



@article {3292,
	title = {Modulation of human dermal microvascular endothelial cell and human gingival fibroblast behavior by micropatterned silica coating surfaces for zirconia dental implant applications},
	journal = {Science and Technology of Advanced Materials},
	volume = {15},
	year = {2014},
	note = {Export Date: 21 November 2014},
	month = {2014},
	abstract = {Dental ceramic implants have shown superior esthetic behavior and the absence of induced allergic disorders when compared to titanium implants. Zirconia may become a potential candidate to be used as an alternative to titanium dental implants if surface modifications are introduced. In this work, bioactive micropatterned silica coatings were produced on zirconia substrates, using a combined methodology of sol-gel processing and soft lithography. The aim of the work was to compare the in vitro behavior of human gingival fibroblasts (HGFs) and human dermal microvascular endothelial cells (HDMECs) on three types of silica-coated zirconia surfaces: flat and micropatterned (with pillars and with parallel grooves). Our results showed that cells had a higher metabolic activity (HGF, HDMEC) and increased gene expression levels of fibroblast-specific protein-1 (FSP-1) and collagen type I (COL I) on surfaces with pillars. Nevertheless, parallel grooved surfaces were able to guide cell growth. Even capillary tube-like networks of HDMEC were oriented according to the surface geometry. Zirconia and silica with different topographies have shown to be blood compatible and silica coating reduced bacteria adhesion. All together, the results indicated that microstructured bioactive coating seems to be an efficient strategy to improve soft tissue integration on zirconia implants, protecting implants from peri-implant inflammation and improving long-term implant stabilization. This new approach of micropatterned silica coating on zirconia substrates can generate promising novel dental implants, with surfaces that provide physical cues to guide cells and enhance their behavior. {\textcopyright} 2014 National Institute for Materials Science.},
	keywords = {bacteria adhesion, Biomaterials, hemolysis, human dermal microvascular endothelial cells (HDMECs), human gingival fibroblasts (HGFs), Micropatterning, Soft lithography},
	url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84898687729\&partnerID=40\&md5=f252b87aeb163775547158cad0cf658b},
	author = {Laranjeira, M.S. and Carvalho, {\^A}. and Pelaez-Vargas, A. and Hansford, D. and Ferraz, M.P. and Coimbra, S. and Costa, E. and Santos-Silva, A. and Fernandes, M.H. and Monteiro, F.J.}
}
@article {2891,
	title = {Response of monocultured and co-cultured human microvascular endothelial cells and mesenchymal stem cells to macroporous granules of nanostructured- hydroxyapatite agglomerates},
	journal = {Journal of Biomedical Nanotechnology},
	volume = {9},
	year = {2013},
	note = {Export Date: 12 December 2013Source: Scopus},
	month = {2013///},
	pages = {1594 - 1606},
	url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84883350324\&partnerID=40\&md5=d78750836664276ab71c67301dab9c83},
	author = {Laranjeira, M.S. and Fernandes, M.H. and Monteiro, F.J.}
}
@article {2193,
	title = {Reciprocal induction of human dermal microvascular endothelial cells and human mesenchymal stem cells: Time-dependent profile in a co-culture system},
	journal = {Cell ProliferationCell Prolif.},
	volume = {45},
	year = {2012},
	note = {Export Date: 21 November 2012Source: ScopusCODEN: CPROEdoi: 10.1111/j.1365-2184.2012.00822.xPubMed ID: 22607133Language of Original Document: EnglishCorrespondence Address: Laranjeira, M.S.; Departamento de Engenharia Metalurgicae de Materiais, Faculdade de Engenharia (FEUP), Universidade do Porto, Rua Roberto Frias, s/n, 4200-465 Porto, Portugal; email: martalaranjeira@gmail.comMolecular Sequence Numbers: GENBANK: AB021221, NM_000088, NM_000552, NM_001200, NM_001795;Chemicals/CAS: DNA, 9007-49-2; F actin, 39409-31-9; alkaline phosphatase, 9001-78-9; calcein, 1461-15-0; calcium phosphate, 10103-46-5, 13767-12-9, 14358-97-5, 7758-87-4; DNA PrimersReferences: Santos, M., Reis, R., Vascularization in bone tissue engineering: physiology, current strategies, major hurdles and future challenges (2010) Macromol. Biosci., 10, pp. 12-20;Grellier, M., Granja, P.L., Fricain, J.-C., Bidarra, S.J., Renard, M., Bareille, R., The effect of the co-immobilization of human osteoprogenitors and endothelial cells within alginate microspheres on mineralization in a bone defect (2009) Biomaterials, 30, pp. 3271-3278; 
Unger, R.E., Sartoris, A., Peters, K., Motta, A., Migliaresi, C., Kunkel, M., Tissue-like self-assembly in cocultures of endothelial cells and osteoblasts and the formation of microcapillary-like structures on three-dimensional porous biomaterials (2007) Biomaterials, 28, pp. 3965-3976; 
Santos, M.I., Pashkuleva, I., Alves, C.M., Gomes, M.E., Fuchs, S., Unger, R.E., Surface-modified 3D starch-based scaffold for improved endothelialization for bone tissue engineering (2009) J. Mater. Chem., 19, pp. 4029-4280; 
