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A bioengineered tridimensional substrate designed for mesenchymal stem cells culture: whole transcriptomic analysis

ABSTRACT: In this work we aimed to evaluate how the three-dimensionality of an engineered scaffold, concieved to emulate the stem cell niche, can influence the whole gene expression profile of mesenchymal stem cells. We performed a differential expression analysis, comparing the transcriptome of MSCs grown in 3D Nichoids with that of MSCs grown on 2D Nichoids, a structure with the same grid geometry, except for the overall tickness which allows a spreading expansion of cells. We found a total of 603 differentially expressed genes that were used also for functional enrichment analysis.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE199846 | GEO | 2022/12/22

REPOSITORIES: GEO

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Project description:Austere environments in which access to medical facilities, medical personnel, or even water and electricity is limited or unavailable pose unique challenges for medical device product design. Currently existing skin substitutes are severely inadequate for the treatment of severe burns, chronic wounds, battlefield injuries, or work-related injuries in resource-limited settings. For such settings, an ideal device should be biocompatible, bioresorbable, promote tissue healing, not require trained medical personnel for deployment and use, and should enable topical drug delivery. As proof of concept for such a device, silk fibroin and an antioxidant hyaluronic acid derivative were chosen as primary constituents. The final formulation was selected to optimize tensile strength while retaining mechanical compliance and protection from reactive oxygen species (ROS). The ultimate tensile strength of the device was 438.0 KPa. Viability of dermal fibroblasts challenged with ROS-generating menadione decreased to 49.7% of control, which was rescued by pre-treatment with the hyaluronic acid derivative to 85.0% of control. The final device formulation was also tested in a standardized, validated, in vitro skin irritation test which revealed no tissue damage or statistical difference from control. Improved topical drug delivery was achieved via an integrated silk fibroin microneedle array and selective device processing to generate crosslinked/through pores. The final device including these features showed a 223% increase in small molecule epidermal permeation relative to the control. Scaffold porosity and microneedle integrity before and after application were confirmed by electron microscopy. Next, the device was designed to be self-adherent to enable deployment without the need of traditional fixation methods. Device tissue adhesive strength (12.0 MPa) was evaluated and shown to be comparable to a commercial adhesive surgical drape (12.9 MPa) and superior to an over-the-counter liquid bandage (4.1 MPa). Finally, the device's wound healing potential was assessed in an in vitro full-thickness skin wound model which showed promising device integration into the tissue and cellular migration into and above the device. Overall, these results suggest that this prototype, specifically designed for use in austere environments, is mechanically robust, is cytocompatible, protects from ROS damage, is self-adherent without traditional fixation methods, and promotes tissue repair.

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A bioengineered tridimensional substrate designed for mesenchymal stem cells culture: whole transcriptomic analysis

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