18 – Electrically active biocomposites as smart scaffolds for bone tissue engineering

: In view of the inherent electrical properties of natural bone, the development of electrically active bone replacement material has attracted significant interest in the biomaterials community. The chapter begins with a brief review of the origin of various electrical responses of natural bone (such as piezoelectricity, pyroelectricity, ferroelectricity, etc.). The effect of an external electric field at the molecular/cellular level in terms of enhanced cell growth and proliferation as well as inhibition of cell growth is discussed. In addition, the development of orthopedic implant materials using hydroxyapatite (HA) as a baseline material is summarized, with a focus on the requirement, importance and processing of electrically active implants.

[1]  S. Mohapatra,et al.  Processing and Properties of Nano-Hydroxyapatite(n-HAp)/Poly(Ethylene-Co-Acrylic Acid)(EAA) Composite Using a Phosphonic Acid Coupling Agent for Orthopedic Applications , 2007 .

[2]  K. Foster,et al.  Dielectric Permittivity and Electrical Conductivity of Fluid Saturated Bone , 1983, IEEE Transactions on Biomedical Engineering.

[3]  K. Khor,et al.  Mechanical properties of injection molded hydroxyapatite-polyetheretherketone biocomposites , 2003 .

[4]  J. W. Vanable,et al.  The glabrous epidermis of cavies contains a powerful battery. , 1982, The American journal of physiology.

[5]  P. Calvert,et al.  The negative side of crystal growth , 1997, Nature.

[6]  R. Domingues,et al.  Microstructural and mechanical study of zirconia-hydroxyapatite (ZH) composite ceramics for biomedical applications , 2001 .

[7]  R. Lakes,et al.  Dielectric relaxation in cortical bone , 1977 .

[8]  C. Brighton,et al.  Electro-Osteograms of Long Bones of Immature Rabbits , 1971, Journal of dentistry research.

[9]  A. Pilla,et al.  Repair of non-unions by pulsing electromagnetic fields. , 1978, Acta orthopaedica Belgica.

[10]  A. Biris,et al.  Bone Tissue: A Relationship Between Micro and Nano Structural Composition and its Corresponding Electrostatic Properties with Applications in Tissue Engineering , 2007, 2007 IEEE Industry Applications Annual Meeting.

[11]  J. Behari,et al.  Effect of ultraviolet light on the dielectric behavior of bone at microwave frequencies , 2006, Annals of Biomedical Engineering.

[12]  C. Hung,et al.  Roles of microtubules, cell polarity and adhesion in electric-field-mediated motility of 3T3 fibroblasts , 2004, Journal of Cell Science.

[13]  S. Ramakrishna,et al.  Biomedical applications of polymer-composite materials: a review , 2001 .

[14]  R. Doremus,et al.  Electron microscopy of the bone-hydroxylapatite interface from a human dental implant , 1992 .

[15]  H. Athenstaedt,et al.  PYROELECTRIC AND PIEZOELECTRIC PROPERTIES OF VERTEBRATES , 1974, Annals of the New York Academy of Sciences.

[16]  Hongyu Wang,et al.  Crack propagation in piezoelectric ceramics under pure mechanical loading , 1998 .

[17]  Chun Peng Huang,et al.  Osteocyte: the impresario in the electrical stimulation for bone fracture healing. , 2008, Medical hypotheses.

[18]  C. Andrew L. Bassett,et al.  Generation of Electric Potentials by Bone in Response to Mechanical Stress , 1962, Science.

[19]  G. Fantozzi,et al.  Mechanical loss and elastic modulus associated with phase transitions of barium titanate ceramics , 1994 .

[20]  S Saha,et al.  Electrical properties of bone. A review. , 1984, Clinical orthopaedics and related research.

[21]  M. Graça,et al.  AC and DC conductivity analysis of hydroxyapatite and titanium calcium phosphate formed by dry ball milling , 2006 .

[22]  A. Bandyopadhyay,et al.  Role of surface charge and wettability on early stage mineralization and bone cell-materials interactions of polarized hydroxyapatite. , 2009, Acta biomaterialia.

[23]  Naser N. Salman,et al.  The effect of direct electrical current stimulation on the bone/porous metallic implant interface. , 1980, Biomaterials.

