Design and Printing Strategies in 3D Bioprinting of Cell-Hydrogels: A Review.

Bioprinting is an emerging technology that allows the assembling of both living and non-living biological materials into an ideal complex layout for further tissue maturation. Bioprinting aims to produce engineered tissue or organ in a mechanized, organized, and optimized manner. Various biomaterials and techniques have been utilized to bioprint biological constructs in different shapes, sizes and resolutions. There is a need to systematically discuss and analyze the reported strategies employed to fabricate these constructs. We identified and discussed important design factors in bioprinting, namely shape and resolution, material heterogeneity, and cellular-material remodeling dynamism. Each design factors are represented by the corresponding process capabilities and printing parameters. The process-design map will inspire future biomaterials research in these aspects. Design considerations such as data processing, bio-ink formulation and process selection are discussed. Various printing and crosslinking strategies, with relevant applications, are also systematically reviewed. We categorized them into 5 general bioprinting strategies, including direct bioprinting, in-process crosslinking, post-process crosslinking, indirect bioprinting and hybrid bioprinting. The opportunities and outlook in 3D bioprinting are highlighted. This review article will serve as a framework to advance computer-aided design in bioprinting technologies.