Formation of hydroxyapatite-polyphosphazene polymer composites at physiologic temperature.

Aspects of the formation of bone analog composites at 37 degrees C are described. The composites are composed of hydroxyapatite (HAp) and the calcium salt of a biocompatible polymer and are capable of forming under in vivo conditions. Composite formation involves the formation of monolithic HAp from particulate calcium phosphate precursors while Ca ions liberated to the aqueous medium in which this reaction is occurring form crosslinks with the acidic polymer. The reactants are poly[bis(carboxylatophenoxy)phosphazene] (acid-PCPP), tetracalcium phosphate [Ca4(PO4)2O, TetCP], and anhydrous dicalcium phosphate (CaHPO4, DCPA). The effects of the proportion of polymer (5, 10, or 15 wt %) on the kinetics of HAp formation were studied. Compositional evolution of the solid calcium phosphates present was followed by X-ray diffraction and infrared spectroscopy analyses. HAp formation through a dissolution-precipitation process provided a mildly alkaline medium suitable for deprotonation of the acid-PCPP and for the formation of the calcium crosslinks, as monitored by infrared spectroscopy. Concurrence of crosslinking of the polymer and HAp formation was established, indicating true composite formation can be realized at physiologic temperature.

[1]  Smadar Cohen,et al.  Ionically crosslinkable polyphosphazene: a novel polymer for microencapsulation , 1990 .

[2]  W. Bonfield,et al.  Initial interaction of osteoblasts with the surface of a hydroxyapatite-poly(methylmethacrylate) cement. , 2001, Biomaterials.

[3]  T. Jongsma,et al.  The effect of filler surface modification on the mechanical properties of hydroxyapatite-reinforced polyurethane composites , 1995 .

[4]  H. Aoki,et al.  Mechanical properties of sintered hydroxyapatite for prosthetic applications , 1981 .

[5]  P. Bennema,et al.  Preparation of pure hydroxyapatite single crystals by hydrothermal recrystallization , 1979 .

[6]  H R Allcock,et al.  Novel polyphosphazene/poly(lactide-co-glycolide) blends: miscibility and degradation studies. , 1997, Biomaterials.

[7]  K. Tenhuisen,et al.  Variations in solution chemistry during calcium-deficient and stoichiometric hydroxyapatite formation from CaHPO4.2H2O and Ca4(PO4)2O. , 1997, Journal of biomedical materials research.

[8]  P. Brown,et al.  The formation of hydroxyapatite‐gelatin composites at 38°C , 1994 .

[9]  John Tomes,et al.  The Structure and Development of Bone , 1853, The American journal of dental science.

[10]  P. Brown,et al.  Variations in Solution Chemistry During the Low‐Temperature Formation of Hydroxyapatite , 1991 .

[11]  Harry R. Allcock,et al.  Synthesis of High Polymeric Alkoxy- and Aryloxyphosphonitriles , 1965 .

[12]  P. Brown,et al.  Low temperature formation of calcium-deficient hydroxyapatite-PLA/PLGA composites. , 2000, Journal of biomedical materials research.

[13]  A. Akamine,et al.  Effect of powder grinding on hydroxyapatite formation in a polymeric calcium phosphate cement prepared from tetracalcium phosphate and poly(methyl vinyl ether-maleic acid). , 1999, Biomaterials.

[14]  K. Yamashita,et al.  Effects of additives on sintering and some properties of calcium phosphates with various Ca/P ratios , 1991 .

[15]  M. Ito,et al.  Effect of hydroxyapatite content on physical properties and connective tissue reactions to a chitosan-hydroxyapatite composite membrane. , 1999, Journal of biomedical materials research.

[16]  W. Tseng,et al.  Water-based sol-gel synthesis of hydroxyapatite: process development. , 2001, Biomaterials.

[17]  S. Chueh,et al.  Microspheres of hydroxyapatite/reconstituted collagen as supports for osteoblast cell growth. , 1999, Biomaterials.

[18]  S. Takagi,et al.  Effect of mixing ratio and pH on the reaction between Ca4(PO4)2O and CaHPO4 , 2000, Journal of materials science. Materials in medicine.

[19]  P. Brown,et al.  α-Tricalcium phosphate hydrolysis to hydroxyapatite at and near physiological temperature , 2000, Journal of materials science. Materials in medicine.

[20]  M. Helmus.  Overview of Biomedical Materials , 1991 .

