Abstract

Here, we have developed a 3D bioprinted microchanneled gelatin hydrogel that promotes human mesenchymal stem cell (hMSC) myocardial commitment and supports native cardiomyocytes (CMs) contractile functionality. Firstly, we studied the effect of bioprinted microchanneled hydrogel on the alignment, elongation, and differentiation of hMSC. Notably, the cells displayed well defined F-actin anisotropy and elongated morphology on the microchanneled hydrogel, hence showing the effects of topographical control over cell behavior. Furthermore, the aligned stem cells showed myocardial lineage commitment, as detected using mature cardiac markers. The fluorescence-activated cell sorting analysis also confirmed a significant increase in the commitment towards myocardial tissue lineage. Moreover, seeded CMs were found to be more aligned and demonstrated synchronized beating on microchanneled hydrogel as compared to the unpatterned hydrogel. Overall, our study proved that microchanneled hydrogel scaffold produced by 3D bioprinting induces myocardial differentiation of stem cells as well as supports CMs growth and contractility. Applications of this approach may be beneficial for generating in vitro cardiac model systems to physiological and cardiotoxicity studies as well as in vivo generating custom designed cell impregnated constructs for tissue engineering and regenerative medicine applications.

Highlights

  • Following myocardial infarction (MI), subsequent cell death and matrix remodeling at the MI foci lead to the degradation of fibrillar collagen network and the accumulation of fibrotic scar tissue

  • We aim to examine the application of 3D bioprinted microbial transglutaminase (mTgase) crosslinked gelatin in generating a cell guidance scaffold with relevance to use in tissue engineered cardiac regeneration

  • We implemented a similar method for gelatin hydrogel formulation

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Summary

Introduction

Following myocardial infarction (MI), subsequent cell death and matrix remodeling at the MI foci lead to the degradation of fibrillar collagen network and the accumulation of fibrotic scar tissue. This causes mechanical dysfunction of the ventricular wall that can lead to wall thinning, ventricular dilation and the subsequent sequelae of congestive heart failure and myocardial rupture [1, 2]. Contractile cardiomyocytes have an extremely low proliferation rate. They are not a feasible source for ex vivo expansion and seeding [3, 8]. Stem cell solutions are currently being sought to generate sufficient functional cardiomyocytes for this application [3, 9, 10]

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