Human cardiomyocyte interaction with electrospun fibrinogen/gelatin nanofibers for myocardial regeneration

Abstract

Myocardial infarction is the major cause of death in many industrialized nations as it leads to end-stage heart failure. Tissue engineering (TE) approaches for treatment of the infarcted tissue have gained huge attention over the recent years and research in this direction mainly aims for the optimization of a biomaterial scaffold with suitable cell source for tissue regeneration. In this regard, we fabricated completely natural polymeric scaffolds using fibrinogen and gelatin in two different weight ratios and performed cross-linking [Fib/Gel(1:4)-CL; Fib/Gel(2:3)-CL] while cross-linked fibrinogen scaffolds were used as the control. The fiber diameters of the fabricated scaffolds were obtained in the range of 150–300 nm. Chemical characterization of the scaffolds confirmed the presence of both the proteins and showed the absence of any chemical reactions between them. The tensile strength and the stiffness values of Fib/Gel(1:4)-CL matrices were found to be 0.0125 and 0.46 MPa, respectively, which were much similar to the innate properties of the native myocardium. Cell culture studies using human cardiomyocytes revealed higher cell proliferation on Fib/Gel(1:4)-CL scaffolds compared to cell proliferation on Fib/Gel(2:3)-CL scaffolds, which was even higher than the cell proliferation on cross-linked fibrinogen scaffolds. Moreover, the cardiomyocytes seeded on composite substrates expressed the typical functional cardiac proteins such as alpha-actinin, troponin I, connexin-43, and myosin heavy chain, and could be potential for application in cardiac TE.

Keywords:

• electrospinning
• cross-linking
• mechanical properties
• infarction
• tissue engineering

Acknowledgments

This research was supported by the Singapore National Research Foundation under CREATE programme: The Regenerative Medicine Initiative in Cardiac Restoration Therapy (NRF-Technion WBS No: R-398-001-065-592) and the Nanoscience and Nanotechnology Initiative, Faculty of Engineering, National University of Singapore, Singapore.