Heart failure after acute myocardial infarction is a major cause of death without effective therapies available. The Horizon Europe REBORN project tackles this issue by designing a piezoelectric patch to restore healthy tissue by the piezoelectric fibre nanoarchitecture and on-demand drug release by nanocarriers upon stimulation with ultrasound (US). Electrospinning (ESP) is suitable to produce matrices with properties matching the ones of the cardiac extracellular matrix, allowing for high flexibility in terms of polymeric formulation and the incorporation of nanocarriers. ESP with a rotating drum was exploited to fabricate polyvinylidene fluoride (PVDF) piezoelectric membranes with aligned fibres and the preliminary incorporation of mesoporous silica nanoparticles (MSN) as drug carriers. PVDF is a piezoelectric biocompatible polymer largely used for electrospun bio-devices, and it was chosen for electromechanical coupling with the myocardium. Non-toxic solvents (acetone and dimethyl sulfoxide) were used to solubilize PVDF. The effects of different formulations and the ESP parameters were investigated. It was possible to obtain aligned fibres, with a diameter of around 300 nm. The piezoelectricity of PVDF depends on the amount of crystalline β phase, and the selected working conditions allow for obtaining high β phase content, about 94%. Furthermore, the overall crystallinity of the polymeric membranes is also high, around 70%. Different thicknesses were obtained, ranging from 90 to 250 μm. Membranes thick about 100 μm had Young’s modulus of about 40 MPa and tensile strength of around 8.4 MP. The contact angle is around 115°. 5 %vol of MSNs was added to the PVDF solution. The nanoparticles were successfully embedded into the fibres, which showed smaller diameters with respect to fibres without MSNs. The PVDF membrane with MSN is a promising platform for the development of the REBORN patch and future work will focus on the optimization of the ESP with MSNs and the investigation of US-triggered drug release.