Programmable Melt Electrowriting to Engineer Soft Connective Tissues with Prescribed, Biomimetic, Biaxial Mechanical Properties

Abstract Appropriate load‐bearing function of soft connective tissues is provided by their nonlinear and often anisotropic mechanics. Recapitulating such complex mechanical behavior in tissue‐engineered structures particularly crucial, as deviation from native tissue mechanics can trigger pathological biomechanical pathways, causing adverse remodeling dysfunction. Here, a novel method combining computational modeling, melt electrowriting (MEW), design experiments (DOE) reported to generate scaffolds composed sinusoidal fibers with prescribed biaxial properties, recapitulating the distinct nonlinear, stress–strain three model tissues: adult aortic valve, pediatric pulmonary pericardium. Finite element analysis used efficiently optimize scaffold architecture over broad parameter space, representing up 65 conditions, define MEW print parameters achieve polycaprolactone target properties. Architectural are further optimized experimentally using DOE regression account for uncertainties involved simulation, yielding functional accurate, The also primarily governs hybrid generated casting cell‐laden fibrin hydrogel within scaffolds. This high‐fidelity approach recapitulates properties range nonlinearity anisotropy generalizable programmed biofabrication variety engineering applications.