Tissue Engineering

The interdisciplinary research field of "Tissue Engineering" occupies the interface between biology (isolation and cultivation of cells), medicine (replacement of missing or diseased tissue) and engineering sciences, including physics and chemistry (development and production of synthetic matrices). Here, multilateral artificial tissues are produced in the laboratory to resemble their biological counterparts as closely as possible in form and function in order to restore the loss of function of diseased or destroyed tissues in a patient. The cultivation process of these tissues requires specific processes, procedural and establishment steps that are optimized on an interdisciplinary basis. In general, tissue-specific cells are cultivated with a form-giving? carrier matrix in a special nutrient solution. By adding special signal molecules and by further specific stimuli, such as mechanical stress, the cells are stimulated to develop in a targeted manner and to behave physiologically.

The cooperation between material development and cell biology, which is indispensable for the processing of such cell-matrix organizations, as well as the inseparable testing by imaging of in vivo, ex vivo and in vitro functionality, has developed excellently in Hannover. In NIFE, excellent groups from eight locations in Hannover with precisely these scientific focal points have been brought together in terms of space and content, which has created a decisive added value for the promotion of innovations.

With the first successful applications in orthopedics (cartilage replacement) and heart surgery (heart valve implants), the immense possibilities of this technology became clear. In particular, the demonstration of the growth of implanted heart valves in the body of a child sheds light on completely new ways of tissue and organ replacement. However, there is a particularly high demand for regenerative therapy and replacement of degenerated tissue in the elderly, making the importance of tissue engineering particularly plausible in the context of an aging population. If the groups presented here initially focus on the organ systems heart-lung-vascular, ear, nose and throat (ENT)-neuro, and musculo-skeletal-dental, this does not preclude developments for other organs, where there is also a dramatically increasing need for tissue engineering products.

Hannover is one of the leading groups worldwide in tissue engineering of heart valves (AG Hilfiker) and heart muscle tissue (AG Gruh/Martin). In the field of heart valves, NIFE will expand the spectrum from pulmonary to aortic and mitral valves, especially with regard to biomechanical resilience and regenerative properties (WG RESPONSE). In the field of vascular tissue engineering (WG Aper/Wilhelmi), bioartificial vascular prostheses and patches based on xenogeneic and autologous fibrin scaffolds are being developed, test methods for immunological compatibility are being established and initial preclinical tests for selected products are being carried out. Furthermore, a working group (AG Goecke/Ramm) has been established at the NIFE site with the aim of enabling xenotransplantation of lungs from genetically modified pigs. For this purpose, among others, the systems and knowledge within the working group Ex-vivo Organ Perfusion (AG Wiegmann) are available. This group has set itself the goal of establishing novel therapeutic approaches from tissue engineering and regenerative medicine on organs that are supplied with body-warm nutrient solution or blood outside the body in a physiological ex vivo environment and then testing them with regard to their functionality and safety in the integrated organ complex. Within the Wiegmann group, tissue engineering methods are also applied for the development and establishment of the biohybrid lung as a permanently applicable alternative procedure to lung transplantation, in particular for the biologization of so-called gas exchange membranes extracorporeal membrane oxygenators, which are analyzed in small and large animal models. Protection and regeneration by applying the principle of tissue engineering in the inner ear is the focus of the Warnecke group. The Heisterkamp group, (LUH, IQO) follows the interaction of experimental implants with surrounding tissues laser-optically in vivo. For future methods of 3D reconstruction of (cardiac and vascular) tissues, the already very successful joint work with the AG Chichkov, (LUH, IQO) but also the Rohde group (rapid prototyping) with Biochemistry (degradable biopolymers) will be of increasing importance. All these groups have so far worked at different locations in Hannover and will be supported in their collaboration by the spatial proximity in NIFE. A collaboration of experimental and clinical researchers with the breadth represented here and already proven deep expertise in tissue engineering has top national and international character.

The goal of all working groups in the research area Tissue Engineering is to achieve faster development of a tissue substitute for corresponding therapy approaches through transdisciplinary approaches from different surgical departments such as cardio-vascular, ENT or dental-mouth-jaw (ZMK). The focus of the joint research and development is on strategies to generate tissue substitutes that are as close as possible to the native model, both structurally and functionally. This is achieved, among other things, by optimizing:

  • Cell Sources and Cell Expansion
  • Cell - Matrix Interactions
  • Vascularized Matrices
  • 3D Matrices
  • In vitro, ex vivo and in vivo models for functional testing
  • Ex vivo organ perfusion
  • Evaluation of immunological compatibility

This collaboration is exemplified by the project "Vascularization of bone substitutes": The lack of vascularization of tissue engineering constructs leads to malabsorption of the implanted tissues. In order to repair bony defects in the maxillofacial region, the Department of Oral and Maxillofacial Surgery (WG Gellrich/Tavassol/Kampmann) is developing a titanium-based bone substitute that is vascularized using a bioartificial vascular prosthesis (WG Aper/Wilhelmi). In these constructs, a dedicated microcirculation should be realized to support healing and prevent failure of the implanted construct. The use of appropriate labeling strategies and optical methods (WG Heisterkamp) allows direct in vivo tracking of the process.

In addition, the Tissue Engineering unit aims to optimize and standardize manufacturing processes and test methods in order to prepare QM-compliant production of individual implants for (pre)clinical testing as advanced therapy medicinal products. The established processes are to be transferable in a modular fashion to GMP-certified operations and thus significantly prepare the production of investigational medicinal products for clinical testing. The implants produced in this way will be tested in animal experiments for their functionality and safety. Furthermore, new methods for quality testing are to be developed and established that are suitable for characterizing the manufactured tissues non-invasively, such as laser-optical methods for characterizing the colonization density.

At the same time, this close cooperation between the various disciplines creates an attractive environment for young scientists, enabling training and continuing education at the interfaces of biomedical engineering research. In this way, the increasing demand for transdisciplinarily trained researchers and employees for universities, hospitals and the medical technology industry is taken into account.