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Objective:A novel 3D Net Mold System enables us to create a myocardial block as a scaffold-free structure. We examined the feasibility and the in-situ regenerative effect of the myocardial block.Methods:The scaffold-free myocardial block incorporated the H9C2 rat cardiomyoblast cell line using the 3D net mold system (Fig. A-D). The myocardial block incorporated with extracellular matrix (ECM) sheet was implanted into right ventricular (RV) free wall of healthy swine model (N=5). After 60 days, the animals underwent cardiac magnetic resonance (CMR) and combined epicardial-endocaridal electroanatomical mapping (EAM) studies as well as post euthanasia analyses including histology and mechanical viscoelasticity of the myocardial ECM near the patches.Results:CMR showed improved regional contractility and enhanced tissue perfusion in the patch area (Fig. F). EAM revealed regenerated electrical conductivity in the patch as evidence by relatively preserved voltage regions (1.11?0.8 mV) compared with the normal RV 4.7?2.8 mV (Fig. G). Cardiomyocyte repopulation was confirmed with tissue analyses including: Hematoxylin-eosin, and immunohistochemical staining (?-actinin, tropomyosin, Von Willebrand factor), Reverse Transcription-Polymerase Chain Reaction, which all indicated premature cardiomyocyte repopulation in the proposed model (Fig. H, I). Viscoelasticity using oscillating disc rheometer at an initial 0.1 rad/sec angular frequency were: for RV patch, ECM shear storage modulus 130?70 Pa, and shear loss modulus 65?36 Pa, versus 420?220 Pa and 130?66 Pa at a LV reference. As the angular frequency increased, both bulk storage and bulk loss modulus increased by 48% (RV patch) and 35% (LV reference) at 1 rad/sec.Conclusions:The scaffold-free myocardial block using the 3D Net Mold System facilitated in-situ myocardial remodeling with functional regeneration such as improved regional contractility, tissue perfusion, and electrical activity.