More than 12 years of the Transregio 67 Project: Functional biomaterials for controlling healing processes in bone and skin tissue – from material to clinic

The demographic trends in Germany and other industrialized nations result in a considerable increase in patients with bone defects and chronic wounds. This requires the development of novel functional biomaterials, which improve bone and skin regeneration in an aging, multimorbid population. Increasing knowledge about the role of the extracellular matrix (ECM) for the regeneration of tissues creates new opportunities for the design of innovative biomaterials. In particular, the structure and composition of ECM significantly influences cellular differentiation and function and the healing of tissues. Hence, the aim of the CRC 67 was to develop and investigate novel functional biomaterials based on naturally occurring and chemically modified, artificial ECM (aECM). Essential functional components of these materials are glycosaminoglycan (GAG) derivatives and proteoglycan (PG) analogs in combination with structural proteins or synthetic carrier components.

It was our vision to exploit the newly gained knowledge on interactions of GAG-derivatives and PG-biomimetics with mediators, matrix components and cells to create novel biomaterials adapted specifically to the needs of patients with impaired regenerative capacities in skin and bone.

From 2009 – 2021 we gained basic insights into the molecular interactions of GAG with different mediators. We could show that aECM-based biomaterials support wound healing of skin and bone; underlying mechanisms were characterized in detail at the atomic level. Finally, we increased the complexity of biomaterials to adapt them to the different phases of wound healing in skin and bone. In a translational setting, these multifunctional biomaterials were tested in relevant preclinical models with physiological and impaired regeneration in skin and bone. This led to the development of innovative treatment strategies for chronic wounds and a first phase I trial in humans to be started soon after completion of the TRR67 funding period.

The CRC 67 was from 1 July 2009 – 31 December 2021 a joint effort of Leipzig University and Technische Universität Dresden with partners from the Technische Universität Berlin, the Helmholtz-Zentrum für Umweltforschung Leipzig-Halle GmbH, the Helmholtz-Zentrum Dresden-Rossendorf, the Leibniz-Institut für Polymerforschung Dresden e.V., INNOVENT e. V. and industry e.g. Firma Mathys Orthopädie GmbH.

The CRC built on four research areas:

1. “Matrix engineering” comprised the material science/chemistry oriented projects, including analytics and modeling.
2. “Biological profiles” bundled projects with cell biological and preclinical orientation.
3. “Transfer” built – together with industrial partners – the base for later clinical testing of the new biomaterials.
4. “Central services” combined methodologically oriented projects that provided service to all subprojects, administration and the graduate school “Matrix Engineering“.

A unique feature of the TRR67 was it‘s highly interdisciplinary character bringing together material science, bioinformatics, biophysics, bio- and glycochemistry, pharmaceutical technology, cell- and matrix biology, immunology and clinical medicine right from the start. This concept was highly succesful to establish very productive and close collaborations, many of which last beyond TRR67 funding.