Projects / Programmes
Piezoelectric Biomaterials for Electro-stimulated Regeneration
| Code |
Science |
Field |
Subfield |
| 2.04.01 |
Engineering sciences and technologies |
Materials science and technology |
Inorganic nonmetallic materials |
| Code |
Science |
Field |
| T152 |
Technological sciences |
Composite materials |
| Code |
Science |
Field |
| 2.10 |
Engineering and Technology |
Nano-technology |
piezoelectric biomaterials; piezoelectric polymers; bioactive hydroxyapatite; bioreactor; electrostimulation of cells
Researchers (21)
Organisations (3)
Abstract
Human body uses natural macromolecules with ordered α-helix structure (collagen, fibronectin, DNA, etc.) with inherent piezoelectric characteristics to generate biological electrical fields. These characteristics allows them to generate biological electrical fields under mechanical deformation, which results from body’s endogeneous mechanical stimuli (body movement, blood pressure, cell attachment). Generated electrical fields have been found to have a significant impact on cell behavior (growth, differentiation, release of cell-signalling factors and gene expression, etc.) and are highly important for tissue regeneration.
Above-mentioned natural-sourced mechanism is the main idea of electro-stimulated regeneration as a novel and highly perspective branch of tissue engineering. However, electro-stimulators which are currently used in clinical practice are mainly constructed as devices formed of bio-inert electrodes implanted within the organism and connected to external power. Although it has been proven that electro-stimulators significantly reinforce recovery of tissues and regeneration of wounds, numerous difficulties are associated with this kind of construction. The main problems are related to: irritation and pain of the surrounding tissue which covers implanted site, toxicity and adverse reactions caused by electrodes and/or electrical supply, urgent need for additional surgical intervention for post-treatment removal of the stimulator, etc.
Having in mind difficulties associated with the construction of electro-stimulators, the main idea of the proposed project is development of the innovative biodegradable, piezoelectric scaffold able to use endogeneous mechanical deformation (attachment and ingrowth of surrounding cells and microcirculation) for self-powered performance which will be cappable to replace currently-used externally-powered electrodes. Innovative piezoelectric biomaterials will be formed as composite of piezopolymers (PVDF and/or PLLA) and bioactive apatite. The main benefits expected from this type of construction are: (i) softer and more compatible contact with surrounding cells and tissues provided by polymeric matrix (PVDF and PLLA), (ii) high level of biocompatibility enabled by FDA approved biocompatible components, (iii) post-regenerative self-elimination enabled by using biodegradable (PLLA) and bioresorbable (apatite) components. The project is conceptualized as three-year research on:
Formation of the innovative piezo-biomaterials and their processing into piezo-scaffolds,
Testing in vitro stability, biodegradability and reliability of piezoscaffolds,
Construction of the bioreactor for proving the concept
Electro-stimulation on liposomes (as cell-like models) and formation of the simulated model which correlates properties of piezoscaffolds with characteristics of cell-like membranes.
Testing heamatocompatibility of the piezoscaffolds and investigation of the effect of electrostimulation on osteoblast, myoblast and neural cell lines as final proof of the concept.
The proposed research project carries strong innovation character and includes high potential for bringing the breakthrough in the field of electro-stimulated regeneration as a new branch of tissue engineering. The collaboration within the project will combine long lasting expertise of Advanced Materials Department of JSI in development of piezoelectric materials and experience in biomaterials of Biomaterials group with strong competences of the Groups for Biophysics at Faculty of Electric Engineering and Faculty of Health in investigations of interactions between materials and cells/cell-like modes. The collaboration will provide important new knowledge in the innovative area of piezoelectric biomaterials and their application in tissue engineering and valuable new expertise which will be effectively used for creation of new consortia, planning and application of further national and international research projects.
Significance for science
A major scientific breakthrough is expected to be obtained in performance of implantable electro-stimulating medical devices, i.e. achieving the correlation between high efficacy and high biocompatibility.
(i) Self-powered device: Our research will be focused on finding a more suitable replacement of the externally powered electro-stimulating medical devices (currently applied in clinics) with more suitable self-powered, piezoelectric electro-stimulators.
