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      Interconnected PolymerS TeChnology (IPSTiC): An Effective Approach for the Modulation of 5α-Reductase Activity in Hair Loss Conditions

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          Abstract

          Hair loss represents a condition that adversely affects the social life of patients. The most common cause is androgenetic alopecia (AGA), which is a genetically determined progressive hair-loss condition involving 5α-reductase. In this study, a novel anti-baldness agent based on Interconnected PolymerS TeChnology (IPSTiC), which is an effective strategy for the delivery of bioactive molecules, was developed. This product (IPSTiC patch hair) is based on a polymeric blend consisting of high molecular weight hyaluronic acid and soybean proteins and is able to improve efficacy and stability of bioactive ingredients such as Origanum vulgare leaf extract, Camellia Sinensis leaf extract, and Capsicum Annuum fruit extract. The efficacy of the developed anti-baldness agent was investigated by performing several tests including NO radical and 5α-reductase inhibition assays, stability studies under different conditions, and in vitro diffusion studies using Franz cells. The biocompatibility of IPSTiC patch hair was also evaluated by in vitro analysis of the pro-sensitising potential and EPISKIN model. The obtained results confirmed both the efficacy and safety of IPSTiC patch hair supporting the potential use of this product in the topical treatment of AGA.

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          Most cited references49

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          Concise Review: The Use of Adipose-Derived Stromal Vascular Fraction Cells and Platelet Rich Plasma in Regenerative Plastic Surgery.

          Tissue engineering has emerged at the intersection of numerous disciplines to meet a global clinical need for technologies to promote the regeneration of tissues. Recently, many authors have focused their attention on mesenchymal stem/stromal cells (MSCs) for their capacity to differentiate into many cell lineages. The most widely studied cell types are bone marrow mesenchymal stem cells and adipose-derived stem cells (ASCs), which display similar results. Biomaterials, cells, and growth factors are needed to design a regenerative plastic surgery approach in the treatment of organ and tissue defects, but not all tissues are created equal. The aim of this article is to describe the advances in tissue engineering through the use of ASCs, platelet rich plasma, and biomaterials to enable regeneration of damaged complex tissue. Stem Cells 2017;35:117-134.
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            Diagnostic and predictive value of horizontal sections of scalp biopsy specimens in male pattern androgenetic alopecia.

            Vertical sections of small scalp biopsy specimens are often inadequate for the diagnosis of male pattern androgenetic alopecia (MPAA). Quantitative analysis of follicular structures in horizontal sections can provide more information. Our purpose was to establish better diagnostic criteria by comparing horizontal and vertical sections of scalp biopsy specimens from MPAA and normal control subjects and to determine the predictive value of horizontal sections, by relating counts of follicular structures in MPAA to subsequent hair regrowth from topical minoxidil therapy. Paired 4 mm punch biopsy specimens were taken from 22 normal control subjects and 106 patients with MPAA, for horizontal and vertical sectioning. In horizontal sections, hair bulbs, terminal anagen, catagen and telogen hairs, telogen germinal units, and vellus hairs were counted, as were follicular units and stelae. The diagnosis of MPAA was confirmed by finding decreased terminal hairs and increased stelae and vellus hairs. The average horizontal section contained 22 terminal and 13 vellus hairs, a 1.7:1 ratio. Changes compatible with MPAA were found in most vertical and horizontal sections, but horizontal sections were required for follicular counts and showed terminal:vellus hair ratios diagnostic of MPAA in 67% of cases. Of 44 patients treated with topical minoxidil, five with less than 2 follicular structures/mm2 showed no hair regrowth, 32 with 2 to 4 follicular structures/mm2 showed regrowth in 72%, and seven with more than 4 follicular structures/mm2 showed regrowth in 86% of cases. In MPAA with no significant inflammation, regrowth occurred in 77% of cases, versus 55% in cases with significant inflammation. Horizontal sections of scalp biopsy specimens in MPAA provide more diagnostic information than vertical sections and appear to have a predictive value for hair regrowth.
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              Effect of minoxidil on proliferation and apoptosis in dermal papilla cells of human hair follicle.

              Minoxidil has been widely used to treat androgenetic alopecia, but little is known about its pharmacological activity or about the identity of its target cells in hair follicles. We hypothesized that minoxidil has direct effects on the proliferation and apoptosis of dermal papilla cells (DPCs) of human hair follicle. To elucidate the mechanism of topical minoxidil action in terms of stimulating hair growth. We evaluated cell proliferations in cultured DPCs by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and measured the expressions of extracellular signal-regulated kinase (ERK), Akt, Bcl-2, and Bax by Western blot. We also measured elongation of hair follicles in organ culture. Minoxidil significantly increased the proliferation of DPCs. The levels of ERK phosphorylation and of phosphorylated Akt increased significantly 1 h post-treatment; percentage increase of ERK phosphorylation was 287% at 0.1 microM and 351% at 1.0 microM of minoxidil, and that of Akt phosphorylation was 168% at 0.1 microM and 257% at 1.0 microM of minoxidil. 1.0 microM of minoxidil increased Bcl-2 expression over 150%, while 1.0 microM of minoxidil decreased Bax expression by more than 50%. Moreover, a significant elongation of individual hair follicles in organ culture was observed after adding minoxidil. Minoxidil promotes the survival of human DPCs by activating both ERK and Akt and by preventing cell death by increasing the ratio of Bcl-2/Bax. We suggest that minoxidil stimulates the growth of human hairs by prolonging anagen through these proliferative and anti-apoptotic effects on DPCs.
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                Author and article information

                Journal
                J Funct Biomater
                J Funct Biomater
                jfb
                Journal of Functional Biomaterials
                MDPI
                2079-4983
                12 July 2018
                September 2018
                : 9
                : 3
                Affiliations
                [1 ]Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende (CS), Italy; ortensiailaria.parisi@ 123456unical.it (O.I.P.); luca.scrivano@ 123456unical.it (L.S.); rocco.malivindi@ 123456unical.it (R.M.); mariarosaruffo8@ 123456gmail.com (M.R.); v.pezzi@ 123456unical.it (V.P.)
                [2 ]Macrofarm s.r.l., c/o Department of Pharmacy, Health and Nutrition Sciences, University of Calabria, 87036 Rende (CS), Italy; amonefabio@ 123456gmail.com (F.A.); vattimoanna@ 123456yahoo.it (A.F.V.)
                Author notes
                [* ]Correspondence: francesco.puoci@ 123456unical.it ; Tel.: +39-0984-493151
                Article
                jfb-09-00044
                10.3390/jfb9030044
                6163819
                30002324
                6d52a8be-e1c3-44fb-b96a-dcc8df700807
                © 2018 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                Categories
                Article

                hair loss,androgenetic alopecia (aga),5α-reductase,polymeric blend,hyaluronic acid,soybean proteins,origanum vulgare leaf extract,camellia sinensis leaf extract,capsicum annuum fruit extract,episkin model

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