Pristine Gellan Gum-Collagen Interpenetrating Network Hydrogels as Mechanically Enhanced Anti-inflammatory Biologic Wound Dressings for Burn Wound Therapy.

ABSTRACT

Gellan gum is a biologically inert natural polymer that is increasingly favored as a material-of-choice to form biorelevant hydrogels. However, as a burn wound dressing, native gellan gum hydrogels do not drive host's biology toward regeneration and are mechanically inadequate wound barriers. To overcome these issues, we fabricateda gellan gum-collagen full interpenetrating network (full-IPN) hydrogel that can house adipose-derived mesenchymal stem cells (ADSCs) and employ their multilineage differentiation potential and produce wound-healing paracrine factors to reduce inflammation and promote burn wound regeneration. Herein, a robust temperature-dependent simultaneous IPN (SIN) hydrogel fabrication process was demonstrated using applied rheology for the first time. Subsequently after fabrication, mechanical characterization assays showed that the IPN hydrogels were easy to handle without deforming and retained sufficient mass to effect ADSCs' anti-inflammation property in a simulated wound environment. The IPN hydrogels' increased stiffness proved conducive for mechanotransduced cell adhesion. Scanning electron microscopy revealed theIPN's porous network, which enabled encapsulated ADSCs to spread and proliferate, for up to 3 weeks of culture, further shown by cells' dynamic filopodia extension observed in 3D confocal images. Successful incorporation of ADSCs accorded the IPN hydrogels with biologic wound-dressing properties, which possess the ability to promote human dermal fibroblast migration and secrete an anti-inflammatory paracrine factor, TSG-6 protein, as demonstrated in the 2D scratch wound assay and ELISA, respectively. More importantly, upon application onto murine full thickness burn wounds, our biologic wound dressing enhanced early wound closure, reduced inflammation, and promoted complete skin regeneration. Altogether, our results highlight the successful mechanical and biological enhancement of the inert matrix of gellan gum. Through completely natural procedures, a highly applicable biologic wound dressing is introduced for cell-based full thickness burn wound therapy.