Talbert, A. | bioRxiv Science

bioRxiv2020

Improved Wound Closure Rates and Mechanical Properties Resembling Native Skin in Murine Diabetic Wounds Treated with a Tropoelastin and Collagen Wound Healing Device

Chronic wounds in patients suffering from type II diabetes mellitus (DMII) where wounds remain open with a complicated pathophysiology, healing, and recovery process is a public health concern. Normal wound healing plays a critical role in wound closure, restoration of mechanical properties, and the biochemical characteristics of the remodeled tissue. Biological scaffolds provide a tissue substitute to help facilitate wound healing by mimicking the extracellular matrix (ECM) of the dermis. In the current study an electrospun biomimetic scaffold, wound healing device (WHD), containing tropoelastin (TE) and collagen was synthesized to mimic the biochemical and mechanical characteristics of healthy human skin. The WHD was compared to a commercially available porcine small intestinal submucosa (SIS) matrix that has been used in both partial and full-thickness wounds, Oasis(R) Wound Matrix. Wound closure rates, histochemistry, qPCR, and mechanical testing of treated wound sites were evaluated. The WHD in a splinted, full-thickness, diabetic murine wound healing model demonstrated an enhanced rate of wound closure, decreased tissue inflammation, skin organ regeneration, and a stronger and more durable remodeled tissue that more closely mimics native unwounded skin compared to the control device.

bioengineering↗

bioRxiv2017

Pervasive epistasis in cell proliferation pathways modulates neurodevelopmental defects of autism-associated 16p11.2 deletion

As opposed to syndromic CNVs caused by single genes, extensive phenotypic heterogeneity in variably-expressive CNVs complicates disease gene discovery and functional evaluation. Here, we propose a complex interaction model for pathogenicity of the autism-associated 16p11.2 deletion, where CNV genes interact with each other in conserved pathways to modulate expression of the phenotype. Using multiple quantitative methods in Drosophila RNAi lines, we identified a range of neurodevelopmental phenotypes for knockdown of individual 16p11.2 homologs in different tissues. We tested 565 pairwise knockdowns in the developing eye, and identified 24 interactions between pairs of 16p11.2 homologs and 46 interactions between 16p11.2 homologs and neurodevelopmental genes that suppressed or enhanced cell proliferation phenotypes compared to one-hit knockdowns. These interactions within cell proliferation pathways were also enriched in a human brain-specific network, providing translational relevance in humans. Our study indicates a role for genetic interactions within CNVs and identifies potential therapeutic targets for neurodevelopmental disorders.

genomics↗