Bio-inspired apatites: from bone to skin
DROUET C. 1, CHOIMET-BERNARD M. 1, GUERIN M. 1,2, SUBRA G. 2, TOURRETTE A. 1, SOULIE J. 1, KUHN L. 3
1 CIRIMAT / Université de Toulouse, Toulouse, France; 2 IBMM / Université de Montpellier, Montpellier, France; 3 UCONN Health / University of Connecticut, USA, Farmington, United States
Apatite-based ceramics have long attracted interest in medicine, especially for hard tissue repair due to similarities with bone mineral. Fine characterization of bone specimens, including fresh ones , allowed identifying the features of the apatite constituting bone mineral. It involves nonstoichiometric nanometric crystals covered by a short-range-ordered hydrated layer with ions in non-apatitic chemical environments, as evidenced by specific spectral signatures (IR, Raman, NMR…). These features, allied to the thermodynamic metastability of these nanocrystalline apatites, contribute to their high surface reactivity allowing for a large variety of ion exchanges/substitutions and molecular adsorptions. Bone-like apatites may be prepared in close-to-physiological conditions by wet chemistry, enabling the production of bioactive and resorbable bone substitutes, and the bioactivity may further be modulated through their ionic composition (e.g. adding antibacterial ions) and/or via the adsorption of drugs (e.g. antibiotics, anticancer drugs, hemostatic agents…).
However, besides bone repair, the intrinsic biocompatibility and nanoscale dimensions of bio-inspired apatites open the way to other fields of applications, as in nanomedicine. Previous data dealt with the preparation of colloidal apatite nanoparticles (NPs) stabilized with an organic corona; and in vitro analyses confirmed their low cytotoxicity and non-proinflammatory character. Plus, the body has learned over millions of years in all vertebrates to degrade these materials, via regular pathways generating natural metabolites reusable by the body. The addition of functionalities like antibacterialness, luminescence, cell targeting, etc. to these NPs was also investigated, making of bio-inspired apatite NPs a genuine multifunctional platform for nanomedical applications .
One domain of interest is dermatology. In this contribution, several strategies will be presented to illustrate the potential of such systems, illustrated by our recent examples on the use of hybrid colloidal apatite-based NPs. We showed for example that apatite NPs could be used as carriers of an anti-acne drug, clindamycin, so as to favor a local topical action on the skin/hair follicles  while limiting secondary effects encountered with anti-acne formulations where the drug is simply solubilized in the liquid phase. We also developed a strategy to provide “smart” releasing properties via the self-regulating action of enzymes secreted by the bacteria at play in acne. More recently, with the view to propose novel local treatments of complex wounds, we developed innovative hybrid apatite NPs decorated by a corona of bioactive peptides. Through the examples of two peptides exposing either the RGD or the YIGSR amino acid sequence, we then showed the tailorable character of such hybrid NPs and explored in vitro their interaction with fibroblast cells and their corresponding potential pro-healing character. Such hybrid NPs present several assets for wound healing that will be summarized; and the preparation of dedicated medical devices has been initiated, e.g. by impregnating commercial wound dressings or by generating original ones from “freeze-cast” porous polymer matrices formed in the presence of colloidal apatite NPs.
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