Laser-based visualization and manipulation of cell regeneration

We establish and apply novel imaging modalities which can be used for implant research, in particular, for imaging on a cellular level. Additionally, we use laser based nanosurgery to better understand processes which are involved in tissue regeneration.

Research

Cellular repair processes and cell regeneration

Cell repair and cellular regeneration is an essential process in life and strongly connected to implant research. The associated intercellular processes and mechanisms are often complex and hard to follow. Key questions, for example, the contribution of specific cell types to regeneration in certain organs need to be addressed to design better implants in the future. Additionally, techniques to understand the interaction with and influence of the cellular environment on regeneration, for example bacterial infections or the implant material, are of high interest.

To address these points, cellular imaging can be applied. In the last decades, several new imaging techniques have become available to researchers in the field of biomedicine. Our group applies an armamentarium of different imaging techniques to follow regenerative processes. For instance, multiphoton microscopy is suitable for imaging in deep tissue regions (down to about 500 µm) on a cellular level. We use this technique, for example, to visualize tissue structures or track cells, in in vitro settings like cell culture and organoids or in vivo in animal models. Concurrently, we are working on the establishment of novel imaging modalities, which benefit the research on implants. For instance, we have developed a small fiber based fluorescence endoscope, which allows minimal-invasive imaging (Bahlmann et al. 2020). We are currently investigating its applicability in lung tissue together with AG Wiegmann and we are also working on algorithms/computer-based approaches to facilitate imaging. As an example, we apply neuronal networks (AI – artificial intelligence) for image enhancement or cell tracking.

Application of (ultra-short pulsed) laser systems

Our second main research topic is the application of (ultrashort pulsed) laser systems for cell manipulation. Due to the short pulse length, the formation of heat is avoided. Nonlinear effects such as multiphoton ionization lead to precise ablation of biological structures. We apply this technique in vitro, for instance, to probe the cellular repair of the muscle sarcomere. We ablate single Z-discs in a myocyte and use biophysical measurements such as calcium imaging or traction force microscopy to evaluate the effect of single Z-disc loss (Müller et al. 2019). We also established the applicability of laser-based nanosurgery in complex in vitro settings. In organoids, we remove single epithelial cells to study local regeneration pathways. Additionally, we have applied nanosurgery in vivo (DeTemple et al. 2020).

GROUP LEADER

Dr.

Stefan Kalies

Institute for Quantum Optics

Sören Donath

PhD student

Lara Gentemann

PhD student

Niklas Rüprich

PhD student

Anna Seidler

PhD student

Publications:

From this AG:

DeTemple DE, Cammann S, Bahlmann J, Buettner M, Heisterkamp A, Vondran FWR, Kalies SK. Longitudinal imaging and femtosecond laser manipulation of the liver: How to generate and trace single-cell-resolved micro-damage in vivo. PLoS One. 2020 Oct 15;15(10):e0240405. doi: 10.1371/journal.pone.0240405.

Müller D, Hagenah D, Biswanath S, Coffee M, Kampmann A, Zweigerdt R, Heisterkamp A, Kalies SMK. Femtosecond laser-based nanosurgery reveals the endogenous regeneration of single Z-discs including physiological consequences for cardiomyocytes. Sci Rep. 2019 Mar 6;9(1):3625. doi: 10.1038/s41598-019-40308-z

Bahlmann J, Madrahimov N, Daniel F, Theidel D, DeTemple DE, Buettner M, Bleich A, Haverich A, Heisterkamp A, Kalies S. Establishment of a guided, in vivo, multi-channel, abdominal, tissue imaging approach. Sci Rep. 2020 Jun 8;10(1):9224. doi: 10.1038/s41598-020-65950-w.

Hagenah D, Heisterkamp A, Kalies S. Effects of cell state and staining on femtosecond laser nanosurgery. J Biophotonics. 2018 Jul;11(7):e201700344. doi: 10.1002/jbio.201700344.

Saklayen N, Kalies S, Madrid M, Nuzzo V, Huber M, Shen W, Sinanan-Singh J, Heinemann D, Heisterkamp A, Mazur E. Analysis of poration-induced changes in cells from laser-activated plasmonic substrates. Biomed Opt Express. 2017 Sep 27;8(10):4756-4771. doi: 10.1364/BOE.8.004756

Gentemann L, Kalies S, Coffee M, Meyer H, Ripken T, Heisterkamp A, Zweigerdt R, Heinemann D. Modulation of cardiomyocyte activity using pulsed laser irradiated gold nanoparticles. Biomed Opt Express. 2016 Dec 8;8(1):177-192. doi: 10.1364/BOE.8.000177.

Participations within NIFE:

Heene S, Thoms S, Kalies S, Wegner N, Peppermüller P, Born N, Walther F, Scheper T, Blume CA. Vascular network formation on macroporous polydioxanone scaffolds. Tissue Eng Part A. 2021 Feb 24. doi: 10.1089/ten.TEA.2020.0232.

Takayama I, Kondo N, Kalies S, Heisterkamp A, Terakawa M. Myoblast adhesion and proliferation on biodegradable polymer films with femtosecond laser- fabricated micro through-holes. J Biophotonics. 2020 Jul;13(7):e202000037. doi:10.1002/jbio.202000037.

Ichanti H, Sladic S, Kalies S, Haverich A, Andrée B, Hilfiker A. Characterization of Tissue Engineered Endothelial Cell Networks in Composite Collagen-Agarose Hydrogels. Gels. 2020 Sep 3;6(3):27. doi: 10.3390/gels6030027.

Brooks P, Zur Bruegge T, Boyle EC, Kalies S, Villarreal SN, Liese A, Bleich A, Buettner M. CD14 and ALPK1 Affect Expression of Tight Junction Components and Proinflammatory Mediators upon Bacterial Stimulation in a Colonic 3D Organoid Model. Stem Cells Int. 2020 Feb 1;2020:4069354. doi: 10.1155/2020/4069354. PMID:

Janßen HC, Angrisani N, Kalies S, Hansmann F, Kietzmann M, Warwas DP, BehrensP, Reifenrath J. Biodistribution, biocompatibility and targeted accumulation of magnetic nanoporous silica nanoparticles as drug carriers in orthopedics. J Nanobiotechnology. 2020 Jan 15;18(1):14. doi: 10.1186/s12951-020-0578-8.

Andrée B, Ichanti H, Kalies S, Heisterkamp A, Strauß S, Vogt PM, Haverich A, Hilfiker A. Formation of three-dimensional tubular endothelial cell networks under defined serum-free cell culture conditions in human collagen hydrogels. Sci Rep. 2019 Apr 1;9(1):5437. doi: 10.1038/s41598-019-41985-6. PMID: 30932006;

Keywords

Microscopy, imaging, multiphoton microscopy, laser nanosurgery, fiber-optic imaging, endoscopy, organoids

Contact

Stefan Kalies

+49 511 532 1364

kalies(at)iqo.uni-hannover.de

NIFE
Stadtfelddamm 34
30625 Hanover

More additional info

Together with IGEM Team Hannover 2020, we participated in the IGEM 2020 competition and received a gold medal. Please visit the Team Hannover website.Team:Hanover
Edmund Optics Education Award 2018: edmundoptics

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