Regeneration and Reconstruction

We are an interdisciplinary research group working tightly together with the clinical colleagues. This cooperation gives us the possibility to identify the problems in orthopedic and trauma surgery and to work on new strategies to solve them. Our main interest focuses on the osseous regeneration, infection prophylaxis and treatment as well as tendon biology. Using in vitro studies of different cell types and different in vivo healing models, we continue to explore various approaches to influence osseous healing, to treat infections and to understand tendon degeneration and repair processes.

Research Focus

Bone regeneration

The bony tissue has the potential to regenerate defect situations under optimal treatment within an appropriate period without the formation of scar tissue. However, even with optimal mechanical stabilization and operative treatment, healing can be delayed or fail. We aim at understanding the biological processes responsible for healing or non-healing of bone. Using an in vivo healing model showing distinct and clinically relevant healing impairments (hypertrophic and atrophic non-union), we were able to demonstrated distinct changes in the formation of the regenerative tissue, the vessel formation and the expression of factors from osteogenic and angiogenic signalling pathways.

A further focus is the optimization of bone grafting material and we have extensive experience in the analysis of bony materials used for defect filling. We established a set-up that allows the quantification of growth factors within the bony grafting materials, the in vitro testing of the effect of the materials on different cell types, and the efficacy testing of the materials in critical size defect models. This approach allows a detailed analysis of existing and newly developed materials. We demonstrated that the effectivity of different demineralized bone matrices (DBM) vary and is inferior to the growth factor BMP. Enriching DBM with BMP resulted in a long term binding of the growth factor lasting for at least 56 days and a significantly better bone healing compared to DBM alone. The enrichment method is easy and reliable and can be used peri-operatively. These projects are performed in tight interaction with the Work Area “Employing mechano-biology and shaping inflammation to enhance endogenous regeneration” of Field Musculoskeletal System.

Infection

A further severe complication in bone healing is osteomyelitis and therefore the group aims to develop a prophylaxis and treatment for this complication. The combination of the adequate grafting material with a specific antimicrobial drug and the optimal dosage and release will be important for a successful therapy.  The before mentioned enrichment method was also investigated for antibiotics, and we showed a distinct release pattern of different antibiotics. This approach allows a release of the antibiotics from the DBM for a clinically relevant period at an antimicrobial concentration without harming osteoblast like cells. Facing the increase of antimicrobial resistance, new antimicrobial active substances are urgently needed. Antimicrobial peptides (AMPs) are promising candidates and in a cooperation project the activity and biocompatibility of designed AMPs was shown.

The microbiological testing of anti-infective substances or surfaces is done in cooperation with PD Dr. Andrej Trampuz from the Work Area: “Compromised patients” in Field Musculoskeletal System.

The combination of the knowledge from the local stimulation of the osseous healing and the analyses of grafting materials can be used for further development and optimization of treatment strategies. Those strategies can be combined to optimize the biomaterials by the addition of bioactive substances to stimulate bone regeneration or treat infections. This research aspect has direct clinical relevance and aims to develop a new grafting material for the stimulation and treatment of bony defects.

Tendon 

Beside the research in the field of bone healing, the research group concentrates on tendon healing since a couple of years. To gain basic knowledge regarding the impact of patient characteristics on the biology of tenocytes we established a cell bank from over 150 well-characterized donors/tendon samples. We demonstrated that age, female sex and fatty infiltration of the muscle –as an indicator for tissue degeneration- impairs the tenocytes. The biological potential was recovered by stimulation with the growth factors BMP-2/7.

The most frequently ruptured tendon is the Achilles tendon and primarily seen in recreational and professional athletes. We aim to elucidate the repair processes of human Achilles tendon. The in depth analysis of the tissue will provide information on the repair process that naturally starts after the damage of tissue and progresses by time. We focus on the analysis of matrix formation and degradation, cell composition as well as inflammatory factors and processes. The correlation to the clinical outcome will allow us to judge the seen biological events. Using an in vitro study we already demonstrated that tenocytes respond to inflammatory environments with altered marker and cytokine profiles and influence macrophage polarization, which could impact the resolution of inflammation. The studies are performed in cooperation with M. Seifert, Field Immune System.