Fuchs, S., Jiang, X., Schmidt, H., Dohle, E., Ghanaati, S., Orth, C., Dynamic processes involved in the pre-vascularization of silk fibroin constructs for bone regeneration using outgrowth endothelial cells (2009) Biomaterials, 30, pp. 1329-1338; 
Santos, M.I., Unger, R.E., Sousa, R.A., Reis, R.L., Kirkpatrick, C.J., Crosstalk between osteoblasts and endothelial cells co-cultured on a polycaprolactone-starch scaffold and the in vitro development of vascularization (2009) Biomaterials, 30, pp. 4407-4415; 
Unger, R.E., Ghanaati, S., Orth, C., Sartoris, A., Barbeck, M., Halstenberg, S., The rapid anastomosis between prevascularized networks on silk fibroin scaffolds generated in vitro with cocultures of human microvascular endothelial and osteoblast cells and the host vasculature (2010) Biomaterials, 31, pp. 6959-6967; 
Stahl, A., Wenger, A., Weber, H., Stark, G.B., Augustin, H.G., Finkenzeller, G., Bi-directional cell contact-dependent regulation of gene expression between endothelial cells and osteoblasts in a three-dimensional spheroidal coculture model (2004) Biochem. Biophys. Res. Commun., 322, pp. 684-692; 
Yu, H., VandeVord, P.J., Mao, L., Matthew, H.W., Wooley, P.H., Yang, S.-Y., Improved tissue-engineered bone regeneration by endothelial cell mediated vascularization (2009) Biomaterials, 30, pp. 508-517; 
Amaral, I.F., Unger, R.E., Fuchs, S., Mendon{\c c}a, A.M., Sousa, S.R., Barbosa, M.A., Fibronectin-mediated endothelialisation of chitosan porous matrices (2009) Biomaterials, 30, pp. 5465-5475; 
Silva Marques, J.M., Gomes, P.S., Silva, M.A., Silv{\'e}rio Cabrita, A.M., Santos, J.D., Fernandes, M.H., Growth and phenotypic expression of human endothelial cells cultured on a glass-reinforced hydroxyapatite (2009) J. Mater. Sci. Mater. Med., 20, pp. 725-731; 
Hofmann, A., Ritz, U., Verrier, S., Eglin, D., Alini, M., Fuchs, S., The effect of human osteoblasts on proliferation and neo-vessel formation of human umbilical vein endothelial cells in a long-term 3D co-culture on polyurethane scaffolds (2008) Biomaterials, 29, pp. 4217-4226; 
Dwight, A.T., The Osteogenic-Angiogenic Interface: novel Insights into the Biology of Bone Formation and Fracture Repair (2008) Bone Biol. Struct., 6, pp. 67-71; 
Soker, S., Machado, M., Atala, A., Systems for therapeutic angiogenesis in tissue engineering (2000) World J. Urol., 18, pp. 10-18; 
Villars, F., Bordenave, L., Bareille, R., Am{\'e}d{\'e}e, J., Effect of human endothelial cells on human bone marrow stromal cell phenotype: role of VEGF? (2000) J. Cell. Biochem., 79, pp. 672-685; 
Lozito, T.P., Kuo, C.K., Taboas, J.M., Tuan, R.S., Human mesenchymal stem cells express vascular cell phenotypes upon interaction with endothelial cell matrix (2009) J. Cell. Biochem., 107, pp. 714-722; 
Saleh, F., Whyte, M., Genever, P., Effects of endothelial cells on human mesenchymal stem cell activity in a three-dimensional in vitro model (2011) Eur. Cells Mater., 22, pp. 242-257; 
Bajada, S., Mazakova, I., Richardson, J.B., Ashammakhi, N., Updates on stem cells and their applications in regenerative medicine (2008) J. Tissue Eng. Regen. Med., 2, pp. 169-183; 
Kolf, C.M., Cho, E., Tuan, R.S., Biology of adult mesenchymal stem cells: regulation of niche, self-renewal and differentiation (2007) Arthritis Res. Ther., 9, p. 204; 
Lang, I., Pabst, M.A., Hiden, U., Blaschitz, A., Dohr, G., Hahn, T., Heterogeneity of microvascular endothelial cells isolated from human term placenta and macrovascular umbilical vein endothelial cells (2003) Eur. J. Cell Biol., 82, pp. 163-173; 
Ciardelli, G., Gentile, P., Chiono, V., Mattioli-Belmonte, M., Vozzi, G., Barbani, N., Enzymatically crosslinked porous composite matrices for bone tissue regeneration (2010) J. Biomed. Mater. Res. A, 92, pp. 137-151; 
Zhang, Y., Andrukhov, O., Bernerd, S., Matejka, M., Wieland, M., Rausch-Fan, X., Osteogenic properties of hydrophilic and hydrophobic titanium surfaces evaluated with osteoblast-like cells (MG63) in coculture with human umbilical vein endothelial cells(HUVEC) (2010) Dent. Mater., 400, pp. 284-292; 
Fuchs, S., Ghanaati, S., Orth, C., Barbeck, M., Kolbe, M., Hofmann, A., Contribution of outgrowth endothelial cells from human peripheral blood on in vivo vascularization of bone tissue engineered constructs based on starch polycaprolactone scaffolds (2009) Biomaterials, 30, pp. 526-534; 
Deb, S., Mandegaran, R., Di Silvio, L., A porous scaffold for bone tissue engineering 45S5 bioglass derived porous scaffolds for co-culturing osteoblasts and endothelial cells (2010) J. Mater. Sci. Mater. Med., 21, pp. 893-905; 
Aguirre, A., Planell, J.A., Engel, E., Dynamics of bone marrow-derived endothelial progenitor cell/mesenchymal stem cell interaction in co-culture and its implications in angiogenesis (2010) Biochem. Biophys. Res. Commun., 26, pp. 1043-1051; 
Grellier, M., Ferreira-Tojais, N., Bourget, C., Bareillke, R., Guillemot, F., Am{\'e}d{\'e}e, J., Role of vascular endothelial growth factor in the communication between human osteoprogenitors and endothelial cells (2009) J. Cell. Biochem., 106, pp. 390-398; 
