Special Issue- Calcium and phosphate-based biomaterials for biomedical applications

Edited by Marc Bohner

This special issue is a showcase of some of the main trends in calcium- and phosphate-based biomaterials research for biomedical applications. As a result, not only “traditional” calcium phosphates investigated, such as β-tricalcium phosphate, biphasic calcium phosphate (1), and hydroxyapatite, but also more “modern” ones are evaluated, such as dicalcium phosphate (2-4), dicalcium phosphate dihydrate (2, 5, 6), octacalcium phosphate (6, 7), α-tricalcium phosphate (8), pyrophosphates (9, 10), polyphosphates (10-15) and Fe- (16), Si- (17-19), Sr- (20), Hf- (21), or Co-doped (22) calcium phosphates. These materials can be produced through the use of rapid prototyping approaches (11, 17, 18, 23-25), or as nanoparticles (21, 26-31), coatings (32-35), cements (20, 24, 36-41), and pastes (42, 43). For bone applications, the focus is set on understanding the mechanism of osteoinduction (44-48), and on the control of the degradation rate (2, 3, 5, 7, 20, 25, 38, 48-52). Furthermore, particular attention is paid to the role of inflammation (28, 46, 48, 53). A number of new therapeutic fields for calcium phosphates are also considered, such as cartilage repair (12, 43), vaccination (26, 27), the treatment of cancer (21, 54), diabetes (30), infections (26, 29, 55, 56), fungus (56), and bleedings (15). Other new topics addressed in this special issue include biomineralization (6, 34, 57-60), angiogenesis (7, 18, 19, 22, 61), modeling (5, 16, 48, 50, 62), tissue engineering (12, 47), and imaging (27, 50, 52, 54).


1) Biphasic calcium phosphate ceramics for bone reconstruction: A review of biological response
J.M. Bouler, P. Pilet, O. Gauthier, E. Verron

2) Effect of processing conditions of dicalcium phosphate cements on graft resorption and bone formation
Zeeshan Sheikh, Yu Ling Zhang, Faleh Tamimi, Jake Barralet

3) Local delivery of iron chelators reduces in vivo remodeling of a calcium phosphate bone graft substitute
Justin Drager, Zeeshan Sheikh, Yu Ling Zhang, Edward J. Harvey, Jake E. Barralet

4) Gelatine modified monetite as a bone substitute material: An in vitro assessment of bone biocompatibility
Benjamin Kruppke, Jana Farack, Alena-Svenja Wagner, Sarah Beckmann, Christiane Heinemann, Kristina Glenske, Sina Rößler, Hans-Peter Wiesmann, Sabine Wenisch, Thomas Hanke

5) The in vitro evolution of resorbable brushite cements: A physico-chemical, micro-structural and mechanical study
Marta Gallo, Solène Tadier, Sylvain Meille, Laurent Gremillard, Jérôme Chevalier

6) A correlative spatiotemporal microscale study of calcium phosphate formation and transformation within an alginate hydrogel matrix
Sindre H. Bjørnøy, David C. Bassett, Seniz Ucar, Berit L. Strand, Jens-Petter Andreassen, Pawel Sikorskia

7) Antiresorptive and anti-angiogenetic octacalcium phosphate functionalized with bisphosphonates: An in vitro tri-culture study
Lucia Forte, Paola Torricelli, Elisa Boanini, Massimo Gazzano, Milena Fini, Adriana Bigi

8) Effect of Mg2+ doping on beta–alpha phase transition in tricalcium phosphate (TCP) bioceramics
Matteo Frasnelli, Vincenzo M. Sglavo

9) From crystalline to amorphous calcium pyrophosphates: A solid state Nuclear Magnetic Resonance perspective
Pierre Gras, Annabelle Baker, Christèle Combes, Christian Rey, Stéphanie Sarda, Adrian J.Wright, Mark E.Smith, John V.Hanna, Christel Gervais, Danielle Laurencin, Christian Bonhomme

10) Development of a new family of monolithic calcium (pyro)phosphate glasses by soft chemistry
Jérémy Soulié, Pierre Gras, Olivier Marsan, Danielle Laurencin, Christian Rey, Christèle Combes

