Development of biodegradable microfluidic networks for tissue engineering

Abstract

Biodegradable tissue engineering scaffolds currently suffer from poorly controlled geometries, lack of reproducibility, and severe mass transport limitations. Microfabrication is an ideal tool for attacking problems in tissue engineering due to its control of diverse size scales, from microns to centimeters, all with micron resolution and submicron precision. By enabling precision geometries and flexible designs, microfabrication has the potential to offer creative solutions to some of the major problems facing the field of tissue engineering; those of achieving rapid vascularization and recapitulating normal complex tissue microarchitecture. In this thesis, silicon micromachining, soft lithography, and traditional polymer processing are combined to develop a fully biodegradable microfabrication platform using poly(DL-lactic-co-glycolic) acid (PLGA 85:15). First, micron scale structures fabricated on silicon substrates are transferred into the surface of biodegradable films using polymer melt replica molding. Next, microchannel networks are sealed and made three-dimensional by stacking and irreversibly bonding the biodegradable films using a newly developed thermal fusion bonding process. The process is modeled and optimized to guide bonding of a wide range of microchannels while avoiding parasitic microstructure deformation. An extruded inlet/outlet scheme is implemented and combined with micromolding and fusion bonding to build fully patent, leak-free biodegradable microfluidic networks with predictable fluidic resistances. Finally, this thesis concludes with the first demonstration of long-term continuous-flow cell culture in prototype microfluidic networks, demonstrating the feasibility of using the newly developed biodegradable microdevices as cell-seeded tissue engineering scaffolds. In comparison to conventional scaffold fabrication techniques, these processes offer two orders of magnitude improvement in fabrication time and spatial resolution while offering flexible designs and unmatched reproducibility. Through these features, they have enabled construction of the first fully biodegradable microfluidic networks.