Tissue Engineering

Research group Tissue Engineering

Complex wounds with exposed bone, nerves or large vessels require rapid defect coverage with vascularized tissue. The transferred tissue has to supply a reliable perfusion in order to avoid infections or unstable scar formation, and to facilitate wound healing with good functional outcomes. In clinical practice, vascularized flaps meet these requirements but are burdened with size limitations and often considerable donor site morbidity. Moreover, in case of large surface burn injuries or extensive trauma, donor sites for free flaps are scarce in general. The replacement of autologous flaps by vascularized tissue engineered constructs is a promising solution to overcome this problem in the future. However, the aforementioned requirements of early and homogenous perfusion are limiting large volume tissue transfer. A way to solve this dilemma is the in vivo creation of axially vascularized constructs, which can be harvested in healthy areas with minimal donor site morbidity allowing defect-adapted custom manufacturing and an accessible vascular connection to recipient vessels because of a given main vascular pedicle. The arteriovenous (AV) loop model generates a unique form of adult neovascularization which is mediated through a vein graft, obtaining angio-inductive properties after being exposed to increased blood flow. With the AV loop model it is possible to create axially vascularized tissue engineered constructs with a functional microcirculation that may become an alternative to autologous free flaps in the future.

 Team

Doctors

  • Dr. Ahmad Eweida
  • Dr. Dominic Henn
  • Dr. Christoph Köpple
  • Dr. Benjamin Thomas
  • Dr. Felix Strübing


Medical doctoral candidates

  • Jan Warszawski
  • Lisa Freier (Tierärztin)
  • Nina Hildenbrand
  • Zizi Zhou (Gastwissenschaftler)
  • Patricia Niedoba
  • Lukas Pollmann
  • Katharina Fischer
  • Nicola Roushansarai

Scientific staff

  • Dr. rer. nat. Matthias Schulte
 Projects

Defect coverage with axially vascularized tissue engineered free flaps (D. Henn)

Free tissue transfer can be associated with significant donor site morbidity. Donor sites for free flaps may be scarce, especially in major burn and trauma patients. Tissue engineering of soft tissue free flaps based on in vivo generated neovascularization may provide a solution to this problem. Our group achieved successful coverage of full thickness wounds with in vivo vascularized arteriovenous (AV) loop based free flaps in a rat model (Schmidt VJ et al. JTERM 2017). With the ultimate goal of clinical translation of AV loop based soft tissue flap engineering in mind, we aim at translating this technique to a large animal model and implementing further refinements with regard to acellular scaffold components and tissue engineering chamber materials. 

The role of miRNAs in flow-induced neoangiogenesis (D. Henn)

MicroRNAs (miRNAs) are short, non-coding RNAs which bind to the 3’ untranslated region of messenger RNAs (mRNAs) leading to their degradation or inhibition of translation into proteins. In vascular tissue samples from patients with arteriovenous (AV) loops and in a corresponding rat model, our group has shown, that elevated vascular shear stress causes a strong deregulation of miRNA and consequently also mRNA expression profiles with an up-regulation of pro-angiogenic expression patterns (Henn D et al. Plast Reconstr Surg. 2018). Therefore, specific miRNAs are important determinants of flow-induced angiogenesis and constitute future targets for therapeutic interventions in diseases associated with dysfunctional blood vessel growth as well as tissue engineering. 

Establishing a novel human xenograft model of venous malformation in the mouse (F. Strübing)

Venous malformations develop due to aberrances in the venous system. Enlarged and dysfunctional venous networks are formed. Over time, the lesions often grow slowly but continuously and eventually cause discomfort, bleeding and disfigurement. To gain insights into the development and possible treatment options of these rare diseases we want to establish a new animal model, using human tissue samples. To achieve this goal, we have a tight collaboration with the center for vascular anomalies at the Mannheim university hospital.

Axially Vascularized Tissue-Engineering Constructs as Chemotaxis Points for Targeted Progenitor Cell Therapy (A. Eweida)

Stem cell therapy is an established technique to enhance tissue regeneration and improve vascularity after ischemic injuries. However, the selective engraftment of the local progenitor cells or the injected stem cells to the site of injury still represents a challenge. A selective chemotaxis of progenitor cells via the SDF1-CXCR4/CXCR7 axis to the ischemic target sites has been already described. The aim of this project is to determine and characterize the comparative efficacy of AVTECs (Axially vascularized tissue engineering constructs) as chemotaxis points for bone marrow derived progenitor cells in a small animal model. Proving and characterizing the ability of AVTECs to selectively attract injected progenitor cells would help applying AVTECs as a method for improving vascularity and selectivity in targeted progenitor cell therapy especially in the field of wound healing, tissue regeneration and vascularization.

