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Background: Hyaluronic acid (HA) formulations are used for aesthetic applications. Different cross-linking technologies result in HA dermal fillers with specific characteristic visco-elastic properties. Objective: Bio-integration of three CE-marked HA dermal fillers, a cohesive (monophasic) polydensified, a cohesive (monophasic) monodensified and a non-cohesive (biphasic) filler, was analysed with a follow-up of 114 days after injection. Our aim was to study the tolerability and inflammatory response of these fillers, their patterns of distribution in the dermis, and influence on tissue integrity. Methods: Three HA formulations were injected intradermally into the iliac crest region in 15 subjects. Tissue samples were analysed after 8 and 114 days by histology and immunohistochemistry, and visualized using optical and transmission electron microscopy. Results: Histological results demonstrated that the tested HA fillers showed specific characteristic bio-integration patterns in the reticular dermis. Observations under the optical and electron microscopes revealed morphological conservation of cutaneous structures. Immunohistochemical results confirmed absence of inflammation, immune response and granuloma. Conclusion: The three tested dermal fillers show an excellent tolerability and preservation of the dermal cells and matrix components. Their tissue integration was dependent on their visco-elastic properties. The cohesive polydensified filler showed the most homogeneous integration with an optimal spreading within the reticular dermis, which is achieved by filling even the smallest spaces between collagen bundles and elastin fibrils, while preserving the structural integrity of the latter. Absence of adverse reactions confirms safety of the tested HA dermal fillers.

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To assess whether the expression of connexins (Cx) by keratinocytes is altered under conditions of abnormal epidermal differentiation, we have compared Cx26, Cx32, Cx37, Cx40, and Cx43 in the epidermis of 11 psoriatic patients who had not been treated for at least 1 mo and of seven healthy individuals. In all samples of fully mature psoriatic plaques, we have observed a massive expression of Cx26, as judged at both the transcript level (northern blot) and the protein level (immunofluorescence). This protein became consistently detected between keratinocytes of the basal and granular layers at the periphery of psoriatic plaques and in all layers of fully developed psoriatic epidermis, except in regions of parakeratosis. None or a minimal amount of Cx26 was observed in both control and nonlesional regions of psoriatic epidermis. Psoriatic plaques also contained Cx43, the prominent gap junction protein in the interfollicular epidermis of normal human skin. The levels of this protein appeared to be slightly higher in psoriatic than in control skin, as judged at both the transcript level (northern blot) and the protein level (immunofluorescence). Three other connexins (Cx32, Cx37, and Cx40), which are not observed in control interfollicular epidermis, were not induced in either nonlesional or lesional regions of psoriatic skin. The data indicate that selective changes in the normal expression of connexins by keratinocytes are associated with the changes in the proliferation and differentiation program that these cells undergo in psoriasis.

Background: Leg ulcers are an important cost factor in health care systems. It has been shown that a telemedical wound care consultation can improve quality of care and help reduce costs. In this study, we evaluated the feasibility of telemedical wound care using a new generation of mobile telephones with integrated cameras.Observations: Three physicians separately evaluated 61 leg ulcers for the following 9 variables: epithelialization, fibrin, necrosis, and granulation tissue at the center and normal border, erythema, cyanosis, eczema, and hyperpigmentation at the periphery. One physician performed the face-to-face consultation (gold standard), and 2 others performed the remote evaluation. The image was obtained with the mobile telephone and immediately sent via e-mail. To measure the agreement of the evaluation among the 3 physicians, we used Cohen statistics. Overall, the agreement between the remote and face-to-face evaluations was very good, with values of up to 0.94 The image quality was judged to be good in 36 cases (59%) and very good in 12 (20%). The participants felt comfortable making a diagnosis based on the pictures in 50 cases (82%). Conclusion:Although this study was performed with the first generation of these devices, we were able to demonstrate the feasibility of such a telemedical wound care consultation.

We have characterized cell-to-cell communication (coupling) within intact human skin by microinjecting single keratinocytes with a gap junction-permeant tracer (Lucifer Yellow). 25-50 keratinocytes from different layers of the epidermis were seen to be coupled after most injections (n = 31). A few noncommunicating cells were also microinjected (a = 3) or observed within large territories of coupled keratinocytes. Microinjections of dermal fibroblasts demonstrated an extensive coupling (> 100 fibroblasts); however, none of the keratinocyte (n = 34) or fibroblast (n = 3) injections revealed coupling between the epidermal and dermal compartments. Cell coupling was found to be more extensive in epidermal ridges than in suprapapillary plates and, in both regions, was less extensive after injection of the basal layer of the epidermis than after that of the suprabasal layers. This study shows that junctional cell-to-cell communications take place in normal and fully differentiated human tissue. The quantitative data gathered also indicate a regional heterogeneity of keratinocyte-to-keratinocyte communication within intact adult skin and the lack of effect of retinoids on this pattern.

The outer root sheath of hair follicles plays an important role in epidermal regeneration in vivo. Keratinocytes isolated by explantation of outer root sheath tissue have extensive proliferative capacity irrespective of donor age, which probably depends on pluripotent epithelial stem cells residing in the outer root sheath. These keratinocytes can be organotypically grown to epidermal equivalents in vitro. We report here that in a multicenter, randomized phase II study, EpiDex trade mark, a tissue-engineered, fully differentiated autologous epidermal equivalent derived from keratinocytes of the outer root sheath of plucked anagen hair follicles, is as effective as split-thickness skin autografting in the promotion of healing and complete closure of recalcitrant vascular leg ulcers.