Biodegradable Microfluidic Scaffolds for Vascular Tissue Engineering

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Biodegradable Microfluidic Scaffolds for Vascular Tissue Engineering C. J. Bettinger1,3, J. T. Borenstein3, R. S. Langer2 1

Department of Materials Science and Engineering, MIT Department of Chemical Engineering, MIT Room E25-342 Cambridge, MA, 02139 2

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Charles Stark Draper Laboratory 555 Technology Square Cambridge, MA, 02139 Abstract This work describes the integration of novel microfabrication techniques for vascular tissue engineering applications in the context of a novel biodegradable elastomer. The field of tissue engineering and organ regeneration has been borne out of the high demand for organ transplants. However, one of the critical limitations in regeneration of vital organs is the lack of an intrinsic blood supply. This work expands on the development of scaffolds for vascular tissue engineering applications by employing microfabrication techniques. Unlike previous efforts, this work focuses on fabricating single layer and three-dimensional scaffolds from poly(glycerolsebacate) (PGS), a novel biodegradable elastomer with superior mechanical properties. The transport properties of oxygen and carbon dioxide in PGS were measured through a series of time-lag diffusion experiments. The results of these measurements were used to calculate a characteristic length scale for oxygen diffusion limits in solid PGS scaffolds. Single layer and three-dimensional microfluidic scaffolds were then produced using fabrication techniques specific for PGS. This work has resulted in the fabrication of solid PGS-based scaffolds with biomimetic fluid flow and capillary channels on the order of 10 microns in width. Fabrication of complex, three-dimensional microfluidic PGS scaffolds was also demonstrated by stacking and bonding multiple microfluidic layers. Introduction Overcoming the problems of nutrient transport is critical in the design of tissue engineering scaffolds that are targeted for the growth of complex organs such as the liver and kidney. One approach to solving this problem involves the integration of an intrinsic vascular network within these scaffolds. More specifically, the application of microfabrication and BioMEMS technology has been focused toward developing microfluidic networks with geometries that simulate vascular networks1, 2. Microfabrication is an attractive tool for vascular tissue engineering because of the ability to produce structures with feature resolution of less than 10 microns, the same approximate dimensions of the smallest capillaries. However, one limiting factor in previous studies of microfluidic scaffolds has been the choice of material. Microfabricated silicon and replica molded poly(dimethyl siloxane) (PDMS), although ubiquitous and inexpensive, are not biodegradable, have limited biocompatibility, and therefore are not suitable biomaterials for a tissue engineering scaffold. Microfluidic scaffolds fabricated

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from poly(L-lactic-glycolic acid) have poor mechanical properties, undesirable degradation kinetics, and questionable biocompatibility. Poly(glycerol-seba