Influence of the pore generator on the evolution of the mechanical properties and the porosity and interconnectivity of a calcium phosphate cement.

Porosity and interconnectivity are important properties of calcium phosphate cements (CPCs) and bone-replacement materials. Porosity of CPCs can be achieved by adding polymeric biodegradable pore-generating particles (porogens), which can add porosity to the CPC and can also be used as a drug-delivery system. Porosity affects the mechanical properties of CPCs, and hence is of relevance for clinical application of these cements. The current study focused on the effect of combinations of polymeric mesoporous porogens on the properties of a CPC, such as specific surface area, porosity and interconnectivity and the development of mechanical properties. CPC powder was mixed with different amounts of PLGA porogens of various molecular weights and porogen sizes. The major factors affecting the properties of the CPC were related to the amount of porogen loaded and the porogen size; the molecular weight did not show a significant effect per se. A minimal porogen size of 40 μm in 30 wt.% seems to produce a CPC with mechanical properties, porosity and interconnectivity suitable for clinical applications. The properties studied here, and induced by the porogen and CPC, can be used as a guide to evoke a specific host-response to maintain CPC integrity and to generate an explicit bone ingrowth.

[1]  J. Jansen,et al.  In vivo bone response to porous calcium phosphate cement. , 2003, Journal of biomedical materials research. Part A.

[2]  Franck Tancret,et al.  Influence of microporosity and macroporosity on the mechanical properties of biphasic calcium phosphate bioceramics: Modelling and experiment , 2010 .

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

[4]  J. Lu,et al.  Role of interconnections in porous bioceramics on bone recolonization in vitro and in vivo , 1999, Journal of materials science. Materials in medicine.

[5]  D. Kaplan,et al.  Porosity of 3D biomaterial scaffolds and osteogenesis. , 2005, Biomaterials.

[6]  H. Aro,et al.  Pore diameter of more than 100 μm is not requisite for bone ingrowth in rabbits , 2001 .

[7]  E. Teller,et al.  ADSORPTION OF GASES IN MULTIMOLECULAR LAYERS , 1938 .

[8]  J. Jansen,et al.  Biocompatibility and degradation of poly(DL-lactic-co-glycolic acid)/calcium phosphate cement composites. , 2005, Journal of biomedical materials research. Part A.

[9]  Cees Otto,et al.  Noninvasive imaging of protein metabolic labeling in single human cells using stable isotopes and Raman microscopy. , 2008, Analytical chemistry.

[10]  Huarong Liu,et al.  Fabrication of novel multihollow superparamagnetic magnetite/polystyrene nanocomposite microspheres via water-in-oil-in-water double emulsions. , 2008, Langmuir : the ACS journal of surfaces and colloids.

[11]  Sergey V. Dorozhkin,et al.  Bioceramics of calcium orthophosphates. , 2010, Biomaterials.

[12]  M. Bohner Physical and chemical aspects of calcium phosphates used in spinal surgery , 2001, European Spine Journal.

[13]  A. Leriche,et al.  Effects of powder stoichiometry on the sintering of β-tricalcium phosphate , 2007 .

[14]  Daeyeon Lee,et al.  Double emulsion templated monodisperse phospholipid vesicles. , 2008, Langmuir : the ACS journal of surfaces and colloids.

[15]  M. D. Vlad,et al.  Modulation of porosity in apatitic cements by the use of alpha-tricalcium phosphate-calcium sulphate dihydrate mixtures. , 2005, Biomaterials.

[16]  F. Tancret,et al.  Modelling the mechanical properties of microporous and macroporous biphasic calcium phosphate bioceramics , 2006 .

[17]  Yi Yan Yang,et al.  Effect of preparation temperature on the characteristics and release profiles of PLGA microspheres containing protein fabricated by double-emulsion solvent extraction/evaporation method. , 2000, Journal of controlled release : official journal of the Controlled Release Society.

[18]  N. Verdonschot,et al.  Injectable calcium phosphate cement for bone repair and implant fixation. , 2005, The Orthopedic clinics of North America.

[19]  J. Jansen,et al.  The effect of ball milling grinding pathways on the bulk and reactivity properties of calcium phosphate cements. , 2011, Journal of biomedical materials research. Part B, Applied biomaterials.

[20]  Josep A Planell,et al.  Factors affecting the structure and properties of an injectable self-setting calcium phosphate foam. , 2007, Journal of biomedical materials research. Part A.

[21]  Harjinder Singh,et al.  PFG-NMR analysis of intercompartment exchange and inner droplet size distribution of W/O/W emulsions. , 2005, Langmuir : the ACS journal of surfaces and colloids.

[22]  C. V. van Blitterswijk,et al.  Raman imaging of PLGA microsphere degradation inside macrophages. , 2004, Journal of the American Chemical Society.

[23]  M. Shive,et al.  Biodegradation and biocompatibility of PLA and PLGA microspheres , 1997 .

[24]  A G Mikos,et al.  Injectable PLGA microsphere/calcium phosphate cements: physical properties and degradation characteristics , 2006, Journal of biomaterials science. Polymer edition.

