Harnessing 3D Printing and Electrospinning for Multiscale Hybrid Patches Mimicking the Native Myocardium

Engineered cardiac tissues show potential for regenerative therapy in ischemic heart disease. Yet, selection of soft biomaterials for scaffold manufacturing is primarily influenced by empirical and compositional factors, raising concerns about arrhythmic risks due to poor electrophysiological integration. Addressing this, we developed multiscale hybrid myocardial patches mimicking native myocardium’s structural and biomechanical attributes, utilizing 3D printing and electrospinning techniques. We compared three patch types: pure silicone and silicone-poly(lactic- co -glycolic acid) (PLGA) with random (S-PLGA-R) and aligned (S-PLGA-A) fibers. S-PLGA-A patches with fiber orientation angles of 95–115° are achieved by applying a secondary electrical field using two parallel aluminum enhancers. With bulk and localized moduli of 350–750 and 13–20 kPa resembling the native myocardium, S-PLGA-A patches demonstrate a sarcomere length of 2.1 ± 0.2 μm, ≥50% higher strain motions and diastolic phase, and a 50–70% slower rise of calcium handling compared to the other two patches. This enhanced maturation and improved synchronization phenomena are attributed to efficient force transmission and reduced stress concentration due to mechanical similarity and linear propagation of electrical signals. This study presents a promising strategy for advancing regenerative cardiac therapies by harnessing the capabilities of 3D printing and electrospinning, providing a proof-of-concept for their effectiveness.