Medivas, LLC

Myocardial Therapeutics, Inc.

Other

Kenneth W Carpenter

Kazuo Sasamine

Michelle Fourmont

Masao Takahashi

Hong Li

William G Turnell

E Thomas Malphus

Elazer E Edelman

Kristin M DeFife

Kathryn A Grako

David Aaron Schwartz

Paul S Teirstein

Ramaz Katsarava

Istvan Szinai

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.

Bioactive stents for type II diabetics and methods for use thereof

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.

Bioactive wound dressings and implantable devices and methods of use

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.

Flexible tissue injection catheters with controlled depth penetration

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.

Sterile aspiration/reinjection systems

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. To stabilize the arm under these conditions, the arm preferably comprises multiple articulated elongate links and a joining piece that substantially increases the friction fit of the arm to the mounting base so as to withstand a counter-force of up to 150 pounds.

Flexible stabilizer arm for forcibly holding an object against a surface

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. Alternatively, macrophage-avid agents, for example a lipid-avid agent attached to a macrophage-specific antibody, can be used in the invention methods. The invention further includes methods for in vitro assays for detecting vulnerable plaque and a porcine animal model of vulnerable plaque useful for testing treatment modalities.

Animal model for detection of vulnerable plaques

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. In one embodiment, the suction body is sized for attachment to the tip of a hollow endoscopic catheter, with the hole in the center of the suction body being mounted around the periphery of the hollow catheter tip and allowing for passage from the catheter into the treatment site of a needle, or trocar for injecting materials such as drugs or genetic constructs into the treatment site or for piercing a treatment site, such as a solid tumor, to remove fluid or tissue therefrom for diagnosis. The suction body is preferably manufactured of a soft, compliant material, such as an elastomeric polymer, to conform to the surface of the heart and may be contoured in overall shape to further enhance its conformation to a contoured surface, such as the surface of the heart.

Device for stabilizing a treatment site and method of use

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. Preferably, the suction channel has a flexible, spreadable outer rim portion which is designed to flatten and spread outwardly against the surface of the treatment site as air is withdrawn from the coiled suction channel to distribute the pressure against the treatment site while maximizing the suction field. The suction body is manufactured of a soft, compliant material, such as an elastomeric polymer, to allow the suction channel to be transformed into the coiled conformation without deformation sufficient to defeat its purpose of use, i.e., clinging to the surface of a treatment site under partial vacuum.

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La Jolla, CA, United States of America

Kenneth W Carpenter