[24]  K. Khor,et al.  Effect of particulate morphology on the tensile behaviour of polymer-hydroxyapatite composites , 2003 .

[25]  S. Zec,et al.  The effect of temperature on the properties of hydroxyapatite precipitated from calcium hydroxide and phosphoric acid , 2001 .

[26]  B. Basu,et al.  Sintering, microstructure, mechanical, and antimicrobial properties of HAp-ZnO biocomposites. , 2010, Journal of biomedical materials research. Part B, Applied biomaterials.

[27]  Dimitris J. Panagopoulos,et al.  A mechanism for action of oscillating electric fields on cells. , 2000, Biochemical and biophysical research communications.

[28]  S. Rebersek,et al.  Tumor Bioelectric Potential and its Possible Exploitation for Tumor Growth Retardation , 1990 .

[29]  Eiichi Fukada,et al.  On the Piezoelectric Effect of Bone , 1957 .

[30]  A. Nowick,et al.  Effect of Moisture on the Electrical Properties of Bone , 1976 .

[31]  A. Singh,et al.  Ti based biomaterials, the ultimate choice for orthopaedic implants – A review , 2009 .

[32]  M. Manfrini,et al.  Effect of electromagnetic fields on patients undergoing massive bone graft following bone tumor resection. A double blind study. , 1994, Clinical orthopaedics and related research.

[33]  B. Basu,et al.  Sintering, Phase Stability, and Properties of Calcium Phosphate-Mullite Composites , 2010 .

[34]  Y. Leng,et al.  Processing and mechanical properties of HA/UHMWPE nanocomposites. , 2006, Biomaterials.

[35]  K. Hong,et al.  Microstructure and mechanical properties of Mg-HAP composites , 2010 .

[36]  S. Hui,et al.  Response of C3H/10T1/2 fibroblasts to an external steady electric field stimulation. Reorientation, shape change, ConA receptor and intramembranous particle distribution and cytoskeleton reorganization. , 1984, Experimental cell research.

[37]  E. Dekel,et al.  Alternating electric fields arrest cell proliferation in animal tumor models and human brain tumors , 2007, Proceedings of the National Academy of Sciences.

[38]  S. Tor,et al.  Microstructures and mechanical properties of powder injection molded Ti-6Al-4V/HA powder. , 2002, Biomaterials.

[39]  A. Kishimoto,et al.  Effect of polarization treatment on bending strength of barium titanate/zirconia composite , 2000 .

[40]  H. Takeda,et al.  Proton transport polarization and depolarization of hydroxyapatite ceramics , 2001 .

[41]  L. Bourguignon,et al.  Electric stimulation of protein and DNA synthesis in human fibroblasts , 1987, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[42]  C. J. DREYER.  Properties of Stressed Bone , 1961, Nature.

[43]  J. B. Park,et al.  Piezoelectric ceramic implants: a feasibility study. , 1980, Journal of biomedical materials research.

[44]  John Kolega,et al.  Effects of Direct Current Electric Fields on Cell Migration and Actin Filament Distribution in Bovine Vascular Endothelial Cells , 2002, Journal of Vascular Research.

[45]  S. Nakamura,et al.  Biocompatibility of dense hydroxyapatite prepared using an SPS process. , 2002, Journal of biomedical materials research.

[46]  A. Volceanov,et al.  Hydroxiapatite - zirconia composites for biomedical applications , 2006 .

[47]  R. Reis,et al.  Processing and properties of bone-analogue biodegradable and bioinert polymeric composites , 2003 .

[48]  S. Nakamura,et al.  A New Approach to Enhancement of Bone Formation by Electrically Polarized Hydroxyapatite , 2001, Journal of dental research.

[49]  R. Bruce Martin,et al.  Comparison of capacitive and inductive bone stimulation devices , 2006, Annals of Biomedical Engineering.

[50]  C. M. Agrawal,et al.  The role of collagen in determining bone mechanical properties , 2001, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[51]  Bing Yang,et al.  Alumina ceramics toughened by a piezoelectric secondary phase , 2000 .

[52]  K. Yamashita,et al.  Extended bioactivity in the proximity of hydroxyapatite ceramic surfaces induced by polarization charges. , 2002, Journal of biomedical materials research.

[53]  C. Brighton,et al.  Treatment of nonunion with constant direct current. , 1977, Clinical orthopaedics and related research.

