All-Protein Electrospun Scaffolds: Profiling Time-dependent Spinnable Regimes and the Addition of Functional Fillers

Electrospinning is a well-established and scalable technology, enabling the production of fibrous scaffolds for the healthcare, packaging, and food technology industries. Given the rising global emphasis on sustainable development, there is broad interest in adapting existing processing technologies, such as electrospinning, for the production of fully bio-based and biodegradable material platforms. However, processing of such materials, including globular proteins, without synthetic carrier polymers remains a considerable challenge. Here, we systematically explore solvent-mediated structural changes of bovine serum albumin (BSA) as a model globular protein and map electrospinnable regimes. Time-resolved circular dichroism and rheological analyses reveal partial protein unfolding and significant rheological changes in a time window that corresponds to electrospinnability, yielding scaffolds with uniform ∼1 μm diameter fibers. We also introduce BSA and hen egg white lysozyme (Lys) protein nanofibrils (PNFs) as functional fillers to modify the resulting scaffold properties. PNFs increase the effective Young’s modulus, particularly for hydrazone crosslinkable BSA and Lys, whereby electrospun scaffold morphology is preserved in both dry and hydrated states. Electrospun scaffolds were non-cytotoxic to NIH/3T3 fibroblasts and sustained their proliferation over the course of 5 days, highlighting such materials as sustainable, water-stable scaffolds for potential biomedical applications.