Guillotin, B., Bareille, R., Bourget, C., Bordenave, L., Am{\'e}d{\'e}e, J., Interaction between human umbilical vein endothelial cells and human osteoprogenitors triggers pleiotropic effect that may support osteoblastic function (2008) Bone, 42, pp. 1080-1091; 
Grellier, M., Bordenave, L., Am{\'e}d{\'e}e, J., Cell-to-cell communication between osteogenic and endothelial lineages: implications for tissue engineering (2009) Trends Biotechnol., 27, pp. 562-571; 
Kirkpatrick, C.J., Peters, K., Hermanns, M.I., Bittinger, F., Krump-Konvalinkova, V., Fuchs, S., In vitro methodologies to evaluate biocompatibility: status quo and perspective (2005) ITBM-RBM, 26, pp. 192-199; 
Peters, K., Unger, R.E., Stumpf, S., Sch{\"a}fer, J., Tsaryk, R., Hoffmann, B., Cell type-specific aspects in biocompatibility testing: the intercellular contact in vitro as an indicator for endothelial cell compatibility (2008) J. Mater. Sci. Mater. Med., 19, pp. 1637-1644; 
Guillotin, B., Bourget, C., Remy-Zolgadri, M., Bareille, R., Fernandez, P., Conrad, V., Human primary endothelial cells stimulate human osteoprogenitor cell differentiation (2004) Cell. Physiol. Biochem., 14, pp. 325-332; 
Laranjeira, M.S., Fernandes, M.H., Monteiro, F.J., Innovative macroporous granules of nanostructured-hydroxyapatite agglomerates: bioactivity and osteoblast-like cell behaviour (2010) J. Biomed. Mater. Res. A, 95, pp. 891-900; 
Gomes, P.S., Fernandes, M.H., Effect of therapeutic levels of doxycycline and minocycline in the proliferation and differentiation of human bone marrow osteoblastic cells (2007) Arch. Oral Biol., 52, pp. 251-259; 
Zhang, Y., Schedle, A., Matejka, M., Rausch-Fan, X., Andrukhov, O., The proliferation and differentiation of osteoblasts in co-culture with human umbilical vein endothelial cells: an improved analysis using fluorescence-activated cell sorting (2010) Cell. Mol. Biol. Lett., 15, pp. 517-529; 
Shi, X., Ren, L., Tian, M., Yu, J., Huang, W., Du, C., In vivo and in vitro osteogenesis of stem cells induced by controlled release of drugs from microspherical scaffolds (2010) J. Mater. Chem., 20, pp. 9140-9148; 
Villars, F., Guillotion, B., Amedee, T., Dutoya, S., Bordenave, L., Bareille, R., Effect of HUVEC on human osteoprogenitor cell differentiation needs heterotypic gap junction communication (2002) Am. J. Physiol. Cell Physiol., 282, pp. C775-C785; 
Kanczler, J., Oreffo, R., Osteogenesis and angiogenesis: the potential for engineering bone (2008) Eur. Cell Mater., 15, pp. 100-114; 
Stiehler, M., Bunger, C., Baatrup, A., Lind, M., Kassem, M., Mygind, T., Effect of dynamic 3-D culture on proliferation, distribution, and osteogenic differentiation of human mesenchymal stem cells (2007) J. Biomed. Mater. Res. A, 89, pp. 96-107; 
Bouletreau, P., Warren, S., Spector, J., Peled, Z., Gerrets, R., Greenwald, J., Longaker, M., Hypoxia and VEGF up-regulate BMP-2 mRNA and protein expression in microvascular endothelial cells: implications for fracture healing (2002) Plast. Reconstr. Surg., 109, pp. 2384-2397; 
Deckers, M., van Bezooijen, R., van der Horst, G., Hoogendam, J., van der Bent, C., Papapoulos, S., L{\"o}wik, C., Bone morphogenetic proteins stimulate angiogenesis through osteoblast-derived vascular endothelial growth factor A (2002) Endocrinology, 143, pp. 1545-1553; 
Whelan, M.C., Senger, D.R., Collagen I initiates endothelial cell morphogenesis by inducing actin polymerization through suppression of cyclic AMP and protein kinase A (2003) J. Biol. Chem., 278, p. 327; 
Li, H., Daculsi, R., Grellier, M., Bareille, R., Bourget, C., Remy, M., Amedee, J., The role of vascular actors in two dimensional dialogue of human bone marrow stromal cell and endothelial cell for inducing self-assembled network (2011) PLoS ONE, 6, pp. e16767; 
Beyer, E.C., Paul, D.L., Goodenough, D.A., Connexin family of gap junction proteins (1990) J. Membr. Biol., 116, pp. 187-194; 
Li, H., Daculsi, R., Grellier, M., Bareille, R., Bourget, C., Amedee, J., Role of neural-cadherin in early osteoblastic differentiation of human bone marrow stromal cells cocultured with human umbilical vein endothelial cells (2010) Am. J. Physiol. Cell Physiol., 299, pp. C422-C430; 
Kyriakidou, K., Lucarini, G., Zizzi, A., Salvolini, E., Mattioli Belmonte, M., Mollica, F., Gloria, A., Ambrosio, L., Dynamic co-seeding of osteoblast and endothelial cells on 3D polycaprolactone scaffolds for enhanced bone tissue engineering (2008) J. Bioact. Compat. Polym., 23, p. 227; 
Saleh, F.A., Whyte, M., Ashton, P., Genever, P.G., Regulation of mesenchymal stem cell activity by endothelial cells (2010) Stem Cells Dev., 20, pp. 391-403; 
Lozito, T.P., Taboas, J.M., Kuo, C.K., Tuan, R.S., Mesenchymal stem cell modification of endothelial matrix regulates their vascular differentiation (2009) J. Cell. Biochem., 107, pp. 706-713; 
Aubin, J.E., Heersche, J.N.M., Osteoprogenitor cell differentiation to mature bone-forming osteoblasts (2000) Drug Dev. Res., 49, pp. 206-215; 