[54]  Y. Leng,et al.  High strength and bioactive hydroxyapatite nano-particles reinforced ultrahigh molecular weight polyethylene , 2007 .

[55]  Y. Zhou,et al.  In vitro bioactivity of a biocomposite fabricated from HA and Ti powders by powder metallurgy method. , 2002, Biomaterials.

[56]  M. Kakihana,et al.  Hydroxyapatite/Hydroxyapatite‐Whisker Composites without Sintering Additives: Mechanical Properties and Microstructural Evolution , 1997 .

[57]  M A El Messiery,et al.  Ferro-electricity of dry cortical bone. , 1979, Journal of biomedical engineering.

[58]  Christopher R. Bowen,et al.  The Structure and Properties of Electroceramics for Bone Graft Substitution , 2007 .

[59]  J. Ong,et al.  Interaction of hydroxyapatite-titanium at elevated temperature in vacuum environment. , 2004, Biomaterials.

[60]  M. Shamos,et al.  Physical bases for bioelectric effects in mineralized tissues. , 1964, Clinical orthopaedics and related research.

[61]  Sergio Mascarenhas,et al.  THE ELECTRET EFFECT IN BONE AND BIOPOLYMERS AND THE BOUND‐WATER PROBLEM * , 1974 .

[62]  R O Becker,et al.  Dielectric Determination of Bound Water of Bone , 1967 .

[63]  Jingchuan Zhu,et al.  Mechanical and biological properties of hydroxyapatite reinforced with 40 vol. % titanium particles for use as hard tissue replacement , 2004, Journal of materials science. Materials in medicine.

[64]  B. Nordenstrom.  Electrochemical Treatment of Cancer. I: Variable Response to Anodic and Cathodic Fields , 1989 .

[65]  C. Bowen,et al.  Characterisation of barium titanate-silver composites, part I: Microstructure and mechanical properties , 2006 .

[66]  R. Tripathi,et al.  Understanding phase stability, microstructure development and biocompatibility in calcium phosphate–titania composites, synthesized from hydroxyapatite and titanium powder mix , 2009 .

[67]  K. Yamashita,et al.  Manipulation of selective cell adhesion and growth by surface charges of electrically polarized hydroxyapatite. , 2001, Journal of biomedical materials research.

[68]  A. Mukhopadhyay,et al.  Nanoindentation response of novel hydroxyapatite–mullite composites , 2009 .

[69]  Christopher R Bowen,et al.  An in vitro study of electrically active hydroxyapatite-barium titanate ceramics using Saos-2 cells , 2009, Journal of materials science. Materials in medicine.

[70]  P. Ajayan,et al.  Novel current-conducting composite substrates for exposing osteoblasts to alternating current stimulation. , 2002, Journal of biomedical materials research.

[71]  A F von Recum,et al.  Piezoelectric ceramic implants: in vivo results. , 1981, Journal of biomedical materials research.

[72]  Xing‐dong Zhang,et al.  Promotion of osteogenesis by a piezoelectric biological ceramic , 1997 .

[73]  F. Sánchez,et al.  Correlation between low-frequency electric conductivity and permittivity in the diaphysis of bovine femoral bone , 1992 .

[74]  G W Hastings,et al.  Electrical effects in bone. , 1988, Journal of biomedical engineering.

[75]  C A Bassett,et al.  Treatment of ununited tibial diaphyseal fractures with pulsing electromagnetic fields. , 1981, The Journal of bone and joint surgery. American volume.

[76]  B. Basu,et al.  In vitro dissolution of calcium phosphate-mullite composite in simulated body fluid , 2010, Journal of materials science. Materials in medicine.

[77]  W. Walsh,et al.  Piezoelectric and Electrokinetic Effects in Bone Tissue–Review , 1993 .

[78]  B. Basu,et al.  Phase stability and microstructure development in hydroxyapatite–mullite system , 2008 .

[79]  F. Braga,et al.  Characterization of PVDF/HAP composites for medical applications , 2007 .

[80]  M. Shamos,et al.  On electrical condution in living bone. , 1975, Clinical orthopaedics and related research.

[81]  A. Dubey,et al.  Mechanical properties of novel calcium phosphate–mullite biocomposites , 2012, Journal of biomaterials applications.

