Patterned glycopeptide-based supramolecular hydrogel promotes the alignment and contractility of iPSC-derived cardiomyocytes

• Published in: Biomaterials advances 2025-02, Vol.167, p.214091, Article 214091
• Main Authors: Castro, Vânia I.B., Amorim, Sara, Caballero, David, Abreu, Catarina M., Kundu, Subhas C., Reis, Rui L., Pashkuleva, Iva, Pires, Ricardo A.
• Format: Article
• Language: English
• Subjects: Cardiac tissue; Cardiomyocytes; Cell Differentiation - drug effects; Cells, Cultured; Glycopeptide; Glycopeptides - chemistry; Glycopeptides - pharmacology; Humans; Hydrogels; Hydrogels - chemistry; Hydrogels - pharmacology; Induced Pluripotent Stem Cells - cytology; Induced Pluripotent Stem Cells - drug effects; Myocardial Contraction - drug effects; Myocardial Contraction - physiology; Myocytes, Cardiac - drug effects; Myocytes, Cardiac - metabolism; Myocytes, Cardiac - physiology; Supramolecular; Tissue Engineering - methods
• ISSN: 2772-9508; 2772-9508
• DOI: 10.1016/j.bioadv.2024.214091

The functional restoration of a damaged cardiac tissue relies on a synchronized contractile capacity of exogenous and/or endogenous cardiomyocytes, which is challenging to achieve. Here, we explored the potential of the short glycopeptide diphenylalanine glucosamine-6-sulfate (FFGlcN6S) conjugated with an aromatic moiety, namely fluorenylmethoxycarbonyl (Fmoc), to enhance cardiac tissue regeneration. At physiological conditions, Fmoc-FFGlcN6S assembles into nanofibrous hydrated meshes, i.e., matrix mimicking hydrogels. These hydrogels can be further micropatterned allowing co-existence of hierarchical structures at different lenght. The patterned hydrogels support the culture of induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) and promote their alignment. The cultured iPSC-CMs exhibit anisotropic synchronized contractions, indicating maturation and electrical interconnectivity. Moreover, the cultures express specific cardiac markers including, connexin-43 and sarcomeric-α-actinin, confirming enhanced cell-cell crosstalk, spontaneous contractility, and efficient transmission of electrical signals. Our results showcase the potential of short amphiphilic glycopeptides to mimic physical and biochemical cues that are essential for cardiomyocytes functionality and thus, these conjugates can be used in cardiac tissue engineering and regeneration. [Display omitted] •Hydrogels comprising hierarchical structures at different scales were developed•The main structural element of the hydrogels is synthetic glycopeptide•The glycosylation of the peptide is essential for the bioactivity of the hydrogels•The hydrogels support the attachment of cardiomyocytes•Micropatterned grooves induce synchronization of cardiomyocytes