Fiber reinforced calcium phosphate cements -- on the way to degradable load bearing bone substitutes?

Calcium phosphate cements (CPC) are well-established materials for the repair of bone defects with excellent biocompatibility and bioactivity. However, brittleness and low flexural/tensile strength so far restrict their application to non-load bearing areas. Reinforcement of CPC with fibers can substantially improve its strength and toughness and has been one major strategy to overcome the present mechanical limitations of CPC. Fiber reinforced calcium phosphate cements (FRCPC) thus bear the potential to facilitate the use of degradable bone substitutes in load bearing applications. This review recapitulates the state of the art of FRCPC research with focus on their mechanical properties and their biological evaluation in vitro and in vivo, including the clinical data that has been generated so far. After an overview on FRCPC constitutes and processing, some general aspects of fracture mechanics of reinforced cementitious composites are introduced, and their importance for the mechanical properties of FRCPC are highlighted. So far, fiber reinforcement leads to a toughness increase of up to two orders of magnitude. FRCPC have extensively been examined in vitro and in vivo with generally good results. While first clinical products focus on the improved performance of FRCPC with regard to secondary processing after injection such as fixation of screws and plates, first animal studies in load bearing applications show improved performance as compared to pure CPCs. Aside of the accomplished results, FRCPC bear a great potential for future development and optimization. Future research will have to focus on the selection and tailoring of FRCPC components, fiber-matrix compatibilization, integral composite design and the adjusted degradation behavior of the composite components to ensure successful long term behavior and make the composites strong enough for application in load bearing defects.

[1]  J. E. Gordon,et al.  Effects of bone ingrowth on the strength and non-invasive assessment of a coralline hydroxyapatite material. , 1989, Biomaterials.

[2]  Victor C. Li,et al.  Engineered Cementitious Composites (ECC) Material, Structural, and Durability Performance , 2008 .

[3]  L. Grover,et al.  Ionic modification of calcium phosphate cement viscosity. Part I: hypodermic injection and strength improvement of apatite cement. , 2004, Biomaterials.

[4]  G. Moze,et al.  Engineered Cementitious Composites for Structural Applications , 2013 .

[5]  W. E. Brown,et al.  A New Calcium Phosphate, Water-setting Cement , 1986 .

[6]  R. Pabst Neuere Methoden der Festigkeitsprüfung keramischer Werkstoffe , 1975 .

[7]  Alberto J Ambard,et al.  Calcium phosphate cement: review of mechanical and biological properties. , 2006, Journal of prosthodontics : official journal of the American College of Prosthodontists.

[8]  L. Grover,et al.  Ionic modification of calcium phosphate cement viscosity. Part II: hypodermic injection and strength improvement of brushite cement. , 2004, Biomaterials.

[9]  Sidney Mindess,et al.  The J-integral as a fracture criterion for fiber reinforced concrete , 1977 .

[10]  F. Eichmiller,et al.  Reinforcement of a self-setting calcium phosphate cement with different fibers. , 2000, Journal of biomedical materials research.

[11]  W. Thein-Han,et al.  Collagen-calcium phosphate cement scaffolds seeded with umbilical cord stem cells for bone tissue engineering. , 2011, Tissue engineering. Part A.

[12]  M. Kakihana,et al.  Processing and mechanical properties of hydroxyapatite reinforced with hydroxyapatite whiskers. , 1996, Biomaterials.

[13]  Hockin H. K. Xu,et al.  Injectable and macroporous calcium phosphate cement scaffold. , 2006, Biomaterials.

[14]  B. Milthorpe,et al.  Interdiffusion in short-fibre reinforced hydroxyapatite ceramics , 1998, Journal of materials science. Materials in medicine.

[15]  Janghwan Kim Handbook of composite reinforcements. Edited by Stuart M. Lee, VCH, Weinheim 1993, 715 pp., hardcover, DM 236, ISBN 3‐527‐89632‐5 , 1993 .

[16]  R. Gibson Principles of Composite Material Mechanics , 1994 .

[17]  Q. Lian,et al.  Mechanical properties and in-vivo performance of calcium phosphate cement—chitosan fibre composite , 2008, Proceedings of the Institution of Mechanical Engineers. Part H, Journal of engineering in medicine.

