Positive effects of hypoxic preconditioning of the extracellular matrix and stromal vascular fraction from adipose tissue.

Background: Numerous approaches have been developed to decelerate the aging process of facial skin. Synthetic fillers and cell-enriched fat grafts are the main procedures employed to fill wrinkles. Objective: The aim of this study was to evaluate the in vitro and in vivo safety and efficiency of a new process developed by SYMBIOKEN: the AmeaCell, which facilitates the extraction of the stromal vascular fraction (SVF) and the associated hypoxia pre-conditioned matrix to promote fat graft survival. Methods: The AmeaCell device allows the extraction from adipose tissue of SVF and pre-conditioned MatriCS and promotes a hypoxic environment. Experiments were carried out on human cells and then in mice. Results: Characterization of cells and MatriCS showed that after their extraction using the new process developed by SYMBIOKEN, the extracted cells expressed stem-cell markers. The presence of characteristic proteins and lipid fractions found in the adipose matrix were confirmed in MatriCS. Cobalt chloride treatment of the matrix using the AmeaCell device induced modifications in the matrix composition with a decrease in laminin and without collagen modification, both of which promote adhesion and differentiation of SVF or adipose-derived stromal cells. The combination of MatriCS and SVF (1 × 106 and 5 × 106, respectively) is safe and efficient to fill winkles induced by UVB irradiation. The cross-talk between MatriCS and SVF can act a durable filler compared to the filling performed using cells or matrix or fat alone, which need to be replaced frequently. Conclusion: These results indicate that the combination of MatriCS and SVF is safe and effective as a biological filler for achieving skin rejuvenation and wrinkle filling.

Novel contributions on luminescent apatite-based colloids intended for medical imaging.

The setup of colloidal hybrid nanosystems based on biomimetic calcium phosphate apatites doped with europium ions has recently raised great interest in the pharmacological community, especially due to their bio-inspired character. This is especially relevant in relation with medical imaging for cancer diagnosis. Questions however remain in relation to a number of applicability aspects, some of which have been examined in this contribution. In a first part of this work, we explored further the luminescence properties of such colloidal nanoparticles. We pointed out, upon excitation of europium, the existence of some non-radiative de-excitation via the vibration of O-H oscillators located at the vicinity of the Eu(3+) luminescent centers. The replacement of Eu(3+) by Tb(3+) ions, less prone to non-radiative de-excitation, was then tested in a preliminary way and can be seen as a promising alternative. In a second part of this work, we inspected the possibility to store these colloids in a dry state while retaining a re-suspension ability preserving the nanometer size of the initial nanoparticles, and we propose a functional protocol involving the addition of glucose prior to freeze-drying. We finally showed for the first time, based on titrations of intracellular Ca(2+) and Eu(3+) ions, that folic acid-functionalized biomimetic apatite nanoparticles were able to target cancer cells that overexpress folate receptors on their membrane, which we point out here in the case of T-47-D breast carcinoma cells, as opposed to ZR-75-1 cells that do not express folate receptors. This contribution thus opens new exciting perspectives in the field of targeted cancer diagnosis, thus confirming the promise of biomimetic apatites-based colloidal formulations.

Biomimetic nanocrystalline apatites: Emerging perspectives in cancer diagnosis and treatment.

Nanocrystalline calcium phosphate apatites constitute the mineral part of hard tissues, and the synthesis of biomimetic analogs is now well-mastered at the lab-scale. Recent advances in the fine physico-chemical characterization of these phases enable one to envision original applications in the medical field along with a better understanding of the underlying chemistry and related pharmacological features. In this contribution, we specifically focused on applications of biomimetic apatites in the field of cancer diagnosis or treatment. We first report on the production and first biological evaluations (cytotoxicity, pro-inflammatory potential, internalization by ZR-75-1 breast cancer cells) of individualized luminescent nanoparticles based on Eu-doped apatites, eventually associated with folic acid, for medical imaging purposes. We then detail, in a first approach, the preparation of tridimensional constructs associating nanocrystalline apatite aqueous gels and drug-loaded pectin microspheres. Sustained releases of a fluorescein analog (erythrosin) used as model molecule were obtained over 7 days, in comparison with the ceramic or microsphere reference compounds. Such systems could constitute original bone-filling materials for in situ delivery of anticancer drugs.