Cardiac Regeneration Revisited: Enhanced Cardiomyocyte Differentiation and Repair Through Composite Microenvironments and Small Molecules

Cardiac Regeneration Revisited: Enhanced Cardiomyocyte Differentiation and Repair Through Composite Microenvironments and Small Molecules Publisher Pubmed

Azhdari M ; Rabbani S ; Tanideh N ; Boroumand S

Source: Biomedicine and Pharmacotherapy Published:2025

Abstract

Background The generation of mature, functional cardiomyocytes from human pluripotent stem cells (hPSCs) remains a major challenge in cardiac regenerative medicine. While fibronectin and Matrigel individually support cardiomyocyte differentiation, their combined potential, particularly when integrated with temporally optimized small-molecule modulation of developmental signaling pathways, has not been systematically investigated. Methods We engineered a biomimetic fibronectin–Matrigel composite extracellular matrix and applied precisely timed small-molecule modulation of key signaling cascades to drive efficient cardiomyocyte differentiation from hPSCs. Differentiation efficiency, structural organization, and functional maturation were assessed using immunocytochemistry, qRT-PCR, sarcomere imaging, and contractility assays. Results This composite microenvironment significantly enhanced cardiac-specific marker expression, promoted highly organized sarcomere architecture, and improved contractile function, producing a maturation profile closely resembling native myocardium. Moreover, the platform supported long-term culture with sustained structural and functional stability and consistently outperformed fibronectin-only or Matrigel-only substrates. Conclusions Our study presents a robust, scalable, and mechanistically informed platform that synergistically integrates ECM engineering with targeted signaling pathway modulation. By combining fibronectin–Matrigel composites with small-molecule-directed differentiation, this strategy provides a powerful tool for cardiac tissue engineering, disease modeling, high-throughput drug screening, and regenerative therapies, representing a significant step toward clinically relevant cardiac repair. © 2025 Elsevier B.V., All rights reserved.

Style	Citing Format
MLA	Azhdari M, et al.. "Cardiac Regeneration Revisited: Enhanced Cardiomyocyte Differentiation and Repair Through Composite Microenvironments and Small Molecules." Biomedicine and Pharmacotherapy, vol. 192, no. , 2025, pp. -.
APA	Azhdari M, Rabbani S, Tanideh N, Boroumand S (2025). Cardiac Regeneration Revisited: Enhanced Cardiomyocyte Differentiation and Repair Through Composite Microenvironments and Small Molecules. Biomedicine and Pharmacotherapy, 192(), -.
Chicago	Azhdari M, Rabbani S, Tanideh N, Boroumand S. "Cardiac Regeneration Revisited: Enhanced Cardiomyocyte Differentiation and Repair Through Composite Microenvironments and Small Molecules." Biomedicine and Pharmacotherapy 192, no. (2025): -.
Harvard	Azhdari M et al. (2025) 'Cardiac Regeneration Revisited: Enhanced Cardiomyocyte Differentiation and Repair Through Composite Microenvironments and Small Molecules', Biomedicine and Pharmacotherapy, 192(), pp. -.
Vancouver	Azhdari M, Rabbani S, Tanideh N, Boroumand S. Cardiac Regeneration Revisited: Enhanced Cardiomyocyte Differentiation and Repair Through Composite Microenvironments and Small Molecules. Biomedicine and Pharmacotherapy. 2025;192():-.
BibTex	@article{ author = {Azhdari M and Rabbani S and Tanideh N and Boroumand S}, title = {Cardiac Regeneration Revisited: Enhanced Cardiomyocyte Differentiation and Repair Through Composite Microenvironments and Small Molecules}, journal = {Biomedicine and Pharmacotherapy}, volume = {192}, number = {}, pages = {-}, year = {2025} }
RIS	TY - JOUR AU - Azhdari M AU - Rabbani S AU - Tanideh N AU - Boroumand S TI - Cardiac Regeneration Revisited: Enhanced Cardiomyocyte Differentiation and Repair Through Composite Microenvironments and Small Molecules JO - Biomedicine and Pharmacotherapy VL - 192 IS - SP - EP - PY - 2025 ER -

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