[18]  J. Knowles,et al.  Effect of porosity reduction by compaction on compressive strength and microstructure of calcium phosphate cement. , 2002, Journal of biomedical materials research.

[19]  R. Carrodeguas,et al.  Fiber reinforced calcium phosphate cement. , 2000, Artificial organs.

[20]  X. Kewei,et al.  Long-term variations in mechanical properties and in vivo degradability of CPC/PLGA composite. , 2007, Journal of biomedical materials research. Part B, Applied biomaterials.

[21]  M. Epple,et al.  Composites of Calcium Phosphate and Polymers as Bone Substitution Materials , 2006, European Journal of Trauma.

[22]  A. Boccaccini,et al.  Mechanical properties of biodegradable polymer sutures coated with bioactive glass , 2002, Journal of materials science. Materials in medicine.

[23]  R. Oyasu,et al.  Vicryl (polyglactin 910) synthetic absorbable sutures. , 1974, American journal of surgery.

[24]  N. Sasaki,et al.  Stress-strain curve and Young's modulus of a collagen molecule as determined by the X-ray diffraction technique. , 1996, Journal of biomechanics.

[25]  V. Li,et al.  Fracture Toughness of Micro-Fiber Reinforced Cement Composites , 2002 .

[26]  L. Hirakata,et al.  Strengthening of calcium phosphate cement by compounding calcium carbonate whiskers. , 2005, Dental materials journal.

[27]  ZhaoHui Pan,et al.  Properties of a Calcium Phosphate Cement Synergistically Reinforced by Chitosan Fiber and Gelatin , 2006 .

[28]  Soon Huat Tan,et al.  Calcium phosphate-based composites as injectable bone substitute materials. , 2010, Journal of Biomedical Materials Research. Part B - Applied biomaterials.

[29]  ZhaoHui Pan,et al.  Assessment of the suitability of a new composite as a bone defect filler in a rabbit model , 2008, Journal of tissue engineering and regenerative medicine.

[30]  R. Carrodeguas,et al.  Fiber-enriched double-setting calcium phosphate bone cement. , 2003, Journal of biomedical materials research. Part A.

[31]  Henrik Stang,et al.  Interface Property Characterization and Strengthening Mechanisms in Fiber Reinforced Cement Based Composites , 1997 .

[32]  B. Darvell,et al.  Uniaxial compression tests and the validity of indirect tensile strength , 1990 .

[33]  Yan Zhang,et al.  Young’s Modulus Surface and Poisson’s Ratio Curve for Orthorhombic Crystals , 2008 .

[34]  Hua Liu,et al.  Self-Hardening Calcium Phosphate Composite Scaffold for Bone Tissue Engineering , 2009 .

[35]  T. Paulalbear,et al.  Mechanical Comparison of 10 Suture Materials before and after in Vivo Incubation , 2004 .

[36]  Toshiro Kamada,et al.  Fracture Toughness of Microfiber Reinforced Cement Composites , 2002 .

[37]  C. B. Carter,et al.  Ceramic Materials: Science and Engineering , 2013 .

[38]  Hockin H. K. Xu,et al.  Effects of synergistic reinforcement and absorbable fiber strength on hydroxyapatite bone cement. , 2005, Journal of biomedical materials research. Part A.

[39]  C. Simon,et al.  Strong and bioactive composites containing nano-silica-fused whiskers for bone repair. , 2004, Biomaterials.

[40]  Baoan Ma,et al.  Mechanical and biocompatible influences of chitosan fiber and gelatin on calcium phosphate cement. , 2007, Journal of biomedical materials research. Part B, Applied biomaterials.

[41]  P. Brown,et al.  Characterization of wollastonite-reinforced HAp--Ca polycarboxylate composites. , 2001, Journal of biomedical materials research.

[42]  Hwai Chung Wu,et al.  Matrix design for pseudo-strain-hardening fibre reinforced cementitious composites , 1995 .

[43]  P. Dalton,et al.  Degradable polyester scaffolds with controlled surface chemistry combining minimal protein adsorption with specific bioactivation. , 2011, Nature materials.

[44]  N. Dunne,et al.  Optimisation of Calcium Phosphate Cements for Bone Augmentation through Vertebroplasty , 2010 .

