Ultrasound-triggerable agents for tissue engineering

Abstract

The present invention is directed to compositions and methods for delivering a tissue scaffold comprising ultrasound-triggerable agents to an individual.

What is claimed is: 
     
         1 . A device comprising:
 (a) a tissue scaffold;   (b) an emulsion that comprises a perfluorocarbon (PFC) droplet comprising a therapeutic agent in the interior thereof, the PFC having a mean droplet diameter that is at least about 20 micrometers (μm), and   the emulsion having a volume fraction in the tissue scaffold of at least about 1% volume: volume.   
     
     
         2 . A device comprising:
 (a) a tissue scaffold; and   (b) an emulsion comprising a first population of perfluorocarbon (PFC) droplets comprising a therapeutic agent in the interior thereof, said first population of PFC droplets having the property of vaporizing at a first ultrasound frequency and/or acoustic pressure threshold.   
     
     
         3 . The device of  claim 2 , further comprising a second population of PFC droplets, said second population of PFC droplets having the property of vaporizing at a second ultrasound frequency and/or acoustic pressure threshold that is different than the first ultrasound frequency and/or acoustic pressure threshold. 
     
     
         4 . The device of  claim 2  or  claim 3 , further comprising a progenitor cell. 
     
     
         5 . The device of  claim 4  wherein the progenitor cell is a fibroblast, a chondrocyte, an osteoblast, a skeletal myocyte, a cardiac myocyte, a mesenchymal progenitor cell, a hematopoietic progenitor cell, a satellite cell, a neural progenitor cell, a pancreatic progenitor cell, a blast cell or a combination thereof. 
     
     
         6 . The device of any of the preceding claims wherein the emulsion is a double emulsion comprising a primary emulsion and a secondary emulsion. 
     
     
         7 . The device of  claim 6  wherein the primary emulsion comprises water-in-PFC, and the secondary emulsion comprises water-in-PFC-in-water. 
     
     
         8 . The device of any of the preceding claims, further comprising a surfactant. 
     
     
         9 . The device of  claim 8 , wherein a first surfactant stabilizing the primary emulsion is a triblock copolymer, and a second surfactant stabilizing the secondary emulsion is an aqueous soluble surfactant. 
     
     
         10 . The device of  claim 9  wherein the triblock copolymer comprises a perfluoroether and polyethylene glycol. 
     
     
         11 . The device of  claim 9  or  claim 10  wherein the aqueous soluble surfactant is selected from the group consisting of a protein, a lipid, an ionic copolymer and a non-ionic copolymer. 
     
     
         12 . The device of any of the preceding claims wherein initial pore size of the tissue scaffold is at least about 100 nanometers (nm). 
     
     
         13 . The device of any of the preceding claims wherein vaporization of the PFC droplet results in a final pore size of the tissue scaffold of at least about 40 μm and up to about 5 millimeters (mm). 
     
     
         14 . The device of any of the preceding claims, wherein the density of the tissue scaffold is between about 100 μg/mL to about 100 mg/mL fibrinogen. 
     
     
         15 . The device of any of the preceding claims which is implantable. 
     
     
         16 . The device of any one of  claims 1 - 14  which is topical. 
     
     
         17 . The device of any of the preceding claims wherein the therapeutic agent is selected from the group consisting of a polypeptide, a peptide, a polynucleotide, a viral particle, a gas, a contrast agent and a small molecule. 
     
     
         18 . The device of any of the preceding claims wherein release of the therapeutic agent is controlled spatially. 
     
     
         19 . The device of any of the preceding claims wherein release of the therapeutic agent is controlled temporally. 
     
     
         20 . A method of delivering an effective amount of a therapeutic agent to an individual in need thereof comprising administering the device of any one of  claims 1 - 19  to the individual.