Hoemann, C.D., El-Gabalawy, H., McKee, M.D., In vitro osteogenesis assays: influence of the primary cell source on alkaline phosphatase activity and mineralization (2009) Pathol. Biol. (Paris), 57, pp. 318-323; 
J{\o}rgensen, N.R., Henriksen, Z., S{\o}rensen, O.H., Civitelli, R., Dexamethasone, BMP-2, and 1,25-dihydroxyvitamin D enhance a more differentiated osteoblast phenotype: validation of an in vitro model for human bone marrow-derived primary osteoblasts (2004) Steroids, 69, pp. 219-226; 
Kaigler, D., Krebsbach, P.H., West, E.R., Horger, K., Huang, Y.C., Mooney, D.J., Endothelial cell modulation of bone marrow stromal cell osteogenic potential (2005) FASEB J., 19, pp. 665-667; 
Kempen, D.H.R., Lu, L., Heijink, A., Hefferan, T.E., Creemers, L.B., Maran, A., Yaszemski, M.J., Dhert, W.J.A., Effect of local sequential VEGF and BMP-2 delivery on ectopic and orthotopic bone regeneration (2009) Biomaterials, 30, pp. 2816-2825; 
M{\"u}ller, A.M., Hermanns, M.I., Skrzynski, C., Nesslinger, M., M{\"u}ller, K.-M., Kirkpatrick, C.J., Expression of the endothelial markers PECAM-1, vWf, and CD34 in vivo and in vitro (2002) Exp. Mol. Pathol., 72, pp. 221-229; 
Bou{\"\i}s, D., Hospers, G., Meijer, C., Molema, G., Mulder, N., Endothelium in vitro: a review of human vascular endothelial cell lines for blood vessel-related research (2001) Angiogenesis, 4, pp. 91-102; 
Martin, T.A., Watkins, G., Lane, J., Jiang, W.G., Assessing microvessels and angiogenesis in human breast cancer, using VE-cadherin (2005) Histopathology, 46, pp. 422-430; 
Augustin, H.G., Kozian, D.H., Johnson, R.C., Differentiation of endothelial cells: analysis of the constitutive and activated endothelial cell phenotypes (1994) Bioessays, 16, pp. 901-906; 
Vestweber, D., Molecular mechanisms that control endothelial cell contacts (2000) J. Pathol., 190, pp. 281-291; 
Talavera-Adame, D., Ng, T.T., Gupta, A., Kurtovic, S., Wu, G.D., Dafoe, D.C., Characterization of microvascular endothelial cells isolated from the dermis of adult mouse tails (2011) Microvasc. Res., 82, pp. 97-104; 
Saharinen, P., Alitalo, K., The yin, the yang, and the Angiopoietin-1 (2011) J. Clin. Investig., 121, pp. 2157-2159; 
Bogdanovic, E., (2010) Regulation of Tie-2 by Angiopoietin-1 and Angiopoietin-2 in Endothelial Cells, , Toronto: University of Toronto; 
Suzuki, T., Miyamoto, T., Fujita, N., Ninomiya, K., Iwasaki, R., Toyama, Y., Suda, T., Osteoblast-specific Angiopoietin 1 overexpression increases bone mass (2007) Biochem. Biophys. Res. Commun., 362, pp. 1019-1025; 
Yuan, H.T., Khankin, E.V., Karumanchi, S.A., Parikh, S.M., Angiopoietin 2 is a partial agonist/antagonist of Tie2 signaling in the endothelium (2009) Mol. Cell. Biol., 29, p. 2011; 
Shilo, S., Roy, S., Khanna, S., Sen, C.K., Evidence for the involvement of miRNA in redox regulated angiogenic response of human microvascular endothelial cells (2008) Arterioscler. Thromb. Vasc. Biol., 28, pp. 471-477; 
Collin-Osdoby, P., Role of vascular endothelial cells in bone biology (1994) J. Cell. Biochem., 55, pp. 304-309
},
	month = {2012///},
	pages = {320 - 334},
	abstract = {Objectives: Angiogenesis is closely associated with osteogenesis where reciprocal interactions between endothelial and osteoblast cells play an important role in bone regeneration. For these reasons, the aim of this work was to develop a co-culture system to study in detail any time-dependent interactions between human mesenchymal stem cells (HMSC) and human dermal microvascular endothelial cells (HDMEC), co-cultured in a 2D system, for 35 days. Materials and methods: HMSC and HDMEC were co-cultured at a ratio of 1:4, respectively. Single-cell cultures were used as controls. Cell viability/proliferation was assessed using MTT, DNA quantification and calcein-AM assays. Cell morphology was monitored using confocal microscopy, and real time PCR was performed. Alkaline phosphatase activity and histochemical staining were evaluated. Matrix mineralization assays were also performed. Results: Cells were able to grow in characteristic patterns maintaining their viability and phenotype expression throughout culture time, compared to HMSC and HDMEC monocultures. HMSC differentiation seemed to be enhanced in the co-culture conditions, since it was observed an over expression of osteogenesis-related genes, and of ALP activity. Furthermore, presence of calcium phosphate deposits was also confirmed. Conclusions: This work reports in detail the interactions between HMSC and HDMEC in a long-term co-culture 2D system. Endothelial and mesenchymal stem cells cultured in the present co-culture conditions ensured proliferation and phenotype differentiation of cell types, osteogenesis stimulation and over-expression of angiogenesis-related genes, in the same culture system. It is believed that the present work can lead to significant developments for bone tissue regeneration and cell biology studies. {\textcopyright} 2012 Blackwell Publishing Ltd.},