[45]  John J. Petrovic,et al.  Tensile mechanical properties of SiC whiskers , 1985 .

[46]  Miqin Zhang,et al.  Biphasic calcium phosphate nanocomposite porous scaffolds for load-bearing bone tissue engineering. , 2004, Biomaterials.

[47]  Mohamed Maalej,et al.  Toughening in cement based composites. Part II: Fiber reinforced cementitious composites , 1996 .

[48]  A. M. Brandt Cement-based Composites: Materials, Mechanical Properties and Performance , 1995 .

[49]  F. Müller,et al.  Whisker‐Reinforced Calcium Phosphate Cements , 2007 .

[50]  Sergey V. Dorozhkin,et al.  Calcium orthophosphate cements for biomedical application , 2008 .

[51]  Arun Shukla,et al.  PULLOUT BEHAVIOR OF POLYPROPYLENE FIBERS FROM CEMENTITIOUS MATRIX , 2004 .

[52]  F. Kummer,et al.  Calcium Phosphate Cement Augmentation of the Femoral Neck Defect Created After Dynamic Hip Screw Removal , 2007, Journal of orthopaedic trauma.

[53]  Hwai Chung Wu,et al.  Effect of Plasma Treatment of Polyethylene Fibers on Interface and ementitious Composite Properties , 2005 .

[54]  Dichen Li,et al.  Fabrication and in Vitro Evaluation of Calcium Phosphate Combined with Chitosan Fibers for Scaffold Structures , 2009 .

[55]  Lu Shen,et al.  Preparation and mechanical properties of chitosan/carbon nanotubes composites. , 2005, Biomacromolecules.

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

[57]  M. Allen,et al.  Polylactide-co-glycolide fiber-reinforced calcium phosphate bone cement. , 2009, Archives of facial plastic surgery.

[58]  C. Canal,et al.  Fibre-reinforced calcium phosphate cements: a review. , 2011, Journal of the mechanical behavior of biomedical materials.

[59]  M. Yoshimura,et al.  Reinforcing of a calcium phosphate cement with hydroxyapatite crystals of various morphologies. , 2010, ACS applied materials & interfaces.

[60]  Alan D. Wilson,et al.  Acid–base cements: Phosphate bonded cements , 1993 .

[61]  R. Ruoff,et al.  Strength and breaking mechanism of multiwalled carbon nanotubes under tensile load , 2000, Science.

[62]  Hani Naguib,et al.  Comparison of morphology and mechanical properties of PLGA bioscaffolds , 2008, Biomedical materials.

[63]  M. Weir,et al.  Self-setting collagen-calcium phosphate bone cement: mechanical and cellular properties. , 2009, Journal of biomedical materials research. Part A.

[64]  R. Legras,et al.  Physico-mechanical properties of poly (epsilon-caprolactone) for the construction of rumino-reticulum devices for grazing animals. , 1995, Biomaterials.

[65]  Tadashi Saito,et al.  Interface tailoring for strain-hardening polyvinyl alcohol-engineered cementitious composite (PVA-ECC) , 2002 .

[66]  Victor C. Li,et al.  A micromechanical model of tension-softening and bridging toughening of short random fiber reinforced brittle matrix composites , 1991 .

[67]  P. Löbmann,et al.  Continuous Sol–Gel Coating of Ceramic Multifilaments: Evaluation of Fiber Bridging by Three‐Point Bending Test , 2006 .

[68]  L. Grover,et al.  Effects of fibre reinforcement on the mechanical properties of brushite cement. , 2006, Acta biomaterialia.

[69]  William D. Callister,et al.  Materials Science and Engineering: An Introduction , 1985 .

[70]  Liang Zhao,et al.  Fatigue and human umbilical cord stem cell seeding characteristics of calcium phosphate-chitosan-biodegradable fiber scaffolds. , 2010, Biomaterials.

[71]  Shenglan Zhang,et al.  Preparation and characterization of biodegradable thermoplastic Elastomers (PLCA/PLGA blends) , 2009 .

[72]  Yiu-Wing Mai,et al.  Fracture Mechanics of Cementitious Materials , 1995 .

