Abstract: One aspect of the invention provides a method for freeze-drying surfactant-stabilized microbubbles. The method includes: preparing vials comprising a mixture comprising microbubbles; partially submerging the vials in a chilled water bath, wherein the water bath has a sub-freezing temperature; placing the vials on a cooled shelf of a lyophilizer; freeze-drying the vials in the lyophilizer; and capping the freeze-dried vials. Another aspect of the invention provides a method for annealing surfactant-stabilized microbubbles. The method includes: preparing vials comprising a mixture comprising microbubbles; passing the vials in and out of liquid nitrogen (LN2) until the mixture is frozen; holding the vials at ?20° C.; placing the vials on a cooled shelf of a lyophilizer; freeze-drying the vials in the lyophilizer; and capping the freeze-dried vials.

Abstract: The present invention provides methods for preparing acoustically-sensitive microbubbles. The method includes the steps of: i) preparing a first surfactant solution comprising a first micelle-forming surfactant at a concentration above the critical micelle concentration (CMC); ii) adding one or more pharmaceutical compounds in a solvent to the first surfactant solution, thereby loading the micelles with the one or more pharmaceutical compounds; iii) preparing a second surfactant solution comprising a second surfactant, wherein the second surfactant comprises one or more matrix forming surfactants; iv) adding heat to the second surfactant solution to melt the surfactant and allowing the mixture to cool under rapid stirring; v) combining the second surfactant solution with the loaded micelles; vi) purging the surfactant mixture with a purging gas; vii) agitating the purged mixture under a constant stream of the purging gas; and, viii) separating the formed microbubbles by size.

Abstract: One aspect of the invention provides a method for freeze-drying surfactant-stabilized microbubbles. The method includes: preparing vials comprising a mixture comprising microbubbles; partially submerging the vials in a chilled water bath, wherein the water bath has a sub-freezing temperature; placing the vials on a cooled shelf of a lyophilizer; freeze-drying the vials in the lyophilizer; and capping the freeze-dried vials. Another aspect of the invention provides a method for annealing surfactant-stabilized microbubbles. The method includes: preparing vials comprising a mixture comprising microbubbles; passing the vials in and out of liquid nitrogen (LN2) until the mixture is frozen; holding the vials at ?20° C.; placing the vials on a cooled shelf of a lyophilizer; freeze-drying the vials in the lyophilizer; and capping the freeze-dried vials.

Abstract: One aspect of the invention provides a method for freeze-drying surfactant-stabilized microbubbles. The method includes: preparing vials comprising a mixture comprising microbubbles; partially submerging the vials in a chilled water bath, wherein the water bath has a sub-freezing temperature; placing the vials on a cooled shelf of a lyophilizer; freeze-drying the vials in the lyophilizer; and capping the freeze-dried vials. Another aspect of the invention provides a method for annealing surfactant-stabilized microbubbles. The method includes: preparing vials comprising a mixture comprising microbubbles; passing the vials in and out of liquid nitrogen (LN2) until the mixture is frozen; holding the vials at ?20° C.; placing the vials on a cooled shelf of a lyophilizer; freeze-drying the vials in the lyophilizer; and capping the freeze-dried vials.

Abstract: Provided is a particle-stabilized ultrasound contrast agent (UCA) and methods of preparing same. Also provided is a method for preparing a lyoprotected UCA, a freeze-dried lyoprotected UCA, and a reconstituted freeze-dried lyoprotected UCA.

Abstract: This invention provides an improvement to methods of drug loading of ultrasound contrast agents. Echogenic drug-loaded polymer microcapsules, nanocapsules, or mixtures thereof produced by the method of the invention wherein the echogenic drug-loaded polymer microcapsules, nanocapsules, or mixtures thereof contain at least 10% more of a drug as compared to (1) echogenic drug-loaded polymer microcapsules, nanocapsules, or mixtures thereof prepared by adding drug prior to emulsifying or (2) echogenic drug-loaded polymer microcapsules, nanocapsules, or mixtures thereof prepared by adding drug to lyophilized polymer microcapsules, nanocapsules, or mixtures thereof.

Abstract: The present invention relates to scaffolds that can physically guide cells, e.g. neurons, while best matching the material properties of native tissue. The present invention also relates to methods of generating such scaffolds, and for the use of such scaffolds, e.g. in spinal cord and peripheral nerve injury repair. The methods of the present invention include a uniquely controlled freeze casting process to generate highly porous, linearly oriented scaffolds. The scaffolds of the present invention not only comprise a highly aligned porosity, but also contain secondary guidance structures in the form of ridges running parallel to the pores to create a series of microstructured and highly aligned channels. This hierarchy of structural guidance aligns and guides neurite outgrowth down the channels created by the ridges, and keep neurites from branching perpendicular to the inter-ridge grooves.

Abstract: One aspect of the invention provides a precursor to an echogenic polymer microcapsule or nanocapsule. The precursor includes an emulsion including a polymer solution and an aqueous solution including a water-soluble sublimable solute. This aspect of the invention can have a variety of embodiments. In one embodiment, the water-soluble sublimable solute can be an ammonium salt. For example, the ammonium salt can be ammonium carbonate.

