In this interview, Prof Christophe Drouet (CNRS Senior Scientist) – an international specialist in bio-inspired apatites – relates the multifunctional potential of these intrinsically biocompatible compounds for a wealth of uses from bone tissue repair, to cell-scale medicine
Open Access Government spoke to Prof Christophe Drouet (CNRS Senior Scientist) – an international specialist in bio-inspired apatites – to learn more about this most absorbing field of research, dealing with regenerative and nanomedicine
Prof Drouet, why study biomimetic apatites? What is the interest in getting inspired from Nature?
“Nature has always been a great source of inspiration for humans… This is especially true considering biomineralisations as in bones and teeth. By appropriately tuning their composition and conditions of formation in vivo, Nature has designed its own biomaterials, capable of cumulating at once with mechanical strength and bioactivity. Such biominerals are essentially composed of calcium phosphates with an “apatite” structure, and we have learned over time to master the preparation and processing of synthetic analogues, so-called “biomimetic apatites”.
“This is one focus of our research group in Toulouse. By mimicking crystals naturally present in our bones, these “intrinsically” biocompatible compounds are particularly well suited to the design of biomaterials for use in vivo: whether in view of bone regeneration or beyond!
“In all cases, it is also possible to convey additional functionalities such as anticancer or antimicrobial by exploiting the exceptional surface reactivity of these compounds.”
What is the potential of biomimetic apatites in medicine?
“Biomimetic apatites are prepared by soft chemistry, thus avoiding the use of high temperatures to preserve their reactivity and intrinsic features. Indeed, as in natural bone mineral, biomimetic apatite crystals are covered by a hydrated non-apatitic ionic layer which confers to these compounds an exceptionally high surface reactivity, which can be exploited because of biomedical applications. (1) It is then possible – provided that the adequate experimental conditions are used – to graft on their surface a large variety of bioactive molecules/drugs to set up medical devices.
“We have, for instance, shown the possibility to associate antibacterial enzymes, antibiotics, anticancer drugs, hemostatic agents, cell-targeting moieties, anti-osteoporotic drugs, vitamins, and so on to design “à la carte” bioactive compounds. Also, the possibility to modulate their ionic composition allows doping them with bioactive ions which may also play a role in the control of microbial colonisation, inflammation, etc.”
What about bone regeneration?
“Biomimetic apatites are increasingly considered by researchers and clinicians for the design of innovative implantable biomaterials in orthopaedics and dentistry. Using such bio-inspired apatites may indeed ensure not only a high biocompatibility, but also a tailorable resorption rate, which may be modulated via their chemical composition and processing approach. Plus, as mentioned above, several strategies can be developed to confer additional therapeutic functionalities.
“Starting in 2004, our group showed for the first time that it was possible to consolidate biomimetic apatite powders into actual 3D scaffolds via “cold sintering” by a technique called Spark Plasma Sintering (SPS). (2) This opened the way to low-temperature consolidation approaches to preserve the characteristics and performances of such bio-inspired apatites. This low-temperature consolidation is possible by the presence of water molecules on the crystal surface, allowing significant ion mobility.
“Lately, this possibility was also extended to amorphous calcium phosphates, often considered as precursors of bone formation in vivo, while preserving again the appealing physicochemical properties of these metastable compounds. (3) We also showed, more recently, that it was possible to coat existing implants (ceramics, metals) such as hip, knee or dental implants with biomimetic apatites so as to significantly increase their bioactivity and osteointegration capacity.
“For instance, we proved the relevance of the cold spray technique. Using such reactive apatites is not only a way to boost the biointegration of the implant and allow faster bone repair, but it also allows associating bioactive ions and molecular species, such as antimicrobials to fight or avoid infections. This approach is notably followed in the starting AIMed EU H2020 programme. (4)”
And beyond bone repair? You mentioned “nanomedicine”?
“Yes indeed. Biomimetic apatites have been developed initially with the idea to propose more efficient bioactive bone substitute materials capable of being functionalised to provide additional effects in vivo, which we showed has great promise. But taking into account their intrinsic biocompatibility, it is also possible to extend the initial usages to a wealth of other medical applications!
“In oncology, haematology, dermatology… in all such domains where “nanomedicine” devices are needed, providing small systems to act at the level of cells. (5) It should probably be reminded that nanosized crystals are already present in our bodies since bone is a natural nanocomposite! Here, by designing bio-inspired apatites, we play with nanocrystals that our body can handle and whose biodegradation leads to natural metabolites.
“We showed that it was possible to associate, to apatite nanoparticles, a cell targeting agent to address more specifically some diseased cells; that the bio-inspired apatite particle formulation could allow modifying the cellular uptake of some biomolecules/drugs; and that it was possible to design apatite systems for a “smart” delivery dependent on the body response.
“This all opens new avenues of research, typically where an action is needed at a cellular or tissular level. Of course, this requires adapting the formulation and composition to the clinical application, which is why a close contact between materials scientists, galenic pharmacists, clinicians and industrials are needed.
“But the role of politicians and decision-makers is also primordial to sustain these developments.”
How could decision-makers help the apatite research community?
“Well, the community now has a strong background on biomimetic/bio-inspired apatites, their elaboration, characterisation, behaviour, processing and properties to certify that these compounds are worth investing further research efforts! However, since the opportunities of use are wide and not yet fully explored by far, additional work is needed in several strategic domains to further ascertain and determine the power of bio-inspired apatites, including in comparison to existing devices often less biocompatible.
“Decision-makers could help to promote an active development of biomimetic apatite-based systems by 1) launching dedicated calls for projects at national and European/international scales and providing the necessary funds, 2) setting up a committee of experts about bio-inspired apatites for coordinating research actions, 3) facilitating the development of standards dedicated to such metastable compounds.
“In my opinion, this all could allow progressing significantly toward the validation and use of highly-bioactive apatite-based systems in tomorrow’s medicine for the good of our patients…and the whole healthcare system since these systems are rather low-cost to produce.”
References
(1) Drouet, C. et al. 2018. Nanocrystalline apatites: The fundamental role of water. Am. Miner. 103;550-564.
(2) Grossin, D. et al. 2010. Biomimetic apatite sintered at very low temperature by spark plasma sintering: Physico-chemistry and microstructure aspects. Acta Biomat. 6;577-585.
(3) Luginina et al., First successful stabilization of consolidated amorphous calcium phosphate (ACP) by cold sintering: toward highly-resorbable reactive bioceramics J. Mat. Chem. B, 8 (2020) 629-635.
(4) Horizon 2020 research and innovation programme, Marie Skłodowska-Curie grant agreement No 861138, http://www.aimed-itn.eu
(5) Drouet, C. et al. 2020. Colloidal apatite particles: a multifunctional platform in (nano)medicine. Juniper Online J. Mater. Sci. 6 (1);art.555676;1-8.
Member (and PhD supervisor) of the H2020 project AIMed.
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