BioTex - Research topics

 

BioTex - RWTH Themen

RWTH - Topics 2/2019 Bringing implants to life

Biohybrid vascular prosthesis, heart valve and airway stent

Diseases of the cardiovascular system and the lungs require complex treatment methods, are often not curable in the long term and are among the most frequent causes of death. Previous approaches have generally pursued the use of exogenous materials, which, however, only provide short-term relief or can lead to complications such as thromboses. To prevent rejection caused by the immune system, lifelong medication is often necessary. After all, it is a foreign body that is introduced into the body to dilate vessels or control the heartbeat. In the Biomedical Engineering cluster, scientists are working on the development of "living" implants that take over the function of the diseased tissue and at the same time are not regarded by the body as foreign bodies are detected.

Biohybrid implants: Cell meets textile

The development of living implants is characterised byis based on the combination of artificial materials with natural, biological components, called biohybrid implants. The demand on the material for vascular prostheses, heart valves and stents lies in the mechanical stability of the plastics or metals. The biologisation of the artificial materials is based on the following principle: By removing healthy patient tissue, living cells are obtained which later take over the tasks and functions of the diseased tissue. By embedding the cells in the body's own gel (fibrin or elastin) or by directly colonising the cells on the supporting structure, the components are combined. The cells should find an environment as familiar as possible in which they feel comfortable and take up their functions as usual. Therefore, in addition to the fibrin gel, water-based artificially produced gels, also known as hydrogels, are used, which form a protective capsule around the cells. The implant can now be exposed to mechanical or biochemical stimuli to further stimulate cell function. This conditioning can be compared to a "fitness studio for cells": The cells are prepared for their application so that they can later optimally fulfil their tasks in the patient's body. The Institute of Applied Medical Technology has developed three biohybrid implants in cooperation with the Institute of Textile Technology (ITA) and the DWI - Leibniz Institute for Interactive Materials.

Vascular prosthesis "StemGraft

Blood vessel constrictions, called stenoses, are caused by deposits on the vessel wall, which disturb the even flow of blood and, in the worst case, lead to occlusion of the vessel. As a result, regions of the body can no longer be adequately supplied with blood, which can lead to considerable tissue damage. This is particularly critical in the case of the heart (heart attack) or the brain (stroke). Dilating the vessels with a stent is an established treatment method. However, due to the mechanical stimulation by the stent material, new tissue is formed, which can grow through the stent's meshes and lead to narrowing again. Therefore, the focus is on the development of a vascular prosthesis that replaces the constricted or even obstructed vessel section. The "StemGraft" has been developed, which combines the patient's own stem cells and an artificial supporting scaffold. It is ready for use after a short conditioning period of only four days. Conditioning takes place in a specially manufactured bioreactor system, which continuously flushes the implant with nutrient fluid (medium), so that the inserted cells are supplied with all nutrients. The medium flow also fulfils another function: by specifically increasing the flow rate at which the medium flows through the vascular prosthesis, the cells become accustomed to the blood flow that prevails in the body and become more resistant to damage. This promising way of producing a long-term stable and biocompatible vascular prosthesis is about to undergo clinical testing. Optimum function in the patient can only be guaranteed if the vascular prostheses are subjected to constant quality control with regard to design and function during their manufacture.

Heart valve

The heart is a complex hollow organ, which, similar to a pump, transports blood through the body to supply the organs with oxygen and nutrients. But not only the aspect of supply is important, the heart also has an emotional meaning for humans. If we are excited, we feel the heart beating faster; if we feel bad, we feel the well-known "heartache". The heart plays a central role, which is why it is all the more important that it functions properly. Many people suffer from diseases of the heart and the related vessels. A defective heart valve, for example, is a common cause of illness. A healthy heart has two halves, each of which is divided into an atrium and an associated chamber. The blood can only flow between these four heart chambers in one direction, which is ensured by heart valves. They function like valves that prevent it from flowing back. If one of the heart valves is no longer intact, the blood will flow back. Problems such as shortness of breath or increased strain on the heart chambers are not uncommon. On the other hand, such a severe calcification of the heart valves can also occur, which leads to them opening only insufficiently. Now the heart has to work much harder to pump a sufficient amount of blood into the circulation. This ultimately leads to permanent damage to the heart muscle. Today, artificial heart valves are used as replacements, which either require lifelong blood thinning or have a tendency to calcify, which ultimately requires replacement. The aim is therefore to develop the biohybrid heart valve prosthesis as a biocompatible and long-term stable alternative. By inserting a textile support structure, called mesh, the patient's own cells can be hybridised with the textile in a fibrin gel. In comparison to the vascular prosthesis, the cells are trained for a much longer period of time, about 21 days. Since the maturation of the heart valve is more protracted, it is all the more necessary to carefully determine all conditioning parameters and control the manufacturing process in such a way that an optimal and individual implant results. This is the task of the joint project "Towards model-based control of biohybrid implant maturation" (PAK 961) funded by the German Research Foundation.

Airway stent "PulmoStent

Thousands of people suffer every year from respiratory diseases such as tracheal or lung cancer and bronchial constriction due to other obstacles. Symptoms such as shortness of breath, hoarseness and severe coughing due to reduced expectoration of mucus lead to massive impairment, which can develop into life-threatening pneumonia. A biohybrid respiratory stent has therefore been developed within the EU project PulmoStent. The biohybrid platform technology combines a specific metal stent with the living tissue of the patient. The "biologization" of the inner side of the stent is the special feature here. The applied cell layer, called the respiratory epithelium, is characterized by the formation of tiny cilia on the surface, which ensure that mucus is transported from the lungs to the mouth. The supporting structure that gives the implant the necessary stability consists of a braided, metallic stent structure, which in turn is embedded in a plastic layer. This dense, multi-layered structure is intended to prevent tissue from growing back. Initial studies have already shown that the PulmoStent has the potential to take its place as an innovative treatment method. Funded by the German Federal Ministry of Education and Research (BMBF), the focus of the work is therefore on quality assurance during production and validation in preparation for an initial clinical trial. Biohybrid implants have a high potential to eliminate the deficits of current implants. For this purpose, the artificial support scaffolds must be prepared even more specifically for the connection with cells and vital tissue. This can be achieved by further biofunctionalising the artificial surfaces so that they allow the body's own cells to settle and function optimally. By increasing the cell attractiveness of the artificial surfaces, there is the prospect of implanting the implant cell-free, which would considerably facilitate production and quality assurance. Thus, the human body could function as a bioreactor by stimulating a rapid colonization of the implant with endogenous cells. Research on biohybrid implants is interdisciplinary and takes place at the Center for Biohybrid Medical Systems, CBMS for short. For example, the Institute of Textile Technology ITA, the Machine Tool Laboratory WZL, the Institute of Control Engineering IRT and the Institute of Technical and Macromolecular Chemistry/ DWI - Leibniz Institute for Interactive Materials are involved.

You can read the whole article in the RWTH THEMEN issue 2/2019 starting on page 10