GRAPHITE4MED · Aerographite as scaffold material for regenerative medicine

Aerographite as scaffold material for regenerative medicine

A publishable version can be found in the attached Graphite4Med factsheet. Please find the unformatted version below: Aerographite as scaffold material for regenerative medicine Graphite4Med The development of new materials to restore, maintain, or improve damaged tissues and organ functionality is one of the great visions of regenerative medicine. Graphite4Med aims to explore the feasibility of aerographite to act as scaffold material for tissue engineering with special focus on directing cell growth. Such an endeavour requires a broad interdisciplinary approach combining aspects of materials science, (bio)chemistry, (bio)physics, biology, and medicine. Background The natural extracellular matrix (ECM) is a three dimensional (3D) network that provides structural and biochemical support to cells. Fibers, pores and features of different dimensions in the macro (30–1000μm), micro (10–30μm) and nano (5nm) regime enable specific cell adhesion, migration, and multiplication within a tissues. Aerographite (AG) is a novel carbon based material that exists as self-supportive 3D network of interconnected hollow microtubes. It can be synthesized in a variety of architectures tailored by the growth conditions. This structural flexibility presents interesting bioengineering possibilities such as the generation of artificial ECM for directed cell growth. Objectives and Results 1. The application of AG in the biomedical field was initially hindered by a major technical barrier. AG - like other carbon materials such as carbon nanotubes or graphene - is strongly water repellent. We developed a procedure that makes use of amphiphilic molecules connected to poly(ethylene glycol) (PEG), which act as surfactant and readily immerse AG in aqueous solutions. PEG is widely used in medicine, e.g. as coating for pharmaceutical products and in eye drops. 2. Next we focused on functionalising AG to promote attachment of cells, and facilitate their migration and multiplication inside the material. We docked the engineered cyclic tri-peptide cRGD the surface of the AG microtubes. RGD is present in a variety of proteins of the natural ECM where it mediates cell adhesion. In order to test our functionalization approach we seeded cells of the connective tissue (fibroblasts) onto AG scaffolds. Fibroblasts play an important role in wound healing, because they produce natural ECM. Over a period of several days the cells were found to progressively grow and migrate into the scaffold. 3. In 2012 the synthesis of AG was reported for the first time. Due its novelty the response of biological systems to AG exposure is completely unexplored. We applied guidelines of ISO 10993-5 for in vitro cytotoxicity testing to examine the effect of AG micro-fragments to cells of different tissues including blood vessels (epithelia), connective tissue, bone and neurons. We found a high tolerance of human neuronal cells for fragmented AG. Cell growth appeared to be stimulated by AG making it a promising new material for research in the field of neuronal regeneration. However, whereas neuronal cells were influenced positively, unmodified AG fragments turned out to be harmful to cells of the epithelia, connective tissue, and bone, though anti-adsorptive surface modification appeared to have an attenuating effect. In response to these preliminary results, existing guidelines for AG production and handling are currently being reviewed with regard to workplace safety and environmental protection. Impact We demonstrated the capacity of AG to provide a scaffold for tissue engineering applications when properly functionalised. A particularly high potential was found for stimulation of neuronal cell growth that warrants further investigation, as the repair of damages in the nervous system remain a major challenge in regenerative medicine. By presenting our project and scientific results at a number of international conferences and in expert panels, we were able to generate and gain international visibility. The scientific results of this project will be published in several manuscripts in international journals in the near future. Funded by the German Academic Exchange Service (DAAD) Graphite4Med is being continued in the scope of a 3-year PhD project. The preliminary results of our pilot project allow better understanding and assessment of biological tolerance and possible benefits, but also of potential health and environmental risks of aerographite as a promising new material. Introducing the requirements for workplace and environmental safety from an early point on is a prerequisite for the responsible application of new technologies. In this way, our project has contributed to promoting future research and technological innovation. Through our contribution we support decision making and, eventually, responsible discussion of new technologies and nanoscience in society. For more information contact the project coordinators: Dr. Constanze Lamprecht Prof. Dr. Christine Selhuber-Unkel Applied Experimental Biophysics Biocompatible Nanomaterials Institute of Biophysics Institute of Materials Science Johannes Kepler University Linz Christian-Albrechts-University Kiel Gruberstr. 40, A-4020 Linz, Austria Kaiserstr. 2, D-24143 Kiel, Germany Phone: +43 732 2468 7652 Phone: +49 431 880 6277 E-mail: constanze.lamprecht@jku.at E-mail: cse@tf.uni-kiel.de http://www.jku.at/biophysics/content http://www.tf.uni-kiel.de/matwis/bnano/ Marie Skłodowska Curie Actions Intra European Fellowship PIEF-GA-2012-330418 Total EU contribution: 161,968.80 € Duration: 24 months Starting date: 01/04/2013

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