Thibaud CORADIN

-Silicon impacts collagen remodelling and mineralization by human dental pulp stem cells in 3D pulp-like matrices. D. Mbitta Akoa, C. Hélary, A. Foda, C. Chaussain, A. Poliard, T. Coradin, Dent. Mater. 40, 1390-1399 (2024)(HAL – DOI)

 

 

 

The two common threads of my research is my expertise in the chemistry of silica and in the elaboration of biopolymer-based hydrogels, as they are performed by living systems, and their applications in the biomedical area. Recently, I developed a new interest for dental tissues characterization and repair.

I. Bio/chemistry of silicon : implications and applications

(1) Silica biomineralization

Because of its wide distribution over our planet, silica SiO₂ is present in many living organisms. The processes by which silica is formed by some of these organisms (biosilicification) is perfectly well controlled (active transport, spatial and temporal control of mineralization) thanks to dedicated biological activities. 

We initially mainly focused on biosilicification by diatoms and some sponges (see above picture, courtesy of A. Pisera – Polish Academy of Science). In these organisms, the control over silica formation is insured by a complex group of biological molecules whose structure, production and organization are regulated by cells, under genetic control.  As chemists, we do not aim at understanding the underlying biological mechanisms but to identify the chemical principles that regulate the interactions between these biological molecules and silica. In particular we have demonstrated that polymers incorporating amine groups could speed up the condensation of silica in aqueous media.

Such a natural ability of several living organisms to live within a silica-based material led us to develop new bioencapsulation processes for bacteria and microalgae via the sol-gel route. A so-called composite approach was discovered that allows for the preservation of living cells over several weeks. This approach was recently used to design biosensors for environmental pollution monitoring. 

(2) Silicon and health

Interactions between silica and life are also interesting to study in mammalians and humans. Silicon species are present in small amounts in physiological fluids (blood) and tissues (bone, teeth). Nevertheless their precise role on the formation of these tissues is still poorly known and constitute a major new topic in my research activities

Silica nanoparticles are widespread in many products of our everyday life. Moreover, they have attracted a huge attention, at least from an academic perspective, for therapeutic applications (« nano medicine »). For example, the following drawing by Y. Shi shows silica particles allowing for the  delivery active molecules to cancer cells.

In this context, it is important to assess the toxicity of silica-based nanoparticles. This includes studying and understanding their interaction with our body on different scales, from organs to cells. We have already conducted several studies on the effect of particle size and surface chemistry on their fate in tissue model. In particular, we could evidence  the ability of some animal cells to dissolve silica intracellularly. Our current questions are : (i) does this dissolution occur under biological control (for instance via specific enzymes) or purely related to silica chemistry (solubility equilibria) ? (ii)  can we modulate this process by tuning the composition or structure of silica ? (iii) what is the influence of the products of dissolution on the biological activity of the cells ? 

II. Designing biological, hybrid and nanocomposite biomaterials for medical applications. 

Materials used in medicine (prosthesis, implants,..) pharmacy (wound dressings, pills,..) and biotechnology (diagnostic tests, biochemical catalysts,…) have all in common a necessity to be compatible with (relatively) simple (enzymes, antibodies) or complex (huma body) biological systems. This compatibility criterion can be so restrictive that the diversity of chemical composition of the materials currently used in these domains is quite limited compared to the whole range of chemical compositions that are available by chemical methods. 

(1) Natural polymers-based hydrogels

In the field of tissue repair, it is often considered that biomimetic materials, i.e. materials that recapitulate the main characteristics of the tissue they should repair or replace, are the most suited alternative to grafts.  Thus it seems logical to use the constituents of these tissues are the building bricks to elaborate biomaterials. Over the last years, the MatBio group have develop several materials using type I collagen, as the major protein constituting most of our tissues. The UR 2496 also use dense collagen hydrogels for craniofacial repair. More recently, I became also interested in fibrin, the protein responsible for blood clotting (see image below by K. Wang, L. Trichet and C. Peccate).

While these two proteins have many common features, especially their ability to form hydrogels by a self-assembly (fibrillogenesis) process, they differ by structure, dimensions and reactivity as well as in their interaction with specific cells. Combining them is one of our current challenge. We have also used other biopolymers, such as gelatin, alginate, chitosan or pectin, taking advantage of their easy gelation or their antibacterial properties. More recently, I also started working on polymer biomaterials based on bio-sourced monomers, in collaboration with Pr DL Versace (ICMPE)

(2) Nanocomposite hydrogels

In parallel, we have demonstrated the benefits associated with the use of silica in medicine. In particular, we are developing bio-materials associating biocompatible polymers with silica. Our past works have demonstrated that silica could improve the mechanical behavior of biological gels without impacting cell response and in vivo behavior. However, this highly depends on the exact chemical composition and morphology of the silica-based systems. As a matter of fact, silica can influence both the organization of the biopolymer network and the ability of cells to adhere on the materials. For instance, the above illustration shows that silica nanorods within collagen matrices can orient the growth of skin cells. The use of silica nanoparticles as carriers of bioactive peptides, antibiotics or genes, that can be incorporated within the biological hydrogels to form functional bionanocomposites is also studied.

Beyond silica, we have also a good expertise in the synthesis of nano-hydroxyapatite particles and their modification with organic molecules. We are also studying the incorporation of natural (cellulose nanocrystals) and synthetic (biodegradable polyesters) nano-objects

III. Material science in a dental context

I recently discovered  the complexity and richness of dental materials science, that encompasses both the formation and structure of dental tissues and the biomaterials used for their repair. Currently, I am strongly involved in the characterization of enamel defects. I am bringing my knowledge in hydroxyapatite chemistry and solid-state analytical methods (electron microscopy, XRD, vibrational spectroscopies,…) to study the structure and composition of pathological teeth at different scales. (see image below by S. Houari et al.)