(556c) Towards Interactive Tissue Patterning Via Spatially Defined Addressable Microfluidic Delivery of Chemical Signals

Despite decades of tremendous investments in R&D, tissue engineering has not yielded any clinical 3D organ or complex tissue products. Two major bottlenecks restricting progress are product size limitation, due to inability to deliver nutrients to inner pore space of large scaffolds; and product variability, due to the lack of control over cells post seeding. For example, bioprinting, which is at the forefront of tissue manufacturing, deposits the cells and the scaffold material at specified locations in 3D. However, any control over, communication with, and observation of the individual cells is lost beyond the initial manufacturing stage. Thus, with the conventional approaches, the cells are effectively expected to finish the building tissue on their own, during the subsequent culturing step. This, of course, will never happen, given the absence of a central nervous system to orchestrate their actions.

Here we hypothesize that in order to overcome these obstacles, an ideal scaffold should be composed of the following elements: (1) Active microfluidic pores for delivery of nutrients, oxygen and chemical signals throughout the scaffold’s pore space, (2) Transparent material for real-time microscopy observation of cell behavior and tissue development, (3) “Addressable” design for tissue patterning and analysis via targeted localized chemical delivery and/or sampling, (4) Interactive, continuous, closed-loop spatial and temporal control of the biology occurring in the scaffold throughout the whole culturing process. Consequently, our talk will present a proof-of-concept microfluidic platform that uses micro-sized channels, connected to automated electronics and pneumatic pumping, for controlling cell migration. This is achieved by delivering predetermined amounts of chemo-attractant to specified XY locations (aka “addresses”) to a cell migration chamber located at the bottom of the chip. The cells sense the gradient formed by the release of the chemoattractant, and follow a path prescribed by the user. Furthermore, the continuous real-time feedback for guiding is accomplished by coupling valve automation with robotized microscopy, computer vision algorithms and transport modeling of the chemo-attractant release within the device.

Current limitations of our prototype are that it only allows for 2D fluid delivery and sampling. Furthermore, it is fabricated from polydimethylsiloxane (PDMS), which is transparent and biocompatible, but not biodegradable. Hence, our future work will concentrate on extending the concept to 3D addressable microfluidic scaffolds/microfluidic devices fabricated from a transparent, biocompatible and biodegradable material. In principle, other aspects of cell behavior, such as differentiation, division and tissue deposition could be manipulated using similar means as well (e.g., by delivering growth factors, differentiation factors, and drugs). Therefore, it is our hope that this technology will ultimately resolve the bottlenecks plaguing tissue engineering technologies today.