Boosting biocompatibility and minimizing inflammation in electrospun polyvinylidene fluoride (PVDF) cardiac patches through optimized low-pressure plasma treatment

: Tailoring surface characteristics is key to guiding scaffold interaction with the biological environment, promoting successful biointegration while minimizing immune responses and inflammation. In cardiac tissue engineering, polyvinylidene fluoride (PVDF) is a material of choice for its intrinsic piezoelectric properties, which can be enhanced through electrospinning, also enabling the fabrication of nanofibrous structures mimicking native tissue. However, the inherent hydrophobicity of PVDF can hinder its integration with biological tissues. To overcome this limitation, electrospun PVDF patches were subjected to radio-frequency low-pressure O2 plasma treatment to enhance surface hydrophilicity and overall biocompatibility. A systematic experimental study identified optimal parameters, revealing that higher gas content and prolonged exposure are preferable to high power levels, which deteriorate the patch's morphological and mechanical properties. X-ray photoelectron spectroscopy confirmed the formation of oxygen-containing surface groups, resulting in the patch's superhydrophilicity. Preservation of the fibrous nanostructure and electroactive phase content was verified using scanning electron microscopy and infrared spectroscopy combined with differential scanning calorimetry, respectively. The optimized plasma treatment maintained the patch's elasticity and demonstrated long-term stability for up to 3 months. In vitro biocompatibility was assessed through indirect and direct tests using AC16 human cardiomyocytes and neonatal human dermal fibroblasts, revealing good cell viability, adhesion, and spreading over 7-days. Finally, plasma-treated patches demonstrated strong adhesion to the myocardial tissue and exhibited markedly reduced inflammatory response compared to the untreated controls, as shown by decreased CD45+ immune cell infiltration around the patch implanted in infarcted mice, highlighting the surface treatment's effectiveness in enhancing in vivo biocompatibility.