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Team

Group Picture AG Wildemann
(LTR) Susann Minkwitz, Franka Klatte-Schulz, Viviane Fleischhacker, Britt Wildemann, Christopher Differ, Thanh Huyen Nguyen, Nicole Bormann, Aysha Schmock

Dipl.-Ing (FH) Nicole Bormann

MSc Christopher Differ
Doctoral Student

Elisabeth Huber
Doctoral Student (med vet)

Dr. rer. medic Franka Klatte-Schulz
Postdoc

Anna Koliszak
Bachelor Student

Dipl.-Ing Susann Minkwitz
Doctoral Student

Sophie Nast
Doctoral Student (med vet)

Aysha Schmock
Master Student


Clinical Partners at the Center for Musculoskeletal Surgery (CMSC):

Dr. Christian Gerhardt
Dr. Sebastian Manegold
Dr. Stephan Pauly
Prof. Dr. Markus Scheibel
Dr. Philipp Schwabe
Dr. Serafeim Tsitsilonis

Alumni:
Thomas Aleyt
Arash Calafi, MD
Dr. med. vet. Mirja Fassbender
Gerry Giese
Jelka Hartwig
Dipl.-Ing (FH) Anka Kadow-Romacker
Stefanie Kasper
Anna Koliszak
Zienab Kronbach
Dr. med. vet. Tanja Schmidt
Larissa Schön
Dr. rer. medic Catrin Strobel
Melanie Ukert

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Methods

In vitro models: primary osteoblast, osteoclast and tenocyt- like cells, cell lines In vivo models: small and large animals models for bone regeneration, different fixation methods for bone defects:

  • Cell culture of different cell types
  • Different animal models
  • Histology and immunohistochemistry (Fig. 2, Research Focus)
  • Biomechanical testing (Fig. 3)
  • Fluorescence Activated Cell Sorting (FACS)
  • Magnetic Cell Sorting
  • Real time-PCR
  • Protein assay and ELISA
  • Local drug release systems

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Cooperations

Within the BCRT and Charité

  • Prof. Dr. Georg Duda, Dr. AM. Pobloth, Dr. H. Schell, Dr. K. Schmidt-Bleek (Field Musculoskeletal System)
  • PD Dr. Annette Moter, Dr. J. Kikhney, Institute for Microbiology and Hygiene, Charité, Biofilmcenter, German Heart Institute Berlin
  • Prof. Dr. Birgit Sawitzki, Institute for Medical Immunology
  • Prof. Dr. M. Sittinger (Field In situ Tissue Engineering)
  • PD Dr. Andrej Trampuz, Anna Koliszak (Field Musculoskeletal System, CMSC)
  • PD Dr. R. Volkmer, Institute for Medical Immunology, Charité, Leibniz-Institut für Molekulare Pharmakologie

External facilities

  • Prof. Dr. A. Diamantis and Prof. Dr. K. Legerlotz, Institute for Sport Science, HU Berlin
  • Prof. M. van Griensven, PD Dr. H. Vester, Technical University Munich
  • Dr. Kai Hilpert, Institute of Infection and Immunity, St George’s University of London
  • Prof. Dr. P. Knaus, FU-Berlin
  • PD Dr. M. Lucke, Chirurgische Klinik Dr. Rinecker, München
  • Prof. Dr. A. Nüssler, Dr. S. Ehnert, Eberhard-Karls-University Tübingen
  • Prof. Dr. D. Scharnweber, Max Bergmann Center of Biomaterials, Dresden
  • Prof. Dr. G. Schmidmaier, Heidelberg University Hospital
  • Prof. Dr. T Schulz, DIfE.
  • Prof. Dr. S. Stricker, FU-Berlin
  • Prof. Dr. Ch. Willy and PD Dr. D. Back, Bundeswehr Hospital Berlin

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Awards

  • 2011 Oskar und Helene-Medizinpreis, Stiftung Oskar-Helene-Heim
  • 2011 APOA-Pfizer Best Scientific Paper Award for Orthopaedic Infection, Asia Pacific Orthopaedic Association
  • 2008 Herbert Lauterbach Preis, Vereinigung Berufsgenossenschaftlicher Kliniken
  • 2004 COPP-Preis, Deutsche Gesellschaft für Osteologie
  • 2002 Forschungspreis, Deutsche Gesellschaft für Biomaterialien
  • 2002 New Investigator Recognition Award, Orthopaedic Research Society
  • 2000 Hans-Liniger-Preis, Deutsche Gesellschaft für Unfallchirurgie

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Publications

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Contact

Prof. Dr. Britt Wildemann
Prof. Dr. Britt Wildemann

Charité - Universitätsmedizin Berlin
Berlin-Brandenburg Center for
Regenerative Therapies
Campus Virchow-Klinikum
Augustenburger Platz 1
13353 Berlin
Germany

Phone: +49 (0)30 450 559 618
Fax: +49 (0)30 450 559 938
Email: britt.wildemann@charite.de

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