	keywords = {alkaline phosphatase, article, Base Sequence, calcein, calcium phosphate, CD31 antigen, Cell culture, cell differentiation, cell growth, cell interaction, cell nucleus, cell population, cell proliferation, cell structure, cell viability, coculture, Coculture Techniques, confocal microscopy, controlled study, DNA, DNA determination, DNA Primers, Endothelium, Vascular, enzyme histochemistry, F actin, flow cytometry, gene overexpression, human, human cell, Humans, immunohistochemistry, in vitro study, Mesenchymal stem cell, Mesenchymal Stem Cells, Microscopy, Confocal, Microscopy, Electron, Scanning, microvascular endothelial cell, Microvessels, mineralization, nucleotide sequence, osteoblast, phenotype, process development, real time polymerase chain reaction, Real-Time Polymerase Chain Reaction, scanning electron microscope, single cell analysis, Skin},
	isbn = {09607722 (ISSN)},
	url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84862878215\&partnerID=40\&md5=4bbe59ef9f5c7b7424b78608e089c571},
	author = {Laranjeira, M.S. and Fernandes, M.H. and Monteiro, F.J.}
}
@article {2245,
	title = {Innovative macroporous granules of nanostructured-hydroxyapatite agglomerates: Bioactivity and osteoblast-like cell behaviour},
	journal = {Journal of Biomedical Materials Research - Part AJ. Biomed. Mater. Res. Part A},
	volume = {95},
	year = {2010},
	note = {Cited By (since 1996): 3Export Date: 21 November 2012Source: ScopusCODEN: JBMRCdoi: 10.1002/jbm.a.32916PubMed ID: 20845490Language of Original Document: EnglishCorrespondence Address: Laranjeira, M. S.; Divis{\~a}o de Biomateriais, INEB-Instituto de Engenharia Biom{\'e}dica, Universidade Do Porto, Rua do Campo Alegre, 823, 4150-180 Porto, Portugal; email: dce06004@fe.up.ptChemicals/CAS: alkaline phosphatase, 9001-78-9; colony stimulating factor 1, 81627-83-0; hydroxyapatite, 1306-06-5, 51198-94-8; osteoprotegerin, 205944-50-9; polyurethan, 61789-63-7; Biocompatible Materials; Biological Markers; Durapatite, 1306-06-5; PolyurethanesReferences: Ferraz, M., Monteiro, F., Manuel, C., Hydroxyapatite nanoparticles: A review of preparation methodologies (2004) J Appl Biomater Biomech, 2, pp. 74-80;Murugan, R., Ramakrishna, S., Development of nanocomposites for bone grafting (2005) Compos Sci Technol, 65, pp. 2385-2406; 
Wahl, D., Czernuszka, J.T., Collagen-hydroxyapatite composites for hard tissue repair (2006) Eur Cell Mater, 11, pp. 43-46; 
Chen, Q.Z., Wong, C.T., Lu, W.W., Cheung, K.M., Leong, J.C., Luk, K.D., Strengthening mechanisms of bone bonding to crystalline hydroxyapatite in vivo (2004) Biomaterials, 25, pp. 4243-4254; 
Watari, F., Yokoyama, A., Gelinsky, M., Pompe, W., Conversion of functions by nanosizing from osteoconductivity to bone substitutional properties in apatite (2007) Interface Oral Health Sci, 23, pp. 139-148; 
Nihouannen, D., Duval, L., Lecomte, A., Julien, M., Guicheux, J., Daculsi, G., Layrolle, P., Interactions of total bone marrow cells with increasing quantities of macroporous calcium phosphate ceramic granules (2007) J Mater Sci Mater Med, 18, pp. 1983-1990; 
Le Nihouannen, D., Daculsi, G., Saffarzadeh, A., Gauthier, O., Delplace, S., Pilet, P., Layrolle, P., Ectopic bone formation by microporous calcium phosphate ceramic particles in sheep muscles (2005) Bone, 36, pp. 1086-1093; 
Kalita, S.J., Bhardwaj, A., Bhatt, H.A., Nanocrystalline calcium phosphate ceramics in biomedical engineering (2007) Mater Sci Eng C, 27, pp. 441-449; 
Kong, L.B., Ma, J., Boey, F., Nanosized hydroxyapatite powders derived from coprecipitation process (2002) J Mater Sci, 37, pp. 1131-1134; 
Habibovic, P., Kruyt, M.C., Juhl, M.V., Clyens, S., Martinetti, R., Dolcini, L., Theilgaard, N., Blitterswijk, C., Comparative in vivo study of six hydroxyapatite-based bone graft substitutes (2008) J Orthop Res, 26, pp. 1363-1370; 
Simon, J.L., Michna, S., Lewis, J.A., Rekow, E.D., Thompson, V.P., Smay, J.E., Yampolsky, A., Ricci, J.L., In vivo bone response to 3D periodic hydroxyapatite scaffolds assembled by direct ink writing (2007) J Biomed Mater Res A, 83, pp. 747-758; 
Clarke, S.A., Hoskins, N.L., Jordan, G.R., Henderson, S.A., Marsh, D.R., In vitro testing of advanced JAX TM bone void filler system: Species differences in the response of bone marrow stromal cells to b tri-calcium phosphate and carboxymethylcellulose gel (2007) J Mater Sci Mater Med, 18, pp. 2283-2290; 
Wei, G., Ma, P.X., Structure and properties of nano-hydroxyapatite/polymer composite scaffolds for bone tissue engineering (2004) Biomaterials, 25, pp. 4749-4757; 
Xu, T., Zhang, N., Nichols, H.L., Shi, D., Wen, X., Modification of nanostructured materials for biomedical applications (2007) Mater Sci Eng C, 27, pp. 579-594; 
Mateus, A.Y.P., Ferraz, M.P., Monteiro, F.J., Microspheres based on hydroxyapatite nanoparticles aggregates for bone regeneration (2007) Key Eng Mater, 330-332, pp. 243-246; 
Potoczek, M., Zima, A., Paszkiewicz, Z., Slosarczyk, A., Manufacturing of highly porous calcium phosphate bioceramics via gel-casting using agarose (2009) Ceram Int, 35, pp. 2249-2254; 
Okamoto, M., Dohi, Y., Ohgushi, H., Shimaoka, H., Ikeuchi, M., Matsushima, A., Yonemasu, K., Hosoi, H., Influence of the porosity of hydroxyapatite ceramics on in vitro and in vivo bone formation by cultured rat bone marrow stromal cells (2006) J Mater Sci Mater Med, 17, pp. 327-336; 
