Nano Surface Materials Induced Global Maturation Of Cardiomyocytes Derived From Human Induced Pluripotent Stem Cells

Background:Human induced pluripotent stem cells(hi PSCs)can proliferate infinitely.Their ability to differentiate into cardiomyocytes provides abundant sources for disease modeling,drug screening and cell transplantation.However,hi PSC-derived cardiomyocytes(hi PSC-CMs)display a low degree of maturation and fetal-like properties.Current in vitro differentiation methods do not mimic the structural,mechanical,or physiological properties of the cardiogenesis niche.To address this issue,bioengineers have investigated the maturation effects on cardiomyocytes(CMs)with numerous techniques for recreating various characteristics of the native heart in vitro.Multiple studies have implicated that biomimetic conductive or mechanical microenvironment may influence cardiac development.On the other hand,surface materials have been reported to influence the cell behavior through various cell-surface interactions.However,little was known about the cellular responses during cardiac differentiation to the conductive or topographical cues.Methods:We applied two kinds of nano surface materials,super-conductive graphene and topographical binary colloidal crystals(BCCs),for hi PSCs maintain and cardiac differentiation.Results:It demonstrated that both strategies induce the globe maturation,including markedly increased the myofibril ultrastructural organization,enhanced both the Ca²⁺handling and electrophysiological properties.In the first part,graphene substrate as a conductive biomimetic surface could facilitate the intrinsic electrical propagation,activating BMP single pathway,to further promote the global maturation of hi PSC-CMs.In the second part,5PM substrate as a highly ordered grainy topography,delivered biophysical stimulation through cell-surface interactions,modifying the cell-cell adhesions,promoting the cadherin switch,that further promoted the global maturation of hi PSC-CMs as well.Conlucsions:Our findings highlight the capability of electrically active or mechanical substrates to influence cardiomyocyte development.We believe that application of graphene and BCCs substrates will be useful for simple,fast,and scalable maturation of hi PSC-CMs,opening up tremendous opportunities in cardiac regenerative medicine.