Nanostructured Carbon Templates for Cell Cultures
Biocompatible Synthetic Templates for Cell Cultures Based on Nanocomposite Carbon Films
Tech Area / Field
- BIO-CGM/Cytology, Genetics and Molecular Biology/Biotechnology
3 Approved without Funding
Research Center of Molecular Diagnostics and Theraphy, Russia, Moscow
- Ural Branch of RAS / Institute of Metal Physics, Russia, Sverdlovsk reg., Ekaterinburg\nMATI, Russia, Moscow\nMoscow Oncology Research Institute, Russia, Moscow
- Massachusetts General Hospital / Center for Engineering in Medicine, USA, MA, Charlestown
Project summaryThe main goal of the Project is in development of biomedical technologies for reconstruction of the structure and functional integrity of organs and tissues through implantation of specific cell cultures including stem cells. Studies with a broad range of candidate materials aimed at the design of substrates and three-dimensional templates for cell cultures with the ultimate goal to effect targeted delivery of cells to organs and tissues are currently under way. However, the problem of obtaining an optimum combination of properties of such candidate materials (e.g., reasonable production cost, biocompatibility, lack of microtraumas of surrounding tissues upon implantation of templates, high stability upon sterilization, etc.) still awaits its production cost, biocompatibility, lack of microtraumas of surrounding tissues upon solution.
In the authors’ opinion, significant progress in this field can be achieved through modification (nanostructuring) of material surfaces and subsequent deposition of thin (about several nanometers) layers of diamond-like carbon (DLC) films obtained by ion-plasma technologies. The choice of materials is determined by high biocompatibility of carbon and unique physicochemical and mechanical properties of DLC. Moreover, the use of advanced ion-plasma technologies, which allows preparation of carbon films with controlled surface morphologies in various allotropic, electronic and structural modifications, opens up fresh opportunities for a purposeful search for materials taking account other important factors, e.g., biological specificities of various cell cultures.
Unfortunately, the papers devoted to biomedical applications of DLC are not numerous, implant coatings and coatings for several medical items being the few successful examples. This can be ascribed to the lack of coordination between specialists working in different fields rather than to the relative novelty of carbon film technologies. The research team employed in the Project (Russian researchers and one foreign collaborator) consists of biologists, physicians and physicists working in different research institutions and currently engaged in activities related to the subject and goals of the Project. In particular, the participating institutions have gained considerable experience in the field of DLC technologies (including research studies and technological developments for various branches of industry), e.g., application of DLC for biomedical purposes. Such a team is capable to establish the criteria determining the relationship of biomedical, e.g. biocompatibility and matrix properties, and physicochemical properties of DLC deposited onto nanostructured surface of substrate materials. In other words it will be criteria determining the relationship between biomedical properties and properties of designed surface. This will not only accelerate the progress in the scientific search and practical development of DLC-based materials for biomedical purposes, but will also determine the trends for efficient contribution of materials to this vitally important trend in modern-day high technologies.
The Project envisages the implementation of fundamental and applied research and development of a novel technology. Studies of DLC films prepared using various basic processes (ion-plasma destruction of hydrocarbons and vacuum sputtering of graphite) performed under variable conditions of sample preparation will be carried out with due regard to the exploratory type of development as well as rigid and perse requirements for products designed for extra- and intracorporeal application. These will include testing of various modifications of organic and ceramic substrates, regimes of modification of chemical compositions and substrate surface relief using ion beams of inert and chemically active gases. Other trends of research will include studies of various coating thickness and deposition conditions, modification of coatings with ion beams, etc. Hydrogen-containing DLC will be prepared by ion-plasma destruction of various hydrocarbons and hydrogen-free DLC films obtained by vacuum sputtering of graphite will be doped. Studies under the Project include testing of more than 30 variants of substrate-film systems. The main methods for the testing of experimental samples according to physicochemical and tribological properties entails the use of atomic power and tunnel microscopes, nuclear microanalysis and Rutherford backscattering techniques for the study of electrophysical properties of material surfaces and properties of interfaces substrate - film, in particular, formation, magnitude, sign and redistribution of charges inside carbon films and in interfaces. The effects of various factors on vital activities of cells in vitro will be estimated in quantitative МТТ- and 3Н-thymidine tests. Cytological, immunocytochemical and morphometric control will be exercised in all the steps of cell manipulations. In vivo studies will be carried out on mice using reinoculated lines of normal human and animal cells.
The results of fundamental studies will be used for elaboration of principles of design of carbon film-based materials for biomedical purposes and establishment of the most general correlations between the physicochemical and mechanical characteristics of substrate-carbon film systems, on the one hand, and a complex of biomedical properties (adhesiveness, cell capacity, etc.), on the other hand. Preliminary experiments have shown that basic processes underlying DLC production, surface reliefs and charge characteristics of carbon films will have a crucial impact on the biomedical parameters of the novel materials.
Applied and technological studies under the Project will be aimed at the solution of various practical tasks, such as mechanical and chemical stabilities of substrate-film systems, optimization of sputtering and other technologies used in template production and implementation of a broad range of biomedical investigations (biocompatibility, adhesiveness and matrix properties for cell cultures) and screening of samples in vitro and in vivo. The main result at this stage of the Project is determination of the most promising trends in the practical application of the novel materials. It is expected that studies in this area will encompass a broad range of potential applications of carbon films and materials thereof, e.g., for reconstruction of resected organs and structural-functional integrity of organs and tissues, elimination of tissue defects after surgical interventions, traumas, etc.
The final stage will include preparation of preproduction for a vast panel of biocompatible compositions as templates for cell cultures in vitro and in vivo. The latter will be used for scientific and business exchanges and contacts with other research groups and industrial enterprises both within the framework of the planned technical schedule and beyond it. The main result in this stage will include technologically, functionally and commercially rationalized recommendations for the application of carbon films and materials thereof in biology and medicine.
The correspondence of the Project to the goals and tasks of ISTC is provided by the fact that it offers broad opportunities for Russian biologists and physicists engaged in the workers connected with defence programmes to unite their efforts, experience and knowledge in the solution of currently the most important clinical task, viz., restoration of the structure and functional integrity of damaged organs and tissues. The practical realization of the Project and the participation of representatives of modern medicine in the solution of this topical problem will contribute to further integration of Russian scientists into the international scientific community. Moreover, taking into account the explosive development of the international market of biomedical technologies in the past decade the Project entails the development of a radically new trend in biomedical technologies which is based on the use of carbon films and materials thereof. Its practical implementation will facilitate the transition to market economy and promote the advancement of various branches, such as chemical production, mechanical engineering, medical service, etc.