(ii) Boosting efficacy: Innovative piezoelectric electro-stimulator will be formed as a thin piezo-scaffold deposited at the surface of implantable medical device. In this form it will be designed to be used at the place of the injury made by surgical insertion which will allow direct electro-stimulation of wound created during implantation.
(iii) Enhancement of the biocompatibility:
Safe components: Instead of the bio-inert, metallic electrodes (used in clinics), we will develop innovative piezoscaffolds formed as composite of piezo-polymeric matrix (formed of PLLA and PVDF polymers, both approved by FDA for the application in medical devices) and bioactive HAp (known as synthetic analogue of the mineral part of the bone).
Better compliance: The piezoelectric composites will have reduced thickness for better contacts with the tissues, therefore preventing the pain in the surrounding tissue which usually occurs during body motion. Besides, utilization of soft and elastic piezoelectric polymers (PLLA and PVDF) is expected to provide better mechanical and biological compliance with cells as well as reduce the chances for occurrence of inflammation induced by the stiffness mismatch between the implanted material and tissue.
Biodegradability: Part of the research within the project will consider fully-degradable piezoelectric composites made of the biodegradable PLLA matrix with incorporated bioresorbable apatite (without non-biodegradable PVDF). In accordance to the available literature, this will be one of the first biodegradable electro-stimulating medical devices as well as one of the first biodegradable piezo-materials considered for electro-simulative regeneration.
(iv) Improved piezoelectric characteristics: HAp-enabled “water shielding” will be used in the current project to improve the piezoelectricity of prepared composites and enable improved electro-stimulation of cells. In addition, it is expected that biodegradation of the composite will result in reduced piezoelectricity of composites. Therefore, the project will aim towards establishing a relationship between biodegradation rate of the composites and their piezoelectric potential.
In accordance with the scientific innovation expected to be achieved from the research proposed within this project other scientific relevancies include new state-of-the-art technology and high-value scientific knowledge.
Significance for the country
Tissue engineering provides unique options for advanced health treatment that cannot be obtained by conventional medication, especially when the damaged sites are too large to be treated by classical procedures.It has been estimated that worldwide needs for the treatment offered by tissue engineering have the highest share for bone regeneration with significant growing trend predicted for the near future. In 2003 there were about 700.000 patients with bone fractures per year. Novel data show significant increase with about 280.000 hip fractures, 700.000 vertebral and 250.000 wrist fractures per year. In sum it is more than a million patents per year in the US that is more than 50% increase of the need for bone tissue engineering procedures obtained for the period of less than 10 years. Today’s demand for tissue engineering is specially highlighted by the number of approximately 4 million operations involving bone grafting or bone substitutes performed annually worldwide. By 2050 the world population is expected to increase to 8.9 milliards with significant ratio of people older than 60, as well as the larger ratio of disabled and injured. Consequently it is expected that investment into innovative technologies such as tissue engineering will be a chance especially for developing countries. Funding promising innovations in these countries brings potential for initiation of their future social and economic growth as well as supports their independent development. 6
Piezoelectric biomaterials are envisaged as the future breakthrough technology in the tissue engineering and postoperative regeneration (for in situ reparation of bone defects, heart and blood vessels, neural tissue etc.). The development of biocompatible piezoelectric biomaterials will represent a major breakthrough in the field of regenerative medicine as it will provide additional advantages compared to currently used electro-stimulators for tissue regeneration. The originality of the project proposal is to use well-known biocompatible materials (PLLA, PVDF, HAp), which are already used in medicine, for fabrication of medical devices with novel electro-stimulating functionality. The project has a high-added value, as aimed piezoelectric composites will be used in regerative medicine, where the need for high-quality medical devices is constantly increasing. We expect that results and knowledge gained during the project will have a positive effect on future collaborations between academia and they will promote further investments in the new technology. Company investments will enable them to become more competitive, inrease their income and consequently employ more workers. Furthermore, the composition of developed piezoelectric composites and the technology for their production and processing will be patented. After filing a patent the results of the study will be published in the most renowned scientific journals in the field of biomaterials and tissue engineering.
Most important scientific results
Final report
Most important socioeconomically and culturally relevant results
Final report