11) 3D printing of hybrid biomaterials for bone tissue engineering: Calcium-polyphosphate microparticles encapsulated by polycaprolactone
Meik Neufurth, Xiaohong Wang, Shunfeng Wang, Renate Steffen, Maximilian Ackermann, Natalie D.Haep, Heinz C.Schröder, Werner E.G.Müller

12) Sol gel-derived hydroxyapatite films over porous calcium polyphosphate substrates for improved tissue engineering of osteochondral-like constructs
Whitaik David Lee, Rahul Gawri, Robert M. Pilliar, William L. Stanford, Rita A. Kandel

13) Fabrication of amorphous strontium polyphosphate microparticles that induce mineralization of bone cells in vitro and in vivo
Werner E.G. Müller, Emad Tolba, Maximilian Ackermann, Meik Neufurth, Shunfeng Wang, Qingling Feng, Heinz C.Schröder, Xiaohong Wang

14) Amorphous polyphosphate–hydroxyapatite: A morphogenetically active substrate for bone-related SaOS-2 cells in vitro
Werner E.G. Müller, Emad Tolba, Heinz C. Schröder, Rafael Muñoz-Espí, Bärbel Diehl-Seifert, Xiaohong Wang

15) Developing an in situ forming polyphosphate coacervate as a new liquid embolic agent: From experimental design to pilot animal study
Arash Momeni, Esther Mae Valliant, Ellen Patricia Brennan-Pierce, Jai Jai Shiva Shankar, Robert Abraham, Patricia Colp, Mark Joseph Filiaggi

16) Atomic scale modeling of iron-doped biphasic calcium phosphate bioceramics
Sandrine Gomes, Amandeep Kaur, Jean-Marc Grenèche, Jean-Marie Nedelec, Guillaume Renaudin

17) 3D silicon doped hydroxyapatite scaffolds decorated with Elastin-like Recombinamers for bone regenerative medicine
Mercedes Vila, Ana García, Alessandra Girotti, Matilde Alonso, Jose CarlosRodríguez-Cabello, Arlyng González-Vázquez, Josep A. Planell, Elisabeth Engel, Julia Buján, NatalioGarcía-Honduvilla, María Vallet-Regí

18) Quantitative analysis of vascular colonisation and angio-conduction in porous silicon-substituted hydroxyapatite with various pore shapes in a chick chorioallantoic membrane (CAM) model
Amandine Magnaudeix, Julie Usseglio, Marie Lasgorceix, Fabrice Lalloue, Chantal Damia, Joël Brie, Patricia Pascaud-Mathieu, Eric Champion

19) Macrotopographic closure promotes tissue growth and osteogenesis in vitro
Laura Juignet, Baptiste Charbonnier, Virginie Dumas, Wafa Bouleftour, Mireille Thomas, Coralie Laurent, Laurance Vico, Nathalie Douard, David Marchat, Luc Malaval

20) Strontium substitution in apatitic CaP cements effectively attenuates osteoclastic resorption but does not inhibit osteoclastogenesis
M. Schumacher, A.S. Wagner, J. Kokesch-Himmelreich, A. Bernhardt, M. Rohnke, S. Wenisch, M. Gelinsky

21) Hafnium-doped hydroxyapatite nanoparticles with ionizing radiation for lung cancer treatment
Min-Hua Chen, Nobutaka Hanagata, Toshiyuki Ikoma, Jian-Yuan Huang, Keng-Yuan Li, Chun-Pin Lin, Feng-Heui Lin

22) Stimulatory effect of cobalt ions incorporated into calcium phosphate coatings on neovascularization in an in vivo intramuscular model in goats
Zeinab Tahmasebi Birgani, Eelco Fennema, Marion J. Gijbels, Jan de Boer, Clemens A. van Blitterswijk, Pamela Habibovic

23) Surface-enrichment with hydroxyapatite nanoparticles in stereolithography-fabricated composite polymer scaffolds promotes bone repair
O. Guillaume, M.A. Geven, C.M. Sprecher, V.A. Stadelmann, D.W. Grijpma, T.T.Tang, L.Qind, Y.Lai, M.Alini, J.D.de Bruijn, H.Yuan, R.G.Richards, D.Eglin

