Laser-based Nano-Technology

For the development and functionalization of innovative implants, the “Laser-Based Nanotechnology” working group at Leibniz Universität Hannover develops and uses processes that use lasers to create micro- and nano-systems, in particular nano-materials, scaffolds and 3D-printed tissue.

Research

Laser-based Nano-Technology

The “Laser-based Nanotechnology” working group at Leibniz Universität Hannover develops and uses laser technology processes on the one hand for the development and functionalization of innovative implants with optimized growth rates and controllable interactions between implant and surrounding tissue and on the other hand for the production of three-dimensional biological structures that simulate natural tissue and can be used as test systems and implants in the future.

The working group pursues different research topics:

Development of nanomaterials (Dr. Annette Hoffmeister)

The objectives of this research direction are the advanced development of novel nanomaterials and their application in biomedical science and regenerative nanomedicine, as well as their translation into clinical use.
Using laser-based and chemical techniques such as pulsed laser ablation in liquids (PLAL) and chemical liquid phase synthesis, we produce inorganic nanoparticles of various shapes and sizes from a variety of materials. In addition, we supplement the particle properties with a bioactive, organic surface functionalization in order to enable their application as biofunctional materials. The functionalized nanoparticles are used as colloids, as well as after embedment into a biocompatible polymer (so-called nanocomposite) and after attachment to a surface.

Defined scaffolds for 3D cell systems (Dr. Anastasia Koroleva)

If cells are cultivated in normal cell cultures in the laboratory, e.g. in Petri dishes or cell culture bottles, they often behave very differently than in the human body. This is because they are in a complex 3D environment in the body, typically having contacts in 3D with many other cells with which they interact, and being exposed to mechanical and various chemical stimuli. In contrast, in cell culture they are located on rigid two-dimensional surfaces, and contact with other cells is rather limited. In order to better simulate natural tissue, a 3D cell culture is necessary, which can be realized with framework structures, so-called scaffolds. Defined properties of these structures in terms of geometry, mechanics and chemistry are important.
With ultrashort pulse lasers, very precisely defined scaffold geometries are implemented in our working group using 2-photon polymerization based on CAD templates with a resolution of less than 100 nanometers. The scaffolds can be made from many different materials, including (biodegradable) polymers, hydrogels, ceramic and electrically conductive materials.

These scaffolds, colonized with cells, are suitable for studying the behavior of the cells and can serve as in vitro test systems and implants. Currently, for instance, we are developing scaffolds for neural systems.

3D printing of cells and tissues (Dr. Lothar Koch)

An alternative to the use of scaffolds is the production of three-dimensional cell systems and biological tissue using 3D bioprinting. Our working group uses a laser-based process for bioprinting, which is also known as laser-induced forward transfer. This enables living cells and biomaterials to be printed, which are then embedded in a sol (the not yet gelled precursor of a hydrogel) and arranged drop by drop, layer-by-layer in three dimensions. A tissue then forms in the following days.

Compared to other, non-laser-based processes, such as inkjet printing or the most-widely-used extrusion printing, our process has the advantage of being able to combine the printing of relatively high-viscosity materials and high cell densities with a high resolution.
Various 3D cell structures for the investigation of cell-cell interactions and tissue have already been printed in our working group. In the future, in addition to replacement organs for implantations, organ-on-chip systems for pharmaceutical or cosmetic test purposes will also be produced. These would then replace animal experiments. That would not only be more ethically unproblematic, but, if human cells are used, it could also be much more meaningful.

At NIFE we are developing:

Biocompatible nanocomposites to produce innovative implants with reduced infection rates for reconstructive therapy
Innovative nanotransporters for specific cell delivery and controlled, stimulus-induced release of active ingredients and genetic material
Permanent nanomarkers for specific immunolabeling of molecules and long-term imaging
Novel nanomaterials with theranostic functions
Highly sensitive nanosensors for the detection and online monitoring of analytes in complex media
Highly efficient nanocatalysts for the regulation of biocatalytic reactions

GROUP LEADER

Prof. Dr.

Boris Chichkov

Institute for Quantum Optics

Andrea Deiwick

Technical assistance

M.Sc.

Saba Rake

Dr.

Lothar Koch

Dr.

Anastasia Koroleva

Publications

L. Koch, A. Deiwick, B. Chichkov. Capillary-like Formations of Endothelial Cells in Deﬁned Patterns Generated by Laser.
Bioprinting. Micromachines 12, 1538 (2021) DOI: 10.3390/mi121538.

A. Koroleva, A. Deiwick, A. El-Tamer, L. Koch, Y. Shi, E. Estévez-Priego, A.-A. Ludl, J. Soriano, D. Guseva, E. Ponimaskin, and B. Chichkov, In Vitro Development of Human iPSC-Derived Functional Neuronal Networks on Laser-Fabricated 3D Scaffolds, ACS Appl. Mater. Mater. Interfaces 13, 7, 7839-7853 (2021) DOI: 10.1021/acsami.0c16616.

N. Jyotsana, A. Sharma, A. Chaturvedi, M. Scherr, F. Kuchenbauer, L. Sajti, A. Barchanski, R. Lindner, F. Noyan, K.W. Sühs, D. Grote-Koska, K. Brand, H.P. Vornlocher, M. Stanulla, B. Bornhauser, J.P. Bourquin, M. Eder, F. Thol, A. Ganser, R. K. Humphries, E. Ramsay, P. Cullis, M. Heuser, RNA Interference Efficiently Targets Human Leukemia Driven by a Fusion Oncogene in vivo, Leukemia 32:224-226 (2018) DOI: 10.1038/leu.2017.269.

