Evaluation of scaffolding, inflammatory response, and wound healing support of a reverse thermal gel for myelomeningocele patching

Abstract

A reverse thermal gel (RTG) is a promising patching material for in utero, minimally invasive coverage of myelomeningocele (MMC) defects. The injectable properties of the RTG brings the potential for significantly reduced surgical risks to the mother and fetus when compared to current open prenatal repair procedures. MMC patching materials require structural and wound healing support for tissue growth over the MMC defect area to allow a watertight seal to form and prevent further neural tissue exposure to the amniotic environment. Here, the previously described RTG is evaluated for the first time as a scaffold for skin cells, for long-term inflammation effects in neonatal mice, and for wound healing capability. Results show that the RTG can support the growth and survival of keratinocytes, dermal fibroblasts, and neuronal cells in vitro. Injections into neonatal mice demonstrate a regressing inflammatory response and support of normal wound healing. Together, these results demonstrate that the RTG has the necessary scaffolding and wound healing support necessary for MMC patching applications.

Extracellular matrix stiffness mediates insulin secretion in pancreatic islets via mechanosensitive Piezo1 channel regulated Ca2+ dynamics

“…To determine suitability of RTG for islet culture and investigation of mechanotransduction signaling, we characterized islet survival, stress, and formation of focal adhesions within a 3D RTG scaffold. PSHU-PNIPAAm RTG was chosen as our scaffold due to its ability to encapsulate islets under physiological conditions, its tunable mechanical properties, its biocompatibility, and its biomimetic nature [58] , [59] , [60] , [61] . Although it is fully synthetic, it mimics naturally occurring ECM biomolecules like heparan sulfate, which undergoes a phase change from solution to gel to aid in blood coagulation for wound healing purposes [62] .…”