24) Self-hardening and thermoresponsive alpha tricalcium phosphate/pluronic pastes
Yassine Maazouz, Edgar B. Montufar, Julien Malbert, Montserrat Espanol, Maria-Pau Ginebra

25) Micropore-induced capillarity enhances bone distributionin vivo in biphasic calcium phosphate scaffolds
Laurence E.Rustom, ThomasBoudou, Siyu Loub, Isabelle Pignot-Paintrand, Brett W.Nemke, Yan Lue, Mark D.Markel, Catherine Picart, Amy J. Wagoner Johnson

26) Delivery of the TLR ligand poly(I:C) to liver cells in vitroand in vivo by calcium phosphate nanoparticles leads to a pronounced immunostimulation
Viktoriya Sokolova, Zou Shi, Shunmei Huang, Yanqin Du, Mathis Kopp, Annika Frede, Torben Knuschke, Jan Buer, Dongliang Yang, Jun Wu, Astrid Maria Westendorf, Matthias Epple

27) Avidin-conjugated calcium phosphate nanoparticles as a modular targeting system for the attachment of biotinylated molecules in vitro and in vivo
Selina Beatrice van der Meer, Torben Knuschke, Annika Frede, Nina Schulze, Astrid Maria Westendorf, Matthias Epple

28) Antioxidant and bone repair properties of quercetin-functionalized hydroxyapatite: An in vitro osteoblast–osteoclast–endothelial cell co-culture study
Lucia Forte, Paola Torricelli, Elisa Boanini, Massimo Gazzano,  Katia Rubini, Milena Fini, Adriana Bigi

29) Physicochemical fabrication of antibacterial calcium phosphate submicrospheres with dispersed silver nanoparticles via coprecipitation and photoreduction under laser irradiation
Maki Nakamura, Ayako Oyane, Yoshiki Shimizu, Saori Miyata, Ayumi Saeki, Hirofumi Miyaji

30) Vitamin B12 functionalized layer by layer calcium phosphate nanoparticles: A mucoadhesive and pH responsive carrier for improved oral delivery of insulin
Ashwni Verma, Shweta Sharma, Pramod Kumar Gupta, Awadhesh Singh, B. Venkatesh Teja, Pankaj Dwivedi, Girish Kumar Gupta, RituTrivedi, Prabhat Ranjan Mishra

31) Selective effect of hydroxyapatite nanoparticles on osteoporotic and healthy bone formation correlates with intracellular calcium homeostasis regulation
Rui Zhao, Pengfei Xie, Kun Zhang, Zhurong Tang, Xuening Chen, Xiangdong Zhu, Yujiang Fan, Xiao Yang, Xingdong Zhang

32) Surface phosphonation enhances hydroxyapatite coating adhesion on polyetheretherketone and its osseointegration potential
Hesameddin Mahjoubi, Emily Buck, Praveena Manimunda, Reza Farivar, Richard Chromik, Monzur Murshed, Marta Cerruti

33) PEGylated poly(glycerol sebacate)-modified calcium phosphate scaffolds with desirable mechanical behavior and enhanced osteogenic capacity
Yifan Ma, Wenjing Zhang, Zihao Wang, Zi Wang, Qing Zie. Haoyi Niu, Han Guo, Yuan Yuan, Changsheng Liu

34) Increased acellular and cellular surface mineralization induced by nanogrooves in combination with a calcium-phosphate coating
Alexey Klymov, Jiankang Song, Xinjie Cai, Joost te Riet, Sander Leeuwenburgh, John A Jansen, X Frank Walboomers

35) In vitro and in vivo bone formation potential of surface calcium phosphate-coated polycaprolactone and polycaprolactone/bioactive glass composite scaffolds
Patrina S.P. Poh, Dietmar W. Hutmacher, Boris M. Holzapfel, Anu K. Solanki, Molly M. Stevens, Maria A. Woodruff

36) A straightforward approach to enhance the textural, mechanical and biological properties of injectable calcium phosphate apatitic cements (CPCs): CPC/blood composites, a comprehensive study
Charlotte Mellier, François-Xavier Lefèvre, Franck Fayon, Valérie Montouillout, Christelle Despas, Myruam Le Ferrec, Florian Boukhechba, Alain Walcarius, Pascal Janvier, Maeva Dutilleul, Olivier Gauthier, Jean-Michel Bouler, Bruno Bujoli