Abstract: Methods for producing echogenic polymer microcapsules and nanocapsules for use in diagnostic imaging and delivery of bioactive compounds as well as targeted imaging and delivery to selected tissues and cells are provided. Compositions containing these echogenic polymer microcapsules and nanocapsules for use in diagnostic imaging and delivery of bioactive agents are also provided.

Abstract: Provided is a particle-stabilized ultrasound contrast agentn (UCA) and methods of preparing same. Also provided is a method for preparing a lyoprotected UCA, a freeze-dried lyoprotected UCA, and a reconstituted freeze-dried lyoprotected UCA.

Abstract: The present invention relates to scaffolds that can physically guide cells, e.g. neurons, while best matching the material properties of native tissue. The present invention also relates to methods of generating such scaffolds, and for the use of such scaffolds, e.g. in spinal cord and peripheral nerve injury repair. The methods of the present invention include a uniquely controlled freeze casting process to generate highly porous, linearly oriented scaffolds. The scaffolds of the present invention not only comprise a highly aligned porosity, but also contain secondary guidance structures in the form of ridges running parallel to the pores to create a series of microstructured and highly aligned channels. This hierarchy of structural guidance aligns and guides neurite outgrowth down the channels created by the ridges, and keep neurites from branching perpendicular to the inter-ridge grooves.

Abstract: A tissue joining device and a surgical instrument for employing the tissue joining device are provided. The tissue joining device may be designed such that a first member may be inserted into a second member in discrete increments so that two lumen structures can properly be combined.

Abstract: Methods for producing echogenic polymer microcapsules and nanocapsules for use in diagnostic imaging and delivery of bioactive compounds as well as targeted imaging and delivery to selected tissues and cells are provided. Compositions containing these echogenic polymer microcapsules and nanocapsules for use in diagnostic imaging and delivery of bioactive agents are also provided.

Abstract: Methods for producing echogenic polymer microcapsules and nanocapsules for use in diagnostic imaging and delivery of bioactive compounds as well as targeted imaging and delivery to selected tissues and cells are provided. Compositions containing these echogenic polymer microcapsules and nanocapsules for use in diagnostic imaging and delivery of bioactive agents are also provided.

Abstract: The invention concerns substrates comprising a biocompatible gel and at least one of a plurality of cells, said cells being capable of producing at least one therapeutic agent. Other aspects of the invention concern methods of making such substrates and methods of repairing and regenerating damaged nervous tissue with the substrates.

Abstract: The instant invention concerns a device for joining tissue comprising a ring and rivet, the ring comprises a biocompatible and biodegradable polymer and contains at least one bioactive agent. The rivet has a hollow lumen. The invention also relates to methods of making such devices and the use of such devices in joining tissue.

Abstract: This invention provides an improvement to methods of drug loading of ultrasound contrast agents. Echogenic drug-loaded polymer microcapsules, nanocapsules, or mixtures thereof produced by the method of the invention wherein the echogenic drug-loaded polymer microcapsules, nanocapsules, or mixtures thereof contain at least 10% more of a drug as compared to (1) echogenic drug-loaded polymer microcapsules, nanocapsules, or mixtures thereof prepared by adding drug prior to emulsifying or (2) echogenic drug-loaded polymer microcapsules, nanocapsules, or mixtures thereof prepared by adding drug to lyophilized polymer microcapsules, nanocapsules, or mixtures thereof.

Abstract: The present invention provides a novel method of manufacturing nanosized polymeric echogenic contrast agents. The method of the present invention comprises a modified salting out process which results on nanosized polymeric capsules encapsulating an aqueous core that is subsequently evacuated. The compositions of the present invention can be used as contrast agents as well as to deliver therapeutic agents to specific targets.

Abstract: A method for producing surfactant-stabilized microcapsules or nanocapsules including the steps of (a) preparing a suspension comprising a non-ionic sorbitan detergent and a salt in phosphate buffered saline; (b) adding to the suspension a nonionic polyoxyethylenesorbitan detergent to produce a solution; (c) heating while stirring the solution of step (b) to 55±5° C. and maintaining the temperature of the solution at 55±5° C. for several minutes; (d) allowing the solution to cool to room temperature; (e) autoclaving the solution; (f) creating surfactant-stabilized microbubbles and nanobubbles in the solution; and (g) collecting surfactant-stabilized nanocapsules and microcapsules formed from the microbubbles and nanobubbles.

Abstract: The present invention comprises minimally invasive methods useful in the treatment of liver cancer. The method of the present invention comprises administering to an individual with liver cancer an injectable, echogenic nanocapsule and/or microcapsule wherein the nanocapsule and/or microcapsule comprises a therapeutic agent, a targeting moiety, or a combination thereof. The method of the present invention further comprises monitoring the distribution of the nanocapsule and/or microcapsule using ultrasound. The method of the invention delivers a therapeutic agent to a liver cancer cell either by biodegradation of a nanocapsule and/or microcapsule comprising a therapeutic agent, or by altering the biodegradation of a nanocapsule and/or microcapsule using ultrasound.