[73]  Yingjun Wang,et al.  Reinforcement of calcium phosphate cement by bio-mineralized carbon nanotube , 2007 .

[74]  J. Quinn,et al.  Calcium phosphate cement containing resorbable fibers for short-term reinforcement and macroporosity. , 2002, Biomaterials.

[75]  A. P. Stetsovskii,et al.  Correlation Between Elastic Properties of Wollastonite-Based Materials and Sintering Temperature , 2003 .

[76]  B. Karihaloo,et al.  Micromechanical modelling of strain hardening and tension softening in cementitious composites , 1997 .

[77]  Rilem Determination of the fracture energy of mortar and concrete by means of three-point bend tests on notched beams , 1985 .

[78]  J. Rice A path-independent integral and the approximate analysis of strain , 1968 .

[79]  C. Bao,et al.  Effects of electrospun submicron fibers in calcium phosphate cement scaffold on mechanical properties and osteogenic differentiation of umbilical cord stem cells. , 2011, Acta biomaterialia.

[80]  Gladius Lewis,et al.  Injectable bone cements for use in vertebroplasty and kyphoplasty: state-of-the-art review. , 2006, Journal of biomedical materials research. Part B, Applied biomaterials.

[81]  Hwai Chung Wu,et al.  Conditions for Pseudo Strain-Hardening in Fiber Reinforced Brittle Matrix Composites , 1992 .

[82]  K. Sun,et al.  Effect of CNTs on Property of Calcium Phosphate Cement , 2007 .

[83]  Besim Ben-Nissan,et al.  Development of carbon nanotube-reinforced hydroxyapatite bioceramics , 2006 .

[84]  A. Boccaccini,et al.  Reinforcement of calcium phosphate cement with multi-walled carbon nanotubes and bovine serum albumin for injectable bone substitute applications. , 2011, Journal of the mechanical behavior of biomedical materials.

[85]  Hwai Chung Wu,et al.  Fiber/cement interface tailoring with plasma treatment , 1999 .

[86]  B. Ben-Nissan,et al.  Micro- and nano-indentation of a hydroxyapatite-carbon nanotube composite. , 2008, Journal of nanoscience and nanotechnology.

[87]  N. Dunne,et al.  Short-fibre reinforcement of calcium phosphate bone cement , 2007, Proceedings of the Institution of Mechanical Engineers. Part H, Journal of engineering in medicine.

[88]  M. Bockmeyer,et al.  Influence of Precursor Densification on Strength Retention of Zirconia‐Coated Nextel™ 610 Fibers , 2008 .

[89]  A. Watts,et al.  In vitro elution of amikacin and ticarcillin from a resorbable, self-setting, fiber reinforced calcium phosphate cement. , 2011, Veterinary surgery : VS.

[90]  Hockin H. K. Xu,et al.  High early strength calcium phosphate bone cement: effects of dicalcium phosphate dihydrate and absorbable fibers. , 2005, Journal of biomedical materials research. Part A.

[91]  M. Elices,et al.  Measurement of the fracture energy using three-point bend tests: Part 1—Influence of experimental procedures , 1992 .

[92]  Hockin H K Xu,et al.  Strong, macroporous, and in situ-setting calcium phosphate cement-layered structures. , 2007, Biomaterials.

[93]  J. Antonucci,et al.  Load-bearing behavior of a simulated craniofacial structure fabricated from a hydroxyapatite cement and bioresorbable fiber-mesh , 2000, Journal of materials science. Materials in medicine.

[94]  Yaping Ye,et al.  Hexagonal Boron Nitride from a Borazine Precursor for Coating of SiBNC Fibers using a Continuous Atmospheric Pressure CVD Process , 2011 .

[95]  J. Rösler,et al.  Mechanisches Verhalten der Werkstoffe , 2003 .

[96]  Ashley A. White,et al.  Hydroxyapatite–Carbon Nanotube Composites for Biomedical Applications: A Review , 2007 .

[97]  S. Dorozhkin Calcium orthophosphate-based biocomposites and hybrid biomaterials , 2009 .

[98]  A. Kelly,et al.  Toughening of cement and other brittle solids with fibres , 1983, Philosophical transactions of the Royal Society of London. Series A: Mathematical and physical sciences.

