Electrospun blood plasma protein scaffolds: Materials feasibility and process development using genipin-based stabilization

BACKGROUND: Electrospun protein-based scaffolds are attractive for biomedical applications, but their fabrication from complex globular protein mixtures such as blood plasma remains challenging. This study presents a proof of concept for producing electrospun scaffolds from blood plasma proteins using a solvent-minimized processing approach. METHODS: Porcine plasma was used as a model system and diafiltrated to reduce ionic conductivity, followed by rotary evaporation to increase protein concentration. Various mixtures of plasma protein concentrate/polyethylene oxide blends were tested for electrospinnability. To stabilize the water-soluble protein fibers, genipin-based crosslinking was investigated using ethanol-water mixtures of varying composition. RESULTS: Under optimized conditions, homogeneous, bead-free fibrous nonwovens were obtained. Scanning electron microscopy and FTIR spectroscopy revealed that scaffold integrity and protein structure after crosslinking strongly depend on ethanol content. Ethanol concentrations between 70 and 90 vol.% preserved fibrous morphology while minimizing protein denaturation. Lower concentrations caused scaffold dissolution, whereas higher concentrations promoted protein aggregation and reduced crosslinking efficiency. CONCLUSION: This work extends carrier-assisted electrospinning from the individual plasma proteins toward the complex plasma proteome and identifies critical processing conditions for scaffold fabrication and stabilization. The established processing windows provide a basis for future mechanical and biological evaluation toward patient-specific vascular scaffolds.