37) Hydration mechanism of partially amorphized β-tricalcium phosphate
Katrin Hurle, Juergen Neubauer, Friedlinde Goetz-Neunhoeffer

38) Incorporation of fast dissolving glucose porogens into an injectable calcium phosphate cement for bone tissue engineering
Brandon T. Smith, Marco Santoro, Eline C. Grosfeld, Sarita R. Shah, Jeroen J.J.P. van den Beucken, John A. Jansen, Antonios G. Mikos

39) Critical review: Injectability of calcium phosphate pastes and cements
R. O'Neill, H.O. McCarthy, E.B. Montufar, M.-P. Ginebra, D.I. Wilson, A. Lennon, N. Dunne

40) Novel bone wax based on poly(ethylene glycol)–calcium phosphate cement mixtures
Theresa Brückner, Martha Schamel, Alexander C. Kübler, Jürgen Groll, Uwe Gbureck

41) A simple and effective approach to prepare injectable macroporous calcium phosphate cement for bone repair: Syringe-foaming using a viscous hydrophilic polymeric solution
Jingtao Zhang, Weizhen Liu, Olivier Gauthier, Sophie Sourice, Paul Pilet, Gildas Rethore, Khalid Khairoun, Jean-Michel Bouler, Franck Tancret, Pierre Weiss

42) Novel bioceramic-reinforced hydrogel for alveolar bone regeneration
Giorgio Iviglia, Clara Cassinelli, Elisa Torre, Francesco Baino, Marco Morra, Chiara Vitale-Brovarone

43) Hydroxyapatite-coated double network hydrogel directly bondable to the bone: Biological and biomechanical evaluations of the bonding property in an osteochondral defect
Susumu Wada, Nobuto Kitamura, Takayuki Nonoyama, Ryuji Kiyama, Takayuki Kurokawa, Jian Ping Gong, Kazunori Yasuda

44) Topography of calcium phosphate ceramics regulates primary cilia length and TGF receptor recruitment associated with osteogenesis
Jingwei Zhang, Melis T. Dalbay, Xiaoman Luo, Erik Vrij, Davide Barbieri, Lorenzo Moroni, Joost D. de Bruijm. Clemens A. van Blitterswijk, J. Paul Chapple, Martin M. Knight, Huipin Yuan

45) Synergistic effects of BMP-2, BMP-6 or BMP-7 with human plasma fibronectin onto hydroxyapatite coatings: A comparative study
Isabelle Brigaud, Rémy Agniel, Johanne Leroy-Dudal, Sabrina Kellouche, Arnaud Ponche, Tahar Bouceba, Natalia Mihailescu, Mihai Sopronyi, Eric Viguier, Carmen Ristoscu, Felix Sima, Ion N. Mihailescu, Ana Claudia O Carreira, Mari Cleide Sogayar, Olivier Gallet, Karine Anselme

46) Role of biphasic calcium phosphate ceramic-mediated secretion of signaling molecules by macrophages in migration and osteoblastic differentiation of MSCs
Jing Wang, Dan Liu, Bo Guo, Xiao Yang, Xuening Chen, Xiangdong Zhu, Yijiang Fan, Xingdong, Zhang

47) Harnessing Wharton’s jelly stem cell differentiation into bone-like nodule on calcium phosphate substrate without osteoinductive factors
S. Mechiche Alami, H. Rammal, C. Boulagnon-Rombi, F. Velard, F. Lazar, R. Drevet, D. Laurent Maquin, S.C. Gangloff, J, Hemmerle, J.C. Voegel, G. Francius, P. Schaaf, F. Boulmedais, H. Kerdjoudj

48) Diversity of multinucleated giant cells by microstructures of hydroxyapatite and plasma components in extraskeletal implantation model
Kota Morishita, Eri Tatsukawa, Yasuaki Shibata, Fumio Suehiro, Masanobu Kamitakahara, Taishi Yokoi, Koji Ioku, Masahiro Umeda, Masahiro Nishimura, Tohru Ikeda

