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Acoustique picoseconde pour l'élastographie cellulaire et l'évaluation de l'adhésion sur biomatériau – PicoBio

Submission summary

In the field of osseous and/or vascular substitution it is necessary to develop innovative techniques to satisfy the request for substitutes and to find solutions combining availability, perenniality and biosecurity of the implants. One of the main strategies in this area of research is to make the biomaterials more 'attractive' for the tissue or the surrounding cells. To do this, one suitable approach is to functionalise the surface of the materials by "pro-adhesive" ligands (peptides) to improve cell adhesion and hence the cell and tissue colonisation of these materials. However there is a great lack of quantitative methods to measure material 'attractivity' and cell adhesion. Picosecond acoustics is the technique in which very high acoustic frequencies (up to 0,1 THz) can be generated with very short laser pulses (100 fs). A pump pulse generates acoustic waves via electronic and thermal effects, and a delayed probe pulse is used to measure the small changes (10-6) of the sample surface transient reflectivity. This technique has demonstrated many important results in the area of non-destructive testing and evaluation of materials in micro-electronics and solid state physics. The advantages of the picosecond ultrasonics, in comparison with acoustic microscopy with piezo-transducers, are the absence of direct contact to the sample and very large frequency bandwidth. The proposed project is dedicated to the first applications of the picosecond ultrasonic technique for the study of biological cells. This ambitious project has been conceived based on the association of three complementary teams, each leader in its respective domain. The old and continuous collaboration between LMP and CPMOH is proved by several successful grant applications, PhD co-supervising, joined patent and joined publications. Due to a strong and reciprocal scientific interest in the promising applications of picosecond ultrasonics in biology, collaboration is developing with team partner 2 (INSERM U577). The project will specially be focused on quantitative measurements of biocompatibility of biomaterials for implants applications. Preliminary experiments, showing very promising results, have been performed in vitro at LMP with living cells of osteoblasts on titanium substrate prepared at LBRT. In these experiments the pump pulse is transmitted through the semi-transparent biologic medium. The pulse is generated in the optical penetration length of titanium. Part of the acoustic energy is transmitted to the cell. The transient acoustic strain is detected in the cell. First experiments have shown the presence of signals at a frequency ~10 GHz! The first work package (WP1) of the project is preliminary up-grading of the experimental set-ups to improve their compatibility with living samples, and to allow fast acquisition of acoustic images with a 0,5 µm lateral resolution. From qualitative results obtained elsewhere an increase of the cytoplasm compressibility is expected when the biocompatibility increases. Cytoplasm elasticity is an indicator that can be provided and mapped from measurements of hypersonic waves velocity. In WP2, near surface cytoplasm elastography will be performed with bulk acoustic waves. The expected result at this stage is statistics of the compressibility of a collection of cells. The non uniform grafting of the cell on the substrate, by mean of variable and controlled peptide density, is expected to improve adhesion of the whole cell. The mapping of the compressibility at a single cell interface will thus be also performed. There is a large literature and a good expertise at LMP on the non destructive ultrasonic evaluation of the bonding between two materials. We believe that the picosecond acoustic technique can be used to achieve the non invasive hypersonic evaluation of the adhesion of cells to the implants. WP3 is dedicated to the adhesion evaluation with interface acoustic waves propagating along the surface between cell and substrate. In comparison with measurements and analysis proposed in WP2, the sensitivity to adhesion shall be improved. However, the space resolution may be less. The bulk wave measurement method and the surface wave measurement method are thus complementary and both are necessary. Near surface acoustic imaging is proposed in WP4. Acoustic imaging of the structure inside the cell, nearby the interface, could be performed making use of the divergent acoustic waves generated in the substrate by focused laser sources, and propagating in the cell. The cell fibroblast deformation and the non homogeneous chemical substances produced by the cell nearby the contact zones could be mapped. Picosecond acoustics offers several other promising potentialities for biologic imaging. This project shall allow the partners to participate efficiently to the emerging strong international competition in the field of non contact and non invasive imaging of living biologic media at a sub µm scale.

Project coordination

Bertrand AUDOIN (Organisme de recherche)

The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.

Partner

Help of the ANR 390,000 euros
Beginning and duration of the scientific project: - 36 Months

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