Progress in cardiac tissue engineering and regeneration: Implications of gelatin-based hybrid scaffolds

Cardiovascular diseases, particularly myocardial infarction (MI), remain a leading cause of morbidity and mortality worldwide. Current treatments for MI, more palliative than curative, have limitations in reversing the disease completely. Tissue engineering (TE) has emerged as a promising strategy to address this challenge and may lead to improved therapeutic approaches for MI. Gelatin-based scaffolds, including gelatin and its derivative, gelatin methacrylate (GelMA), have attracted significant attention in cardiac tissue engineering (CTE) due to their optimal physical and biochemical properties and capacity to mimic the native extracellular matrix (ECM). CTE mainly recruits two classes of gelatin/GelMA-based scaffolds: hydrogels and nanofibrous. This article reviews state-of-the-art gelatin/GelMA-based hybrid scaffolds currently applied for CTE and regenerative therapy. Hybrid scaffolds, fabricated by combining gelatin/GelMA hydrogel or nanofibrous scaffolds with other materials such as natural/synthetic polymers, nanoparticles, protein-based biomaterials, etc., are explored for enhanced cardiac tissue regeneration functionality. The engraftment of stem/cardiac cells, bioactive molecules, or drugs into these hybrid systems shows great promise in cardiac tissue repair and regeneration. Finally, the role of gelatin/GelMA scaffolds combined with the 3D bioprinting strategy in CTE will also be briefly highlighted.