate ceramics in constructions with complicated mechanical requirements such as joints, other than as a coating material.

REFERENCES
Albee, F.H.,Ann. Surgery 1920,71,32 Haldeman, K.O. and Moore, J.O., Arch. Surg. 1934,29,385 Stewart, W.J., Surg. Gynec. Obst. 1934,59,867 Schram, W.R., Fosdick, L.S., J. Oral Surgery 1943,1,191 Ray, R.D., Proc. 37th Clin. Congr. of Am. Coil of Surg., W.B. Saunders Company, Philadelphia and London, 1952, 6 429 Getter, L., Bhaskar, S.N., Cutright. D.E., Perez, B., Brady, J.M., Driskeil, T.D., Offara, M.J., J. Oral Surg. 1972,30, 263 Cutright, D.E., Bhaskar,S.N., Brady, J.M., Getter, L., Posey, W.R., Oral Surg., Oral Med., Oral Path. 1972,33,860 Termine, J.D., Clin. Orrh. Rei. Res. 1972,85,207 Engstrom, A., in The Biochemistry and Physiology of Bone, Vol. I, 2nd Edn. (Ed. G.H. Bourne) Academic Press, NY and London, 1972 Elliott, J.C., Clin. Orth. Rel. Res. 1973.93, 313 Hayek, E., Klin. Wochensch. 1967, 45. 857 Young, R.A., C/in. Orth. Rel. Res. 1975, 113,249 Elliott, J.C., Clin. Orth. Rel. Res. 197393, 313 Griffith, E.J., Environmental Phosphorus Handbook, Publ. John Wiley 81 Sons, 1973,203 Brown. W.E. and Chow, LC.,Ann. Rev. Mater. Sci. 1976, 6,213 M~nzen~rg, KJ., ~iominera/isat;on 1970,1,67 M~nzen~rg, K.J., Gebhardt, M., C/in. Orth. Rel. Res. 1973, 90,271 Narayana Kutty, T.R., Ind. J. of Chem. 1973,11,695 Skinner, H.C.W., Kittelbergen, J.S., Beebe, R.A., J. Phys. Chem. 1975,79,2017 Newesely, H., J. Oral Rehab. 1977,4.97 Bhaskar, S.N., Brady, J.M., Getter, L., Gromer, M.F., Driskell, T., Oral Surg. 1971,32,336 Clarke, W.J., Driskell, T.D., Hassler, CR., Tennery, V.J., McCoy, L.R., IADR 51st General Meeting, Washington 1973, Abstr. 259 Driskell, T.D., Hassler. CR., Tennery, V.J., McCoy, L.R., Clark, W.J., IADR, Sfst #eeting,Chicago 1973, Abstr. 259 Driskell, T.D., Hassler. CR., McCoy, L.G., froc. 26th Meeting A CEMB, 1973 Tennery, V.J., Driskell, T.D., Ceramic 3u//etin, Society ~m~osiorn on Biomaterials, 430. 1973 Mors, W.A., Kaminski, E.J., Rosenstein, S., Perry, H.T., J. Dent. Res. 53, Abstr. 129.1974 Driskell, T.D., Hassler, C.R., McCoy, L.C., Froc. 26th Meeting ACEMB, 1973

7 8 9

10 11 12 13 14 15 16 17 18 19 20 21 22

CONCLUSION
Calcium phosphate salts with Ca/P = 1.5-1.7 will have apatitic structures when sintered at temperatures of up to 13OOC. Degradation takes place in two steps: physicochemical interaction with body liquids releases individual particles, which in turn are digested intracellularly by phagocytosing cells. Depending on microporosity, the release of isolated particles, and hence the rate of degradation, may occur fast or slow. Thus degradable and non-degradable calcium phosphate ceramics can be easily prepared. Animal and clinical studies show that this group of

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Biomaterials

1980,

Vol 1 January

49

Calcium phosphate ceramics: K. de Groot 28 29 30 31 32 33 Levitt, M.P., Getter, L., Gutright, DE., Bhaskar, S.N., Oral Burg. 197436.344 Levin, M.P., Getter, L., Cutright, DE., .f. Eiomed. Mat. Res. 19759,183 Jar&o, Ml, Salsburg, R.L., Thomas, M-6.. Doremus, R.H., J. Mater. Sci. 1979,14,142 Jarcho, M., Bolen, C.H., Thomas, MB., Bobick, J., Kay, J.F., Doremus. R.H...l. Mater. Xi. 1976, tl. 2027 Jarcho, M., Kay, J.F.. Gumaer, K.I., Doremus. R.H., Drobeck, HP., Tissue, J. of Bioeng. 1977,1,79 Jarcho, M., Kay, J.F., Gumaer, K.I., Doremus, R.H., Abstr. 3rd Ann. Meeting of the BocieQ for Biometerials, New Orleans, 1977. Jarcho, M., OConnor, JR., Paris, D.A., J. Dent Res. 1977, 56,151 Jarcho, M., Jasty, V.. Gumaer, K.I., Kay, J.F., Doremus, R.H., Abstr. 4th Ann. Meeting of the Society for Biomaterials, San Antonio, 1978 Rejda, B.V., Peelen, J.G.J., De Groot, K., J. of Bioeng. 1977, 1.93 Rejda, B.V., Peelen, J.G.J., Vermeiden, J.P.W., De Groot, K., Ned. T. v.Geneeskunde 1979122,625 38 39 40 41 42 43 44 45 46 47 4% 49 50 Holmes, R.E., Plastic and Reconstructive Surgery 1979.63, 626-633 Peelen, J.G.J., Rejda. E.V., Vermeiden, J.P.W., De Groot, K., Science of Ceramics 1977.9,226 Denissen. H.W., Van Dijk, HJ,A., Gehring, A.P., Da Groot. K., IADR 57th General Meeting, New Orleans 1979 Abstr. 613, Denissen, H.W., De Groot, K., Van Dijk, H.J., Gehring, A.P., Abstr. B&ceramics Symposium, Keele (En~fand~, 1978 Denissen, H.W., Rejda, B.V., De Groot, K., Peelen, J.G.J., N.T.v.T.~l979,86.173 Denissen, H.W., De Groot, K., J. Pros&. Dent. 1978 Riess, G., Heide, H., Koster, K., Reiner, R., Dtsch. ZahnZirtzl. Z. 1978.33.287 Wedgwood, D., Lavelfe, C.L.B., Riess, G., MDR 57th Genera/ Session, New Orleans, 197.9, Abstr. 1283 Swat%, J.G.N., Feenstra, L., Ponssen, H., De Groot, K., Ned. T. Geneeskunde 1979 Kent, J., Personal communication, 1979 Snyder, A.J., Levin, M.P., lADR 57th General Session, New Orefans, 1979, Abstr. 1696 Ferraro, J., App, G., Foreman, D., IADR 57th Genera/ Meeting, New Orleans, 1979, Abstr. 1278 Cronin, A.N.,etal., J.A.D.A, 1977,94.315-320

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