Abstract

Cardiac tissue engineering (CTE) aims to generate potential scaffolds to mimic extracellular matrix (ECM) for recreating the injured myocardium. Highly porous scaffolds with properties that aid cell adhesion, migration and proliferation are critical in CTE. In this study, electrospun porous poly (l-lactic acid) (PLLA) porous scaffolds were fabricated and modified with different ECM derived proteins such as collagen, gelatin, fibronectin and poly-L-lysine. Subsequently, adult human cardiac fibroblasts (AHCF) were cultured on the protein modified and unmodified fibers to study the cell behavior and guidance. Further, the cytotoxicity and reactive oxygen species (ROS) assessments of the respective fibers were performed to determine their biocompatibility. Excellent cell adhesion and proliferation of the cardiac fibroblasts was observed on the PLLA porous fibers regardless of the surface modifications. The metabolic rate of cells was on par with the conventional cell culture ware while the proliferation rate surpassed the latter by nearly two-folds. Proteome profiling revealed that apart from being an anchorage platform for cells, the surface topography has modulated significant expression of the cellular proteome with many crucial proteins responsible for cardiac fibroblast growth and proliferation.

Highlights

  • Myocardial infarction—or ‘heart attack’—is one of the leading causes of death worldwide, which ensues upon the blockage of coronary artery that cuts oxygen supply to the heart muscles, which adversely affects cell orientation and often leads to the injury or death of myocytes [1]

  • PLLA fiber were fabricated by electrospinning technique, further simple drop casting method was used to surface functionalize the electrospun scaffolds to evaluate their purpose as better niche for enhanced cell adhesion and proliferation

  • Many previous reports are suggestive that chloroform and DMF are a good solvent system in comparison with other solvents for porous fiber fabrication due to the change in entanglement ratio [48], wherein the high vaporization rate of chloroform is overcome by DMF with a low vapor pressure which helps to lower the drying of electrospinning solution, preventing needle blockage [49]

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Summary

Introduction

Myocardial infarction—or ‘heart attack’—is one of the leading causes of death worldwide, which ensues upon the blockage of coronary artery that cuts oxygen supply to the heart muscles, which adversely affects cell orientation and often leads to the injury or death of myocytes [1]. Tissue engineering offers a promising avenue to mimic the extracellular matrix (ECM), where the potential use of biomaterial-based scaffolds can improve cell retention, survival and differentiation while promoting adhesion, proliferation and migration with an appropriate microenvironment [2,3]. Numerous kinds of scaffolds from both natural and synthetic biomaterials have been exploited as a potential substrate for cardiac tissue engineering. Though the natural biomaterials have superior biocompatibility, their inconsistency in fabrication and lack of key characteristics such as degradation rate, mechanical, physical properties that are ideal for a scaffold have limited their use [4]. A synthetic biomaterial-based scaffold is expedient due to its excellent mechanical property, pure chemical composition and degradation rate, these synthetic scaffolds lack. Requiring an ideal scaffold to closely mimic both the structural and biochemical microenvironment of ECM

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