Bio-Material Development

Biomaterial development can be seen as a fundamental example of interdisciplinary cooperation in NIFE. From everyday clinical practice, requirements are defined for synthetic and biological materials for implants, which are produced either conventionally, artificially, biohybrid with a resorbable structure or completely biologically. Natural science working groups at Leibniz Universität Hannover and the Laserzentrum Hannover are developing smart materials and methods for targeted modification and/or functionalization. The engineering sciences use these approaches to derive industrial-scale materials for tissue engineering and implant technology according to GMP requirements . Materials must be tested in advance for desired mechanical and biological properties. Medical groups from the audio-neurology, cardiovascular, dental, orthopedic, and skeletal fields influence material development by clearly defining and communicating subsequent requirements in a clinical context to patients so that a clear vision is sought on the part of the chemical and technical groups and can be developed to meet needs.

In the development of materials, nanoporous, nanoparticulate as well as polymeric materials and composites are in focus. The materials must exhibit the mechanical, physical, biological and (bio)chemical properties defined by the clinical application in the bulk and on the surface. Thus they must show suitable mechanical strength, biocompatible and possibly be resorbable as well as sterilizable . With regard to the desired cell and tissue integration, prevention of biofilm formation and resistance to infections they are functionally modified on the surface or are equipped with nanoporous depots for the spatially controlled release of bioactive substances (small-molecule drugs, specific growth factors, adhesion proteins). Surface-structured or nanoporous materials should control targeted growth of individual cell systems and specifically enable material-cell contacts (for example, signal transmission, adhesion, permission). Scaffolds for tissue engineering are manufactured and appropriately equipped, for example, using template methods by chemical means, cryogenic processes or electrospinning/spraying, or 3D printing. In the process, the materials must be tailored to each medical task.

To achieve this goal, it is necessary to design the materials in a modular way. This includes not only the structure of the basic materials, their structuring and characterization, but also the targeted chemical preparation of their surfaces to endow them with the desired chemical, physicochemical and biological surface properties. Close, direct cooperation between the individual working groups for each field of application is necessary for this transfer of knowledge to be effective. The demand-oriented adjustment of the biological properties of the carrier materials requires the close cooperation of the Materials- and drug-oriented working groups (AG Ehlert, Kirschning) as well as the use of biotechnological and medical expertise (AG Blume/Scheper)to decorate surfaces with adhesion factors, toxins and cytokines as well as antibiotics and to examine these under functional conditioning and stress in adapted bioreactors (AG Blume/Scheper, AG Blume eNIFE) and to further develop them into implantable tissues. A wide variety of innovative processing methods for the implants and hybrids are offered by the engineering groups in close cooperation with the partners (AG Heisterkamp, Chichkov, Glasmacher) . Various analysis, sensor and imaging systems for production monitoring and functionality testing (incl. control technology and integrated electronics) are provided by LUH working groups (AG Blume eNIFE, Heisterkamp, Glasmacher, Rosenhahn, Blume/Scheper, Ostermann, Zimmermann) . Test procedures for the different hybrids, implants and functional tissues are supervised, cooperation with the different working groups, mainly by the engineering side (AG Glasmacher).

The newly developed materials are tested and trained in the WG Blume/ Scheper for biocompatibility and also for specific clinical requirements. For this purpose, a staged assay system, as well as a preclinical 3 D cell culture model is made available, which works with human cells from cell lines but also with primary cells. In addition, the possibility of demand-driven bioreactor development for testing the dynamic cultivation of colonized scaffold materials is used. Adapted bioreactors are equipped with sensors and associated electronics for recording important cultivation and cell metabolism parameters (e.g. oxygen, glucose, pH, temperature) and developed (in cooperation with AG H. Blume, eNIFE). In addition, a functional loading of the cell-based implants (mechanotransduction) by means of defined applied shear stress for the cardiovascular, tensile stress in the musculoskeletal or compressive stress for the bony area is applied. The aim is to further develop such soft- or hard-tissue products to the point of implantability, using large animal models.

On-demand modified and functionalized biomacromolecules and organic-inorganic composites are synthesized for the implants to be developed. The Institute for Technical Chemistry produces and supplies the cytokines or growth factors required for this purpose, as well as biomolecules for scaffolds such as fibrinogen or human collagen, etc., in close cooperation with MHH working groups. The biologically active substances are produced in bacterial or mammalian cell cultures. The substances are purified and tested for their biological activity before they are used to functionalize the biomaterials of the institutes of Organic and Inorganic Chemistry . With optogenetic methods and in cooperation with various groups, biohybrid implants are developed, which allow an optical control of cell functions or high-resolution stimulation of nerve and muscle cells (AG Heisterkamp, AG Blume/Scheper, AG Ehlert, LUH).

A structuring takes place through cooperation with the Nanomaterials and Nanotechnology WGs of the Laser Center Hannover (WG Chichkov, Ripken); here methods are available based on optical methods for surface functionalization, assembly by two-photon ion polymerization or by using specific nanoparticles. . The materials for tissue engineering and implant coating are colonized with suitable cell systems under controlled static and dynamic cultivation conditions. So-called LIFT processes (Laser-induced Forward Transfer) enable direct colonization with cells in 3D. Via different laser based methods the developed constructs can be studied and characerized at high resolution and over a wide range of scales .

In collaboration with clinical groups function testing devices for endoprostheses (knee, hip) or dental implants are available. Bioreactor developments are initiated as in vivo test systems, for example for growing heart valves (tissue engineering). Here, the direct cooperation with the cross-sectional area of in vivo imaging with innovative video-based image analysis for online monitoring of cell growth is essential (AG Rosenhahn, eNIFE).