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  6. Research Group for nanoBiomaterials

Research Group for nanoBiomaterials

Multifunctional biomaterials

Our interdisciplinary research team is interested in understanding cell-material interactions on different length scales. Based on fundamental biophysical principles, we develop new biofabrication techniques to prepare fibrous and porous biopolymer scaffolds for cell culture studies. The results of our research will be highly interesting for the development of multifunctional biomaterials for future tissue engineering applications.

Contact

Porträtfoto Dorothea Brüggemann

Prof. Dr. rer. nat. Dorothea Brüggemann
+49 421 5905 3477
Email

Research

Fibrous biopolymer scaffolds for tissue engineering

Research focus

Research focus

Our research focus

Tissues are composed of different cell types, which are surrounded by the extracellular matrix (ECM), a dense network of different protein nanofibers. When an injury occurs in a tissue, a nanofibrous fibrin clot initially closes the wound to facilitate cell growth and tissue repair.

Although nanofibrous biopolymer scaffolds are highly attractive for regenerative medicine it still remains challenging to prepare such scaffolds under physiological in vitro conditions. Therefore, our interdisciplinary research focuses on the multi-scale development and characterization of novel biomimetic fiber scaffolds for tissue engineering.

Our research activities span several length scales from the molecular level of protein fibrillogenesis via the nano- and microscale of scaffold assembly towards the development of macroscopic biomaterials.

In vitro fiber assembly

Salt-induced self-assemblly of nanofibrous fibrinogen scaffolds

© Stapelfeldt et al., Nano Letters 19 (2019)

Key techniques

Based on biophysical studies on fiber formation our group develops new biofabrication techniques for the preparation of fibrous scaffolds under physiological in vitro conditions.

Key techniques to fabricate biopolymer fibers that have been developed in our group are:

  • Salt-induced self-assembly of fibrinogen into nanofibers
  • Template-assisted extrusion of proteins through ceramic nanopores

We also use established methods to develop fibrous biomaterials with new compositions and tailored functionality:

  • Self-assembly of nanofibrous collagen scaffolds
  • Wet-spinning of polysaccharide microfibers, e.g. chitosan

Molecular level

What are the driving forces during in vitro fibrillogenesis?

Changes on the molecular level of a biomaterial can influence its biofunctionality on different length scales. These structural changes can affect molecular signaling and the interaction with cells. For the development of future biomaterials, it is therefore important to understand the molecular mechanisms that occur during fiber assembly.

Our goal is to establish fibrous protein scaffolds as a biophysical model system for protein fibrillogenesis in a cell-free environment. To analyze conformational changes in fibrous protein scaffolds we use various modern characterization methods including Förster resonance energy transfer (FRET) measurements, circular dichroism (CD) and Fourier transform infrared (FTIR) spectroscopy.

We correlate our experimental studies with molecular dynamics (MD) simulations on protein interactions (collaboration with S. Köppen, Uni Bremen).

Molucar Level

© Kulke et al., Journal of Chemical Information and Modeling 59 (2019)

Nano-/microscale

Fg fibers

© Stapelfeldt et al., Biofabrication 11 (2019) and Stapelfeldt et al., Nano Letters 19 (2019)

How can the nanoarchitecture and functionality of fibrous biomaterials be tailored?

In native tissue, a complex interplay of topographical, biochemical and mechanical cues governs molecular and cellular interactions. Hence, controlling the nano-/microarchitecture and biofunctionality of a biomaterial is important to achieve tailored interactions during wound healing and tissue repair.

We use state-of-the-art microscopy techniques to characterize our fibrous biomaterials from the nano- to the microscale including scanning electron, atomic force and confocal microscopy. Towards future applications in tissue engineering we also characterize the stability and degradation properties of fibrous biopolymer scaffolds under varying environmental conditions including temperature changes or enzyme activity.

Cell interaction

© Suter et al., Materials Science & Engineering C 126 (2021)

How do cells interact with fibrous biomaterials?

The complex interplay of cell-biomaterial interactions is one of the most important challenges in tissue engineering. Towards future applications in regenerative medicine we want to understand the interaction of our new fibrous biomaterials with different cell types, such as fibroblasts or keratinocytes.

We study how cells proliferate and migrate on fibrous biomaterials and how the actomyosin cytoskeleton and cell morphology are changed. Moreover, we are interested in the interaction of fiber scaffolds with bacterial cultures to screen them for antimicrobial properties. Typical techniques we use to study cell interactions are viability assays, fluorescence microscopy or live-cell tracking in combination with scanning electron microscopy.

Macroscopic scaffolds

Fg Scaffold optimized

© AG Brüggemann

How can fibrous biopolymer scaffolds be scaled up?

