Active nanomaterials for biomedical applications

Transcription

1 Engineering Conferences International ECI Digital Archives Nanotechnology in Medicine: From Molecules to Humans Proceedings Active nanomaterials for biomedical applications Gianni Ciofani Italian Institute of Technology, Italy, Follow this and additional works at: Part of the Engineering Commons Recommended Citation Gianni Ciofani, "Active nanomaterials for biomedical applications" in "Nanotechnology in Medicine: From Molecules to Humans", Prof. Lola Eniola-Adefeso, Department of Chemical Engineering, University of Michigan, USA Prof. Paolo Decuzzi, Italian Institute of Technology, Italy Eds, ECI Symposium Series, (2016). This Abstract and Presentation is brought to you for free and open access by the Proceedings at ECI Digital Archives. It has been accepted for inclusion in Nanotechnology in Medicine: From Molecules to Humans by an authorized administrator of ECI Digital Archives. For more information, please contact

2 Nanotechnology in Medicine: From Molecules to Humans July3-7, 2016 Hernstein, Austria Active nanomaterials for biomedical applications Gianni Ciofani Polytechnic University of Torino DIMEAS Corso Duca degli Abruzzi, Torino, Italy Italian Institute of Technology Center for Viale Rinaldo Piaggio, Pontedera (Pisa), Italy

3 OUR GROUP

4 PIEZOELECTRICITY IN NANOMEDICINE ACS Nano, 4(10): (2010) ACS Nano, 9(7): (2015)

5 Piezoelectric nanomaterials ZnO nanorods Ciofani G., Genchi G.G. and Mattoli V. ZnO nanowire arrays as substrates for cell proliferation and differentiation. Mat Sci Eng C 32: (2012) Barium titanate nanoparticles Boron nitride nanotubes Rocca A., [ ], Ciofani G. Barium titanate nanoparticles and hypergravity stimulation improve differentiation of mesenchymal stem cells into osteoblasts. Int. J. Nanomed.10: (2015) CiofaniG., [ ], MattoliV. Cytocompatibility evaluation of gum Arabic-coated ultra-pure boron nitride nanotubes on human cells. Nanomed. UK9: (2014)

6 Barium Titanate Nanoparticles ex: 633 nm em: nm 20 µm Intensity(a.u.) Intensity(a.u.) G. Ciofani, [ ], V. Mattoli, Effects of barium titanate nanoparticles on proliferation and differentiation of mesenchymal stem cells. Coll. Surf. B: Biointerfaces 102: (2013) 2θ Tetragonal Cubic θ

7 Barium Titanate Nanoparticles

8 BTNP-MEDIATED STIMULATION ΔF/F US (0.8 W/cm 2 ) 2.0 ΔF/F0 0.0 ΔF/F US (0.8 W/cm 2 ) + BTNPs 2.0 ΔF/F ?F/F time (s) US (0.8 W/cm 2 ) + cubiccrystalbtnps ?F/F time (s) time(s) Marino A., [ ], Ciofani G. Piezoelectric nanoparticle-assisted wireless neuronal stimulation. ACS Nano, 9(7): (2015)

9 P(VDF-TrFE)/BaTiO3 nanoparticle composite films Genchi G.G. [ ], Ciofani G. P(VDF- TrFE)/BaTiO3nanoparticle composite films mediate piezoelectric stimulation and promote differentiation of SH-SY5Y neuroblastomacells. Advanced Healthcare Materials, /adhm

10 Sample preparation and characterization: Electron Microscopy 1) Powderdissolution/dispersionin methylethylketone: 200 mg/ml P(VDF-TrFE, 70/30) 40% P(VDF-TrFE) and 60% BTNPs(w/w) 2) Sonication at 8 W for10 min 3) Casting 4) Annealing at 40 C 5) Under vacuumfor12 h P(VDF-TrFE) 10 µm P(VDF-TrFE) + BTNPs P(VDF-TrFE) + BTNPs(cryosection) 10 µm 10 µm

