Three‐Dimensional Microfluidic Tissue‐Engineering Scaffolds Using a Flexible Biodegradable Polymer

Organ loss and failure is one of the most critical issues facing the healthcare industry in developed nations. The shortage of available organ donors has driven the growth and expansion of the field of tissue engineering as a means of developing replacement tissues and organs[1,2] including the liver.[3] Microfabrication and bio-microelectromechanical system (bio-MEMS) technology is an attractive tool for developing tissue-engineering systems because of the improved spatial resolutions over traditional scaffold fabrication techniques such as casting and porogen leaching,[4] gas foaming,[5] and three-dimensional printing.[6] Polymer scaffolds replica-molded on micromachined silicon substrates can achieve feature resolutions of less than 10 µm,[7] the same lengthscale of mammalian cells. Microfluidic bioreactors have been both fabricated and seeded with a variety of cell types, including endothelial cells[7–10] and hepatocytes.[10–12] However, one limiting factor in previous studies of microfluidic scaffolds has been the choice of material. Microfabricated silicon and replica-molded poly(dimethylsiloxane) (PDMS), although ubiquitous and inexpensive, are not biodegradable and have limited biocompatibility, and therefore are not suitable biomaterials for a tissue-engineering scaffold. Microfluidic scaffolds fabricated from poly(L-lactic-co-glycolic acid) (PLGA),[13] while biodegradable, exhibit suboptimal properties for an implant material, such as rigid mechanical properties,[14] undesirable bulk degradation kinetics,[15] and limited biocompatibility in some cases.[16] High concentrations of PLGA byproducts has also been shown to be cytotoxic,[17] which is a major limitation in the prospect of fabricating large, organ-size scaffolds.