title: Hyaluronan Hybrid Cooperative Complexes as a Novel Frontier for Cellular Bioprocesses Re-Activation.
abstract: Hyaluronic Acid (HA)-based dermal formulations have rapidly gained a large consensus in aesthetic medicine and dermatology. HA, highly expressed in the Extracellular Matrix (ECM), acts as an activator of biological cascades, stimulating cell migration and proliferation, and operating as a regulator of the skin immune surveillance, through specific interactions with its receptors. HA may be used in topical formulations, as dermal inducer, for wound healing. Moreover, intradermal HA formulations (injectable HA) provide an attractive tool to counteract skin aging (e.g., facial wrinkles, dryness, and loss of elasticity) and restore normal dermal functions, through simple and minimally invasive procedures. Biological activity of a commercially available hyaluronic acid, Profhilo®, based on NAHYCO™ technology, was compared to H-HA or L-HA alone. The formation of hybrid cooperative complexes was confirmed by the sudden drop in η0 values in the rheological measurements. Besides, hybrid cooperative complexes proved stable to hyaluronidase (BTH) digestion. Using in vitro assays, based on keratinocytes, fibroblasts cells and on the Phenion® Full Thickness Skin Model 3D, hybrid cooperative complexes were compared to H-HA, widely used in biorevitalization procedures, and to L-HA, recently proposed as the most active fraction modulating the inflammatory response. Quantitative real-time PCR analyses were accomplished for the transcript quantification of collagens and elastin. Finally immunofluorescence staining permitted to evaluate the complete biosynthesis of all the molecules investigated. An increase in the expression levels of type I and type III collagen in fibroblasts and type IV and VII collagen in keratinocytes were found with the hybrid cooperative complexes, compared to untreated cells (CTR) and to the H-HA and L-HA treatments. The increase in elastin expression found in both cellular model and in the Phenion® Full Thickness Skin Model 3D also at longer time (up to 7 days), supports the clinically observed improvement of skin elasticity. The biomarkers analyzed suggest an increase of tissue remodeling in the presence of Profhilo®, probably due to the long lasting release and the concurrent action of the two HA components.
authors.affiliation: Department of Experimental Medicine, Section of Biotechnology, Medical Histology and Molecular Biology, Second University of Naples, Bioteknet, Naples, Italy.
authors.forename: Antonietta
authors.initials: A
authors.lastname: Stellavato
authors.affiliation: Department of Experimental Medicine, Section of Biotechnology, Medical Histology and Molecular Biology, Second University of Naples, Bioteknet, Naples, Italy.
authors.forename: Luisana
authors.initials: L
authors.lastname: Corsuto
authors.affiliation: Department of Experimental Medicine, Section of Biotechnology, Medical Histology and Molecular Biology, Second University of Naples, Bioteknet, Naples, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: D'Agostino
authors.affiliation: Department of Experimental Medicine, Section of Biotechnology, Medical Histology and Molecular Biology, Second University of Naples, Bioteknet, Naples, Italy.
authors.forename: Annalisa
authors.initials: A
authors.lastname: La Gatta
authors.affiliation: Department of Experimental Medicine, Section of Biotechnology, Medical Histology and Molecular Biology, Second University of Naples, Bioteknet, Naples, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Diana
authors.affiliation: IBSA Farmaceutici Italia Srl, Lodi, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Bernini
authors.affiliation: Department of Experimental Medicine, Section of Biotechnology, Medical Histology and Molecular Biology, Second University of Naples, Bioteknet, Naples, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: De Rosa
authors.affiliation: Department of Experimental Medicine, Section of Biotechnology, Medical Histology and Molecular Biology, Second University of Naples, Bioteknet, Naples, Italy.
authors.forename: Chiara
authors.identifier: http://orcid.org/0000-0002-1066-843X
authors.initials: C
authors.lastname: Schiraldi
mesh_terms: D002460:Cell Line; D003094:Collagen / Q000096:biosynthesis; D003358:Cosmetics / Q000494:pharmacology*; D005347:Fibroblasts / Q000378:metabolism*; D006801:Humans; D006820:Hyaluronic Acid / Q000494:pharmacology*; D015603:Keratinocytes / Q000378:metabolism*; D008954:Models, Biological; D015595:Skin Aging / Q000187:drug effects*
chemical_list: D003358:Cosmetics; D006820:Hyaluronic Acid; D003094:Collagen