Valorization of a Levulinic Acid Platform through Electrospinning of Polyhydroxyalkanoate-Based Fibrous Membranes for In Vitro Modeling of Biological Barriers

In vitro models of biological barriers provide a reliable tool for investigating the physiopathological processes involved in the development of numerous diseases. Producing sustainable in vitro models obtained from solvents and biopolymers derived from industrial by-products add an important value to this underestimated source of valuable (bio)materials. This works aims at demonstrating the suitability of processing together solvents derived from levulinic acid (LA) (extracted from biomasses) and poly(3-hydroxybutyrate-co-3-hydroxyvalerate (PHBV) (whose production is facilitated by LA) to produce electrospun membranes as proof-of-concept of a sustainable, engineered biological barrier fully derived from LA as the starting feedstock. The electrospinning process is initially optimized by identifying the most suitable conditions for obtaining self-supporting microporous membranes. In particular, LA-derived solvents (gamma-valerolactone, 2-methyltetrahydrofuran, methyl ethyl ketone, and methyl and ethyl levulinate), PHBV concentration, and electrospinning process parameters were investigated. Self-standing and hydrophobic PHBV mats with a micropore size in the range of 1-7 mu m and an average elastic modulus of 75 MPa are successfully obtained by using methyl ethyl ketone/formic acid as solvent. Preliminary cell experiments demonstrate that the developed fibrous PHBV mats promote the formation of a confluent monolayer of epithelial cells after 48 h and therefore they can potentially be used to mimic biological epithelial barriers.