49) In vitro degradation of calcium phosphates: Effect of multiscale porosity, textural properties and composition
A. Diez-Escudero, M. Espanol, S. Beats, M.-P. Ginebra

50) A novel method for segmenting and aligning the pre- and post-implantation scaffolds of resorbable calcium-phosphate bone substitutes
Ahmed Sweedy, Marc Bohner, G. Harry van Lenthe, Gamal Baroud

51) Osteoclast differentiation from human blood precursors on biomimetic calcium-phosphate substrates
Gabriela Ciapetti, Gemma Di Pompo, Sofia Avnet, Desirée Martini, Anna Diez-Escudero, Edgar B. Montufar, Maria-Pau Ginebra, Nicola Baldini

52) The effect of particle size on the in vivo degradation of poly(d,l-lactide-co-glycolide)/α-tricalcium phosphate micro- and nanocomposites
Sarah M. Bennett, Meera Arumugam, Samuel Wilberforce, Davide Enea, Neil Rushton, Xiang C. Zhang, Serena M. Best, Ruth E. Cameron, Roger A. Brooks

53) Calcium supplementation decreases BCP-induced inflammatory processes in blood cells through the NLRP3 inflammasome down-regulation
Patricia Lagadec, Thierry Balaguer, Florian Boukhechba, Grégory Michel, Sebastien Bouvet-Gerbettaz, Jean-Michel Bouler, Jean-Claude Scimeca, Nathalie Rochet

54) Tumor acidity-activatable manganese phosphate nanoplatform for amplification of photodynamic cancer therapy and magnetic resonance imaging
Yongwei Hao, Cuixia Zheng, Lei Wang, Jinjie Zhang, Xiuziu Niu, Qingling song, Qianhua Feng, Hongjuan Zhao, Li Li, Hongling Zhang, Zhenzhong Zhang, Yun Zhang

55) Composite material consisting of microporous β-TCP ceramic and alginate for delayed release of antibiotics
Michael Seidenstuecker, Juergen Ruehe, Norbert P. Suedkamp, Annerose Serr, Annette Wittmer, Marc Bohner, Anke Bernstein, Hermann O. Mayr

56) Adsorption of benzoxaboroles on hydroxyapatite phases
Marie-Alix Pizzoccaro, Ondrej Nikel, Saad Sene, Coralie Philippe, P. Hubert Mutin, Sylvie Begu, Deepak Vashishth, Danielle Laurencin

57) Amorphous surface layer versus transient amorphous precursor phase in bone – A case study investigated by solid-state NMR spectroscopy
Stanislas Von Euw, Widad Ajili, Tsou-Hsi-Camille Chan-Chang, Annette Delices, Guillaume Laurent, Florence Babonneau, Nadine Nassif, Thierry Azais

58) The synergic role of collagen and citrate in stabilizing amorphous calcium phosphate precursors with platy morphology
José Manuel Delgado-López, Federica Bertolotti, Jeppe Lyngsø, Jan Skov Pedersen, Antonio Cervellino, Norberto Masciocchi, Antonietta Guagliardi

59) Electric field-assisted formation of organically modified hydroxyapatite (ormoHAP) spheres in carboxymethylated gelatin gels
C. Heinemann, S. Heinemann, B. Kruppke, H. Worch, J. Thomas, H.P. Wiesmann, T. Hanke

60) A combinatorial approach towards achieving an injectable, self-contained, phosphate-releasing scaffold for promoting biomineralization in critical size bone defects
Lamees Nayef, Mina Mekhail, Laila Benameur, Juan S. Rendon, Reggie Hamdy, Maryam Tabrizian

61) The proangiogenic potential of a novel calcium releasing biomaterial: Impact on cell recruitment
Hugo Oliveira, Sylvain Catros, Claudine Boiziau, Robin Siadous, Joan Marti-Munoz, Reine Bareille, Sylvie Rey, Oscar Castano, Josep Planell, Joelle Amedee, Elisabeth Engel.

62) A comparative study of simulated body fluids in the presence of proteins
Weitian Zhao, Jacques Lemaître, Paul Bowen