POLITECNICO DI TORINO Repository ISTITUZIONALE Copper-containing mesoporous bioactive glass nanoparticles as multifunctional agent for bone regeneration /

The application of mesoporous bioactive glasses (MBGs) containing controllable amount of different ions, with the aim to impart antibacterial activity, as well as stimulation of osteogenesis and angiogenesis, is attracting an increasing interest. In this contribution, in order to endow nano-sized MBG with additional biological functions, the framework of a binary SiO2-CaO mesoporous glass was modified with different concentrations of copper ions (2 and 5%mol.), through a one-pot ultrasound-assisted sol-gel procedure. The Cu-containing MBG (2%mol.) showed high exposed surface area (550m2g-1), uniform mesoporous channels (2.6nm), remarkable in vitro bioactive behaviour and sustained release of Cu2+ ions. Cu-MBG nanoparticles and their ionic dissolution extracts exhibited antibacterial effect against three different bacteria strains, E. coli, S. aureus, S. epidermidis, and the ability to inhibit and disperse the biofilm produced by S. epidermidis. The obtained results suggest that the developed material, which combines in single multifunctional agent excellent bioactivity and antimicrobial ability, offers promising opportunities for the prevention of infectious diseases and the effective treatment of bone defects. STATEMENT OF SIGNIFICANCE In order to endow mesoporous bioactive glass, characterized by excellent bioactive properties, with additional biological functions, Cu-doped mesoporous SiO2-CaO glass (Cu-MBG) in the form of nanoparticles was prepared by an ultra-sound assisted one pot synthesis. The analysis of the bacterial viability, using different bacterial strains, and the morphological observation of the biofilm produced by the Staphylococcus epidermidis, revealed the antimicrobial effectiveness of the Cu-MBG and the relative ionic extracts against both the bacterial growth and the biofilm formation/dispersion, providing a true alternative to traditional antibiotic systemic therapies. The proposed multifunctional agent represents a promising and versatile platform for bone and soft tissues regeneration.

[1]  M. Mozafari,et al.  Investigation of the physico-chemical reactivity of a mesoporous bioactive SiO2–CaO–P2O5 glass in simulated body fluid , 2010 .

[2]  L. Visai,et al.  Nano-biocomposite films with modified cellulose nanocrystals and synthesized silver nanoparticles. , 2014, Carbohydrate polymers.

[3]  Yin Xiao,et al.  Copper-doped mesoporous silica nanospheres, a promising immunomodulatory agent for inducing osteogenesis. , 2016, Acta Biomaterialia.

[4]  J. E. Pemberton,et al.  XPS Characterization of a Commercial Cu/ZnO/Al2O3 Catalyst: Effects of Oxidation, Reduction, and the Steam Reformation of Methanol , 1988 .

[5]  Abdul Hameed,et al.  Investigations into the antibacterial behavior of copper nanoparticles against Escherichia coli , 2010, Annals of Microbiology.

[6]  Kyungjae Lee,et al.  Hydrogel networks as nanoreactors: A novel approach to silver nanoparticles for antibacterial applications , 2007 .

[7]  Molly M Stevens,et al.  Spherical bioactive glass particles and their interaction with human mesenchymal stem cells in vitro. , 2011, Biomaterials.

[8]  V. Yu,et al.  INACTIVATION OF MYCOBACTERIUM AVIUM BY COPPER AND SILVER IONS , 1998 .

[9]  A. Bueno-López,et al.  Role of surface and lattice copper species in copper-containing (Mg/Sr)TiO3 perovskite catalysts for soot combustion , 2009 .

[10]  Kai Zheng,et al.  Nanoscale Bioactive Glasses in Medical Applications , 2013 .

[11]  H. Rohde,et al.  The Photodynamic Effect of Tetra-Substituted N-Methyl-Pyridyl-Porphine Combined with the Action of Vancomycin or Host Defense Mechanisms Disrupts Staphylococcus Epidermidis Biofilms , 2009, The International journal of artificial organs.

[12]  Quansheng Chen,et al.  Enhancing the antimicrobial activity of natural extraction using the synthetic ultrasmall metal nanoparticles , 2015, Scientific Reports.

[13]  Rozalia Dimitriou,et al.  Bone regeneration: current concepts and future directions , 2011, BMC medicine.

[14]  van der Henny C. Mei.  Microbial Adhesion in Flow Displacement Systems , 2006 .

[15]  M. Vallet‐Regí,et al.  Bioactivity of a CaO−SiO2 Binary Glasses System , 2000 .

[16]  Jiang Chang,et al.  Study on antibacterial effect of 45S5 Bioglass® , 2009, Journal of materials science. Materials in medicine.

