title: Endothelialized networks with a vascular geometry in microfabricated poly(dimethyl siloxane).
abstract: One key challenge in regenerating vital organs is the survival of transplanted cells. To meet their metabolic requirements, transport by diffusion is insufficient, and a convective pathway, i.e., a vasculature, is required. Our laboratory pioneered the concept of engineering a vasculature using microfabrication in silicon and Pyrex. Here we report the extension of this concept and the development of a methodology to create an endothelialized network with a vascular geometry in a biocompatible polymer, poly(dimethyl siloxane) (PDMS). High-resolution PDMS templates were produced by replica-molding from micromachined silicon wafers. Closed channels were formed by bonding the patterned PDMS templates to flat PDMS sheets using an oxygen plasma. Human microvascular endothelial cells (HMEC-1) were cultured for 2 weeks in PDMS networks under dynamic flow. The HMEC-1 cells proliferated well in these confined geometries (channel widths ranging from 35 mum to 5 mm) and became confluent after four days. The HMEC-1 cells lined the channels as a monolayer and expressed markers for CD31 and von Willebrand factor (vWF). These results demonstrate that endothelial cells can be cultured in confined geometries, which is an important step towards developing an in vitro vasculature for tissue-engineered organs.
authors.affiliation: Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Shin
authors.forename: Kant
authors.initials: K
authors.lastname: Matsuda
authors.forename: Osamu
authors.initials: O
authors.lastname: Ishii
authors.forename: Hidetomi
authors.initials: H
authors.lastname: Terai
authors.forename: Mohammed
authors.initials: M
authors.lastname: Kaazempur-Mofrad
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Borenstein
authors.forename: Michael
authors.initials: M
authors.lastname: Detmar
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Vacanti
mesh_terms: D001672:Biocompatible Materials / Q000032:analysis / Q000737:chemistry; D001808:Blood Vessels / Q000166:cytology* / Q000254:growth & development*; D018929:Cell Culture Techniques / Q000295:instrumentation / Q000379:methods; D002454:Cell Differentiation / Q000502:physiology; D002460:Cell Line; D049109:Cell Proliferation; D002470:Cell Survival / Q000502:physiology; D004129:Dimethylpolysiloxanes / Q000032:analysis / Q000737:chemistry*; D042783:Endothelial Cells / Q000166:cytology* / Q000502:physiology*; D005240:Feasibility Studies; D006801:Humans; D008420:Manufactured Materials / Q000032:analysis; D008422:Materials Testing; D012828:Silicones / Q000032:analysis / Q000737:chemistry*; D013499:Surface Properties; D023822:Tissue Engineering / Q000295:instrumentation / Q000379:methods*
chemical_list: D001672:Biocompatible Materials; D004129:Dimethylpolysiloxanes; D012828:Silicones; C013830:baysilon