Extracellular matrix type 0: From ancient collagen lineage to a versatile product pipeline - JellaGel™

Extracellular matrix type 0 is reported. The matrix is developed from a jellyfish collagen predating mammalian forms by over 0.5 billion years. With its ancient lineage, compositional simplicity, and resemblance to multiple collagen types, the matrix is referred to as the extracellular matrix type 0. Here we validate the matrix describing its physicochemical and biological properties and present it as a versatile, minimalist biomaterial underpinning a pipeline of commercialised products under the collective name of JellaGel^TM. We describe an extensive body of evidence for folding and assembly of the matrix in comparison to mammalian matrices, such as bovine collagen, and its use to support cell growth and development in comparison to known tissue-derived products, such as Matrigel™. We apply the matrix to co-culture human astrocytes and cortical neurons derived from induced pluripotent stem cells and visualise neuron firing synchronicity with correlations indicative of a homogenous extracellular material in contrast to the performance of heterogenous commercial matrices. We prove the ability of the matrix to induce spheroid formation and support the 3D culture of human immortalised, primary, and mesenchymal stem cells. We conclude that the matrix offers an optimal solution for systemic evaluations of cell-matrix biology. It effectively combines the exploitable properties of mammalian tissue extracts or top-down matrices, such as biocompatibility, with the advantages of synthetic or bottom-up matrices, such as compositional control, while avoiding the drawbacks of the two types, such as biological and design heterogeneity, thereby providing a unique bridging capability of a stem extracellular matrix.