Abstract: Oral cavity wound healing occurs in an environment that sustains ongoing physical trauma and is rich in bacteria. Patients undergoing cleft palate repair have a high degree of wound healing complications, such as oronasal fistula (ONF) formation. Following hard palate injury, ONF was created that demonstrated little change in pro-regenerative monocytes LY6Clo monocytes; however, there were increased M2 macrophages observed. Delivery of FTY720 nanofiber scaffolds following hard palate injury prevented ONF formation, allowed complete wound healing and was associated with increased LY6Clo monocytes and pro-regenerative M2 macrophages. Evaluation of interleukin gene expression revealed reduction in pro-inflammatory IL1 and IL6 and increased expression of pro-regenerative IL10 with FTY720 nanofiber delivery.

Abstract: 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.

Abstract: 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, S1P1/S1P3 activation with FTY720 impeded inflammatory cell infiltration and recruited endothelial progenitor cells (EPCs) with the potential to increase microvascular remodeling. S1P3 expression on marrow-derived cells was essential for this remodeling. Concurrent systemic S1P3 and 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.

Abstract: 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.

Abstract: 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.

Abstract: 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, S1P1/S1P3 activation with FTY720 impeded inflammatory cell infiltration and recruited endothelial progenitor cells (EPCs) with the potential to increase microvascular remodeling. S1P3 expression on marrow-derived cells was essential for this remodeling. Concurrent systemic S1P3 and 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.

Abstract: The invention provides compositions and methods useful for treating wounds and enhancing wound healing. The present invention discloses a continuous polymer coating system to provide sustained localized delivery of bioactive agents. The data demonstrate the efficacy of a bioactive coating comprising the polymer PLAGA and the agent FTY720, a selective agonist for sphingosine 1-phosphate receptors, and biologically active derivatives and analogs thereof, for use in wound healing. In vitro drug release studies validated 64% loading efficiency with complete release of compound following 14 days. Mechanical evaluation of healing bone showed significant enhancement of mechanical stability in FTY720 treatment groups. Superior osseous integration across the host-graft interface, significant enhancement in smooth muscle cell investment, and reduction in leukocyte recruitment were evident in FTY720 treated groups. The present invention is useful for enhancing angiogenesis for wound healing.

Abstract: 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.

Abstract: The present invention encompasses methodologies and parameters for the formation of nanofibrous (to microfibrous) laminin via electrospinning. The present application discloses conditions and appropriate parameters to synthesize laminin fibers from a diameter of about 10 nM to a diameter of over 1,000 nM via electrospinning.