Existing methodologies for human induced pluripotent stem cell (hiPSC) cardiac differentiation are efficient but require the use of complex, undefined medium constituents that hinder further elucidation of the molecular mechanisms of cardiomyogenesis. Using hiPSCs derived under chemically defined conditions on synthetic matrices, we systematically developed a highly optimized cardiac differentiation strategy, employing a chemically defined medium consisting of just three components: the basal medium RPMI 1640, L-ascorbic acid 2-phosphate, and rice-derived recombinant human albumin. Along with small molecule-based differentiation induction, this protocol produced contractile sheets of up to 95% TNNT2+ cardiomyocytes at a yield of up to 100 cardiomyocytes for every input pluripotent cell, and was effective in 11 hiPSC lines tested. This is the first fully chemically defined platform for cardiac specification of hiPSCs, and allows the elucidation of cardiomyocyte macromolecular and metabolic requirements whilst providing a minimally complex system for the study of maturation and subtype specification.

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Sensing the force digitally Our skin provides us with a flexible waterproof barrier, but it also contains a sensor array that feels the world around us. This array provides feedback and helps us to avoid a hot object or increase the strength of our grip on an object that may be slipping away. Tee et al. describe an approach to simulate the mechanoreceptors of human skin, using pressure-sensitive foils and printed ring oscillators (see the Perspective by Anikeeva and Koppes). The sensor successfully converted pressure into a digital response in a pressure range comparable to that found in a human grip. Science , this issue p. 313 ; see also p. 274

Natural hydrogels are promising scaffolds to engineer epidermis. Currently, natural hydrogels used to support epidermal regeneration are mainly collagen- or gelatin-based, which mimic the natural dermal extracellular matrix (ECM) but often suffer from insufficient and uncontrollable mechanical and degradation properties. In this study, a photocrosslinkable gelatin (i.e., gelatin methacrylamide (GelMA)) with tunable mechanical, degradation and biological properties is used to engineer the epidermis for skin tissue engineering applications. The results reveal that the mechanical and degradation properties of the developed hydrogels can be readily modified by varying the hydrogel concentration, with elastic and compressive moduli tuned from a few kPa to a few hundred kPa and the degradation times varied from a few days to several months. Additionally, hydrogels of all concentrations displayed excellent cell viability (>90%) with increasing cell adhesion and proliferation with increase in hydrogel concentrations. Furthermore, the hydrogels are found to support keratinocyte growth, differentiation and stratification into a reconstructed multi-layered epidermis with adequate barrier functions. The robust and tuneable properties of GelMA hydrogels have suggested that the keratinocyte laden hydrogels can be used as epidermal substitutes, wound dressings or substrates to construct various in vitro skin models.