[17]  Yinghong Zhou,et al.  Strontium-containing mesoporous bioactive glass scaffolds with improved osteogenic/cementogenic differentiation of periodontal ligament cells for periodontal tissue engineering. , 2012, Acta biomaterialia.

[18]  Heungsoo Shin,et al.  Biomimetic Scaffolds for Tissue Engineering , 2012 .

[19]  Larry L Hench,et al.  Twenty-first century challenges for biomaterials , 2010, Journal of The Royal Society Interface.

[20]  M. Vallet‐Regí,et al.  Substitutions of cerium, gallium and zinc in ordered mesoporous bioactive glasses. , 2011, Acta biomaterialia.

[21]  M. Villanueva,et al.  Antimicrobial Activity of Starch Hydrogel Incorporated with Copper Nanoparticles. , 2016, ACS applied materials & interfaces.

[22]  Jiang Chang,et al.  The enhancement of bone regeneration by a combination of osteoconductivity and osteostimulation using β-CaSiO3/β-Ca3(PO4)2 composite bioceramics. , 2012, Acta biomaterialia.

[23]  Chikara Ohtsuki,et al.  A unified in vitro evaluation for apatite-forming ability of bioactive glasses and their variants , 2015, Journal of Materials Science: Materials in Medicine.

[24]  D. Ferguson,et al.  (ii) An update on fracture healing and non-union , 2010 .

[25]  Aldo R Boccaccini,et al.  Accelerated mineralization of dense collagen-nano bioactive glass hybrid gels increases scaffold stiffness and regulates osteoblastic function. , 2011, Biomaterials.

[26]  M. Vallet‐Regí,et al.  Revisiting silica based ordered mesoporous materials: medical applications , 2006 .

[27]  F. Gao,et al.  Synthesis, characterization, and catalytic performance of copper-containing SBA-15 in the phenol hydroxylation. , 2012, Journal of colloid and interface science.

[28]  J. Mano,et al.  Preparation and characterization of bioactive glass nanoparticles prepared by sol–gel for biomedical applications , 2011, Nanotechnology.

[29]  Yong-cheng Hu,et al.  Osteostimulation of bioglass. , 2009, Chinese medical journal.

[30]  Yufang Zhu,et al.  Composition–structure–property relationships of the CaO–MxOy–SiO2–P2O5 (M = Zr, Mg, Sr) mesoporous bioactive glass (MBG) scaffolds , 2011 .

[31]  D. Caputo,et al.  Silver-containing mesoporous bioactive glass with improved antibacterial properties , 2013, Journal of Materials Science: Materials in Medicine.

[32]  María Vallet-Regí,et al.  Structure and functionalization of mesoporous bioceramics for bone tissue regeneration and local drug delivery , 2012, Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Sciences.

[33]  María Vallet-Regí,et al.  Ordered Mesoporous Bioactive Glasses for Bone Tissue Regeneration , 2006 .

[34]  C. Chiang,et al.  Preparation of cotton fibers with antibacterial silver nanoparticles , 2008 .

[35]  Song Li,et al.  Biomimetic scaffolds for tissue engineering , 2004, The 26th Annual International Conference of the IEEE Engineering in Medicine and Biology Society.

[36]  J. Kaplan,et al.  Susceptibility of staphylococcal biofilms to enzymatic treatments depends on their chemical composition , 2007, Applied Microbiology and Biotechnology.

[37]  Chengzhong Yu,et al.  Mesoporous bioactive glasses for controlled drug release , 2008 .

[38]  L. Visai,et al.  Data in support of Gallium (Ga3+) antibacterial activities to counteract E. coli and S. epidermidis biofilm formation onto pro-osteointegrative titanium surfaces , 2016, Data in Brief.

[39]  Chengtie Wu,et al.  Bioactive mesoporous calcium–silicate nanoparticles with excellent mineralization ability, osteostimulation, drug-delivery and antibacterial properties for filling apex roots of teeth , 2012 .

[40]  L. Kuhn,et al.  Design and characterization of calcium phosphate ceramic scaffolds for bone tissue engineering. , 2016, Dental materials : official publication of the Academy of Dental Materials.

[41]  Brendan Duffy,et al.  Preparation and rapid analysis of antibacterial silver, copper and zinc doped sol-gel surfaces. , 2012, Colloids and surfaces. B, Biointerfaces.

[42]  Jiang Chang,et al.  Multifunctional mesoporous bioactive glasses for effective delivery of therapeutic ions and drug/growth factors. , 2014, Journal of controlled release : official journal of the Controlled Release Society.

[43]  H. Kim,et al.  Capacity of mesoporous bioactive glass nanoparticles to deliver therapeutic molecules. , 2012, Nanoscale.

[44]  J. Costerton,et al.  Bacterial biofilms: a common cause of persistent infections. , 1999, Science.