To identify future strategies that efficiently treat large tissue defects, the scalability of a biofabrication processes is very important. We therefore aim to upscale our new biofabrication routines for future tissue engineering applications, for example by introducing polymer molding.

To facilitate optimum tissue regeneration the mechanical properties of macroscopic biomaterials need to be tailored. Hence, we also aim at optimizing the tensile and compression properties of our fibrous biomaterials for tissue repair.

Moreover, we want to understand how cells react to changes in the nanotopography in real time. Therefore, we combine protein self-assembly with polymer printing to prepare protein scaffolds with spatially controlled surface topographies to study their interaction with cells

Nanoporous protein-ceramic composites

How do inorganic nanomaterials interact with proteins and cells?

When inorganic nanomaterials like various ceramics are used for tissue engineering, they are immediately coated with proteins from blood and other body fluids, forming a new material interface. To tailor the reaction of these new surfaces with the surrounding tissue, we want to understand the interaction of porous ceramic surfaces with proteins and cells. In this project, we use anodized alumina (AAO) nanopores and alumina microporous textiles as ceramic surfaces to study their interaction with different ECM proteins, fibroblasts, and keratinocytes. Based on these studies, we explore new applications of porous ceramic nanomaterials for soft tissue engineering.  

 

AAO nanopores

© Dutta et al., ACS Applied Bio Materials 4 (2021)

Head of Group

Porträtfoto Dorothea Brüggemann

Prof. Dr. rer. nat. Dorothea Brüggemann
+49 421 5905 3477
Email

PhD students

Auf dem Bild ist Titinun Nuntapramote zusehen. Er hat kurze schwarze Haare und trägt eine Brille und ein weißes T-Shirt unter einer graues Sweatshirtjacke.

Titinun Nuntapramote
+49 421 5905 3452
Email

Lea Dierker
+49 421 5905 3452
Email

Auf dem Foto ist Antoine Eyram Kwame zusehen. Er hat kurzes schwarzes Haar und trägt ein blaues Hemd unter einem roten Pullover.

Antoine Eyram Kwame
+49 421 5905 3452
Email

Publications

    • Topography-mediated induction of epithelial mesenchymal transition via alumina textiles for potential wound healing applications, Dutta, D., Nuntapramote, T., Rehders, M., Brix, K., Brüggemann, D., J. Biomed. Mater. A., accepted

    • The Future of Bioinspired Innovation: Exploring the Potential of Nanobiomimetics, Dirks, J-H., Brüggemann, D.,  Nano Lett., 2024, 24 (38), 11765-11767

    • Structure, Properties and Degradation of Self-Assembled Fibrinogen Nanofiber Scaffolds, Strunk, T., Joshi, A., Moeinkhah, M., Renzelmann, T., Dierker, L., Grotheer, D., Graupner, N., Müssig, J., Brüggemann, D., ACS Appl. Bio Mater. 2024, 7, 9, 6186–6200

    • Alumina ceramic textiles as novel bacteria-capturing wound dressings, Dutta, D., Almeida, R., Karim, M.D., Brüggemann, D., Rezwan, K., Maas, M., Adv. Mater. Interfaces, 2024, 2400232

    • Assembly of rolled-up collagen constructs on porous alumina textiles, Dutta, D., Graupner, N., Müssig, J., Brüggemann, D., ACS Nanoscience Au, 2023, 3(4), 286–294

    • Self-Assembled fibrinogen scaffolds support cocultivation of human dermal fibroblasts and HaCaT keratinocytes, Joshi, A., Nuntapramote, T., Brüggemann, D., ACS Omega, 2023, 8, 9, 8650–8663

    • Nanofiber topographies enhanceD platelet-fibrinogen scaffold interactions, Kenny, M., Stamboroski, S., Taher, R., Brüggemann, D., Schoen, I., Advanced Healthcare Materials, 2022, 2200249

