Xeno-Free Peptide-Functionalized Hydrogels Support hiPSC Encapsulation and In Situ Differentiation into Cardiomyocytes with Enhanced Structural Maturation

A xeno-free, cyclic RGD–functionalized alginate hydrogel platform supports hiPSC encapsulation and in situ differentiation, yielding hiPSC-CM with a markedly increased Desmin- and MYH7-positive structural maturation proportion.

• Why it matters: Existing defined substrates largely rely on 2D culture and produce structurally immature cardiomyocytes, constraining disease modeling and regenerative medicine applications.
• What they did: The authors encapsulated hiPSCs in fully defined cRGD-functionalized alginate hydrogels, finding cRGD essential for survival and pluripotency with maximal support at 25 M ligand density. They then compared softer versus more rigid gels during in situ differentiation and assessed structural maturation markers Desmin and MYH7.
• The result: Softer gels made with lower molecular weight alginates improved hiPSC expansion and cardiogenesis, and 3D in situ differentiation increased the proportion of Desmin- and MYH7-positive cardiomyocytes; retrieved cells from softer gels formed tissue-engineered myocardium with superior contractile stress.

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