[99]  J. Aveston,et al.  Single and Multiple Fracture , 1971 .

[100]  M. Swain,et al.  Fracture toughness of bovine bone: influence of orientation and storage media. , 2001, Biomaterials.

[101]  S. H. Tan,et al.  The effect of interfacial bonding of calcium phosphate cements containing bio-mineralized multi-walled carbon nanotube and bovine serum albumin on the mechanical properties of calcium phosphate cements , 2011 .

[102]  G. Hannink,et al.  Injectable bone-graft substitutes: current products, their characteristics and indications, and new developments. , 2011, Injury.

[103]  B. Milthorpe,et al.  Stability of hydroxyapatite while processing short-fibre reinforced hydroxyapatite ceramics. , 1997, Biomaterials.

[104]  A. Boccaccini,et al.  Optimization of the mechanical properties of calcium phosphate/multi-walled carbon nanotubes/bovine serum albumin composites using response surface methodology , 2011 .

[105]  Dorel Feldman,et al.  Polypropylene fiber–matrix bonds in cementitious composites , 2000 .

[106]  M. Mozafari,et al.  Synergistically reinforcement of a self-setting calcium phosphate cement with bioactive glass fibers , 2011 .

[107]  J. Quinn,et al.  Strong and macroporous calcium phosphate cement: Effects of porosity and fiber reinforcement on mechanical properties. , 2001, Journal of biomedical materials research.

[108]  T. Schaer,et al.  Evaluation of a Fiber Reinforced Drillable Bone Cement for Screw Augmentation in a Sheep Model—Mechanical Testing , 2010, Clinical and translational science.

[109]  N. Nezafati,et al.  Evaluation of a prepared sol-gel bioactive glass fiber-reinforced calcium phosphate cement , 2010 .

[110]  G. P. Cherepanov Crack propagation in continuous media , 1967 .

[111]  C. Simon,et al.  Self-hardening calcium phosphate cement-mesh composite: reinforcement, macropores, and cell response. , 2004, Journal of biomedical materials research. Part A.

[112]  F. Eichmiller,et al.  Effects of fiber length and volume fraction on the reinforcement of calcium phosphate cement , 2001, Journal of materials science. Materials in medicine.

[113]  Rilem FMC 1 Determination of the fracture energy of mortar and concrete by means of three-point bend tests on notched beams , 1985 .

[114]  V. Li J-integral Applications to Characterization and Tailoring of Cementitious Materials , 2000 .

[115]  M. Gelinsky,et al.  Histologic study of incorporation and resorption of a bone cement-collagen composite: an in vivo study in the minipig. , 2008, Oral surgery, oral medicine, oral pathology, oral radiology, and endodontics.

[116]  John A Jansen,et al.  Incorporation of biodegradable electrospun fibers into calcium phosphate cement for bone regeneration. , 2010, Acta biomaterialia.

[117]  M. Bohner,et al.  Design of ceramic-based cements and putties for bone graft substitution. , 2010, European cells & materials.

[118]  H. Tattersall,et al.  The work of fracture and its measurement in metals, ceramics and other materials , 1966 .

[119]  M. Bohner,et al.  Technological issues for the development of more efficient calcium phosphate bone cements: a critical assessment. , 2005, Biomaterials.

[120]  B. Felekoglu,et al.  A comparative study on the flexural performance of plasma treated polypropylene fiber reinforced cementitious composites , 2009 .

[121]  D. Dean,et al.  Fiber-reinforced calcium phosphate cement formulations for cranioplasty applications: a 52-week duration preclinical rabbit calvaria study. , 2012, Journal of Biomedical Materials Research. Part B - Applied biomaterials.

[122]  V. Li On Engineered Cementitious Composites (ECC) , 2003 .

[123]  P. Eklund,et al.  Electronic properties of semiconductor nanowires. , 2008, Journal of nanoscience and nanotechnology.

[124]  G. With,et al.  Metal fibre reinforced hydroxy-apatite ceramics , 1989 .

[125]  M. Weir,et al.  Effect of cell seeding density on proliferation and osteodifferentiation of umbilical cord stem cells on calcium phosphate cement-fiber scaffold. , 2011, Tissue engineering. Part A.