Manufacture of Macroporous Hydroxyapatite and TCP Bioceramics

Manufacture of MacroPorous *
Calcium Hydroxyapatite and Tri-Calcium Phosphate
Bioceramics

N. Ozgur ENGIN and A. Cuneyt TAS
Dept. of Metallurgical and Materials Engineering
Middle East Technical University
Ankara 06531, Turkey

* N. O. Engin and A. C. Tas, "Manufacture of Macroporous Calcium Hydroxyapatite Bioceramics," Journal of The European Ceramic Society, Vol. 19 (13-14), 2569-2572 (1999). (--> download pdf)

* N. O. Engin and A. C. Tas, ”Preparation of Porous Ca10(PO4)6(OH)2 and Beta-Ca3(PO4)2 Bioceramics,” Journal of The American Ceramic Society, 83(7), 1581-1584 (2000). (--> download: ha-tcp-porous.pdf)

* N. O. Engin and A. C. Tas, "Manufacture of Macroporous Calcium Hydroxyapatite Bioceramics,"
100th Annual Meeting of the American Ceramic Society,
May 3-8, 1998, Cincinnati, Ohio, USA, Oral Presentation.

* N. O. Engin and A. C. Tas, "Manufacture of Macroporous HA Bioceramics,"
New Developments in High-Temperature Ceramics Conference
(Sponsored by Office of Naval Research (USA), Air Force Office of Scientific Research (AFOSR, USA), and
NASA Lewis Research Center),
August 12-15, 1998, Istanbul, Turkey, Poster Presentation.

* N. O. Engin and A. C. Tas, "Manufacture of Macroporous Calcium Hydroxyapatite Bioceramics,"
IV. Ceramics Congress, September 22-25, 1998, Eskisehir, Turkey, Poster Presentation.

* N. O. Engin, "Manufacture of Macroporous Calcium Hydroxyapatite (HA) and Tr-Calcium Phosphate (TCP) Bioceramics,"
M.Sc. Thesis, January 1999 (Supervisor: Dr. A.C. Tas) .

* Patent No: TR-9900038, January 11, 1999, Turkish Patent Institute, Ankara, Turkey.

Trabecular bones of almost all vertebrate organisms do basically consist of macroporous (55 to 70% interconnected porosity) bone mineral, i.e., calcium hydroxyapatite (HA: Ca10(PO4)6(OH)2). The macroporosity observed in the trabecular bones then allows the ingrowth of the soft tissues and organic cells into the bone matrix.

Sub-micron, chemically uniform, and high phase-purity HA (or TCP) powders produced in our laboratory were mixed, under vigorous ultrasonification, with either methyl cellulose or polyethyleneimine of appropriate amounts in the form of an aqueous slurry of proper viscosity and thickness. The ceramic cakes produced in this way were then carefully dried in an oven in the temperature range of 50 to 90°C. Dried cakes of porous HA (or TCP) were then physically cut into various prismatic shapes. These parts were then slowly heated in an air atmosphere to the maximum sintering temperature of 1250°C. The HA (or TCP) bioceramic parts obtained by this “foaming technique” were found to have tractable and controllable interconnected porosity in the range of 60 to 90%, with typical average pore sizes ranging from 100 to 250 microns. Sample characterization was mainly achieved by SEM (scanning electron microscopy) studies and three-point bending tests.

INTRODUCTION

With the growing demands of bioactive materials for orthopaedic as well as maxillofacial surgery, the utilization of calcium hydroxyapatite (HA, with Ca/P = 1.667) and tricalcium phosphate (TCP, with Ca/P = 1.50) as fillers, spacers, and bone graft substitutes has received great attention mainly during the past two decades, primarily because of their biocompatibility, bioactivity, and osteoconduction characteristics with respect to host tissue (1-3).

For certain periods, attention was particularly placed on the fabrication of bioceramics with “porous” configuration because the porous network allows the tissue to infiltrate, which further enhances the implant-tissue attachment (4-13). In a porous form, hydroxyapatite ceramics can be colonized by bone tissue with the same characteristics as peri-implanted tissues (14). For colonization of the pores to take place, they must be larger than 50-100 µm (13) or even 250-300 µm according to some researchers (15-17).

EXPERIMENTAL PROCEDURE

The hydroxyapatite (and tri-calcium phosphate) powders produced in our laboratory (18), with average particle size of 0.6-0.7 µm, were used (19) to prepare an HA (or TCP) slurry essentially consisting of methyl cellulose to form spongy bioceramic cakes and bodies of differing porosity simulating that typical of bone. Solutions containing the HA (or TCP) powders and polymeric agents were treated with an ultrasonic disruptor (Misonix, Inc., Model: XL2015, NY, USA) to homogenize and degas the slurries (20). Polymeric slurries were slowly dried in an oven in the temperature range of 50 to 90°C. Thus obtained green cakes were then physically cut into any desired shape, and finally sintered at 1250°C for 3 hours in a stagnant air atmosphere.

Scanning electron microscopy (SEM, Jeol Corp., Model: JSM-6400, Tokyo, Japan) was used for the visual characterization of the pore size and morphology distribution in the bioceramic parts and samples. Mercury intrusion porosimetry and computerized tomography techniques were also employed to determine and monitor the relative porosity, pore volumes, and pore morphology.

RESULTS

The novel foaming method used in this study (19-20), to produce macroporous calcium hydroxyapatite bioceramic parts, were shown to be successful in the attainment of relative porosity over the range of 60 to 90%. The control of porosity in the HA samples were found to be achieved by essentially changing the amount of polymeric agent used in the slurries.

