title: Spatiotemporal oxygen sensing using dual emissive boron dye-polylactide nanofibers.
abstract: Oxygenation in tissue scaffolds continues to be a limiting factor in regenerative medicine despite efforts to induce neovascularization or to use oxygen-generating materials. Unfortunately, many established methods to measure oxygen concentration, such as using electrodes, require mechanical disturbance of the tissue structure. To address the need for scaffold-based oxygen concentration monitoring, a single-component, self-referenced oxygen sensor was made into nanofibers. Electrospinning process parameters were tuned to produce a biomaterial scaffold with specific morphological features. The ratio of an oxygen sensitive phosphorescence signal to an oxygen insensitive fluorescence signal was calculated at each image pixel to determine an oxygenation value. A single component boron dye-polymer conjugate was chosen for additional investigation due to improved resistance to degradation in aqueous media compared to a boron dye polymer blend. Standardization curves show that in fully supplemented media, the fibers are responsive to dissolved oxygen concentrations less than 15 ppm. Spatial (millimeters) and temporal (minutes) ratiometric gradients were observed in vitro radiating outward from the center of a dense adherent cell grouping on scaffolds. Sensor activation in ischemia and cell transplant models in vivo show oxygenation decreases on the scale of minutes. The nanofiber construct offers a robust approach to biomaterial scaffold oxygen sensing.
authors.affiliation: Department of Biomedical Engineering, University of Virginia , Charlottesville, Virginia 22908, United States.
authors.forename: Daniel T
authors.initials: DT
authors.lastname: Bowers
authors.forename: Michael L
authors.initials: ML
authors.lastname: Tanes
authors.forename: Anusuya
authors.initials: A
authors.lastname: Das
authors.forename: Yong
authors.initials: Y
authors.lastname: Lin
authors.forename: Nicole A
authors.initials: NA
authors.lastname: Keane
authors.forename: Rebekah A
authors.initials: RA
authors.lastname: Neal
authors.forename: Molly E
authors.initials: ME
authors.lastname: Ogle
authors.forename: Kenneth L
authors.initials: KL
authors.lastname: Brayman
authors.forename: Cassandra L
authors.initials: CL
authors.lastname: Fraser
authors.forename: Edward A
authors.initials: EA
authors.lastname: Botchwey
mesh_terms: D000818:Animals; D001895:Boron / Q000737:chemistry*; D002460:Cell Line; D004396:Coloring Agents / Q000737:chemistry*; D007515:Islets of Langerhans / Q000166:cytology; D019344:Lactic Acid / Q000737:chemistry; D051379:Mice; D057139:Nanofibers / Q000737:chemistry*; D036103:Nanotechnology / Q000295:instrumentation*; D010100:Oxygen / Q000378:metabolism*; D011091:Polyesters / Q000737:chemistry*; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D019736:Prostheses and Implants; D062211:Spatio-Temporal Analysis; D023822:Tissue Engineering; D054457:Tissue Scaffolds / Q000737:chemistry
chemical_list: D004396:Coloring Agents; D011091:Polyesters; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; C033616:poly(lactide); D001895:Boron; D010100:Oxygen
keywords: cell transplant; electrospinning; hypoxia; nanofibers; oxygen; ratiometric; scaffold