Abstract: A suspension of a therapeutic substance (e.g., embolic beads) dispersed within a liquid can be delivered via a catheter by using a bidirectional pump to rapidly draw the mixture of the therapeutic substance and liquid from an external syringe into an internal reservoir, then rapidly push the mixture back out into the external syringe. The rapid operation of the bidirectional pump mixes the two constituents so that the therapeutic substance is temporarily suspended within the liquid. Then, a low-speed pump is used to inject the mixture out via the catheter. In some embodiments, the parameters of the low-speed pump are controlled so that the fluid exiting the catheter will experience laminar flow. When the therapeutic substance comprises embolic beads, this can advantageously prevent reflux of the embolic beads, which can be dangerous.

Abstract: Embolization particles can be safely delivered to the left gastric artery of a patient by introducing the distal end of a catheter in the patient's left gastric artery, inflating a balloon located near the distal end of the catheter so that the balloon prevents blood from flowing through the left gastric artery, and injecting a mixture of particles and contrast agent into the proximal end of the catheter so that they flow through the catheter. In addition, a path is provided for blood to flow into the catheter through an opening in the sidewall of the catheter at a position that is proximal to the balloon, and out through the distal end of the catheter. This blood flow helps to carry the particles along to their destination in the distal portion of the left gastric artery. The particles are also prevented from flowing into portions of the patient's artery system that are proximal of the balloon.

Abstract: A suspension of a therapeutic substance (e.g., embolic beads) dispersed within a liquid can be delivered via a catheter by using a bidirectional pump to rapidly draw the mixture of the therapeutic substance and liquid from an external syringe into an internal reservoir, then rapidly push the mixture back out into the external syringe. The rapid operation of the bidirectional pump mixes the two constituents so that the therapeutic substance is temporarily suspended within the liquid. Then, a low-speed pump is used to inject the mixture out via the catheter. In some embodiments, the parameters of the low-speed pump are controlled so that the fluid exiting the catheter will experience laminar flow. When the therapeutic substance comprises embolic beads, this can advantageously prevent reflux of the embolic beads, which can be dangerous.

Abstract: Tumors can be treated by introducing a first embolization agent (e.g., small embolic beads) into a blood vessel that supplies blood to the tumor, then introducing a therapeutic substance into the blood vessel at a position that is proximal with respect to the first embolization agent, and then introducing a second embolization agent (e.g., large embolic beads) into the blood vessel at a position that is proximal with respect to at least a portion of the therapeutic substance. The first embolization agent prevents complete systemic release of the substance, and the second embolization agent prevents retrograde washout of the substance. In some embodiments, the first embolization agent is omitted, and the second embolization agent impedes systemic release by impeding the forward flow of blood. In some embodiments, the therapeutic substance is an immunotherapy substance (e.g., CAR T-cells).

Abstract: The invention disclosed herein relates to methods and compositions useful for the production of composites for bone implantation. The invention includes methods for production of lyophilized bone fragments seeded with lyophilized stem cells, mesenchymal stem cells, bone marrow stem cells, periosteal cells or osteocytes that are derived either from the recipient of the bone implant or from allogeneic sources. The methods of the invention comprise production of bone implant material including the steps of cutting solid bone into fragments, decellularizing the bone fragments, seeding stem cells, mesenchymal stem cells, bone marrow stem cells, periosteal cells or osteocytes onto the decellularized bone fragments and lyophilizing the complex of bone fragments and cells. The stabilized bone matrix and complex of bone and cells increases the ease of transport, storage and reconstitution of bone and cells for bone implantation.

Abstract: Devices and methods for reducing, eliminating, preventing, suppressing, or treating tissue responses to hemostatic devices e.g., biological sealants or vascular procedures are disclosed. The invention employs a combination of resorbable, biocompatible matrix materials and a variety of therapeutic agents, such as antiproliferatives or antibiotics, applied to a vascular puncture or incision to achieve hemostasis following diagnostic or interventional vascular catheterizations and to treat neointimal hyperplasia and stenosis. A matrix of a material such as collagen provides a reservoir of a therapeutic agent such as rapamycin (sirolimus) and its derivatives and analogs for delivery at a tissue site at risk for vasculoproliferation, infection, inflammation, fibrosis or other tissue responses.

Abstract: Devices and methods for reducing, eliminating, preventing, suppressing, or treating tissue responses to hemostatic devices e.g., biological sealants or vascular procedures are disclosed. The invention employs a combination of resorbable, biocompatible matrix materials and a variety of therapeutic agents, such as antiproliferatives or antibiotics, applied to a vascular puncture or incision to achieve hemostasis following diagnostic or interventional vascular catheterizations and to treat neointimal hyperplasia and stenosis. A matrix of a material such as collagen provides a reservoir of a therapeutic agent such as rapamycin (sirolimus) and its derivatives and analogs for delivery at a tissue site at risk for vasculoproliferation, infection, inflammation, fibrosis or other tissue responses.

Abstract: Administration of a formulation comprising a antirestenotic compound conjugated to a microparticle carrier is effective to inhibit stenosis formation in a blood vessel. Such stenosis typically results, in the absence of treatment, from trauma to a vessel, such as an incision, excessive pressure, an angioplasty procedure and/or stent implantation. The antirestenotic compound is typically an antiproliferative, immunosuppressive, or antiinflammatory drug, such as rapamycin, tacrolimus, paclitaxel, dexamethasone, or an active analog or derivative, an antisense oligonucleotide, or combinations thereof. The microparticle carrier comprises a suspension of gas-filled microbubbles or biocompatible polymeric microparticles, in a pharmaceutically acceptable liquid vehicle, and is effective to deliver the conjugated therapeutic to the site of vessel injury.