Tas, A.C., Preparation of porous apatite granules from calcium phosphate cement (2008) J Mater Sci Mater Med, 19, pp. 2231-2239; 
Joschek, S., Nies, B., Krotz, R., Gokpferich, A., Chemical and physicochemical characterization of porous hydroxyapatite ceramics made of natural bone (2000) Biomaterials, 21, pp. 1645-1658; 
Turhani, D., Cvikl, B., Watzinger, E., Wei{\ss}enb{\"o}ck, M., Yerit, K., Thurnher, D., Lauer, G., Ewers, R., In vitro growth and differentiation of osteoblast-like cells on hydroxyapatite ceramic granule calcified from red algae (2005) J Oral Maxillofac Surg, 63, pp. 793-799; 
Teixeira, S., Ferraz, M.P., Monteiro, F.J., Biocompatibility of highly macroporous ceramic scaffolds: Cell adhesion and morphology studies (2008) J Mater Sci Mater Med, 19, pp. 855-859; 
Kim, Z., Oak, J., Kimura, H., Goto, T., Inoue, A., Yoon, S., Architecture of porous hydroxyapatite scaffolds using polymer foam process (2009) J Biomech Sci Eng, 4, pp. 377-383; 
Chevalier, E., Viana, M., Cazalbou, S., Makein, L., Dubois, J., Chulia, D., Ibuprofen-loaded calcium phosphate granules: Combination of innovative characterization methods to relate mechanical strength to drug location (2010) Acta Biomater, 6, pp. 266-274; 
Taboas, J.M., Maddox, R.D., Krebsbach, P.H., Hollister, S.J., Indirect solid free form fabrication of local and global porous, biomimetic and composite 3D polymer-ceramic scaffolds (2003) Biomaterials, 24, pp. 181-194; 
Wang, X., Ruan, J., Chen, Q., Effects of surfactants on the microstructure of porous ceramic scaffolds fabricated by foaming for bone tissue engineering (2009) Mater Res Bull, 44, pp. 1275-1279; 
Mateus, A.Y.P., Barrias, C.C., Ribeiro, C., Ferraz, M.P., Monteiro, F.J., Comparative study of nanohydroxyapatite microspheres for medical applications (2008) J Biomed Mater Res A, 86, pp. 483-493; 
Gibson, I.R., Best, S.M., Bonfield, W., Chemical characterization of silicon-substituted hydroxyapatite (1999) J Biomed Mater Res, 44, pp. 422-428; 
Panda, R.N., Hsieh, M.F., Chung, R.J., Chin, T.S., FTIR, XRD, SEM and solid state NMR investigations of carbonate-containing hydroxyapatite nano-particles synthesized by hydroxide-gel technique (2003) J Phys Chem Solids, 64, pp. 193-199; 
Penel, G., Leroy, G., Rey, C., Sombret, B., Huvenne, J.P., Bres, E., Infrared and Raman microspectrometry study of fluor-fluor-hydroxy and hydroxy-apatite powders (1997) J Mater Sci Mater Med, 8, pp. 271-276; 
Elliott, J.C., Holcomb, D.W., Young, R.A., Infrared determination of the degree of substitution of hydroxyl by carbonate ions in human dental enamel (1985) Calcif Tissue Int, 37, pp. 372-375; 
Rouahi, M., Gallet, O., Champion, E., Dentzer, J., Hardouin, P., Anselme, K., Influence of hydroxyapatite microstructure on human bone cell response (2006) J Biomed Mater Res A, 78, pp. 222-235; 
Fierz, F.C., Beckmann, F., Huser, M., Irsen, S.H., Leukers, B., Witte, F., Degistirici, O., Muller, B., The morphology of anisotropic 3D-printed hydroxyapatite scaffolds (2008) Biomaterials, 29, pp. 3799-3806; 
Singh, R., Lee, P.D., Lindley, T.C., Dashwood, R.J., Ferrie, E., Imwinkelried, T., Characterization of the structure and permeability of titanium foams for spinal fusion devices (2009) Acta Biomater, 5, pp. 477-487; 
Wei, J., Jia, J., Wu, F., Wei, S., Zhou, H., Zhang, H., Shin, J.W., Liu, C., Hierarchically microporous/macroporous scaffold of magnesium-calcium phosphate for bone tissue regeneration (2010) Biomaterials, 31, pp. 1260-1269; 
Rucker, M., Laschke, M.W., Junker, D., Carvalho, C., Tavassol, F., Mulhaupt, R., Gellrich, N.C., Menger, M.D., Vascularization and biocompatibility of scaffolds consisting of different calcium phosphate compounds (2007) J Biomed Mater Res A, 68, pp. 1002-1011; 
Klenke, F.M., Liu, Y., Yuan, H., Hunziker, E.B., Siebenrock, K.A., Hofstetter, W., Impact of pore size on the vascularization and osseointegration of ceramic bone substitutes in vivo (2007) J Biomed Mater Res A, 85, pp. 777-786; 
Lee, S.J., Choi, J.S., Park, K.S., Khang, G., Lee, Y.M., Lee, H.B., Response of MG63 osteoblast-like cells onto polycarbonate membrane surfaces with different micropore sizes (2004) Biomaterials, 25, pp. 4699-4707; 
Kim, H., Lee, E., Kim, H., Salih, V., Knowles, J.C., Effect of fluoridation of hydroxyapatite in hydroxyapatite- polycaprolactone composites on osteoblast activity (2005) Biomaterials, 25, pp. 4395-4404; 
Son, E., Do, H., Joo, H., Pyo, S., Induction of alkaline phosphatase activity by L-ascorbic acid in human osteoblastic cells: A potential role for CK2 and Ikaros (2007) Nutrition, 23, pp. 745-753; 
Guo, X., Gough, J.E., Xiao, P., Liu, J., Shen, Z., Fabrication of nanostructured hydroxyapatite and analysis of human osteoblastic cellular response (2007) J Biomed Mater Res A, 82, pp. 1022-1032; 
Webster, T.J., Ergun, C., Doremus, R.H., Siegel, R.W., Bizios, R., Enhanced functions of osteoblasts on nanophase ceramics (2000) Biomaterials, 21, pp. 1803-1810; 
