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Micropatterned dermal–epidermal regeneration matrices create functional niches that enhance epidermal morphogenesis

Paper ID Volume ID Publish Year Pages File Format Full-Text
650 53 2013 11 PDF Available
Title
Micropatterned dermal–epidermal regeneration matrices create functional niches that enhance epidermal morphogenesis
Abstract

Although tissue engineered skin substitutes have demonstrated some clinical success for the treatment of chronic wounds such as diabetic and venous ulcers, persistent graft take and stability remain concerns. Current bilayered skin substitutes lack the characteristic microtopography of the dermal–epidermal junction that gives skin enhanced mechanical stability and creates cellular microniches that differentially promote keratinocyte function to form skin appendages and enhance wound healing. We developed a novel micropatterned dermal–epidermal regeneration matrix (μDERM) which incorporates this complex topography and substantially enhances epidermal morphology. Here, we describe the use of this three-dimensional (3-D) in vitro culture model to systematically evaluate different topographical geometries and to determine their relationship to keratinocyte function. We identified three distinct keratinocyte functional niches: the proliferative niche (narrow geometries), the basement membrane protein synthesis niche (wide geometries) and the putative keratinocyte stem cell niche (narrow geometries and corners). Specifically, epidermal thickness and keratinocyte proliferation is significantly (p < 0.05) increased in 50 and 100 μm channels while laminin-332 deposition is significantly (p < 0.05) increased in 400 μm channels compared to flat controls. Additionally, β1brip63+ keratinocytes, putative keratinocyte stem cells, preferentially cluster in channel geometries (similar to clustering observed in native skin) compared to a random distribution on flats. This study identifies specific target geometries to enhance skin regeneration and graft performance. Furthermore, these results suggest the importance of μDERM microtopography in designing the next generation of skin substitutes. Finally, we anticipate that 3-D organotypic cultures on μDERMS will provide a novel tissue engineered skin substitute for in vitro investigations of skin morphogenesis, wound healing and pathology.

Keywords
3-D organ model; Keratinocyte function; Microtopography; Dermal–epidermal junction
First Page Preview
Micropatterned dermal–epidermal regeneration matrices create functional niches that enhance epidermal morphogenesis
Publisher
Database: Elsevier - ScienceDirect
Journal: Acta Biomaterialia - Volume 9, Issue 12, December 2013, Pages 9474–9484
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering