The German Ministry of Education and Research (BMBF) is providing REGiNA with funds of around 7.5 million euros for a period of five years to support new medical developments and enhance the region’s competence in the field of regenerative medicine. This sum is matched by private funding provided by the 30 or so REGiNA partners from clinics, scientific institutions and industry. A large proportion of the money flows into applied research projects that lead directly to new treatment methods or enable the further development of existing regenerative therapies. The goal is to enable a larger number of patients to benefit from regenerative medicine, including older patients with degenerative diseases that cannot yet be treated satisfactorily with regenerative methods.

Many REGiNA developments are based on the use of cells, where autologous cells, i.e. cells from a patient’s own body, are used to produce a transplant. This can be cells of diseased or damaged tissue or bone marrow stem cells that can develop into tissue cells. The cells are expanded in the laboratory and in many cases combined with a biological carrier material to create a biomechanically stable tissue substitute that can be implanted into a patient.

REGiNA also focuses on the development and optimisation of suitable biomaterials and the development of methods with which cells can be brought to the site in the body where they are needed, with precision and without damaging healthy tissue. Further developments relate to the biofunctionalisation of medical devices, where biocompatible surfaces create ideal cellular response and increase the healing options.

The REGiNA projects concentrate on four therapeutic areas in which the region has made particular progress: the musculoskeletal system, the skin- and wound system and the cardiovascular, respiratory and urogenital systems. The musculoskeletal system therapeutic area focuses on the development of cartilage and bone substitutes. Researchers associated with the University of Tübingen and its well-known hospitals, academic and industrial research institutions have developed a state-of-the-art regenerative therapy for the treatment of joint cartilage defects. This therapy is known as ACT, i.e. autologous chondrocyte transplantation. ACT has been successfully applied in hospitals for several years and will now be further developed by the REGiNA consortium. One of the goals is to use ACT for the treatment of arthrosis patients. Another project combines autologous cells with adaptive carrier materials with the goal of developing therapies that take into account the characteristics and requirements of individual patients.

The skin- and wound system therapeutic area is focused on developing artificial tissue that is as similar as possible to natural tissue. Laboratories are already able to produce a single-layer skin substitute from a patient’s own cells; researchers of the REGiNA consortium are now concentrating on the development of a multilayered skin substitute that consists of several cell types, just like normal skin. R&D relating to the regeneration of soft tissue also involves the combination of several cell types. In this case, fatty tissue and blood vessel cells are co-cultured in order to produce a skin substitute that is well supplied with blood, and hence very similar to natural human skin. Such innovative developments can be used to replace tissue following the surgical removal of tumours, to name just one example.

The cardiovascular and respiratory systems therapeutic area focuses on therapies that enable the regeneration of large vessels in the human body. The development of artificial blood vessels for the treatment of circulatory disorders is a medical progress that saves a great deal of lives. However, artificial vessels can also close and obstruct the blood flow. In order to enable the unrestricted flow of blood, REGiNA researchers have developed a strategy that allows them to endothelialise artificial vessels, i.e. coat them with the patient’s own cells. Other researchers are working on increasing the biocompatibility of artificial respiratory stents using a coating that helps the stents to adhere to the wall at the same time as immobilising them and preventing bacteria from colonising the implant.

The urogenital system therapeutic area deals with regenerative support in the truest sense of the word. Surgical removal of the prostate in men suffering from prostate tumours can lead to the impairment of nerve function in this area and result in incontinence and impotence. One REGiNA project is focused on the development of a gel-like substance that fills the entire prostate. And yet another project focuses on the development of novel nervous guidance conduits from biomaterials.

The REGiNA consortium is specifically interested in assessing the health-economic conditions and reimbursement of the new therapies. This has the major advantage that economical approaches can be identified and implemented very early on in the development process. The REGiNA health region takes into account economic issues at such an unusually early time in the R&D process that the region has a pilot character.

Medical ethics is another area of interdisciplinary research and consulting dealt with by REGiNA researchers. Experts from the renowned Institute of Ethics and History of Medicine at the University of Tübingen support the project partners in ethical issues relating to the medical treatment of patients and also bring in own scientific aspects into the project.

In addition to developing new therapeutic methods and products, the REGiNA consortium is also focused on information and education and training as well as consulting. Scientists, entrepreneurs and clinicians are given information about drug approval as well as reimbursement issues. They are also provided with detailed insights into the legal framework with regard to the production of advanced therapy medicinal products (ATMPs). Innovative products involving cells fall under the European Medicine Agency’s (EMA) ATMP category. As the legal regulations are relatively new and still require greater clarity, the education and training events organised by REGiNA are designed to provide the members of the consortium as well as interested members of the public with a greater understanding of what is involved.

The REGiNA team has developed a web presence that provides insights into achievements in the field of regenerative medicine. Written in an easy to understand style, the REGiNA website is aimed at doctors, patients and the public. A special section with in-depth expert information is available for doctors. The consortium has also established InfoLine, a telephone service providing expert information and advice to medical doctors. Patients and their relatives can also use the telephone service and are transferred to specialists if required. Anybody interested in the topic of regenerative medicine is welcome to use the telephone service to find answers to questions about: “the things I’ve always wanted to know”.

REGiNA research projects - overview:

Area I:  musculoskeletal system

• development of an autologous cell therapy for the regeneration of spinal discs
• production of improved joint cartilage that functions as well as the original tissue (use of autologous cells and novel carrier materials)
• treatment of pseudoarthroses using autologous mesenchymal stem cells (MSCs) that improve bone regeneration  
• development of innovative substitutes and implants from autologous periosteum cells for use in the regeneration of bones, specifically in the field of oral and maxillofacial surgery

Area II: skin and wounds

• development of a synthetic, absorbable wound glue for external and internal application for the regeneration of tissue
• generation of autologous, vascularised fatty tissue for use as soft tissue substitute
• development of autologous full-skin transplants
• development of mRNA-based regenerative treatment methods
• development of cell- and nucleic acid free products for the treatment of deep wounds and use as dermis and soft tissue replacements
  
• wound healing and regeneration of gastrointestinal defects by injecting healing-competent cells using water jet technology

Area III: Cardiovascular and respiratory systems

• development of an absorbable and quick fastener for use in the regeneration of blood vessels
• development of a bioactive surface coating for respiratory stents that enhances the regeneration of respiratory defects
• development of standardised methods that allow the application and labelling of cell therapeutics in the field of vascular medicine
• in vivo tissue engineering of small-lumen prostheses for the regeneration of blood vessels.
  

Area IV: Urogenital system

• development of an injectable growth matrix based on hydrogel that facilitates the regeneration of nerves, especially for the treatment of impotence and incontinence problems following prostate cancer
• further development of cell-free nerve guidance conduits that can be colonised with autologous Schwann cells and also enable the regeneration of peripheral nerves with larger defects.

Further information:

ZRM - Center for Regenerative Biology and Medicine 
Paul-Ehrlich-Str. 15
72076 Tübingen
Germany
Tel.: +49 (0)7071/ 29 - 85034
Fax: +49 (0)7071/ 29 - 4553
E-mail: info(at)regmed.uni-tuebingen.de