A 3D in vitro model of the dermoepidermal junction amenable to mechanical testing

Abstract

Recessive dystrophic Epidermolysis Bullosa (RDEB) is caused by mutations in collagen‐type VII gene critical for the dermoepidermal junction (DEJ) formation. Neither tissues of animal models nor currently available in vitro models are amenable to the quantitative assessment of mechanical adhesion between dermal and epidermal layers. Here, we created a 3D in vitro DEJ model using extracellular matrix (ECM) proteins of the DEJ anchored to a poly(ethylene glycol)‐based slab (termed ECM composites) and seeded with human keratinocytes and dermal fibroblasts. Keratinocytes and fibroblasts of healthy individuals were well maintained in the ECM composite and showed the expression of collagen type VII over a 2‐week period. The ECM composites with healthy keratinocytes and fibroblasts exhibited yield stress associated with the separation of the model DEJ at 0.268 ± 0.057 kPa. When we benchmarked this measure of adhesive strength with that of the model DEJ fabricated with cells of individuals with RDEB, the yield stress was significantly lower (0.153 ± 0.064 kPa) consistent with our current mechanistic understanding of RDEB. In summary, a 3D in vitro model DEJ was developed for quantification of mechanical adhesion between epidermal‐ and dermal‐mimicking layers, which can be utilized for assessment of mechanical adhesion of the model DEJ applicable for Epidermolysis Bullosa‐associated therapeutics. © 2018 The Authors. Journal Of Biomedical Materials Research Part A Published By Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 3231–3238, 2018.

The Human Epidermal Basement Membrane: A Shaped and Cell Instructive Platform That Aging Slowly Alters

“…Models have been developed to specifically measure dermal-epidermal interaction strength in the context of diseases in which specific DEJ components are defective, such as EB. One group attempted to quantify the strength of the DEJ in a mouse model of EB by measuring the tension from the pull-push force gauge when a sleeve of tail skin was removed [96], and in vitro 3-dimensional (3D) useful models are currently being developed for quantitative assessment of the mechanical adhesion between the dermal and epidermal layers [97,98]. A biomechanical modeling of the DEJ undulating pattern was proposed, relying on the mechanical instability between dermal and epidermal layers and taking in account their microstructural properties and geometrical constraints [99,100].…”

Loss of Acta2 in cardiac fibroblasts does not prevent the myofibroblast differentiation or affect the cardiac repair after myocardial infarction

“…Thus, we employed rheology to test the effect of cardiac fibroblasts on the stability of the collagen gel they reside in. In rheology, the storage modulus indicates the ability of the material to store deformation energy in an elastic manner while maintaining structural integrity and has been used to measure the strength of biomaterials (21)(22)(23). Hydrogels with a greater level of crosslinking have a higher storage modulus (24).…”

The Reconstructed Human Epidermis in vitro — a Model for Basic and Applied Research of Human Skin

“…Трехмерная природа эквивалентов кожи позволяет моделировать различные патологические состояния кожи, такие как, например, атопический дерматит [33], псориаз [35] и генодерматозы [36], за счет включения в эквиваленты клеток пациентов, гиперпигментацию [37] за счет включения в эквиваленты меланоцитов [38], клеток Лангерганса [39].…”