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In 2020, nearly 107,000 people in the U.S needed a lifesaving organ transplant, but due to a limited number of donors, only ∼35% of them have actually received it. Thus, successful bio-manufacturing of artificial tissues and organs is central to satisfying the ever-growing demand for transplants. However, despite decades of tremendous investments in regenerative medicine research and development conventional scaffold technologies have failed to yield viable tissues and organs. Luckily, microfluidic scaffolds hold the promise of overcoming the major challenges associated with generating complex 3D cultures: 1) cell death due to poor metabolite distribution/clearing of waste in thick cultures; 2) sacrificial analysis due to inability to sample the culture non-invasively; 3) product variability due to lack of control over the cell action post-seeding, and 4) adoption barriers associated with having to learn a different culturing protocol for each new product. Namely, their active pore networks provide the ability to perform automated fluid and cell manipulations (e.g., seeding, feeding, probing, clearing waste, delivering drugs, etc.) at targeted locations in-situ . However, challenges remain in developing a biomaterial that would have the appropriate characteristics for such scaffolds. Specifically, it should ideally be: 1) biocompatible —to support cell attachment and growth, 2) biodegradable —to give way to newly formed tissue, 3) flexible —to create microfluidic valves, 4) photo-crosslinkable —to manufacture using light-based 3D printing and 5) transparent —for optical microscopy validation. To that end, this minireview summarizes the latest progress of the biomaterial design, and of the corresponding fabrication method development, for making the microfluidic scaffolds. 

Abstract Directed cell migration in complex micro-environments, such as in vivo pores, is important for predicting locations of artificial tissue growth and optimizing scaffold architectures. Yet, the directional decisions of cells facing multiple physiochemical cues have not been characterized. Hence, we aim to provide a ranking of the relative importance of the following cues to the decision-making of individual fibroblast cells: chemoattractant concentration gradient, channel width, mitosis, and contact-guidance. In this study, bifurcated micro-channels with branches of different widths were created. Fibroblasts were then allowed to travel across these geometries by following a gradient of platelet-derived growth factor-BB (PDGF-BB) established inside the channels. Subsequently, a combination of statistical analysis and image-based diffusion modeling was used to report how the presence of multiple complex migration cues, including cell-cell influences, affect the fibroblast decision-making. It was found that the cells prefer wider channels over a higher chemoattractant gradient when choosing between asymmetric bifurcated branches. Only when the branches were symmetric in width did the gradient become predominant in directing which path the cell will take. Furthermore, when both the gradient and the channels were symmetric, contact guidance became important for guiding the cells in making directional choices. Based on these results we were able to rank these directional cues from most influential to the least as follows: mitosis > channel width asymmetry > chemoattractant gradient difference > and contact-guidance. It is expected that these results will benefit the fields of regenerative medicine, wound healing and developmental biology.