Multi-material 3D bioprinting of human stem cells to engineer complex human corneal structures with stroma and epithelium

Abstract

Developing cost-effective and scalable multi-material bioprinting technologies that combine multiple cell types is crucial to produce biomimetic, complex human tissue substitutes and overcome the scarcity of transplantable tissues. These technological developments can revolutionize the treatment of several conditions currently dependent on donor tissues, such as corneal blindness. Here, corneal structures consisting of two layers, stroma and epithelium, were manufactured by extrusion-based 3D bioprinting. To take steps towards clinical translation of bioprinting, three clinically compatible hyaluronic acid based bioinks were combined with human adipose tissue and induced pluripotent stem cell derived cell types. Each of the three bioinks was customized to suit the needs of different cells and to provide mechanical stability for the bioprinted structure. Along with offering a 3D environment with excellent cytocompatibility, these bioprinted corneal structures facilitated cellular interactions and network formation, which are essential for creating functional tissue substitutes. Consequently, this study provides important insight on how to bring together the technical aspects of multi-material bioprinting as well as the biological relevance and scalability of the bioprinted constructs, advancing the field of additive manufacturing for clinical applications.