Highly porous, bioresorbable electrospun sensors for optical detection of tissue oxygenation

A process of making a sensor, said process comprising the steps of:

• a.) electrospinning a solution comprising a solvent, polymer and chromophore to form a sensor scaffold;
• said solution, comprising, based on total solution weight, of from about 3% to about 20% polymer, said chromophore being present in mass ratio of chromophore to polymer of from about 1:2000 to about 1:100, and said solvent being selected from the group of 1,1,1,3,3,3-hexafluoro-2-propanol, dichloromethane, and mixtures thereof;
• said electrospinning process having one or more syringes containing said solution, each said syringe being attached to an electrospinning needle, each electrospinning needle independently having an electrospinning needle gauge of from about 14 gauge to 24 gauge, each said needle being translated or being stationary, each electrospinning needle independently having a flow rate of solution comprising a polymer and chromophore of from about 0.5 mL/hr to about 15 mL/hr, each electrospinning needle independently having a voltage applied to said electrospinning needle of from about +5 kV to about +28 kV, and one or more electrospinning collectors, each said electrospinning collector having a voltage applied to each said electrospinning collector of from about −0.2 kV to about −10 kV, each said electrospinning collector independently having an electrospinning collector motion linear velocity of from about 50 cm/s to about 600 cm/s, said process having a distance between electrospinning needle(s) and electrospinning collector(s) of from 12 cm to about 30 cm, said process having a controlled electrospinning exposure temperature of from about 20° C. to about 40° C., and said process having a controlled electrospinning exposure relative humidity of from about 0% relative humidity to about 50% relative humidity;
• and
• b.) processing said sensor scaffold into a sensor by a process comprising rolling and/or cutting said scaffold.

A method of determining tissue oxygenation comprising:

• a.) stimulating a sensor that is implanted in an animal or human with light having a peak wavelength of from about 600 nm to about 700 nm to cause the emission of light, said light having an emission maximum wavelength of from about 750 nm to about 900 nm, wherein said sensor comprises a chromophore and a polymer matrix, said chromophore being uniformly dispersed within said polymer matrix, said sensor having a pore length of at least 20 μm, said chromophore being present in mass ratio of chromophore to polymer of from about 1:2000 to about 1:100, said chromophore when in said polymer matrix exhibiting a red-most absorption maxima and emission maximum of from about 600 nm to about 1300 nm, said chromophore when in said polymer matrix having a difference between the red-most absorption maxima and the emission maximum that is greater than or equal to 50 nm, and said polymer matrix comprising one or more copolymers and/or homopolymers;
• said copolymers having each independently a weight-average molecular weight of at least 75,000 Da, said homopolymers having each independently a weight-average molecular weight of at least 75,000 Da and/or said homopolymers having each independently an inherent viscosity of at least 1.0 dL/g;
• b.) fitting the intensity of the emitted light versus time with an exponential function;
• c.) obtaining a phosphorescence lifetime from said fit;
• and
• d.) optionally monitoring said phosphorescence lifetime versus time and/or comparing said phosphorescence lifetime to a calibration.

A sensor comprising a chromophore and a polymer matrix, said chromophore being uniformly dispersed within said polymer matrix, said sensor having a pore length of at least 20 μm, said chromophore being present in mass ratio of chromophore to polymer of from about 1:2000 to about 1:100, said chromophore when in said polymer matrix exhibiting a red-most absorption maxima and emission maximum of from about 600 nm to about 1300 nm, said chromophore when in said polymer matrix having a difference between the red-most absorption maxima and the emission maximum that is greater than or equal to 50 nm, and said polymer matrix comprising one or more copolymers and/or homopolymers;

• said copolymers having each independently a weight-average molecular weight of at least 75,000 Da, said homopolymers having each independently a weight-average molecular weight of at least 75,000 Da and/or said homopolymers having each independently an inherent viscosity of at least 1.0 dL/g;
• and
• wherein said sensor comprises a chromophore and a polymer matrix, said chromophore being uniformly dispersed within said polymer matrix, said sensor has a pore length of from about 20 μm to about 50 μm, said chromophore being present in mass ratio of chromophore to polymer of from about 1:1000 to about 1:100, said chromophore when in said polymer matrix having a deaerated phosphorescence lifetime in 37° C. phosphate-buffered saline of at least 50 μs, said chromophore when in said polymer matrix exhibiting a red-most absorption maxima and emission maximum of from about 600 nm to about 1000 nm, said chromophore when in said polymer matrix having a difference between the red-most absorption maxima and the emission maximum that is from about 100 nm to about 300 nm, said chromophore being selected from the group consisting of Pd (II) and Pt (II) benzoporphyrins and mixtures thereof, and said polymer matrix comprising one or more copolymers and/or homopolymers, said one or more copolymers being selected from the group consisting of biocompatible and bioresorbable polyesters, said copolymers each independently having a weight-average molecular weight of from about 75,000 Da to about 350,000 Da, said one or more homopolymers being selected from the group consisting of biocompatible and bioresorbable polyesters, said homopolymers having each independently a weight-average molecular weight of from about 75,000 Da to about 350,000 Da, and/or said homopolymers having each independently an inherent viscosity of from about 1.0 dL/g to about 3.0 dL/g.

A sensor comprising a chromophore and a polymer matrix, said chromophore being uniformly dispersed within said polymer matrix, said sensor having a pore length of at least 20 μm, said chromophore being present in mass ratio of chromophore to polymer of from about 1:2000 to about 1:100, said chromophore when in said polymer matrix exhibiting a red-most absorption maxima and emission maximum of from about 600 nm to about 1300 nm, said chromophore when in said polymer matrix having a difference between the red-most absorption maxima and the emission maximum that is greater than or equal to 50 nm, and said polymer matrix comprising one or more copolymers and/or homopolymers;

• said copolymers having each independently a weight-average molecular weight of at least 75,000 Da, said homopolymers having each independently a weight-average molecular weight of at least 75,000 Da and/or said homopolymers having each independently an inherent viscosity of at least 1.0 dL/g;
• and
• wherein said sensor comprising a chromophore and a polymer matrix, said chromophore being uniformly dispersed within said polymer matrix, said sensor having a pore length of from about 20 μm to about 40 μm, said chromophore being present in mass ratio of chromophore to polymer of from about 1:1000 to about 1:125, said chromophore when in said polymer matrix having a deaerated phosphorescence lifetime in 37° C. phosphate-buffered saline of from about 90 μs to about 500 μs, said chromophore when in said polymer matrix exhibiting a red-most absorption maxima and emission maximum of from about 600 nm to about 1000 nm, said chromophore when in said polymer matrix having a difference between the red-most absorption maxima and the emission maximum that is from about 100 nm to about 300 nm, said chromophore being selected from the group consisting of Pd (II) tetramethacrylated benzoporphyrin, Pt (II) tetramethacrylated benzoporphyrin, Pd (II) meso-tetraphenyl tetrabenzoporphyrin, or Pt (II) meso-tetraphenyl tetrabenzoporphyrin, more preferably said chromophore is Pd (II) tetramethacrylated benzoporphyrin and said polymer matrix comprises poly(ε-caprolactone-co-p-dioxanone) and/or homopolymers selected from the group consisting of poly(p-dioxanone), poly(ε-caprolactone), and mixtures thereof;
• said copolymers having each independently a weight-average molecular weight of from about 115,000 Da to about 350,000 D;
• said homopolymers having each independently a weight-average molecular weight of from about 115,000 Da to about 350,000 Da and/or said homopolymers each independently having an inherent viscosity of from about 1.5 dL/g to about 3.0 dL/g.