Mimicking Native Heart Tissue Physiology and Pathology in Silk Fibroin Constructs through a Perfusion‐Based Dynamic Mechanical Stimulation Microdevice

Abstract In vitro cardiomyocyte (CM) maturation is an imperative step to replicate native heart tissue‐like structures as cardiac tissue grafts or as drug screening platforms. CMs are known to interpret biophysical cues such as stiffness, topography, external mechanical stimulation or dynamic perfusion load through mechanotransduction and change their behavior, organization, and maturation. In this regard, a silk‐based cardiac tissue (CT) coupled with a dynamic perfusion‐based mechanical stimulation platform (DMM) for achieving maturation and functionality in vitro is tried to be delivered. Silk fibroin (SF) is used to fabricate lamellar scaffolds to provide native tissue‐like anisotropic architecture and is found to be nonimmunogenic and biocompatible allowing cardiomyocyte attachment and growth in vitro. Further, the scaffolds display excellent mechanical properties by their ability to undergo cyclic compressions without any deformation when places in the DMM. Gradient compression strains (5% to 20%), mimicking the native physiological and pathological conditions, are applied to the cardiomyocyte culture seeded on lamellar silk scaffolds in the DMM. A strain‐dependent difference in cardiomyocyte maturation, gene expression, sarcomere elongation, and extracellular matrix formation is observed. These silk‐based CTs matured in the DMM can open up several avenues toward the development of host‐specific grafts and in vitro models for drug screening.