Mendon{\c c}a, G., Mendon{\c c}a, D.B., Sim{\~o}es, L.G., Ara{\'u}jo, A.L., Leite, E.R., Duarte, W.R., Arag{\~a}o, F.J., Cooper, L.F., The effects of implant surface nanoscale features on osteoblast-specific gene expression (2009) Biomaterials, 30, pp. 4053-4062
},
	month = {2010///},
	pages = {891 - 900},
	abstract = {To modulate the biological response of implantable granules, two types of bioactive porous granules composed of nanostructured-hydroxyapatite (HA) agglomerates and microstructured-HA, respectively, were prepared using a polyurethane sponge impregnation and burnout method. The resulting granules presented a highly porous structure with interconnected porosity. Both types of granules were characterized using Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), scanning electron microscopy (SEM), and mercury intrusion porosimetry. Results showed that nanostructed-HA granules presented higher surface area and porosity than microstructured-HA granules. In vitro testing using MG63 human osteoblast-like cells showed that on both types of surfaces cells were able to adhere, proliferate, and migrate through the macropores, and a higher growth rate was achieved on nanostructured-HA granules than on microstructured-HA granules (76 and 40\%, respectively). In addition, these cells maintained similar expression levels of osteoblastic-associated markers namely collagen type I, alkaline phosphatase, bone morphogenetic protein-2, macrophage colony-stimulating factor, and osteoprotegerin. These innovative nanostructured-HA granules may be considered as promising bioceramic alternative matrixes for bone regeneration and drug release application. {\textcopyright} 2010 Wiley Periodicals, Inc.},
	keywords = {Agglomeration, alkaline phosphatase, Apatite, article, Bioceramics, Biocompatible Materials, Biological Markers, Biological materials, Biological response, Biomaterials, Bone, bone morphogenetic protein 2, Bone morphogenetic protein-2, Bone Regeneration, cell adhesion, cell function, cell granule, cell migration, cell proliferation, Cells, Cultured, collagen type 1, Collagen type I, colony stimulating factor 1, Colony-stimulating factor, drug activity, Drug release, Durapatite, Expression levels, Fourier transform infrared spectroscopy, Fourier transforms, Granulation, Granules, growth rate, human, human cell, Human osteoblast-like cells, Humans, hydroxyapatite, In-vitro, infrared spectroscopy, Interconnected porosity, Macro-porosity, Macropores, Macroporosity, Macroporous, materials testing, matrix, Mercury (metal), Mercury intrusion porosimetry, Microscopy, Electron, Scanning, Microstructured, Nano-materials, Nano-structured, nanomaterial, Nanomaterials, Nanostructured materials, Nanostructures, osteoblast, Osteoblast response, Osteoblast-like cells, Osteoblasts, Osteoprotegerin, Phosphatases, polyurethan, Polyurethane sponge, Polyurethanes, porosity, Porous structures, Reverse Transcriptase Polymerase Chain Reaction, Scanning electron microscopy, SEM, Spectroscopy, Fourier Transform Infrared, Surface area, surface property, X ray diffraction, X-Ray Diffraction},
	isbn = {15493296 (ISSN)},
	url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-78249252998\&partnerID=40\&md5=09d51d6c49d9f10e6c2d479b1fe4ace0},
	author = {Laranjeira, M.S. and Fernandes, M.H. and Monteiro, F.J.}
}
@article {2310,
	title = {In vitro biological characterization of macroporous 3D Bonelike                    {\textregistered} structures prepared through a 3D machining technique
},
	journal = {Materials Science and Engineering CMater. Sci. Eng. C},
	volume = {29},
	year = {2009},
	note = {Export Date: 21 November 2012Source: Scopusdoi: 10.1016/j.msec.2008.08.009Language of Original Document: EnglishCorrespondence Address: Fernandes, M.H.; Universidade do Porto, Faculdade de Medicina Dent{\'a}ria, Laborat{\'o}rio de Farmacologia e Biocompatibilidade Celular, Rua Dr. Manuel Pereira da Silva, 4200-392 Porto, Portugal; email: mhrf@portugalmail.ptReferences: Bauer, T.W., Muschler, G.F., (2000) Clin. Orthop. Relat. Res., 371, p. 10;Boskey, A.L., (1999) Dynamics of Bone and Cartilage Metabolism, p. 154. , Seibel M.J., Robins S.P., and Bilezikian J.P. (Eds), Academic Press, London; 
Rosa, A., Belotia, M.M., van Noortb, R., (2003) Dent. Mater., 19, p. 768; 
Lopes, M.A., Monteiro, F.J., Santos, J.D., (1998) J. Biomed. Mater. Res. (Appl Biomater)., 48, p. 734; 
Georgiou, G., Knowles, J.C., (2001) Biomaterials, 22, p. 2811; 
Lopes, M.A., Santos, J.D., Monteiro, F.J., Knowles, J.D., (1998) J. Biomed. Mater. Res., 39, p. 244; 
Hench, L.L., Wilson, J., (1993) An Introduction to Bioceramics, p. 7. , Hench L.L., and Wilson J. (Eds), World Scientific, London; 
Hulmatcher, D.W., Schantz, T., Zein, I., Ng, K.W., Teoh, S.H., Tang, K.C., (2001) J. Biomed. Mater. Res., 55, p. 203; 
Ishaug, S.L., Crane, G.M., Miller, M.J., Yasko, A.W., Yaszemski, M.J., Mikos, A.G., (1997) J. Biomed. Mater. Res., 36, p. 17; 
Wilson, C.E., de Bruijn, J.D., van Blitterswijk, C.A., Verbout, A.J., Dhert, W.J.A., (2004) J. Biomed. Mater. Res., 68 A, p. 123; 
Roy, D.M., Linnehan, S.K., (1974) Nature, 247, p. 220; 
