Three-dimensional cellular construct with impregnated silicon nanowires for intracellular optoelectronic biointerface

Three-dimensional tissue models are considered a more comprehensive replica of the in vivo microenvironment than their traditional monolayer counterparts. Therefore, tissue engineering methods have the potential to revolutionize biomedical research by allowing researchers to shift away from animal models while improving model relevance. However, while state-of-the-art electrical devices can perturb the biophysical cell niche in 2D monolayers, the biomodulation "toolkit" available for 3D application does not meet the required level of complexity, specificity, and accuracy, limiting the ability to perform intracellular electrical modulation of cells inside 3D cellular constructs. In this work, a 3D e-scaffold impregnated with free-standing silicon nanowires was developed to enable local and leadless optoelectronic modulation at subcellular resolution. The versatility, simplicity, and biocompatibility of e-scaffolds, comprised of alginate and/or collagen, were demonstrated with a fibroblast cell line and primary cardiac cells. Their utility for bioelectrical modulation was demonstrated by optically stimulating intracellular nanowires and visualizing the calcium response using confocal microscopy. The e-scaffold was used to study the coupling between cardiac myofibroblasts and cardiomyocytes in a 3D context. The e-scaffold was found to enable straightforward 3D tissue culture as well as intracellular electrical modulation at subcellular resolution.