Biodegradable Polymer Microfluidics for Tissue Engineering Microvasculature
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Biodegradable Polymer Microfluidics for Tissue Engineering Microvasculature Kevin R. King1,2,3, Chiaochun Wang1,2,3, Joseph P. Vacanti2, and Jeffrey T. Borenstein3 Massachusetts Institute of Technology, Cambridge MA 02139 2 Harvard Medical School, Massachusetts General Hospital, Boston, MA 02114 3 The Charles Stark Draper Laboratory, 555 Technology Sq., Cambridge, MA 02139 1
ABSTRACT In this work, we present for the first time, the fabrication of a fully biodegradable microfluidic device with features of micron-scale precision. This implantable MEMS device is a transition from poorly defined porous scaffolds to reproducible precision scaffolds with built-in convective conduits. First, conventional photolithography is used to create a master mold by bulk micromachining silicon. Next, polydimethylsiloxane (PDMS) silicone elastomer is replica molded to form a flexible inverse mold. The commonly used biodegradable polymer Poly-lactic-co-glycolic acid (PLGA 85:15) is then compression micromolded onto the PDMS to form micropatterned films of the biodegradable polymer. Finally, a thermal fusion bonding process is used to seal the biodegradable PLGA films, forming closed microfluidic channels at the capillary sizescale. Film thicknesses from 100µm-1mm are demonstrated with features having 2µm resolution and 0.2µm precision. Scanning electron micrographs of bonded biodegradable films reveal no observable bond interface and no significant pattern deformation. Bonded microfluidic channels are capable of supporting more than 30psi during flow studies, and we have used the processes to develop complex microfluidic networks for cell culture and implantation as well as simple channels to verify the fluid dynamics in the degradable microchannels. The processes described here are high resolution and fully biodegradable. In addition, they are fast, inexpensive, reproducible, and scalable, making them ideal for both rapid prototyping and manufacturing of tissue engineering scaffolds. INTRODUCTION Tissue engineering is emerging as a therapeutic alternative to organ transplantation for the more than 75,000 patients currently on the organ donor waiting list. In one approach, autologous cells are seeded on biodegradable porous scaffolds, cultured in vitro, then implanted in vivo, enabling tissue integration during polymer degradation [1]. While this approach has demonstrated early successes, cell-polymer constructs without integrated blood supplies are limited to millimeters in thickness. Porous scaffolds rely solely on diffusion for mass transport while normal tissues leverage convection from blood vessels to enable oxygenation of large tissues [2]. We have proposed fabricating and seeding biodegradable microfluidic channels with cells to provide functional equivalents of the microvasculature and enable scale-up of tissue engineering scaffolds [3]. Toward this end, we have recently demonstrated endothelial cell culture in prototype elastomeric microfluidic networks [4], and in this work, we describe fabrication processes to build microf
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