University of Virginia Patent Foundation

Edward A Botchwey, Iii

Kevin R Lynch

Roy Ogle

Kenneth Brayman

Cassandra L Fraser

Mary J Laughlin

Anthony Awojoodu

Daniel Bowers

Rebekah A Neal

Anusuya Das

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 dye polymer blend. Standardization curves show that in fully supplemented media, the fibers are responsive to dissolved oxygen concentrations less than 15 parts per million. Spatial and temporal ratiometric gradients were observed in vitro radiating outward from the center of a dense adherent cell grouping. Sensor activation in ischemia and cell transplant models in vivo show oxygenation decreases on the scale of minutes.

Compositions and methods for making and using oxygen sensing nanofibers and scaffolds

The present application discloses strategies to recruit and mobilize stem cells using S1P receptor selective agonists and antagonists as wells as regulators of chemokine receptors. In an in vivo ischemic model, S1P/S1Pactivation with FTY720 impeded inflammatory cell infiltration and recruited endothelial progenitor cells (EPCs) with the potential to increase microvascular remodeling. S1Pexpression on marrow-derived cells was essential for this remodeling. Concurrent systemic S1Pand CXCR4 antagonism mobilized hematopoietic stem cells (HSCs) with the ability to engraft and repopulate blood cells. Pre-treatment of donor HSCs with FTY720 increased homing toward SDF-1 and improved engraftment in marrow. FTY720-coated bone allografts coupled with systemic administration of VPC01091 enhanced bone allograft integration and new bone formation in bone defects. MSCs pre-treated with FTY720 exhibited increased migration toward SDF-1, a CXCR4+ ligand. The results show that S1P is a very powerful role player in pharmacological marrow-derived stem cell mobilization and recruitment.

Compositions and methods for tissue engineering and cell based therapies

The present invention provides methodologies and parameters for fabrication of the hybrid biomaterial by blending pure laminin or complex extracts of tissues containing laminin with biopolymers such as polycaprolactone (PCL), polylactic/polyglycolic acid copolymer (PLGA) or Polydioxanone (PDO) in fluoroalcohols (HFP, TFA), fabrication of substrates and scaffolds and devices from the hybrid biomaterial in forms such as films, nanofibers by electrospinning or microspheres, and the biological or biomedical use of the material or devices derived from it.

Compositions and methods for making and using laminin nanofibers

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Charlottesville, VA, United States of America

Edward A Botchwey, Iii