[25]  Christian Rey,et al.  Preparation, physical-chemical characterisation and cytocompatibility of calcium carbonate cements. , 2006, Biomaterials.

[26]  L. Grover,et al.  Preparation of macroporous calcium phosphate cement tissue engineering scaffold. , 2002, Biomaterials.

[27]  J. Jansen,et al.  Effect of polymer molecular weight on the bone biological activity of biodegradable polymer/calcium phosphate cement composites. , 2009, Tissue engineering. Part A.

[28]  J. Gardella,et al.  Surface chemistry of biodegradable polymers for drug delivery systems. , 2005, Chemical reviews.

[29]  J. van den Dolder,et al.  Mechanical evaluation of implanted calcium phosphate cement incorporated with PLGA microparticles. , 2006, Biomaterials.

[30]  Rui L Reis,et al.  Morphology, mechanical characterization and in vivo neo-vascularization of chitosan particle aggregated scaffolds architectures. , 2008, Biomaterials.

[31]  P. Salmon Loss of Chaotic Trabecular Structure in OPG‐Deficient Juvenile Paget's Disease Patients Indicates a Chaogenic Role for OPG in Nonlinear Pattern Formation of Trabecular Bone , 2004, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[32]  F. Tancret,et al.  Fabrication and mechanical properties of calcium phosphate cements (CPC) for bone substitution , 2011 .

[33]  C. Silva,et al.  Raman spectroscopy measurements of hydroxyapatite obtained by mechanical alloying , 2004 .

[34]  Surface Entrapment of Polylysine in Biodegradable Poly(dl-lactide-co-glycolide) Microparticles , 2001 .

[35]  W. Stark,et al.  Effect of thermal treatments on the reactivity of nanosized tricalcium phosphate powders , 2008 .

[36]  J. Sohier,et al.  Macrophage and osteoblast responses to biphasic calcium phosphate microparticles. , 2009, Journal of biomedical materials research. Part A.

[37]  Dan S. Tawfik,et al.  Flow cytometry: a new method to investigate the properties of water-in-oil-in-water emulsions. , 2004, Langmuir : the ACS journal of surfaces and colloids.

[38]  D. Grijpma,et al.  Injectable calcium phosphate cement with PLGA, gelatin and PTMC microspheres in a rabbit femoral defect. , 2011, Acta biomaterialia.

[39]  William E. Lorensen,et al.  Marching cubes: A high resolution 3D surface construction algorithm , 1987, SIGGRAPH.

[40]  J. Jansen,et al.  Trabecular bone response to injectable calcium phosphate (Ca-P) cement. , 2002, Journal of biomedical materials research.

[41]  Amy J Wagoner Johnson,et al.  Multiscale osteointegration as a new paradigm for the design of calcium phosphate scaffolds for bone regeneration. , 2010, Biomaterials.

[42]  M. Fujiwara,et al.  Preparation and formation mechanism of silica microcapsules (hollow sphere) by water/oil/water interfacial reaction , 2004 .

[43]  A Sasov,et al.  A post-scan method for correcting artefacts of slow geometry changes during micro-tomographic scans. , 2009, Journal of X-ray science and technology.

[44]  D. Ayala,et al.  Quantitative analysis of the resorption and osteoconduction of a macroporous calcium phosphate bone cement for the repair of a critical size defect in the femoral condyle. , 2009, Veterinary journal.

[45]  Josep A Planell,et al.  Micro-finite element models of bone tissue-engineering scaffolds. , 2006, Biomaterials.

[46]  D. Chappard,et al.  Inflammatory reaction in rats muscle after implantation of biphasic calcium phosphate micro particles , 2007, Journal of materials science. Materials in medicine.

[47]  Antonios G Mikos,et al.  Introduction of enzymatically degradable poly(trimethylene carbonate) microspheres into an injectable calcium phosphate cement. , 2008, Biomaterials.

[48]  R. Legeros,et al.  Properties of osteoconductive biomaterials: calcium phosphates. , 2002, Clinical orthopaedics and related research.

[49]  S. Sahoo,et al.  Characterization of porous PLGA/PLA microparticles as a scaffold for three dimensional growth of breast cancer cells. , 2005, Biomacromolecules.

[50]  R M Pilliar,et al.  The optimum pore size for the fixation of porous-surfaced metal implants by the ingrowth of bone. , 1980, Clinical orthopaedics and related research.

[51]  L. Chow Calcium phosphate cements. , 2001, Monographs in oral science.

[52]  A. Leriche,et al.  Manufacture of macroporous β-tricalcium phosphate bioceramics , 2008 .

[53]  G. Mestres,et al.  New processing approaches in calcium phosphate cements and their applications in regenerative medicine. , 2010, Acta biomaterialia.

[54]  J. Bouler,et al.  A new technological procedure using sucrose as porogen compound to manufacture porous biphasic calcium phosphate ceramics of appropriate micro- and macrostructure , 2010 .