[21]  P. Brown,et al.  An evaluation of mechanical property and microstructural development in HAP-Ca polycarboxylate biocomposites prepared by hot pressing. , 2000, Journal of biomedical materials research.

[22]  Shozo Takagi,et al.  Synergistic reinforcement of in situ hardening calcium phosphate composite scaffold for bone tissue engineering. , 2004, Biomaterials.

[23]  C. Randall,et al.  Fluoride uptake by hydroxyapatite formed by the hydrolysis of α‐tricalcium phosphate , 1998 .

[24]  P. Brown,et al.  Thermal Stability and Compressive Strength of Calcium-Deficient Hydroxyapatite− Poly[bis(carboxylatophenoxy)phosphazene] Composites , 1996 .

[25]  G. Muschler,et al.  Bone graft materials. An overview of the basic science. , 2000, Clinical orthopaedics and related research.

[26]  X. D. Zhu,et al.  Tissue response to nano-hydroxyapatite/collagen composite implants in marrow cavity. , 1998, Journal of biomedical materials research.

[27]  H. Precheur.  Bone graft materials. , 2007, Dental clinics of North America.

[28]  P. Brown,et al.  Hydrolysis of tetracalcium phosphate in the presence of a poly(alkenoic acid) , 1999 .

[29]  A. Wan,et al.  Preparation of a chitin-apatite composite by in situ precipitation onto porous chitin scaffolds. , 1998, Journal of biomedical materials research.

[30]  M. Klimkiewicz,et al.  Formation and properties of a synthetic bone composite: hydroxyapatite-collagen. , 1995, Journal of biomedical materials research.

[31]  R. D. Archer,et al.  Inorganic and Organometallic Polymers , 2001 .

[32]  P. Brown,et al.  Aqueous formation of hydroxyapatite. , 1997, Journal of biomedical materials research.

[33]  C. Friedman,et al.  Synthetic bone graft substitutes. , 1994, Otolaryngologic clinics of North America.

[34]  W. E. Brown,et al.  Infra-red spectra of hydroxyapatite, octacalcium phosphate and pyrolysed octacalcium phosphate. , 1966, Archives of oral biology.

[35]  M. Gebhardt,et al.  The use of frozen cadaveric allografts in the management of patients with bone tumors of the extremities. , 1987, The Orthopedic clinics of North America.

[36]  P. Brown,et al.  Phase evolution during the formation of stoichiometric hydroxyapatite at 37.4 °C , 2003 .

[37]  J A Planell,et al.  Fabrication of low temperature macroporous hydroxyapatite scaffolds by foaming and hydrolysis of an alpha-TCP paste. , 2004, Biomaterials.

[38]  K. Ishikawa,et al.  Formation of hydroxyapatite in new calcium phosphate cements. , 1998, Biomaterials.

[39]  P. Caliceti,et al.  Peripheral nerve repair using a poly(organo)phosphazene tubular prosthesis. , 1995, Biomaterials.

[40]  P. Brown,et al.  Kinetics of Hydroxyapatite Formation at Low Temperature , 1991 .

[41]  O. Beirne.  Comparison of complications after bone removal from lateral and medial plates of the anterior ilium for mandibular augmentation. , 1986, International journal of oral and maxillofacial surgery.

[42]  Andrianov,et al.  Protein release from polyphosphazene matrices. , 1998, Advanced drug delivery reviews.

[43]  P. Brown,et al.  Chemically formed HAp-Ca poly(vinyl phosphonate) composites. , 2001, Biomaterials.

[44]  R. Bareille,et al.  Preliminary report on a new composite material made of calcium phosphate, elastin peptides and collagens , 1993 .

[45]  J. Mulliken,et al.  Donor-site morbidity after harvesting rib and iliac bone. , 1984, Plastic and reconstructive surgery.

[46]  W. Bonfield,et al.  Processing, characterisation, and evaluation of hydroxyapatite reinforced polyethylene composites , 1994 .

[47]  P. Brown,et al.  The formation of hydroxyapatite–calcium polyacrylate composites , 1999, Journal of materials science. Materials in medicine.

[48]  P. Brown,et al.  Hydrolysis of dicalcium phosphate dihydrate to hydroxyapatite , 1998, Journal of materials science. Materials in medicine.

[49]  Geoffrey Frohnsdorff,et al.  A multichambered microcalorimeter for the investigation of cement hydration , 1985 .