    • Effect of interface-active proteins on the salt crystal size in waterborne hybrid materials, Stamboroski, S., Boateng, K., Cavalcanti, W. L., Noeske, M., Beber, V. C., Thiel, K,, Grunwald, I., Schiffels, P., Dieckhoff, S., & Brüggemann, D., Applied Adhesion Science 9, 7, 2021
    • Influence of divalent metal ions on the precipitation of the plasma protein fibrinogen, Stamboroski, S., Boateng, K., Lierath J., Kowalik, T., Thiel, K., Köppen, S., Noeske, P.-L. M., & Brüggemann, D., Biomacromolecules, 2021, 22, 11, 4642-4658
    • Principles of fibrinogen fiber assembly in vitro, Stamboroski, S., Joshi, A., Noeske, P. L. M., Köppen, S., & Brüggemann, D., Macromolecular Bioscience, 2021, 2000412.
    • Self-assembled fibrinogen nanofibers support fibroblast adhesion and prevent E. coli infiltration, Suter, N., Joshi, A., Wunsch, T., Graupner, N., Stapelfeldt, K., Radmacher, M.,  & Brüggemann, D., Materials Science and Engineering: C, 2021, 112156.
    • Effect of collagen nanofibers and silanization on the interaction of HaCaT keratinocytes and 3T3 fibroblasts with alumina nanopores, Dutta., D., Markhoff, J., Suter, N., Rezwan, K., Brüggemann, D., ACS Applied Bio Materials, 2021, 4(2), 1852-1862
    • Spatial patterning of nanofibrous collagen scaffolds modulates fibroblast morphology, Suter, N., Stebel, S., Rianna, C. Radmacher, M., Brüggemann, D. Biofabrication, 2021, 13(1), 015007-18
    • Wet-spinning of magneto-responsive helical chitosan microfibers, Brüggemann, D., Michel, J., Suter, N., de Aguiar, M. G., & Maas, M., Beilstein Journal of Nanotechnology 11 (1), 991-999, 2020
    • Controlling the multiscale structure of nanofibrous fibrinogen scaffolds for wound healing, Stapelfeldt, K., Stamboroski, S., Walter, I., Suter, N., Kowalik, T., Michaelis, M., & Brüggemann, D. Nano letters 19 (9), 6554-6563, 2019
    • Phosphorylation of fibronectin influences the structural stability of the predicted interchain domain, Kulke, M., Uhrhan, M., Geist, N., Brüggemann, D., Ohler, B., Langel, W., & Köppen, S., Journal of Chemical Information and Modeling 59 (10), 4383-4392, 2019
    • Fabrication of 3D-nanofibrous fibrinogen scaffolds using salt-induced self assembly, Stapelfeldt, K., Stamboroski, S., Mednikova, P., & Brüggemann, D., Biofabrication 11 (2), 025010, 2019
    • Template-assisted extrusion of biopolymer nanofibers under physiological conditions, Raoufi, M., Aslankoohi, N., Mollenhauer, C., Boehm, H., Spatz, J. P., & Brüggemann, D., Integrative Biology 8 (10), 1059-1066, 2016
    • Single-molecule mechanics of protein-labelled DNA handles, Jadhav, V. S., Brüggemann, D., Wruck, F., & Hegner, M., Beilstein Journal of Nanotechnology 7 (1), 138-148, 2016
    • Nanopore diameters tune strain in extruded fibronectin fibers, Raoufi, M., Das, T., Schoen, I., Vogel, V., Brüggemann, D., & Spatz, J. P., Nano Letters 15 (10), 6357-6364, 2015
    • Minimal synthetic cells to study integrin‐mediated adhesion, Frohnmayer, J. P., Brüggemann, D., Eberhard, C., Neubauer, S., Mollenhauer, C., Boehm, H., Kessler, H., Geiger, B., Spatz, J. P. Angewandte Chemie International Edition 54 (42), 12472-12478, 2015
    • Model systems for studying cell adhesion and biomimetic actin networks, Brüggemann, D., Frohnmayer, J. P., & Spatz, J. P., Beilstein Journal of Nanotechnology 5 (1), 1193-1202, 2014
    • Nanoporous aluminium oxide membranes as cell interfaces, Brüggemann, D. Journal of Nanomaterials 1-18, 2013
    • Adhesion and survival of electrogenic cells on gold nanopillar array electrodes, Brüggemann, D., Michael, K. E., Wolfrum, B., & Offenhäusser, A. International Journal of Nano and Biomaterials 17 4 (2), 108-127, 2012
    • A nanoporous alumina microelectrode array for functional cell–chip coupling, Wesche, M., Hüske, M., Yakushenko, A., Brüggemann, D., Mayer, D., Offenhäusser, A., & Wolfrum, B. Nanotechnology 23 (49), 495303, 2012
    • Force measurements of the disruption of the nascent polypeptide chain from the ribosome by optical tweezers, Katranidis, A., Grange, W., Schlesinger, R., Choli-Papadopoulou, T., Brüggemann, D., Hegner, M., & Büldt, G., FEBS letters 585 (12), 1859-1863, 2011
    • Nanostructured gold microelectrodes for extracellular recording from electrogenic cells, Brüggemann, D., Wolfrum, B., Maybeck, V., Mourzina, Y., Jansen, M., & Offenhäusser, A., Nanotechnology 22 (26), 265104, 2011
    • Large-scale patterning of gold nanopillars in a porous anodic alumina template by replicating gold structures on a titanium barrier, Weber, D., Mourzina, Y., Brueggemann, D., & Offenhäusser, A., Journal of Nanoscience and Nanotechnology 11 (2), 1293-1296, 2011
    • Analyzing the electroactive surface of gold nanopillars by electrochemical methods for electrode miniaturization, Schröper, F., Brüggemann, D., Mourzina, Y., Wolfrum, B., Offenhäusser, A., & Mayer, D., Electrochimica Acta 53 (21), 6265-6272, 2008
    • Structure and morphology of perylene films grown on different substrates, Beigmohamadi, M., Niyamakom, P., Farahzadi, A., Effertz, C., Kremers, S., Brueggemann, D., & Wuttig, M., Journal of Applied Physics 104 (1), 013505, 2008

