Diffusion-Based Modeling and Drug Delivery of Gasotransmitters from Electrospun Scaffolds

Delivery of gasotransmitters including carbon monoxide (CO) from scaffolds provides local-controlled delivery of cell-signaling molecules to a diseased area that may improve endothelialization in the tissue engineered vascular graft. However, it is important to understanding the proper dose of CO into the cells to determine the endothelial cell response because endogenous levels of CO are anti-inflammatory and required for vascular function, high levels are toxic, and levels in between demonstrate seemingly conflicting results in various tissues [1]. Our previous studies included incorporating CO releasing molecules (CORMs) within electrospun scaffolds and determining the impacts of CO on endothelial cells, where we found the need to better understand CO dose available to the cells. This study aimed to develop a two-part theoretical model designed to simulate diffusion of CO and other traditional drugs from fibrous scaffolds, and determine the temporal concentration of drug available to cells. Our modeling system included: 1) one model that generates the simulated fibrous scaffold structure, and 2) a model that simulates the transport from the fibrous representative volume. For experimental validation, poly(ε-caprolactone) (PCL) was electrospin with 2%w/w (FITC)-incorporated and CORM-loaded scaffolds. Samples were prepared and the fluorescence was measured for up to 16 hours to determine the drug release. The model can be used to predict drug availability to cells for a variety of scaffolds and drug molecules. For CO release, this model is necessary because of the limitations with real-time experimental analysis. Results suggest that only a fraction of the initial concentration of gasotransmitters released from fibers that enters the interstitial fluid in vivo, or culture media in vitro, will be available to cells. We concluded that fiber diameter and fiber density are important parameters not just for traditional tissue engineering, but also for drug delivery.

[1] Washington et. al., Frontiers in Pharmacology, 2017.