[82]  S. Pollack,et al.  Treatment of denervation/disuse osteoporosis in the rat with a capacitively coupled electrical signal: Effects on bone formation and bone resorption , 1988, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[83]  W. Bonfield,et al.  Hydroxyapatite reinforced polyethylene--a mechanically compatible implant material for bone replacement. , 1981, Biomaterials.

[84]  Buddy D. Ratner,et al.  Biomaterials Science: An Introduction to Materials in Medicine , 1996 .

[85]  Larry L. Hench,et al.  Bioceramics: From Concept to Clinic , 1991 .

[86]  K. Liao,et al.  Tensile properties, tension-tension fatigue and biological response of polyetheretherketone-hydroxyapatite composites for load-bearing orthopedic implants. , 2003, Biomaterials.

[87]  E. Dekel,et al.  Disruption of cancer cell replication by alternating electric fields. , 2004, Cancer research.

[88]  Hyoun‐Ee Kim,et al.  Various Ca/P ratios of thin calcium phosphate films , 2002 .

[89]  J. Katz.  Anisotropy of Young's modulus of bone , 1980, Nature.

[90]  J. Ong,et al.  Growth of calcium phosphate on poling treated ferroelectric BaTiO3 ceramics. , 2002, Biomaterials.

[91]  S. Lang,et al.  Pyroelectric Effect in Bone and Tendon , 1966, Nature.

[92]  D. Bernache-Assollant,et al.  Processing, microstructure and toughness of Al2O3 platelet-reinforced hydroxyapatite , 1997 .

[93]  S. Saha,et al.  Electric and dielectric properties of wet human cortical bone as a function of frequency , 1992, IEEE Transactions on Biomedical Engineering.

[94]  J. Aubin,et al.  Osteoclasts and osteoblasts migrate in opposite directions in response to a constant electrical field , 1986, Journal of cellular physiology.

[95]  P. Williams,et al.  Effect of various storage methods on the dielectric properties of compact bone , 1988, Medical and Biological Engineering and Computing.

[96]  L. Kloth,et al.  Acceleration of wound healing with high voltage, monophasic, pulsed current. , 1988, Physical therapy.

[97]  R. Tandon,et al.  Dielectric and piezoelectric properties of sol-gel-derived barium titanate ceramics , 1993 .

[98]  R. J. Pawluk,et al.  Electromechanical characteristics of bone under physiologic moisture conditions. , 1968, Clinical orthopaedics and related research.

[99]  Motohiro Uo,et al.  Biocompatibility of materials and development to functionally graded implant for bio-medical application , 2004 .

[100]  Masahiro Yoshimura,et al.  Processing and properties of hydroxyapatite-based biomaterials for use as hard tissue replacement implants , 1998 .

[101]  J. Chaudhuri,et al.  Dielectric and piezoelectric properties of hydroxyapatite-BaTiO3 composites , 2006 .

[102]  J. Ong,et al.  Effect of poling conditions on growth of calcium phosphate crystal in ferroelectric BaTiO3 ceramics , 2002, Journal of materials science. Materials in medicine.

[103]  T. McMahon,et al.  The tensile behavior of demineralized bovine cortical bone. , 1996, Journal of biomechanics.

[104]  C. Eriksson.  CHAPTER 8 – Electrical Properties of Bone , 1976 .

[105]  Gil Rosenman,et al.  Piezoelectric Effect in Human Bones Studied in Nanometer Scale , 2004 .

[106]  A. Rapacz-Kmita,et al.  Mechanical properties of HAp–ZrO2 composites , 2006 .

[107]  B. Basu,et al.  In vivo response of novel calcium phosphate-mullite composites: results up to 12 weeks of implantation. , 2009, Journal of biomedical materials research. Part B, Applied biomaterials.

[108]  R. L. Reis,et al.  Coupling of HDPE/hydroxyapatite composites by silane-based methodologies , 2003, Journal of materials science. Materials in medicine.

[109]  S Rakowski,et al.  Mechano-electrical properties of bone. , 1981, Biomaterials.

[110]  U. Joos,et al.  Electrical stimulation influences mineral formation of osteoblast-like cells in vitro. , 2001, Biochimica et biophysica acta.

[111]  T. Webster,et al.  Greater osteoblast proliferation on anodized nanotubular titanium upon electrical stimulation , 2008, International journal of nanomedicine.

