Scaffold mediated delivery of dual miRNAs to transdifferentiate cardiac fibroblasts

• Published in: Materials Science & Engineering C Vol. 128; p. 112323
• Main Authors: Muniyandi, Priyadharshni, Palaninathan, Vivekanandan, Mizuki, Toru, Mohamed, M. Sheikh, Hanajiri, Tatsuro, Maekawa, Toru
• Format: Journal Article
• Language: English
• Published: Lausanne Elsevier B.V 01.09.2021; Elsevier BV
• Subjects: Biomolecules; Cardiomyocytes; Cell fate; Combinatorial analysis; Direct reprogramming; Drug delivery; Electrospinning; Electrospun fibers; Electrostatic properties; Extracellular matrix; Fibers; Fibroblasts; Fibronectin; Heart; Materials science; MicroRNA; MicroRNAs; miRNA; Molecular modelling; Muscles; Polyethyleneimine; Polylactic acid; Regeneration; Scaffolds; Tissue engineering; Topology; Transdifferentiation; Transfection; Direct reprogramming; Transfection; MicroRNA; Transdifferentiation; Electrospun fibers
• ISSN: 0928-4931; 1873-0191
• DOI: 10.1016/j.msec.2021.112323

The standard scaffold-mediated delivery of drugs/biomolecules has been successful due to the unique attributes of scaffolds, specifically the electrospun polymeric scaffolds that mimic ECM are well suited for advanced regenerative applications. Cardiac tissue engineering includes the interpretation of cellular and molecular mechanisms concerning heart regeneration and identifying an efficient reprogramming strategy to overcome the limitation of delivery systems and enhance the reprogramming efficiency. This study is a step towards developing a functional scaffold through a parallel interpretation of electrospun PLLA scaffolds with two distinct topologies to achieve sustained delivery of two muscle-specific microRNAs (miR-1 and miR-133a) to directly reprogram the adult human cardiac fibroblasts into cardiomyocyte-like cells. Polyethyleneimine was used to form stable PEI-miRNA complexes through electrostatic interactions. These complexes were immobilized on the electrospun smooth and porous scaffolds, where a loading efficiency of ~96% for the fibronectin modified and ~38% for unmodified surfaces was observed, regardless of their surface topology. The in-vitro release experiment exhibited a biphasic release pattern of PEI-miRNA polyplexes from the scaffolds. These dual miRNA scaffold systems proved to be an excellent formulation since their combinatorial effect involving the topographic cues of electrospun fibers, and dual miRNAs helped control the cardiac fibroblast cell fate precisely. [Display omitted] •Fibronectin-modified porous and smooth electrospun PLLA fibers were immobilized with dual cardiac muscle-specific miRNAs.•Adult human cardiac fibroblasts were successfully cultured on the modified scaffolds that promoted cell adhesion and proliferation.•Immobilized miRNAs showed a pH-dependent biphasic release from scaffolds, which were significantly uptaken by cells.•7 days post-transfection, expression of cTnT, and GATA 4 markers confirmed the presence of cardiomyocyte-like cells.