Metastatic nices (B. Thomas)

What enables tumors to metastasize and how do circulating tumor cells interact with metastatic niches? An unprecedented in vivo model system based on a microvascular vessel loop embedded in a biological matrix within an implantable teflon chamber will help us to answer this unsolved question. This will enable us to better understand the mechanisms underlying the metastatic process, and identify new potential targets for novel future anti-cancer therapies.

Breast reconstruction small animal model (B. Thomas)

For breast reconstruction following tumor resection, both autologous and allogenic materials are used. Each method has specific advantages, but also disadvantages. Long treatment duration, numerous follow-up operations, surgical site infections, disfiguring scars and functional restrictions have to be accepted in the context of various conventional therapeutic approaches. The use of breast prostheses and fat transplants are said to be "scar sparing" or "minimally invasive". These breast reconstructive procedures are often preferred in order to minimalize the above mentioned disadvantages. The scientifically proven advantages of both these methods cannot be dismissed. Important questions, however, such as triggering of inflammatory processes or fibrotic changes, remain unanswered. So far, it has not been clarified which components of foreign materials or lipoaspirates have certain biological effects, nor how the different breast reconstructive methods differ in this regard. In order to investigate and reduce the potential adverse effects of minimally invasive and tissue sparing procedures, we seek to establish the first complete small animal breast reconstruction model. Thus, we hope to reproduce the entire spectrum of breast reconstruction on an experimental scale.

 Cooperation partners
  • Prof. Dr. C. de Wit, Institut für Physiologie der Universität zu Lübeck
  • Dr. rer. nat. C. Weis, Diagnostische und Interventionelle Radiologie, Universitätsklinikum Heidelberg
  • PD Dr. C. Wängler, Molekulare Bildgebung & Radiochemie und biomedizinische Chemie, Universität Heidelberg
  • Institut für klinische Radiologie und Nuklearmedizin, Medizinische Fakultät Mannheim der Universität Heidelberg
  • PD Dr. rer. nat.  C. Daniel, Nephropathologische Abteilung, Universitätsklinikum Erlangen
  • Prof. Dr. E. Meese, Institut für Humangenetik, Universitätsklinikum des Saarlandes
  • Prof. Dr. Andreas Keller, Klinische Bioinformatik, Universität des Saarlandes
  • Fraunhofer-Institut für Lasertechnik ILT, Aachen
  • Prof. Dr. Jonathan Paul Sleeman, Centrum für Biomedizin und Medizintechnik Mannheim, Sektion Mikrovaskuläre Biologie und Pathobiologie, Medizinische Fakultät Mannheim der Universität Heidelberg
  • Fraunhofer-Institut für angewandte Polymerforschung IAP, Potsdam
    Dr. rer. nat. S. Zahnreich, Radioonkologie, Universität Mainz
    Prof. Dr. Aldo Boccaccini, Institut für Biomaterialien, Universität Erlangen-Nürnberg 
 Publications

Here you will find all publications of the Tissue Engineering research group in the overview for download

  Leiter Forschungsgruppe Tissue Engineering

Priv.-Doz. Dr. med. Volker Schmidt

volker.schmidt@bgu-ludwigshafen.de

  Teilprojektleiter

Dr. med. Dominic Henn

dominic.henn@bgu-ludwigshafen.de

  Teilprojektleiter

Dr. med. Christoph Köpple

christoph.koepple@bgu-ludwigshafen.de

  Teilprojektleiter

Benjamin Thomas

benjamin.thomas@bgu-ludwigshafen.de

  Teilprojektleiter

Felix Strübing

felix.struebing@bgu-ludwigshafen.de

  Teilprojektleiter

Florian Falkner

florian.falkner@bgu-ludwigshafen.de

  Teilprojektleiter

Dr. med. Ahmed Eweida

ahmed.eweida@bgu-ludwigshafen.de