Exploring the possibilities of L-alanine- and L-phenylalanine-based poly(ester amide)s with electrospinning and melt electrowriting for soft tissue biomedical applications.

Despite decades of advancements in melt electrowriting (MEW) and electrospinning (ES), poly(ε-caprolactone) (PCL) remains the gold standard polymer for these techniques. Its widespread use is attributed to its processability in both melt and solution, thermal stability, and low melting temperature. MEW and ES enable the fabrication of micro- and nanofibrous scaffolds that can mimic the extracellular matrix of specific tissues. This makes them especially attractive for biomedical applications. However, PCL lacks key properties, e.g., elasticity and suitable biodegradation time, for soft tissue applications. We report for the first time the successful introduction of α-amino acid-based poly(ester amide)s (AAA-PEAs) for MEW processing. Additionally, ES outcomes have been improved compared to existing literature. These polymers were synthesized via polycondensation containing ester and amide functionalities, yielding high molar masses (> 40 kg mol⁻¹). L-alanine and L-phenylalanine were selected as α-amino acids, differing in hydrophobic side groups (methyl vs. benzyl), resulting in distinct material properties. Both AAA-PEAs showed excellent ES processability, producing uniform fibers (1-3 μm) without the need of adding PCL. Notably, only the phenylalanine-based PEA was so far processable by MEW, yielding smooth, uniform fibers (25-30 μm) with no pulsing, fusing, or surface defects. As proof-of-concept, excellent stacking behavior up to 15 layers was achieved. Scaffolds exhibited enhanced ultimate tensile strength (13.70 ± 1.60 MPa) and accelerated biodegradation (72-77% remaining mass after 16 weeks in PBS at 37°C) compared to PCL. In vitro studies with MC3T3-E1 cells confirmed cytocompatibility. The above findings underscore the potential of AAA-PEAs as promising biomaterials for soft tissue biomedical applications.