Characterization Platform of Biomaterial-Cell Interfaces in the context of bone tissue engineering – CharaBioC
Calcium phosphate ceramics (CPC), including hydroxyapatite (HA), have been used as bone substitutes for more than 30 years. Their chemical composition, close to that of the bone mineral, confers them good biological properties. However, they are not sufficient to fit with all the needs in bone regenerative medicine, such as in the context of large bone defects. Therefore, it is essential to improve their biological performances in order to extend their application domains. Two approaches are mainly used in this way: 1) the substitution of the calcium phosphate crystalline lattice with chemical elements able to stimulate bone repair. 2) the modulation of the CPC architecture to optimize the cellular responses at the interface. However, a single action is sufficient to modify both their chemical physical characteristics and the associated biological properties. In addition, the variability of the methodologies for production of defined biomaterial and to characterize induce a lack of consensus from the results published in the literature. Theses observations highlight the need to develop consistent methods for characterizing the interface between living cells and materials and to set up relevant in vitro models. It will be integrated into the chain of ceramic materials manufacturing process, the historical and recognized core activity of the IRCER laboratory (University of Limoges, CNRS) in which it will be applied. CharaBioc will bring new skills in the field of life sciences for a better knowledge of material/living interactions and the development of innovative biomaterials meeting public health needs.
This biological analysis platform will lead to the sequential association of the elaboration processes with the physico-chemical properties of three-dimensional structured CPCs (e.g. chemical composition, porosity, roughness...) and their biological performance. Micro-macroporous CPCs based on stoichiometric HA or substituted by chemical elements of interest (CO3, Si, Cu), fully characterized from a physico-chemical point of view, will be produced. The variables will be modified step by step and associated with the changes in the characteristics of the final ceramics. Their dissolution properties in biological environment will first be evaluated under dynamic conditions through the identification and dosage of the chemical species released over time. The effects of these dissolution products will be tested on different cell lines involved in triggering the repair process via recruitment of progenitors (innate immunity cells), vascularization (endothelial cells), an essential process, and bone formation (bone cells). In a second step, the living/material interface will be studied in detail. After validating the biocompatibility of the materials tested, cell proliferation, activation and/or differentiation will be studied in three-dimensional flow perfusion bioreactor cultures. The impact of biomaterials on cellular communication will also be taken into account through the analysis of secreted soluble factors. This will lead, at the end of the project, to the implementation of a reliable and robust 3D cellular model of bone microenvironment, based on co-cultures of cells from the three physiological systems mentioned above. Finally, the use of multiparametric statistical analysis will help to identify direct connections between all collected data, whatever their origin. The final objective is to link biological and chemical physical data in a rational way to identify pertinent levers for the optimization and the enhancement of the ceramic biomaterials applicative performances .
Madame Amandine MAGNAUDEIX (institut de recherche sur les céramiques)
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.
IRCER institut de recherche sur les céramiques
Help of the ANR 232,740 euros
Beginning and duration of the scientific project: September 2019 - 48 Months