Electrospinning and Cross‐Linking of Gelatin‐Poly(2‐Isopropenyl‐2‐Oxazoline) Nanofibers: A Route to Stable Hybrid Biomaterials

Engineering biohybrid nanofibers with tailored morphologies addresses the need to meet various requirements in medical applications. Blending natural and synthetic polymers in a synergistic manner, though often challenging, improves the physical properties of natural polymers and the biocompatibility of synthetic ones. The present work showcases a straightforward protocol to manufacture biohybrid hydrophilic nanofibers by electrospinning fish gelatin (FG) with poly(2-isoproprenyl-2-oxazoline) (PiPOx) from aqueous solution. FTIR spectroscopy and thermal analysis demonstrate favorable interactions within the FG-PiPOx biohybrid nanofiber mats, indicating that the electrospinning process not only enables nanofiber formation, but also promotes preferential interchain arrangements that facilitate in situ cross-linking, eliminating the need of catalysts or additional cross-linkers. Furthermore, the thermal and aqueous stability of the biohybrid nanofiber mats significantly improves by dual cross-linking the two polymers with small organic cross-linkers, taking advantage of the well-known reaction of PiPOx with carboxylic acids and of FG with glutaraldehyde. The cross-linked biohybrids maintain a stable nanosized morphology and exhibit improved cell-interactive properties, particularly in hybrids with moderate PiPOx content. The FG-PiPOx biohybrids show superior cell-interactive properties compared to pristine gelatin due to their favorable surface energy and hydrophilicity, highlighting the advantages of the hybrid materials over the individual polymers.