In vitro cardiomyocyte maturation is an imperative step to replicate native heart tissue-like structures as cardiac tissue grafts or as drug screening platforms. Cardiomyocytes are known to interpret biophysical cues such as stiffness, topography, external mechanical stimulation or dynamic perfusion load through mechanotransduction and change their behaviour, organization and maturation. In this regard, we have tried to deliver a silk-based cardiac tissue coupled with a dynamic perfusion-based mechanical stimulation platform (DMM) for achieving maturation and functionality in vitro. Silk fibroin was used to fabricate lamellar scaffolds to provide native tissue-like anisotropic architecture and were found to be non-immunogenic and biocompatible allowing cardiomyocyte attachment and growth in vitro. Further, the scaffolds displayed excellent mechanical properties by their ability to undergo cyclic compressions without any deformation when placed in the DMM. Gradient compression strains (5% to 20%), mimicking the native physiological and pathological conditions, were 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 ECM formation was observed. These silk-based cardiac tissues matured in the DMM could open up several avenues towards the development of host-specific grafts and in vitro models for drug screening.

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