The pore sizes in our HA (or TCP) bioceramics were typically distributed in the range of 100 to 400 µm. The pores were interconnected. The SEM micrographs given in Figures 1 to 3 display the microstructures of macroporous HA parts produced in our laboratory with 60, 75, and 90% relative porosity, respectively.

This technique of porous ceramic manufacture may easily be used in other ceramic phases and materials, and therefore, has a vast potential for future technological applications.

Click on the pics to display

Figs. 1a & 1b SEM micrographs of 60% porosity HA (or TCP) bioceramic parts

Click on the pics to display

Figs 2a & 2b SEM micrographs of 75% porosity HA bioceramic parts

Figs 3a & 3b SEM micrographs of 90% porosity HA bioceramic parts

Click on the pics to display

Acknowledgments

This study has been supported by the research project of TÜBITAK / Misag-58. The authors are also thankful to the staff and researchers of the Department of Petroleum and Natural Gas Engineering (METU) for performing the mercury porosimetry and computerized tomography analysis.

REFERENCES

1. K. de Groot, “Bioceramics Consisting of Calcium Phosphate Salts,” Biomaterials, 1, 47-50 (1980).
2. M. Jarcho, “Calcium Phosphate Ceramics as Hard Tissue Prosthetics,” Clin. Orthop. Rel. Res., 157, 259 (1981).
3. C. J. Damien and J. R. Parsons, “Bone Graft and Bone Graft Substitutes: A Review of Current Technology and Applications,” J. Appl. Biomaterials, 2, 187-208 (1990).
4. E. W. White and E. C. Shors, “Biomaterial Aspects of Interpore 200 Porous Hydroxyapatite,” Dental Clin. N. Am., 30, 49, (1986).
5. R. E. Holmes, V. Mooney, R. Bucholz, and A. Tencer, “A Coralline Hydroxya
patite Bone Graft Substitute,” Clin. Orthop. Rel. Res., 188, 252-262, (1984).
6. R. E. Holmes, “Bone Regeneration within a Coralline Hydroxyapatite Implant,” Plast. Reconstr. Surg., 63, 626 (1979).
7. E. C. Shors, E. W. White, and G. Kopchok, “Biocompatibility, Osteoconduction and Biodegradation of Porous Hydroxyapatite and Calcium Carbonate in Rabbit Bone Defects,” Mater. Res. Soc. Symp. Proc., 110, 211-217 (1989).
8. H. Ohgushi, M. Okumura, and T. Yoshikawa, “Bone Formation Process in Porous Calcium Carbonate and Hydroxyapatite,” J. Biomed. Mater. Res., 26, 885-895 (1992).
9. Dean-Mo Liu, “Fabrication and Characterization of Porous Hydroxyapatite Granules,” Biomaterials, 17, 1955-1957 (1996).
10. C. Klein, K. de Groot, C. Weiqun, L. Yubao, and Z. Xingdong, “Osseous Substance Formation Induced in Porous Calcium Phosphate Ceramics in Soft Tissues,” Biomaterials, 15, 31-34 (1994).
11. M. Fabbri, G. C. Celotti, and A. Ravaglioli, “Hydroxyapatite-based Porous Aggregates: Physico-chemical Nature, Structure, Texture and Architecture,” Biomaterials, 16, 225-228 (1995).
12. M. Fabbri, G. C. Celotti, and A. Ravaglioli, “Granulates Based on Calcium Phosphate with Controlled Morphology and Porosity for Medical Applications: Physico-chemical Parameters and Production Technique,” Biomaterials, 15, 474-477 (1994).
13. J. C. Le Huec, T. Schaeverbeke, D. Clement, J. Faber, and A. Le Rebeller, “Influence of Porosity on the Mechanical Resistance of Hydroxyapatite Ceramics under Compressive Stress,” Biomaterials, 16, 113-118 (1995).
14. N. Passuti, G. Daculsi, J. M. Rogez, S. Martin, and J. V. Bainvel, “Macroporous Calcium Phosphate Ceramics Performance in Human Spine Fusion,” Clin. Orthoped., 248, 169-176 (1989).
15. J. J. Klawiter, J. G. Bagwell, A. M. Weinstein, B. W. Sauer, and J. R. Pruitt, “An Evaluation of Bone Growth into Porous High Density Polyethylene,” J. Biomed. Mater. Res., 10, 311-321 (1976).
16. P. S. Eggli, W. Müller, and R. K. Schenk, “Porous Hydroxyapatite and Tricalcium Phosphate Cylinders with Two Different Pore Size Ranges Implanted in the Cancellous Bone of Rabbits,” Clin. Orthoped., 232, 127-138 (1987).
17. G. Daculsi and N. Passuti, “Effect of the Macroporosity for Osseous Substitution of Calcium Phosphate Ceramics,” Biomaterials, 11, 86-87 (1990).
18. A. C. Tas, “Synthesis of the Two Inorganic Phases (HA: Ca10(PO4)6(OH)2 and TCP: Ca3(PO4)2) of Synthetic Bone Applications by A Chemical Precipitation Method,” Patent No: TR 1995 01422 B, Turkish Patent Institute, November 14, 1995, Ankara, Turkey.
19. N. Ö. Engin, “Manufacture of Macroporous Hydroxyapatite Bioceramics,” M.Sc. Thesis, METU, January 1999 (Thesis supervisor: Dr. A. Cüneyt Tas)
20. A. C. Tas (Inventor), “Manufacture of Macroporous Calcium Hydroxyapatite (HA) and Tri-calcium Phosphate (TCP) Bioceramics,” Patent No: TR-9900038 (Owner: Turkish Scientific and Technical Research Organization, TUBITAK), Turkish Patent Institute, Ankara, Turkey.