Recent Developments in Biohybrid Systems for Human Pluripotent Stem Cells and Beyond

Dear Colleagues,

Biohybrid systems are systems that combine biological components with synthetic materials or devices to create functional entities. These systems exploit the unique properties of biological elements, such as cells, tissues, or biomolecules, together with the versatility and controllability of synthetic materials or devices. This is of particular interest for human pluripotent stem cells and derived tissues, which have a great potential for regenerative medicine. The goal is to achieve functionalities or capabilities that neither biological nor synthetic systems could achieve alone. More detailed basic research is needed. Open questions include, among others, the following: (i) Which cell surface receptors integrins are activated by synthetic materials? (ii) Which signalling cascades are activated? (iii) What are the short- and long-term effects of synthetic material interaction with cells or tissues? (iv) Do cells and tissues adapt, compensate, differentiate, proliferate, degenerate, and undergo apoptosis? (v) How are exudates of materials distributed within the body, i.e., systemic actions? Could this be measured using nuclear medicine methods? (vi) What is the electrical integration? (vii) What is the mechanical integration—elasticity modules—and what role do mechanical stimuli play in tissue regeneration?

Biohybrid systems can manifest in various forms, spanning from simple combinations of biological and synthetic components to intricate engineered constructs. Here are some examples: (i) Biosensors: these systems incorporate biological molecules, such as enzymes or antibodies, onto a synthetic surface to detect specific analytes or molecules in the environment. The biological component recognizes the target molecule, leading to a measurable signal that can be detected and analysed. (ii)  Biomedical devices: biohybrid devices combine living cells or tissues with synthetic materials to create functional constructs or implants. For instance, biohybrid implants might integrate synthetic scaffolds with living cells to promote tissue regeneration or healing. (iii) Bioelectronics: these systems integrate biological components, such as neurons or proteins, with electronic elements to develop functional devices. Biohybrid electronics could be used in neural interfaces, biosensors, or other medical devices. (iv) Biocompatible materials: biohybrid materials combine synthetic polymers or nanoparticles with biological molecules to create materials with enhanced biocompatibility or specific functionalities. These materials find applications in drug delivery, tissue engineering, or medical implants. (v) Biological computing: biohybrid computing systems integrate biological components, such as DNA or proteins, with synthetic elements to perform computational tasks. These systems exploit the parallel processing capabilities and information storage capacity of biological molecules to create novel computing architectures.

Overall, biohybrid systems represent a convergence of biology, engineering, and materials science. They offer promising avenues for innovation in fields like biomedicine, biotechnology, and environmental monitoring, where the integration of biological and synthetic elements can lead to new functionalities, improved performance, and novel applications. This Special Issue will cover all these points and thus hopefully contribute to our understanding of material–cell interactions and medical device optimisation in our bodies.

Prof. Dr. Jürgen Hescheler
Dr. Anna Jezierski
Guest Editors

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• biohybrid systems
• cell–material interaction
• stem cells