Mimicking the topography of the epidermal-dermal interface with elastomer substrates.

In human skin the interface between the epidermis and dermis is not flat, but undulates. The dimensions of the undulations change as a function of age and disease. Epidermal stem cell clusters lie in specific locations relative to the undulations; however, whether their location affects their properties is unknown. To explore this, we developed a two-step protocol to create patterned substrates that mimic the topographical features of the human epidermal-dermal interface. Substrates with negative patterns were first fabricated by exposing a photocurable formulation to light, controlling the topographical features (such as diameter, height and center-to-center distance) by the photomask pattern dimensions and UV crosslinking time. The negative pattern was then translated to PDMS elastomer to fabricate substrates with 8 unique surface topographies on which primary human keratinocytes were cultured. We found that cells were patterned according to topography, and that separate cues determined the locations of stem cells, differentiated cells and proliferating cells. The biomimetic platform we have developed will be useful for probing the effect of topography on stem cell behaviour.

The interfollicular epidermis of adult mouse tail comprises two distinct cell lineages that are differentially regulated by Wnt, Edaradd, and Lrig1.

Current models of how mouse tail interfollicular epidermis (ife) is maintained overlook the coexistence of two distinct terminal differentiation programs: parakeratotic (scale) and orthokeratotic (interscale). lineage tracing and clonal analysis revealed that scale and interscale are maintained by unipotent cells in the underlying basal layer, with scale progenitors dividing more rapidly than interscale progenitors. Although scales are pigmented and precisely aligned with hair follicles, melanocytes and follicles were not necessary for scale differentiation. Epidermal Wnt signaling was required for scale enlargement during development and for postnatal maintenance of scale-interscale boundaries. Loss of Edaradd inhibited ventral scale formation, whereas loss of Lrig1 led to scale enlargement and fusion. In wild-type skin, Lrig1 was not expressed in IFE but was selectively upregulated in dermal fibroblasts underlying the interscale. We conclude that the different IFE differentiation compartments are maintained by distinct stem cell populations and are regulated by epidermal and dermal signals.

Do we know the strength of the chorioamnion? A critical review and analysis.

The chorioamnion is the membrane that surrounds the fetus during gestation. Normally, it must remain intact for the duration of pregnancy, 37-42 weeks, and only rupture during or just before labour and delivery of the fetus. In a significant number (3%) of all births, this does not happen, and membranes rupture before term, resulting in preterm birth and significant perinatal morbidity. It is known that the material properties of chorioamnion may play a major role in mechanical rupture; a number of studies have been undertaken to characterise the physical nature of chorioamnion and examine factors that may predispose to rupture. However, the existing literature is inconsistent in its choice of both physical testing methods and data analysis techniques, motivating the current review. Experimental data from a large number of chorioamnion mechanical studies were collated, and data were converted to standard engineering quantities. The failure strength of the chorioamnion membrane was found consistently to value approximately 0.9 MPa. It is hoped that past and future studies of membrane mechanics can provide insight into the role of chorioamnion in labour and delivery. In addition, biomechanical approaches can help elucidate the potential causes of early rupture, and suggest future protocols or treatments that could both diagnose and prevent its occurrence.