Cell and organ printing turns 15: Diverse research to commercial transitions

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Introduction The field of cell and organ printing had humble beginnings near the turn of the millennium when a few groups of scientists had a common interest in merging the physical and biological worlds with design engineering.1–4 From the physical world came well-defined energetic mechanisms such as laser ablation, piezoelectric stimulation, and thermal actuators. Light-based mechanisms have emerged as powerful tools to create and modify biomaterials, so much so that MRS Bulletin5 dedicated an entire issue to this area in 2011. From the biological world came the emerging fields of stem cell culture, tissue engineering (TE), and three-dimensional tissue culturing. Through design engineering, information was added a priori to guide the development of rapid prototyping and computer-aided design/ computer-aided manufacturing. It was difficult to see an immediate connection or synergy between the fields, but through creative insight and determination, the field of cell and organ printing was born from researchers melding the three together. The goal is the same now as it was 15 years ago; only today, researchers are getting closer to actually replicating the three-dimensional structure and function of natural tissue and organs in vitro.6 The mainstream TE perspective began with

creating polymer scaffolds to recruit or differentiate cells that then adhere, grow, and ultimately transform distinct starting material into living tissue. Over time, the approach has become more sophisticated so as to incorporate stem cells and disparate biochemical factors to ultimately create a tissue construct that could use autologous cues and differentiation or recruitment to create synthetic tissue. This research has succeeded for thin tissues (bladder,7 skin8,9) with appropriate functionality to become viable alternatives to transplantation. The larger problem of regenerating truly 3D organs remains problematic primarily due to the inability to replicate the intricate heterogeneous structure and maturity of natural organs, including vascular and microvascular subsystems as well as stroma.10 If one could arrange and assemble different types of cells, scaffold, and factors the way nature intended, not just in two dimensions but in three, then could a synthetic tissue’s ability to replicate both structure and function in vitro and ultimately in vivo also be replicated? Enter cell and organ printing11,wherein early studies focused on whether cell arrangement and assembly caused deleterious effects on the deposited cells—physical energetics have the potential to destroy fragile membranes containing even more fragile cytoskeletal and supramolecular

Bradley R. Ringeisen, US Naval Research Laboratory; [email protected]. Russell K. Pirlo, US Naval Research Laboratory; [email protected] Peter K. Wu, Southern Oregon University; [email protected] Thomas Boland, University of Texas at El Paso; [email protected] Yong Huang, University of Florida, Gainesville; yongh@ufl.edu Wei Sun, Drexel University; [email protected] Qudus Hamid, Drexel University