Abstract: The present invention is based on the discovery that a vascular stent or other implantable medical device can be coated with a biodegradable biocompatible polymer to which is attached a bioligand that specifically captures progenitors of endothelial cells (PECs) from the circulating blood to promote endogenous formation of healthy endothelium in Type II diabetics. In one embodiment, the bioligand is a peptide that specifically binds to an integrin receptor on PECs. The invention also provides methods for using such vascular stents and other implantable devices to promote vascular healing in Type II diabetics, for example following mechanical intervention.

Abstract: The present invention is based on the discovery that a vascular stent or other implantable medical device can be coated with a biodegradable biocompatible polymer to which is attached a bioligand that specifically captures progenitors of endothelial cells (PECs) from the circulating blood to promote endogenous formation of healthy endothelium in Type II diabetics. In one embodiment, the bioligand is a peptide that specifically binds to an integrin receptor on PECs. The invention also provides methods for using such vascular stents and other implantable devices to promote vascular healing in Type II diabetics, for example following mechanical intervention.

Abstract: The present invention provides wound dressings, optionally surgically implantable, containing biodegradable, polymers and hydrogels having allogenic or autologous precursor cells, such as stem cells and progenitor cells dispersed within. Alternatively, the wound dressings can have conditioned medium obtained from the precursor cells dispersed within. The wound dressings promote tissue restoration processes at a site of application or implantation. Additional bioactive agents can also be dispersed within the polymer/hydrogel matrix, which can be formulated to biodegrade at a controlled rate by adjusting the composition. Methods are also provided for using such biodegradable wound dressings as a delivery device or carrier for the precursor cells, conditioned medium and bioactive agents, or as coatings on implantable medical devices, to promote tissue restoration at a lesion site.

Abstract: The invention provides bioabsorbable elastomeric arterial support devices fabricated using elastomeric polymer networks and semi-interpenetrating networks in which a linear polymer is crosslinked by ester or alpha-amino-acid containing cross-linkers that polymerize upon exposure to active species. The invention devices are designed for implant into curved segments of artery and can be expanded during arterial implant and cross-linked in vivo in the expanded state to restore a clogged artery to extended function. The invention devices are useful for in vivo implant in diseased arteries and for delivery of a variety of therapeutic molecules in a time release fashion to surrounding tissues to reduce or eliminate arterial response to implant of the device.

Abstract: The present invention is based on the discovery that a vascular stent or other implantable medical device can be coated with a biodegradable biocompatible polymer to which is attached a bioligand that specifically captures progenitors of endothelial cells (PECs) from the circulating blood to promote endogenous formation of healthy endothelium in Type II diabetics. In one embodiment, the bioligand is a peptide that specifically binds to an integrin receptor on PECs. The invention also provides methods for using such vascular stents and other implantable devices to promote vascular healing in Type II diabetics, for example following mechanical intervention.

Abstract: The invention provides systems containing a sterile container for aspiration, filtering, treating and reinjection into a subject of a bodily fluid in a sterile environment. The systems are particularly designed to facilitate transfection of cells within the sterile container by gene therapy molecules and reinjection of the transfected cells into the donor at controlled depth in precisely controlled volumes such as is useful for revascularization of ischemic cardiac tissue. For injection, a pressure actuator, preferably hand-held, applies force to liquids held within the sterile container in precisely controlled increments, thereby expressing liquids through a hollow needle or injection catheter in precisely controlled microvolumes. The invention systems include a hand-held injection device with audible cues that correspond to an operator-selected injection volume and/or audible cues that correspond to needle penetration depth selected by the operator.

Abstract: The invention tissue injection catheters are designed to facilitate injection of a therapeutic or diagnostic agent to an interior body cavity, especially the myocardium or epicardium of the heart with precisely controlled depth penetration. The invention injection catheters, which include mechanisms for precisely controlling the length of needle tip exposed for tissue penetration, are designed to be used in an assemblage with a sterile container and delivery actuator for reinjection of autologous cell-containing fluids, such as autologous bone marrow aspirate. In preferred embodiments, the assemblage is designed to be hand-held. When used in such an assemblage, the invention catheters are particularly useful as a gene delivery device to effect angiogenesis of ischemic areas of the heart.

Abstract: The present invention is based on the discovery that stents can be coated with biodegradable, bioactive polymers that promote endogenous healing processes at a site of stent implantation. The polymers biodegrade over time, releasing agents which establish or re-establish the natural healing process in an artery. Preferably, the stent is implanted at the time an artery is damaged, such at the time of angioplasty to protect the damaged artery against deleterious blood-borne factors that initiate proliferation of smooth muscle cells.

