Biohybride / BiokompatibilitätBiohybrid, Biocompatibility, and Biodegradation

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Biohybrid, Biocompatibility, and Biodegradation

These three keywords describe the following characteristics of biomedical implants.

Biohybrid: by colonizing long-lasting artificial (rarely: natural) implant material with functionally specific cells, the implant’s application period can be extended by several years and its application as a permanent biocompatible implant can be improved.

Biocompatibility: implant tolerance with respect to toxicity, blood tolerance (hemocompatibility), tissue reactions, allergenic potential (irritations, sensitization), genetic alterations, as well as the prevention of foreign body reactions (describes specific immune reactions), cancer development, and implant-associated infections. These parameters will be studied locally (at the implant site) as well as systemically (throughout the body). Initially, we will screen for critical minimum requirements (e.g. no cytotoxicity, mechanical stability, degradation). Based on these results, further tests will be done on selected materials.

Biodegradation: a degradable implant that initially demonstrates long-term stability in the body and supports the regeneration of damaged tissue junctions, but is ultimately degraded. Bioresorption is the complete elimination of degradable material from the body without causing side effects. Degradation dynamics (especially over time) and other characteristics can be determined and adjusted to selected anatomical sites in the body through physical, chemical, or biologic manipulations.

While most implants must remain functional in the body for life, it is often preferred e.g. with osteosynthesis screws (orthopedics) or stents (cardiology) that they safely biodegrade after they have fulfilled their function. In the case of osteosynthesis screws, for example, a new operation and thus an additional burden on the patient can be avoided. Successful preclinical trials with biodegradable magnesium-based metals have been done. This concept has revolutionized the previous dogma of developing preferably corrosion-resistant implants. It is considered a challenge and opportunity for new implants in surgery. First implants for foot operations have already been clinically applied. Pioneering in implantology are also biohybrid systems in their various clinical applications from biodegradable metal stents or degradable bone screws to endothelialized bioartificial lungs: by biohybridizing long-lasting implant material with function-specific cells, the implant’s application period can be extended by several years and its application as a permanent biocompatible implant can be improved.

Controlling the tolerance (biocompatibility) and the interaction of the implant with the surrounding tissue is especially challenging if the temporarily stable (biodegradable, resorbable) implant materials (e.g. polymers, biodegradable metal) are used as full material or coatings. This is because their metabolites can interact with the degradation process and/or the surrounding tissue. It is therefore the goal to control these material-tissue interactions in long-term stable (permanent) and temporary implants. Depending on the clinical necessity, the aim is to improve their ingrowth by targeted interaction with specific cell type or in the case of other clinical applications to prevent uncontrolled tissue growth around the implant.

Aside from their biocompatibility and mechanical suitability, clinically implants have to dependably fulfill many specific functions. Important reasons for an early failure are foreign body reactions and implant-associated infections. However, even materials with ideal mechanical traits and special coatings can cause foreign body reactions through interface interactions between the implant and the tissue. These can lead to impaired tissue integrity and implant functionality. Therefore before they are clinically applied, these materials have to be tested with regard to their toxicity, tissue reaction, allergenic potential, and genetic alterations. Beyond the area of implant research, similar biocompatibility issues are important in regenerative medicine (development of organ replacement procedures), in using colonized materials for tissue engineering (tissue replacement procedures), or for so called biohybrid systems made of cells in or on synthetic matrices. Thus, for all approaches that deal with the replacement of lost body functions, a detailed biocompatibility evaluation will be necessary. The biodegradable material component of coatings with cell or growth factors must be tested especially for their biocompatibility, because the degradation products can directly or indirectly affect the cell coating or the surrounding tissue. The aim is the controllable and controlled degradation of implant material and the avoidance of foreign body reactions in the surrounding tissue.

The focus of the biocompatibility and biodegradation studies is therefore to understand the tissue-implant-interaction of biodegradable metals, polymers, alginate systems, and other hydrogels. The biocompatibility of open-porous materials or surfaces, of (bio-)functionalized implants with growth factors, and of biohybrids made of material-cell-constructs will be studied in the different clinical application fields. Animal models are unavoidable, because of the complexity of the processes. However, to keep the number of animal experiments at a minimum, these foreign body responses will be followed non-destructively in one animal over the complete implantation period. Aside from reducing the number of animals, it can provide the analysis of study progression. Here as a universal analysis system, a fluorescence-based in vivo imaging is useful. Using an implantable lung replacement system (“ECMO”) as an example, it will be investigated which factors affecting endothelial cells applied to an artificial matrix improve the blood tolerance (hemocompatibility). Currently used materials lead to blood cell clumping and to thrombus formation. In addition, blood proteins bind to the structures needed for gas exchange and thus lower their efficacy. The focus here is on material-technical issues, structuring and functionalization of surfaces, as well as problems of cell cultivation. The goal is to improve the hemocompatibility and thus to extend the biohybrid’s application period from currently some weeks to several months and even years.

All of the issues mentioned require intensive collaborations between engineers, scientists, and physicians. There are manifold cooperation possibilities in NIFE that are currently, for example, supported nationally or EU-wide in large cluster projects such as BIOFABRICATION for NIFE and the DFG-research group 2180. See also:,,,