Tissue engineering aims to repair or replace deficient tissue by delivering constructs that mimic the native in vivo structure. One challenge in cardiac tissue engineering approaches is to achieve intrinsic cardiac organization, particularly the alignment of cardiomyocytes. Here, we propose a strategy for 3D manipulation and alignment of cardiomyocytes by combining magnetism and a hydrogel. The advantage of using magnetic forces is that they act remotely on the cells when these are endowed with magnetization via the internalization of magnetic nanoparticles. The magnetic actuation then allows obtaining, almost instantaneously and before gel transition, an aligned biomimetic cardiac tissue construct. Gel transition enables us to keep the cellular pattern once the magnetic field was removed. This cardiac tissue engineering approach was tested with both H9c2 cell line and primary cardiomyocytes, and with both a synthetic hydrogel and a natural one, Pluronic F-127 and fibrin, respectively. Key parameters of the anisotropic tissue formation were assessed. Hydrogel rheology is provided, and the impact of cell density and magnetic labeling on cell-cell alignment is assessed. Immunofluorescence confirms the presence of several cardiac markers upon chaining, demonstrating the functionality of the tissue-like cell alignment obtained via magnetic actuation.
Keywords: 3D cell organization; cardiac tissue engineering; hydrogel; magnetic actuation; magnetic nanoparticles.