11 Sample preparation and characterization: AFM & PFM P(VDF-TrFE) P(VDF-TrFE) + BTNPs AFM PFM

12 X-Ray Diffraction X-ray diffraction P(VDF-TrFE) P(VDF-TrFE) + BTNPs αphase Crystallinity (%) βphase total

13 EXTENSIMETRY 12 Tensile stress (MPa) P(VDF-TrFE) P(VDF-TrFE)/BTNPs Cube-within-cube model by Ogorkiewicz and Weidmann Tensile strain (%) Young s modulus (MPa) * P(VDF-TrFE) P(VDF-TrFE)/ BTNPs Ultimate tensile strength (MPa) P(VDF-TrFE) P(VDF-TrFE)/ BTNPs Extension at maximum load (%) P(VDF-TrFE) * P(VDF-TrFE)/ BTNPs Extension at break (%) P(VDF-TrFE) * P(VDF-TrFE)/ BTNPs

14 Piezoresponse characterization res./sample PTFE (non piezo) P(VDF-TrFE) P(VDF-TrFE) + BTNPs V out1 [mv RMS ] Q ε r ε S d 31,1 [pm/v] g 31,1 [mv/n]

15 Ca 2+ imaging P(VDF-TrFE) F/F 0 Acute ultrasound stimulation: 1 W/cm 2, 100 Hz BurstRate Ctrl US Time(s) F/F 0 F/F US Time(s) P(VDF-TrFE) + BTNPs US Time(s)

16 Neurite emission and analysis US- US+ Chronicultrasound stimulation: 1 W/cm 2, 100 Hz BurstRate, 2X/day, 6 dd Ctrl *p<0.01 * * P(VDF-TrFE) Neurite length (µm) * 20 P(VDF-TrFE) +BTNPs 50 µm Tubulin Nuclei 0 US- US+ US- US+ US- US+ Ctrl P(VDF-TrFE) P(VDF-TrFE) + BTNPs

17 DIRECT LASER WRITING 3D Laser Lithography Resolution < 100 nm Two-photon polymerization (laser 780 nm, power > 60 mw) Dedicated resist

18 DIRECT LASER WRITING

19 DIRECT LASER WRITING: THE PROCESS

20 THE OSTEOPRINT 3D model of trabecular bone Adhesion of SaOS-2 cells 50 µm Marino A., [ ], CiofaniG. The Osteoprint: A two-photon polymerized 3D structure for the enhancement of bone-like cell differentiation. Acta Biomaterialia, 10(10): (2014) Differentiation of SaOS-2 cells (confocal & SEM)

21 BTNP-DOPED RESIST BTNP mixed with ormocomp Sonication 2pp process SEM/FIB/EDX analysis: BTNP uniformely dispersed in the structures

22 BTNP-DOPED STRUCTURES 2pp of complex structures BTNP uniformely dispersed in the 3D scaffolds SHG signal detection

23 BTNP-DOPED STRUCTURES Piezoelectric characterization: AFM & PFM 10 Topography nm 10 Piezoresponse amplitude mv 8 8 Y[µm] 6 4 Y[µm] nm mv X[µm] X[µm] d 33 = 0.6 pm/v

24 BTNP-DOPED OSTEOPRINTS BTNPs actin nuclei merging Marino A., [ ], CiofaniG. Two-photon lithography of 3D nanocompositepiezoelectric scaffolds for cell stimulation. ACS Applied Materials and Interfaces, 7(46): (2015)

25 PIEZOELECTRIC STIMULATION Human Saos-2 cell testing Stimulation with US for 5 days (30 s, 3 timesper day, 0.8 W/cm 2 ) OP OP + US OP + BTNPs OP + US + BTNPs HA deposit area (%) Osteoimage ** OP OP + US OP + BTNPs OP + BTNPs + US Evaluation of the mineralization Osteoimage staining Quantification of HA deposits

26 CONCLUSIONS 2D/3D micro/nanofabrication High resolution Nanostructured surfaces Biomimetic substrates Tuning of physical properties Marino A., [ ], CiofaniG. Biomimicryat the nanoscale: Current research and perspectives of two-photon polymerization. Nanoscale, 7(7): (2015)

27 Thank you for your attention!