Abstract: Methods are provided for enhancing capacity of impaired bone marrow cells to promote angiogenesis when introduced into an ischemic site in a patient by transfecting early attaching cells derived from bone marrow in culture with an angiogenesis promoting transgene. Methods are also provided for utilizing such early attaching cells derived from autologous bone marrow, or media derived from these cells while the cells are grown in culture (which need not be from autologous cells) to deliver angiogenesis-promoting transgenes or proteins to a patient. The transfected early attaching cells, or media derived from these cells while the cells are grown in culture, are introduced into an ischemic tissue, such as the heart, to enhance formation of collateral blood vessels.

Abstract: A flexible stabilizer arm assembly is provided that can be positioned in a desired three-dimensional attitude and then fixed in place to forceably hold an object against an undulating surface. In one embodiment, the invention assembly comprises a mounting base for attachment of the arm to a stationary fixture, a flexible arm of multiple articulated elongate links rotatably joined to adjacent links, a freely rotatable turret joint at the distal end of the arm that is adapted to attach an appendage in freely rotatable fashion to the distal end of the arm. Once positioned, a tightening mechanism is actuated to fix the attitude of the arm with respect to the mounting base. Optionally, the appendage is a two-tined foot adapted for holding a surgical instrument, such as a suction body, against a beating heart. The flexible arm, which ranges up to 12 inches in length, can withstand an undulating force exerted against the distal end of up to 20 pounds while remaining in the fixed position.

Abstract: The present invention provides in vivo methods for detection of vulnerable plaque in a subject in need thereof. In the invention method the subject is administered a diagnostic amount of a biologically compatible detectable lipid-avid agent, the detectable lipid-avid agent is allowed to penetrate arterial walls and attach to any lipid accumulations of oxidized LDL-cholesterol in arterial walls in the wall of an artery; unbound detectable lipid-avid agent is allowed to clear from the body by natural processes, and the presence of the detectable lipid-avid agent attached to the lipid accumulation in the wall of the artery is detected. Detection of bound lipid-avid agent indicates the presence of a vulnerable plaque and predicts a heightened risk of lethal heart attack or thrombus. The detectable lipid-avid agent is selected for its ability to penetrate arterial walls and bind with oxidized LDL-cholesterol in the lipid accumulation in a vulnerable plaque.

Abstract: The invention provides systems containing a sterile container for aspiration, filtering, treating and reinjection into a subject of a bodily fluid in a sterile environment. The systems are particularly designed to facilitate transfection of cells within the sterile container by gene therapy molecules and reinjection of the transfected cells into the donor at controlled depth in precisely controlled volumes such as is useful for revascularization of ischemic cardiac tissue. For injection, a pressure actuator, preferably hand-held, applies force to liquids held within the sterile container in precisely controlled increments, thereby expressing liquids through a hollow needle or injection catheter in precisely controlled microvolumes. The invention systems include a hand-held injection device with audible cues that correspond to an operator-selected injection volume and/or audible cues that correspond to needle penetration depth selected by the operator.

Abstract: The invention tissue injection catheters are designed to facilitate injection of a therapeutic or diagnostic agent to an interior body cavity, especially the myocardium or epicardium of the heart with precisely controlled depth penetration. The invention injection catheters, which include mechanisms for precisely controlling the length of needle tip exposed for tissue penetration, are designed to be used in an assemblage with a sterile container and delivery actuator for reinjection of autologous cell-containing fluids, such as autologous bone marrow aspirate. In preferred embodiments, the assemblage is designed to be hand-held. When used in such an assemblage, the invention catheters are particularly useful as a gene delivery device to effect angiogenesis of ischemic areas of the heart.

Abstract: The present invention provides a flexible suction body and method of its use for temporarily immobilizing a local area of tissue during surgery or a diagnostic procedure. The invention device and method are particularly well suited for immobilizing a local area of heart tissue to thereby permit surgery, for example, minimally invasive or micro-surgery, on a coronary vessel without significant deterioration of the pumping function of the beating heart. The invention suction device, which is coupled to a vacuum source, has a ring- or horseshoe-shaped suction channel with a flexible, spreadable outer rim that flattens and spreads outwardly against the surface of the treatment site as air is withdrawn from the suction channel. This design distributes the pressure of the suction body against the treatment site while maximizing the suction field to minimize bruising and suction hemorrhage at the treatment site caused by the suction body.