Lin, F.H., Liao, C.J., Chen, K.S., Sun, J.S., Lin, C.Y., (2000) J. Biomed. Mater. Res., 51, p. 157; 
Lee, L.J., Zeng, C., Cao, X., Han, X., Shen, J., Xu, G., (2005) Compos. Sci. Tech., 65, p. 2344; 
Nam, Y., Yoon, J.J., Park, T., (2000) J. Biomed. Mater. Res. (Appl Biomater)., 53, p. 1; 
Haugen, P., Ried, V., Brunner, M., Will, J., Wintermantel, E., (2004) J. Mater. Sci.: Mater Med., 15, p. 343; 
Leatrese, D.H., Byung-Soo, K., David, J.M., Higa, O.Z., (1998) J. Biomed. Mater. Res., 42, p. 396; 
Fabbri, M., Celotti, C.G., Ravaglioli, A., (1995) Biomaterials, 16, p. 225; 
Leong, K.F., Cheah, C.M., Chua, C.K., (2003) Biomaterials., 24, p. 2363; 
Hollister, S.J., Maddox, R.D., Taboas, J.M., (2002) Biomaterials., 23, p. 4095; 
Gutierres, M., Dias, A.G., Lopes, M.A., Hussein, S., Cabral, A.T., Almeida, L., Santos, J.D., (2007) J. Mater. Sci.: Mater. Med., 18, p. 2377; 
Jarcho, M., Bolen, C., Thomas, M.B., Bobick, J., Kay, J.F., Doremus, R.H., (1976) J. Mater. Sci., 11, p. 2027; 
Lopes, M.A., Knowles, J.C., (2000) J.D. Santos, 21, p. 1905; 
Lopes, M.A., Monteiro, F.J., Santos, J.D., (1999) Biomaterials, 20, p. 2085; 
Elliott, J.C., Holcomb, D.W., Young, R.A., (1985) Calcif. Tissue Int., 37, p. 372; 
Lobato, J., Hussain, S., Botelho, C.F., Maur{\'\i}cio, A., Afonso, A., Ali, N., Santos, J.D., (2006) Thin Solid Films, 515, p. 362; 
Oliveira, J.M., Miyazaki, T., Lopes, M.A., Ohtsuki, C., Santos, J.D., (2005) J. Mater. Sci: Mater. Med., 16, p. 253; 
Ducheyne, P., (1994) J. Bone Joint Surg., 76, p. 861; 
Gross, K.A., Berndt, C.C., Stephens, P., Dinnebier, (1998) J. Mater. Sci., 33, p. 3985; 
Shen, Z., Adolfsson, E., Nygren, M., Goan, L., Kawaoka, H., Niihara, K., (2001) Adv. Mater., 13, p. 214; 
Glass, S.J., Mahoney, F.M., Gwsuk, K.G., (1995) American Society International Symposium on Manufacturing Practices and Technology, , New Orleans; 
Cheng, P., Kim, G., Ni, J., J Mater Process Technol, 190 (190), p. 243; 
Kraft, T., (2003) Model. Simul. Mater. Sci. Eng., 11, p. 381; 
Gu, Y., Henderson, R.J., Chandler, H.W., (2006) J. Eur. Ceram. Soc., 26, p. 2265; 
Reiterer, M., Kraft, T., Janosovits, U., Riedel, H., (2004) Ceram. Inter., 30, p. 177; 
Sachlos, E., Czernuszka, J.T., (2003) Eur. Cell Mater., 5, p. 29; 
Freshney, R.I., (2000) Culture of Cells for Tissue Engineering, p. 25. , Freshney R.I., and vunjak-Novakovic G. (Eds), Wiley-Liss, New Jersey; 
Baksh, D., Song, L., Tuan, R.S., (2004) J. Cell. Mol. Med., 3, p. 301; 
Coelho, M.J., Fernandes, M.H., (2000) Biomaterials, 21, p. 1095; 
Bo-Yi, Y., Pei-Hsun, C., Yi-Ming, S., Yu-Tsang, L., Tai-Horng, Y., (2005) J. Membrane Sci., 273, p. 31; 
Ohgushi, H., Caplan, A.I., (1999) J. Biomed. Mater. Res. (Appl. Biomater.), 48, p. 913; 
Salgado, A.J., Coutinho, O.P., Reis, R.L., (2004) Macromo. Biosc., 4, p. 743; 
Cao, Y., Mitchell, G., (2006) Biomaterials, 27, p. 2854; 
Bignon, A., Chouteau, J., Chevalier, J., Fantozzi, G., Carret, J.P., Chavassieux, P., Boivin, G., Hatmann, D., (2003) J. Mater. Sci.: Mater. Med., 14, p. 1089; 
Holy, C.E., Shoichet, M.S., Davies, J.E., (2000) J. Biomed. Mater. Res., 51, p. 376
},
	month = {2009///},
	pages = {930 - 935},
	abstract = {3D bioactive macroporous structures were prepared using a 3D machining technique. A virtual 3D structure model was created and a computer numerically controlled (CNC) milling device machined Bonelike                        {\textregistered} samples. The resulting structures showed a reproducible macroporosity and interconnective structure. Macropores size after sintering was approximately 2000~μm. In vitro testing using human bone marrow stroma showed that cells were able to adhere and proliferate on 3D structures surface and migrate into all macropore channels. In addition, these cells were able to differentiate, since mineralized globular structures associated with cell layer were identified. Results obtained showed that 3D structures of Bonelike
                        {\textregistered} successfully allow cell migration into all macropores, and allow human bone marrow stromal cells to proliferate and differentiate. This innovative technique may be considered as a step-forward preparation for 3D interconnective macroporous structures that allow bone ingrowth while maintaining mechanical integrity. {\textcopyright} 2008 Elsevier B.V. All rights reserved.
},
	keywords = {3-D structures, 3D machining techniques, Biological characterizations, Bone, Bone ingrowths, Bone marrow stroma cells, Bone substitute, Bonelike, Cell layers, Cell migrations, Computer control systems, cytology, Globular structures, Human bone marrow stromal cells, Human bone marrows, In-vitro, Machining, Macro porosities, Macro-pores, Macroporous, Macroporous structures, Mechanical integrities, Porous materials, Sintering, Surface testing, Three dimensional, {\textregistered}},
	isbn = {09284931 (ISSN)},
	url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-64749093404\&partnerID=40\&md5=1619bc1101d98c34c6e43726f52e851c},
	author = {Laranjeira, M.S. and Dias, A.G. and Santos, J.D. and Fernandes, M.H.}
}
