Biohybrids, Bio-Compatibility, Bio-Stabilization and Bio-Degradation

These three keywords describe the following characteristics of Bio-Medical Implants:

Bi-Hybrids:

By equipping non-biological artificial (more rarely: natural) implant materials with living, function-specific cells, the longevity of the implants can be extended to several years, their functionality can be improved, and entirely novel products with innovative functionality can be created.

Bio-Compatibility:

Compatibility of the implant with regard to toxicity, blood compatibility (hemocompatibility), tissue reaction, allergenic potential (irritation, sensitization), genetic changes, supplemented by the avoidance of foreign body reactions (describes certain immune reactions), cancer development and implant-associated infections. These parameters are recorded both locally (at the implantation site) and systemically (looking at the entire body). First of all, the fulfillment of critical minimum requirements (e.g. no cytotoxicity, mechanical stability, degradation) is screened; Based on the results, further tests are then carried out for selected materials.

Bio-Degradation:

A degradable implant that is initially stable in the body for a long time and supports the rebuilding (ideally in the sense of regeneration) of a tissue that is no longer intact, but then dissolves. Bioresorbability means that a degradable material is completely eliminated from the body without causing any side effects. Through physical, chemical or biological manipulations, the degradation behavior (especially over time) and other properties can be adjusted and thus adapted to selected anatomical locations within the body.

Why is it important to develop implants with these properties?

While most implants have to remain functional in the organism lifelong, it is often desirable - for example with Osteosynthesis screws (orthopedics) or Stents (cardiovascular area) - that they degrade in a biologically compatible manner after their task has been accomplished. In the case of osteosynthesis screws, e.g., a new surgery and thus an additional burden on the patient is avoided. For this purpose, preclinical investigations with biodegradable metals based on Magnesiumwere successfully conducted. This concept revolutionizes the previous dogmas of developing implants that are as corrosion-resistant as possible, and is seen as a challenge and future opportunity for new implants in surgery. The first biodegradable implants for foot surgery have already been successfully used in the clinics. The biohybrid systems in implantology are also pioneers in their various clinical applications: biodegradable metal stents, biodegradable bone screws or endothelialized, bioartificial lungs. In all examples, by biohybridizing long-term stable implant materials with function-specific Cells the duration of use of the implants can be extended to several years and the possible use as a permanent biocompatible implant can be improved.

The challenge of controlling the compatibility (biocompatibility) and the interaction of an implant with the surrounding tissue becomes particularly great when temporary-stable (biodegradable, resorbable) implant materials (e.g. polymers, biodegradable metals) are used as a solid material or coating, since their degradation products may interact with the degradation process and/or the surrounding tissue. The aim is therefore to control this material-tissue interaction in long-term stable (permanent) and temporary implants and, depending on clinical need, to improve their ingrowth behavior by directed interaction with specific cell types or, in other clinical applications, to prevent uncontrolled tissue growth around the implant.

Clinically, implants must reliably fulfill many specific functions resulting from their physical, chemical and biological parameters, in addition to their biocompatibility and mechanical suitability. Here are Foreign object reactions and Implant-Associated Infections a major reason for early failure. However, even materials with ideal mechanical properties and special coatings can cause foreign body reactions due to interfacial reactions between implant and tissue, leading to impaired tissue integrity and implant functionality. Therefore, these materials need to be evaluated for toxicity, tissue reaction, allergenic potential, and genetic alterations before they enter clinical use. Beyond the field of implant research, analogous questions of biocompatibility also arise in the context of the Regenerative medicine (development of organ replacement procedures) and in the use of colonized materials in the Tissue Engineering (Tissue replacement procedures) or in so-called Bio-Hybrid systems of cells in or on a synthetic matrix. For all approaches dealing with the replacement of lost body functions, a detailed assessment of their biocompatibility is therefore required. In particular, the biodegradable material component of the cell- or growth factor-bearing coatings must be examined from the biocompatibility point of view, since the degradation products may act directly or indirectly on the applied cells or neighboring tissue. The aim is the controllable and controlled degradation of the implant material and the avoidance of foreign body reactions in the surrounding tissues.

What do we do in NIFE?

The main focus of our work is the elucidation of tissue-implant interactions of biodegradable metals, polymers, hydrogels and many others. We investigate the cyto- and biocompatibility of open-pored materials or surfaces, of (bio-)functionalized implants with growth factors and biohybrids of material-cell constructs including the use of autologous stem cells in the different clinical application areas. For the assessment of biocompatibility, the investigation in animal models is inevitable due to the complex processes involved. In order to limit the number to the lowest possible level, the goal is to follow this foreign body response in an animal non-destructively over the entire implantation period. In addition to reducing the number of animals required, this also allows the detection of time courses of the investigations. For this purpose Fluorescence-based in vivo imaging represents a universal analysis system. Using the example of an implantable lung replacement system ("ECMO"), the aim is to investigate which factors can improve blood compatibility (hemocompatibility) by endothelial cells applied to an artificial matrix. Currently used materials lead to clumping of blood cells and thrombus formation. In addition, blood proteins bind to the structures required for gas exchange, thus reducing their efficiency. Here, work is focusing on material technology issues, structuring and functionalization of surfaces, and cell biology issues. The aim is to extend the service life of such a biohybrid system from the current few weeks to several months to years.

All of the above-mentioned issues require intensive collaboration between engineers, natural scientists and physicians. There are a number of joint projects and cooperations in NIFE. For more detailed information please have a look at if you are interested, please contact the following websites:

https://nife-hannover.de/en/forschung/forschungsverbuende

https://gradierte-implantate.de/en/

https://lbb2-mhh.de/wp_lbb/de/startseite/

https://nife-hannover.de/en/ags/biodegradable-und-bioaktive-orthopadische-implantate

https://nife-hannover.de/forschungsprogrammatik/ag-biohybrid-lunge-dr-bettina-wiegmann

https://nife-hannover.de/forschungsprogrammatik/biohybride-biokompatibilitaet/ag-biostabilization-prof-wf-wolkers

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