[112]  A. S. Posner,et al.  Crystal Structure of Hydroxyapatite , 1964, Nature.

[113]  Eiichi Fukada,et al.  Piezoelectric Effects in Collagen , 1964 .

[114]  L. Hermansson,et al.  Hydroxyapatite-alumina composites and bone-bonding. , 1995, Biomaterials.

[115]  D. Golan,et al.  Transmembrane calcium influx induced by ac electric fields , 1999, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[116]  K. Niihara,et al.  Fabrication of piezoelectric particle-dispersed ceramic nanocomposite , 1999 .

[117]  K. Yamashita,et al.  Acceleration and Deceleration of Bone-Like Crystal Growth on Ceramic Hydroxyapatite by Electric Poling , 1996 .

[118]  J. Mcelhaney,et al.  The charge distribution on the human femur due to load. , 1967, The Journal of bone and joint surgery. American volume.

[119]  Andrew A. Marino,et al.  Origin of the piezoelectric effect in bone , 2005, Calcified Tissue Research.

[120]  Heppenstall Rb.  Constant direct-current treatment for established nonunion of the tibia. , 1983 .

[121]  B. Basu,et al.  Designing Materials for Hard Tissue Replacement , 2008 .

[122]  I. G. Turner,et al.  Electrically Active Bioceramics: A Review of Interfacial Responses , 2010, Annals of Biomedical Engineering.

[123]  S. Goldstein,et al.  Elastic modulus and hardness of cortical and trabecular bone lamellae measured by nanoindentation in the human femur. , 1999, Journal of biomechanics.

[124]  S. Mohapatra,et al.  Chemical synthesis and characterization of hydroxyapatite (HAp)-poly (ethylene co vinyl alcohol) (EVA) nanocomposite using a phosphonic acid coupling agent for orthopedic applications , 2009 .

[125]  Maria E. Mycielska,et al.  Cellular mechanisms of direct-current electric field effects: galvanotaxis and metastatic disease , 2004, Journal of Cell Science.

[126]  Michael Jarcho,et al.  Calcium phosphate ceramics as hard tissue prosthetics. , 1981, Clinical orthopaedics and related research.

[127]  M. Barbosa,et al.  Investigation of the dissolution of the bioceramic hydroxyapatite in the presence of titanium ions using ToF-SIMS and XPS. , 1997, Biomaterials.

[128]  M. Chu,et al.  Ceramic - Polymer Nanocomposite: Alternate Choice of Bone , 2008 .

[129]  J. B. Park,et al.  Mechanical property changes of barium titanate (ceramic) after in vivo and in vitro aging. , 1977, Biomaterials, medical devices, and artificial organs.

[130]  D. Burr.  The contribution of the organic matrix to bone's material properties. , 2002, Bone.

[131]  A. Huttenlocher,et al.  Wound healing with electric potential. , 2007, The New England journal of medicine.

[132]  V. Topolov,et al.  Piezoelectric Activity and Sensitivity of Novel Composites Based on Barium Titanate-Hydroxyapatite Composite Ceramics , 2007 .

[133]  Yasuaki Seki,et al.  Biological materials: Structure and mechanical properties , 2008 .

[134]  Y. Miyashita,et al.  Microstructure and fracture toughness of a spark plasma sintered Al2O3-based composite with BaTiO3 particulates , 2003 .

[135]  R. Reis,et al.  Structure development and interfacial interactions in high-density polyethylene/hydroxyapatite (HDPE/HA) Composites molded with preferred orientation , 2002 .

[136]  J. Jeffery,et al.  The influence that bone density and the orientation and particle size of the mineral phase have on the mechanical properties of bone. , 1978, Journal of bioengineering.

[137]  Subrata Saha,et al.  The electrical and dielectric properties of human bone tissue and their relationship with density and bone mineral content , 1996, Annals of Biomedical Engineering.

[139]  B. Yang,et al.  A new approach for toughening of ceramics , 1997 .

[140]  Hyoun‐Ee Kim,et al.  Improvement in biocompatibility of ZrO2-Al2O3 nano-composite by addition of HA. , 2005, Biomaterials.

[141]  S. Lang.  Pyroelectricity: Occurrence in biological materials and ossible physiological implications , 1981 .