Room 136, Intercollege Materials Research Laboratory
Pennsylvania State University
University Park, PA 16802
Tel:814-865-5352
Fax:814-865-2326
Email:pwb1@alpha.mrl.psu.edu
Website: Paul Brown
Dr. Brown's research is focused on establishing the parameters which control the formation of hydroxyapatite monoliths under conditions compatible with those in vivo. Hydroxyapatite monoliths have mechanical integrity and, therefore, can emulate certain functions of hard tissues serve as models for hard tissues, or serve as substrates on which cellular functions can proceed The rationale for investigating monolithic hydroxyapatite is twofold. Firstly, hydroxyapatite which can be formed in vivo may eventually serve a variety of needs in orthopaedics, plastic and reconstructive surgery, and dentistry; interest has been expressed by clinicians regarding in vivo formation. Secondly, the synthesis methods we have developed are unique in that hydroxyapatite monoliths having compositions bracketing the range of those of biological apatites can be formed. This is not possible using conventional high temperature preparation techniques. Because a variety of compositions can be prepared, it is possible to explore the effects of hydroxyapatite composition on cellular functions which control the mineralization and demineralization of hard tissues.
A perspective important to this research program is that of materials science. Strategies that have been developed in materials disciplines are being applied to obtain a more complete understanding of phenomena normally investigated in biological disciplines. The rationale for this is that mechanisms underlying phenomena which involve the normal mineralization of hard tissues pathological mineralization, and pathological demineralization can be described using thermodynamic, kinetic and micro structural models. Among the processes of importance in this regard are the normal growth and remodelling of bone, osteoporotic bone loss, formation of dental caries, and the formation of renal calculi.
Mechanical integrity of bone is optimized with respect to weight minimization and the ability to rapidly deliver calcium to support histological processes. The latter two factors require porosity. The mechanical disadvantages of the presence of pores in bone, which are regarded as flaws from the standpoint of fracture mechanics, are overcome by the incorporation of a large proportion of collagen reinforcement. The conflicting requirements of mechanical integrity and porosity make it unlikely that a single material would be capable of closely approximating the mechanical functional requirements of bone. Indeed, none has been found. The alternative is to consider a composite which would exhibit adequate mechanical properties. Dr. Browns work has shown that hydroxyapatite based composite materials can be formed at physiological temperature and in a pH range compatible with conditions in vivo. Limited data indicate that the HAp-based composites we produce exhibit mechanical properties in the range of those reported for bone.
Unlike bone, teeth contain only a relatively small proportion of proteinaceous material. Because of their high mineral content and lower porosity as compared to bone, teeth are harder, stronger and more brittle than bone. We haveproduced hydroxyapatite monoliths which develop compressive strengths of 175 MPa within 24 hours with the bulk of this property development occurring within about 1 hour. Although a compressive strength of this value is somewhat below that reported for enamel, it is in the range of values reported for dentin. Analyses have also shown that the composition of the hydroxyapatite formed strongly influences strength. Two levels of porosity are observed with the large pores being strength limiting. In unsubstituted hydroxyapatite, the porosity tends to be monodisperse, and we can produce material which has strengths comparable to sintered hydroxyapatite having the equivalent total porosity. For other apatite compositions, however, the larger pores dominate the micro structure. Because these are strength limiting, the mechanical property values are lower.
The present research program has demonstrated the ability to produce hydroxyapatite compositions which include the range of those reported for hard tissues. It has also been demonstrated that substituted hydroxyapatites, involving substitutions which strongly influence solubility, can be produced as monolithic forms. Also, it has been demonstrated that fluorapatite and fluoride-substituted hydroxyapatite can be formed. Because of the crystal chemistry of carbonated hydroxyapatite, these compositions cannot be produced by the conventional high temperature synthesis of hydroxyapatite. We have also shown that apatites in which paired substitution of sodium for calcium and carbonate for phosphate can be formed in a similar manner. This demonstrates that the solubility of hydroxyapatite formed at physiological temperature can be controlled. We appear to be the first to have synthesized monolithic, phase pure, and compositionally homogeneous hydroxyapatite of the compositions of hard tissue.
Morphological variants of hydroxyapatite, 10.6K magnification. (click for 300DPI image, 638KB)
Morphological variants of hydroxyapatite, 50.6K magnification. (click for 300DPI image, 576KB)
R.I. Martin and P.W. Brown. "Effects of Sodium Fluoride, Potassium fluoride, and Ammonium Fluoride on the Hydrolysis of CaHPO4 at 37.4 C," J. Cryst. Growth 183, 417-26 (1998).
P.W. Brown, "Biomaterials," in The Era of Materials, S.K. Majumdar, R.E. Tressler, and E.W. Miller, Eds, PA Academy of Science.
R.I. Martin and P.W. Brown, "CaHPO4 Hydrolysis in NaF Solutions at 37.4 C," Caries Res. 32, 365-77 (1998).
P. Leamy, P.W. Brown, K.S. TenHuisen, and C.R. Randall, "Fluoride Uptake by Hydroxyapatite Formed by the Hydrolysis of a-Tricalcium Phosphate," J. Biomed. Mater. Res., 42(3) 458-464 (1998).
K.S. TenHuisen and P.W. Brown, "Formation of Calcium-Deficient Hydroxyapatite Formation from a-Ca3(PO4)2," Biomaterials 19, 2209-2217 (1998).
Ten Huisen, K. and P.W. Brown, "The formation of hydroxyapatite-ionomer cements at 38C," J Dent Res. (1994).
Martin, R. I. and P.W. Brown, "Hydroxyapatite formation in serum," J Mater Sci Matls in Medicine (1994).
Ten Huisen, K. and P.W. Brown, "The formation of hydroxyapatite-gelatin composites at 38C," J Biomed Mater Res 28: 27-33 (1994).
Brown, P. W., J. Gulick, and J. Dumm, "The ternary diagram of MgO-H3PO4-H2O at 25C," J Am Cer Soc 76: 1558-62 (1993).
Martin, R. I. and P.W. Brown, "Hydration of tetracalcium phosphate," Adv Cem Res. 5: 119-25 (1993).