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Tissue Engineering

Tissue Engineering is defined as tissue cultivation combing a matrix that simulates the natural tissue form and living tissue-specific cells. Ideally, cells are isolated and expanded from the recipient. The necessary cooperation between material development and cell biology of such cell-matrix entities has been outstandingly established in Hannover. This also includes the testing involving imaging of the in vivo and in vitro functionality. In NIFE excellent groups from eight sites in Hanover with exactly these scientific foci were joined with regard to location and content. This has enhanced innovation.

The concept of tissue engineering is at the interface between biology (cell isolation and culture), medicine (replacement of missing or diseased tissue), and engineering including physics and chemistry (synthetic matrix development and production). The enormous possibilities of this technology became apparent with the first successful applications in orthopedics (cartilage replacement) and cardiology (heart valve implants). Especially the growth of implanted heart valves in children gives completely new perspectives to tissue and organ replacement. A particularly high demand for regenerative therapies and replacement of degenerated tissue is seen in older individuals. This makes the importance of tissue engineering in view of the aging population especially important. The groups introduced here will initially focus on the organ systems heart-lung-vasculature, ear-nose-throat, neuronal, musculoskeletal and dental. However, this does not mean that the development for other organs, which are also in dramatically rising demand for tissue engineering products, is excluded.

Hanover is one of the world’s leading groups in tissue engineering of heart valves (research groups of Prof. Haverich/ Cebotari/ Hilfiker) and heart muscle tissue (research groups of Prof. Gruh/ Martin). In NIFE, the heart valve spectrum will be expanded from pulmonal to aorta and mitral valves especially with regard to the biomechanical resilience (research group of Dr. Korossis). In vascular tissue engineering (research group of Prof. Böer/Wilhelmi) bioartificial vessel prostheses will be developed on the basis of xenogeneic and autologous fibrin scaffolds, test methods on immunologic tolerance will be established, and first preclinical trials will be done for selected products. The research group of Prof. Heisterkamp, LZH is studying the interaction of experimental implants with the surrounding tissue in vivo using laser optics. For future 3D-reconstruction procedures of (heart and vessel) tissue, the already very successful collaboration with the Laserzentrum Hanover (research group of Prof. Chichkov) as well as Rapid Prototyping (research group Prof. Rohde) and the biochemistry research group of Prof. Kirschning (degradable biopolymers) will become increasingly important. So far, all these groups have worked at different locations in Hanover. Their collaborations will be supported by their close proximity in NIFE. This cooperation of experimental and clinical researchers with its broad and renowned strong expertise in tissue engineering is nationally as well as internationally state-of-the-art.

The goal of all work groups in the tissue engineering research area is the quick development of tissue replacements for specific treatments using transdisciplinary approaches of various surgical departments such as cardiovascular, ENT, or dental-oral-maxillofacial. In the focus of the joint research and development are strategies to generate tissue replacements that are as close as possible in structure and function to the native original. This can be achieved by optimizing:

  • cell source and cell expansion

  • 3D-matrices

  • vascularized matrices

  • in vitro- and in vivo-models for functional testing

  • evaluation of immunologic tolerability.

The cooperation becomes clear using „Vascularization of Bone Replacement“: the lacking vascularization of tissue engineering constructs leads to a malfunction in blood supply of the implant tissue. To be able to correct bone defects in the maxillofacial area the Clinic for Cranio-Maxillo-Facial Surgery (research group of Prof. Gellrich, Dr. Tavassol, Dr. Kampmann) is developing a titanium-based bone replacement that is vascularized with the help of bioartificial vessel prostheses (research group of Dr. Aper, Prof. Böer/Wilhelmi). A separate microcirculation will be realized in these constructs that will support integration and prevent implant failure. The use of suitable marking strategies and optical methods (research group of Prof. Nolte/ Heisterkamp) allows direct in vivo process surveillance.

In addition, the tissue engineering area has the goal to optimize and standardize the production process and testing in such a way as to prepare QM-appropriate production of individual implants for (pre-)clinical testing of drug products as novel treatments. The established processes will be transferable to GMP-certified operations in the form of modules. This will be essential to prepare investigational products for clinical trials. The produced implants will be tested in animals for their functionality and safety. Furthermore, new methods that are suited to non-invasively characterize the produced tissue will be developed and established for quality control. These are for example laser optical procedures to characterize the colonization density.

At the same time through close cooperation of the different disciplines, an environment will be created for scientific young talents. Training and further education will be possible at the interface of biomedical-technical research. This will accommodate the increasing demand for transdisciplinarily trained researchers and personnel for universities, hospitals, and the medical-technical industry.