[45]  Y. Kameshima,et al.  Formation of hydroxyapatite on CaSiO3 powders in simulated body fluid , 2002 .

[46]  K. Lewis,et al.  Persister cells and tolerance to antimicrobials. , 2004, FEMS microbiology letters.

[47]  H. Ohgushi,et al.  Bone formation process in porous calcium carbonate and hydroxyapatite. , 1992, Journal of biomedical materials research.

[48]  Chengtie Wu,et al.  Strontium-incorporated mesoporous bioactive glass scaffolds stimulating in vitro proliferation and differentiation of bone marrow stromal cells and in vivo regeneration of osteoporotic bone defects. , 2013, Journal of materials chemistry. B.

[49]  Nicola Cioffi,et al.  Synthesis and Antimicrobial Activity of Copper Nanomaterials , 2011, Nano-Antimicrobials.

[50]  Wei Fan,et al.  Hypoxia-mimicking mesoporous bioactive glass scaffolds with controllable cobalt ion release for bone tissue engineering. , 2012, Biomaterials.

[51]  Tadashi Kokubo,et al.  How useful is SBF in predicting in vivo bone bioactivity? , 2006, Biomaterials.

[52]  O. Salazar,et al.  Toward Tailor-Made Biocide Materials Based on Poly(propylene)/Copper Nanoparticles. , 2010, Macromolecular rapid communications.

[53]  Xufeng Zhou,et al.  Highly ordered mesoporous bioactive glasses with superior in vitro bone-forming bioactivities. , 2004, Angewandte Chemie.

[54]  E. Saino,et al.  Photodynamic Action of Tri-meso (N-methylpyridyl), meso (N-tetradecyl-pyridyl) Porphine on Staphylococcus Epidermidis Biofilms Grown on Ti6Al4V Alloy , 2010, The International journal of artificial organs.

[55]  J. Knowles,et al.  Characterisation of antibacterial copper releasing degradable phosphate glass fibres. , 2005, Biomaterials.

[56]  M. Alizadeh,et al.  Development of injectable biocomposites from hyaluronic acid and bioactive glass nano-particles obtained from different sol-gel routes. , 2013, Materials science & engineering. C, Materials for biological applications.

[57]  Linlin Li,et al.  Mesoporous Silica Nanoparticles: Synthesis, Biocompatibility and Drug Delivery , 2012, Advanced materials.

[58]  Lei Chen,et al.  Copper-containing mesoporous bioactive glass scaffolds with multifunctional properties of angiogenesis capacity, osteostimulation and antibacterial activity. , 2013, Biomaterials.

[59]  F. Qu,et al.  In vitro hydroxyapatite-forming ability and antimicrobial properties of mesoporous bioactive glasses doped with Ti/Ag , 2013 .

[60]  Arnab Roy,et al.  Characterization of enhanced antibacterial effects of novel silver nanoparticles , 2007, Nanotechnology.

[61]  M. Fathi,et al.  Antibacterial effects of sol-gel-derived bioactive glass nanoparticle on aerobic bacteria. , 2010, Journal of biomedical materials research. Part A.

[62]  D. Gray,et al.  Inhibition of active bone resorption by copper , 2006, Calcified Tissue International.

[63]  P Stoodley,et al.  Survival strategies of infectious biofilms. , 2005, Trends in microbiology.

[64]  H. Oudadesse,et al.  Investigation of the surface reactivity of a sol-gel derived glass in the ternary system SiO2-CaO-P2O5 , 2008 .

[65]  T. Yamamuro,et al.  The bonding behavior of calcite to bone. , 1991, Journal of biomedical materials research.

[66]  T. Hyeon,et al.  A general strategy for site-directed enzyme immobilization by using NiO nanoparticle decorated mesoporous silica. , 2014, Chemistry.

[67]  H. Malekinejad,et al.  A cytotoxicity and comparative antibacterial study on the effect of Zataria multiflora Boiss, Trachyspermum copticum essential oils, and Enrofloxacin on Aeromonas hydrophila , 2012, Avicenna journal of phytomedicine.

[68]  K. Adibkia,et al.  Antimicrobial activity of the metals and metal oxide nanoparticles. , 2014, Materials science & engineering. C, Materials for biological applications.

[69]  B. Larijani,et al.  ADEQUATE SERUM COPPER CONCENTRATION COULD IMPROVE BONE DENSITY, POSTPONE BONE LOSS AND PROTECT OSTEOPOROSIS IN WOMEN , 2007 .

[70]  M. Petris,et al.  Copper tolerance and virulence in bacteria. , 2015, Metallomics : integrated biometal science.

[71]  Marcello Imbriani,et al.  The Interaction of Bacteria with Engineered Nanostructured Polymeric Materials: A Review , 2014, TheScientificWorldJournal.