Abstract: A flexible stabilizer arm assembly is provided that can be positioned in a desired three-dimensional attitude and then fixed in place to forceably hold an object against an undulating surface. In one embodiment, the invention assembly comprises a mounting base for attachment of the arm to a stationary fixture, a flexible arm of multiple articulated elongate links rotatably joined to adjacent links, a freely rotatable turret joint at the distal end of the arm that is adapted to attach an appendage in freely rotatable fashion to the distal end of the arm. Once positioned, a tightening mechanism is actuated to fix the attitude of the arm with respect to the mounting base. Optionally, the appendage is a two-tined foot adapted for holding a surgical instrument, such as a suction body, against a beating heart. The flexible arm, which ranges up to 12 inches in length, can withstand an undulating force exerted against the distal end of up to 20 pounds while remaining in the fixed position.

Abstract: The present invention provides in vivo methods for detection of vulnerable plaque in a subject in need thereof. In the invention method the subject is administered a diagnostic amount of a biologically compatible detectable lipid-avid agent, the detectable lipid-avid agent is allowed to penetrate arterial walls and attach to any lipid accumulations of oxidized LDL-cholesterol in arterial walls in the wall of an artery; unbound detectable lipid-avid agent is allowed to clear from the body by natural processes, and the presence of the detectable lipid-avid agent attached to the lipid accumulation in the wall of the artery is detected. Detection of bound lipid-avid agent indicates the presence of a vulnerable plaque and predicts a heightened risk of lethal heart attack or thrombus. The detectable lipid-avid agent is selected for its ability to penetrate arterial walls and bind with oxidized LDL-cholesterol in the lipid accumulation in a vulnerable plaque.

Abstract: The present invention provides stabilizing devices and methods of use for temporarily remotely immobilizing a local area of tissue, such as a local area of tissue on a beating heart, or other internal organ, to thereby permit minimally-invasive or robotic surgery thereon. The invention stabilizing device, which is coupled to a vacuum source, features an elastomeric suction body mounted on the steerable tip of a rod-like instrument, such as a steerable catheter. The flexible or steerable tip and elongate suction channel are sized for introduction into an interior body cavity via a small surgical opening. A steering mechanism mounted at the proximal end of the device is used to coil the elongate tip and suction channel into a ring- or horseshoe-shape within the body cavity.

Abstract: The present invention is a stent for insertion into an artery or other vessel. The stent is formed from a series of tubular shaped bands each formed with a first end which overlaps a second end. The overlap between the first and second ends is variable and allows each band to move between a contracted configuration and a fully expanded configuration which are within the elastic limits of the band. Each band includes a plurality of receivers and a first tab on a first edge of the band to secure each band at or near the fully expanded configuration and allow the stent to conform to the contours of the vessel. The bands are distributed along a substantially common axis to form a tube interconnected by a pair of elongated strips. In use, the stent is placed over a balloon catheter and compressed to adopt the contracted configuration. The stent may be maintained in the contracted configuration by a retainer.

Abstract: The present invention is a stent for insertion into an artery or other vessel. The stent is formed from a series of tubular shaped bands each formed with a first end which overlaps a second end. The overlap between the first and second ends is variable and allows each band to move between a contracted configuration and a fully expanded configuration which are within the elastic limits of the band. Each band includes a plurality of receivers and a first tab on a first edge of the band to secure each band at or near the fully expanded configuration and allow the stent to conform to the contours of the vessel. The bands are distributed along a substantially common axis to form a tube interconnected by a pair of elongated strips. In use, the stent is placed over a balloon catheter and compressed to adopt the contracted configuration. The stent is maintained in the contracted configuration by a retainer.

Abstract: The present invention provides a self-expanding stent for insertion into an artery or other internal vessel. The stent is formed from a series of radial bands each formed with overlapping first and second ends. The overlap between the first and second ends is variable, allowing each band to move between a contracted configuration and an expanded configuration. The first and second ends of each band are both formed to include a tab which is folded to hold the first and second end against the band. The bands are distributed along a common axis to form a cylinder and interconnected by a pair of elongated strips. In use, the stent is placed over a balloon catheter and compressed to adopt the contracted configuration. The balloon catheter and stent are then advanced through a placement catheter and to a target site where the balloon is partially inflated to free the stent for self-expansion. The balloon may then be more fully inflated to further expand any of the radial bands in the stent.