L. Koch, A. Deiwick, A. Franke, K. Schwanke, A. Haverich, R. Zweigerdt, and B. Chichkov, Laser bioprinting of human induced pluripotent stem cells-the effect of printing and biomaterials on cell survival, pluripotency, and differentiation, Biofabrication 10 035005 (2018) DOI: 10.1088/1758-5090/aab981.

M.N. Barshutina, A. Barchanski, Pulsed Laser Ablation for Obtaining Contrast Agents Based on Dysprosium Oxide (Dy2O3) Nanoparticles, Nanometrology 60(3): 216-219 (2017) DOI: 10.1007/s11018-017-1176-5.

L. Koch, O. Brandt, A. Deiwick, and B. Chichkov, Laser-assisted bioprinting at different wavelengths and pulse durations with a metal dynamic release layer: A parametric study, Int J of Bioprinting 3(1): 42-53 (2017) DOI: 10.18063/IJB.2017.01.001.

A. Barchanski, Laser-Generated Functional Nanoparticle Bioconjugates - Design for Application in Biomedical Science and Reproductive Biology, Springer Spektrum Research (2016) DOI: 10.1007/978-3-658-13515-7.

A. Koroleva, A. Deiwick, A. Nguyen, R. Narayan, A. Shpichka, O. Kufelt, R. Kiyan, V. Bagratashvili, P. Timashev, T. Scheper, and B. Chichkov, Hydrogel-based microfluidics for vascular tissue engineering, BioNanoMat. 17, 19 (2016) DOI: 10.1515/bnm-2015-0026.

Katharina Doll, Elena Fadeeva, Nico S. Stumpp, Sebastian Grade, Boris N. Chichkov, Meike Stiesch, Reduced bacterial adhesion on titanium surfaces micro-structured by ultra-short pulsed laser ablation, BioNanoMaterials 17, (1-2), 53-57 (2016) DOI: 10.1515/bnm-2015-0024.

A. N. Generalova, V. V. Rocheva, A. V. Nechaev, D. A. Khochenkov, N. V. Sholina, V. A. Semchishen, V. P. Zubov, A. V. Koroleva, B. N. Chichkov, E. V. Khaydukova, PEG-modified upconversion nanoparticles for in vivo optical imaging of tumors, RSC Adv. 6, 30089-30097 (2016) DOI: 10.1039/C5RA25304G.

Behnam Taidi, Guillaume Lebernede, Lothar Koch, Patrick Perre, Boris Chichkov, Colony development of laser printed eukaryotic (yeast and microalga) microorganisms in co-culture, International Journal of Bioprinting 2(2), 37-43 (2016) DOI: 10.18063/IJB.2016.02.001.

A. Barchanski, D. Funk, O. Wittich, C. Tegenkamp, B. N. Chichkov, C. L. Sajti, Picosecond laser fabrication of functional gold-antibody nanoconjugates for biomedical applications, Journal of Physical Chemistry C 119(17): 9524-9533; (2015) DOI:10.1021/jp511162n.

A. Barchanski, U. Taylor, C. L. Sajti, L. Gamrad, W. A. Kues, D. Rath, S. Barcikowski, Bioconjugated gold nanoparticles penetrate into spermatozoa depending on plasma membrane status, Journal of Biomedical Nanotechnology 11(9):1597-1607(2015) DOI:10.1166/jbn.2015.2094.

Olga Kufelt, Ayman El-Tamer, Camilla Sehring, Marita Meißner, Sabrina Schlie-Wolter, Boris N. Chichkov, Water-soluble photopolymerizable chitosan hydrogels for biofabrication via two-photon polymerization, Acta Biomaterialia 18, 186-195 (2015) DOI: 10.1016/j.actbio.2015.02.025.

Keywords

Laser-based micro- and nanotechnology, nanoparticle generation and functionalization, precise surface structures and scaffolds for selective cell control, 3D printing of cells and tissues, two-photon polymerization, bioprinting.

Contact

Laser Nanotechnology:

Prof. Dr. Boris Chichkov

+49 511 762 17771

chichkov(at)iqo.uni-hannover.de

Development of nanomaterials:

Dr. Annette Hoffmeister

+49 511 532 1344

hoffmeister(at)iqo.uni-hannover.de

Scaffolds:

Dr. Anastasia Koroleva

+49 511 762 18894

info.koroleva(at)gmail.com

Laser Bioprinting:

Dr. Lothar Koch

+49 511 532 1329

koch(at)iqo.uni-hannover.de

Institute for Quantum Optics
Leibniz University Hanover

Specials

Annette Barchanski: "Laser fabrication of smart nanoparticles," Invited talk at the International Conference on Nanomaterials & Nanotechnology, Oct. 09-12, 2018, Stockholm, Sweden.

Lothar Koch: "Tissue Engineering by Laser-Generated 3D Structures - Of Controlled Cell Behavior and Printed Organs", Invited lecture, Witten-Herdecke University, Feb. 8, 2017.

Annette Barchanski: "Laser-generated nanomaterials for biomedical implants" Poster award at the International Symposium of Biofabrication, 25-26.06.2015, Hannover.

Lothar Koch: "Laser Cell Printing for Tissue Engineering", Invited talk at the Macromolecular Colloquium Freiburg, Feb. 24, 2016, Freiburg (Breisgau), Germany.

Lothar Koch: "Laser Cell Printing for Tissue Engineering", Invited talk at the 7th Innovation Forum "Light & Light Technology" of the 65th Lindau Nobel Laureate Meeting, June 27, 2015, Lindau, Germany.

Boris Chichkov: "Laser printing of nanoparticles and living cells", Invited talk as Plenary Lecture, International Forum on MicroManufacturing & Biofabrication 2015, 19.05.2015, Toyama, Japan.

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