Abstract: Microparticle carriers, particularly protein-encapsulated microbubbles, are used to deliver antiproliferative drugs to target sites in a subject. In particular, antirestenotic drugs are delivered to areas of vascular injury for treatment or prevention of hyperproliferative disease, e.g. stenosis, in blood vessels; and antineoplastic drugs are targeted to tumor sites.

Abstract: A treatment system to provide energy therapy to a patient includes an implantable device and an activation system having a plurality of energy emitters that transmit energy towards the device. In one embodiment, the implantable device is a stent carrying a treatment agent. The treatment agent can be selectively activated by the activation system before, during, or after implantation in a subject's body. The activated treatment agent can react with adjacent tissues.

Abstract: A drug-eluting stent is disclosed; together with various methods for treating atherosclerotic plaques and other cardiovascular diseases via intervention on vasa vasorum.

Abstract: This invention is a prosthetic device generally placed on the outside surface of the vessel or graft which then elutes antiproliferative drugs or agents from a drug-eluting matrix material. Methods of perivascular antiproliferative drug administration also are disclosed.

Abstract: A method and system of embolizing an organ or vessel is disclosed. An embolization device such as a coil, balloon, spheres, stents or occlusive plaques is used. The embolization device has a surface, which may be coated with composition retaining material such as a polymer, bio-polymer or non-polymer based technology that allows sustained release of drug or material from drug eluting occlusive device. For example, an anti-angiogenic composition is coated on the application surface. The embolization device is then inserted in the vessel and embolization is enhanced by the composition.

Abstract: Devices and methods for reducing, eliminating, preventing, suppressing, or treating tissue responses to hemostatic devices e.g., biological sealants or vascular procedures are disclosed. The invention employs a combination of resorbable, biocompatible matrix materials and a variety of therapeutic agents, such as antiproliferatives or antibiotics, applied to a vascular puncture or incision to achieve hemostasis following diagnostic or interventional vascular catheterizations and to treat neointimal hyperplasia and stenosis. A matrix of a material such as collagen provides a reservoir of a therapeutic agent such as rapamycin (sirolimus) and its derivatives and analogs for delivery at a tissue site at risk for vasculoproliferation, infection, inflammation, fibrosis or other tissue responses.

Abstract: A method of treating or preventing high-risk plaque is provided. The method may include applying to a medical device an effective amount of a composition comprising a sex hormone, anti-hormone, sex-hormone agonist, steroid-hormone inhibitor/antagonist (partial or full), selective estrogen receptor modulator (SERM), or a combination thereof. The medical device may be inserted into an area of a living organism that is or has a propensity to be affected by high-risk plaque.

Abstract: Microparticle carriers, particularly protein-encapsulated microbubbles, are used to deliver antiproliferative drugs to target sites in a subject. In particular, antirestenotic drugs are delivered to areas of vascular injury for treatment or prevention of hyperproliferative disease, e.g. stenosis, in blood vessels; and antineoplastic drugs are targeted to tumor sites.

Abstract: Administration of a formulation comprising a antirestenotic compound conjugated to a microparticle carrier is effective to inhibit stenosis formation in a blood vessel. Such stenosis typically results, in the absence of treatment, from trauma to a vessel, such as an incision, excessive pressure, an angioplasty procedure and/or stent implantation. The antirestenotic compound is typically an antiproliferative, immunosuppressive, or antiinflammatory drug, such as rapamycin, tacrolimus, paclitaxel, dexamethasone, or an active analog or derivative, an antisense oligonucleotide, or combinations thereof. The microparticle carrier comprises a suspension of gas-filled microbubbles or biocompatible polymeric microparticles, in a pharmaceutically acceptable liquid vehicle, and is effective to deliver the conjugated therapeutic to the site of vessel injury.

Abstract: Administration of a formulation comprising a antirestenotic compound conjugated to a microparticle carrier is effective to inhibit stenosis formation in a blood vessel. Such stenosis typically results, in the absence of treatment, from trauma to a vessel, such as an incision, excessive pressure, or an angioplasty procedure. The antirestenotic compound is typically an antiproliferative, immunosuppressive, or antiinflammatory drug, such as rapamycin, tacrolimus, paclitaxel, dexamethasone, or an active analog or derivative, or combinations thereof. The microparticle carrier comprises a suspension of gas-filled microbubbles or biocompatible polymeric microparticles, in a pharmaceutically acceptable liquid vehicle, and is effective to deliver the conjugated therapeutic to the site of vessel injury.

Abstract: A method of treating or preventing vascular disease in a living organism. The method includes delivering an effective amount of a composition including a sex hormone, anti-hormone, sex-hormone agonist, steroid-hormone inhibitor/antagonist (partial or full), selective estrogen receptor modulator (SERM), or a combination thereof, to an affected area of a living organism.

Abstract: A method of treating or preventing vascular disease in a living organism. The method includes delivering an effective amount of a composition including a sex hormone, anti-hormone, sex-hormone agonist, steroid-hormone inhibitor/antagonist (partial or full), selective estrogen receptor modulator (SERM), or a combination thereof, to an affected area of a living organism.