     

    • Brüggemann, D.; Wolfrum, B.; de Silva, J.P.: Fabrication, properties and applications of gold nanopillars, in: Handbook of Nanomaterials Properties, Springer Berlin Heidelberg 2014, 317-354

    • Hegner, M., Brüggemann, D., Skoko, D.: Optical Tweezers, in: Encyclopedia of Nanotechnology, Springer Netherlands 2012, 1981-1991

     

    • Dutta., D., Brüggemann, D.: Self-assembly of rolled-up nanofibrous collagen-based tubular scaffolds for soft tissue engineering, DE Patent application 102022109408.1, 2022 
       
    • Suter, N., Brüggemann, D.: Verfahren zur Herstellung von Biomateralien mit porösen und glatten Topographien und deren Verwendung, DE patent 10 2019 123 799.8, 2021
       
    • Stapelfeldt, K., Mednikova, P., Brüggemann, D.: Methods of production of fibrous fibrinogen scaffolds and products thereof, EU Patent EP3801657, 2024
       
    • Brüggemann, D., Dirks, J.-H., Raoufi, M., Spatz, J.P.: Methods for preparing and orientating biopolymer nanofibres and a composite material comprising the same, DE patent application PCT/DE2014/14003414.1, 2014

Media coverage

    • Biologisches Pflaster aus körpereigenen Proteinen, NDR Info, 29.04.2019
    • Bremer Forscher entwickeln biologisches Pflaster, Bremen Zwei, 31.05.2019
    • Biophysiker erfinden Pflaster aus Menschenblut, buten un binnen, 12.06.2020
    • Abbaubare Wundauflagen, Bayern Zwei, 11.12.2020  
    • „Schorf aus der Tube“: V. Reineking, Kreiszeitung, 13.04.2019
    • „Die Pflaster-Revolution“: D. Kovacevic & H. Blöhte, Bild-Zeitung, 06.05.2019
    • „Die neuen Wunderheiler“: M. Knoke, P.M. Magazin 06/2020
    • "Proteine und Patente": S. Wilke, Weser Kurier, 24.05.2021

     

    • Biological bandage could help heal wounds, News Informationsdienst Wissenschaft idw online, 28.3.2019
    • Biologisches Wundpflaster aus Eigengewebe entwickelt: A. Hillienhof, Deutsches Ärzteblatt, 16.4.2019
    • Biologisches Pflaster in Entwicklung, Nordwest-Zeitung online, 17.4.2019
    • Biologisches Pflaster könnte bei Wundheilung helfen: A. Körber, Karger Kompass Dermatologie, 07/2019
    • Nanogerüste für die Medizin von morgen: K.-U. Bohn, up2date, 11/2019
    • Dem körpereigenen Reparaturprogramm abgeschaut: Was Bremer Forscher sich von Nanofasern zur Wundheilung versprechen, A. Blankenburg, Nürnberger Wundkongress, 29.11.2020
    • Ich habe nicht Deutschland gewählt – Deutschland hat mich gewählt“ Akademischer Mittelbau im Fokus: Dr. Arundhati Joshi aus dem Institut für Biophysik,  Kai Uwe Bohn, up2date, Jun. 2021

     

Collaborations

    • MAPEX Center for Materials and Processes, University of Bremen
    • Institute for Biophysics, University of Bremen
    • Hybrid Materials Interfaces Group, University of Bremen
    • MIMENIMA research training group, University of Bremen
    • Fraunhofer Institute for Manufacturing Technology and Advanced Materials IFAM, Bremen
    • Biomimetics-Innovation-Centre B-I-C, Bremen University of Applied Sciences
    • Forschungsgruppe Gradierte Implantate FOR 2180
    • Institut für Zellbiologie und Biophysik, Leibniz University Hannover
    • Institute for Biochemistry, University of Greifswald
    • Royal College of Surgeons Ireland, School of Pharmacy and Biomolecular Sciences, Dublin
    • Zircar Zirconia Inc., Florida, NY, USA
    • Biotest AG, Dreieich, Germany

Team

If you are interested in joining our interdisciplinary team for PhD projects, B.Sc. or M.Sc. theses, please send us your application including curriculum vitae and research interests. We are always looking for new tem members with a strong background in biophysics, cell biology, biochemistry, materials science and related disciplines.

 

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