Medical implants and methods for regulating the tissue response to vascular closure devices

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.

Description

BACKGROUND The present invention relates generally to therapeutic implants, devices, and methods useful for preventing, suppressing, or treating failure of hemodialysis vascular access grafts and other vascular procedures. The invention also relates to therapeutic implants comprising a matrix material and a therapeutic agent, wherein the composition placed in external contact with a blood vessel (perivascular implant of the composition) can be used to achieve hemostasis, e.g., to seal a breach in the vascular wall and to deliver a therapeutic agent capable of regulating the amount of tissue response to the implanted matrix. Vascular procedures such as construction of hemodialysis access grafts and angioplasty are performed to provide vascular access in patients with renal failure in need of hemodialysis dysfunction and treat conditions such as atherosclerosis. Hemodialysis vascular access grafts can be constructed as an arterio-venous fistula (e.g., Brecisa-Cimino), or as a graft ...

AI Technical Summary

Benefits of technology

Although the perivascular placement of the matrix (e.g., collagen matrix) is effective in sealing the point of vascular wall breach thereby achieving hemostasis, the biodegradable collagen matrix can provoke tissue response(s) that can potentially envelop the blood vessel at the site of placement of the matrix. Such tissue response(s) may increase the morbidity of the vascular closure device, may render palpation of the arterial pulse (a helpful clinical pre-requisite for obtaining future vascular access) more difficult and make future percutaneous access at or through the placement of such matrices more difficult. By combining a therapeutic agent or agents to the collagen matrix, it is an object of the present invention to provide a method and a composition for reducing the host response to the perivascular collagen matrix vascular sealant applied to the wall of an arterial or venous puncture site.

One embodiment of the invention comprises a device composed of a resorbable, biocompatible matrix combined with at least one therapeutic agent. The device may optionally further comprise pharmaceutically acceptable adjuvants or additives. The device may be placed on the outer surface of a vessel to elute a tissue response regulating amount of a therapeutic agent, such as an agent that inhibits smooth muscle cell proliferation. The biocompatible matrix creates a reservoir of the therapeutic agent and controls the delivery kinetics.

Yet another aspect of the present invention comprises a method for reducing, eliminating or prophylactically treating the host response to the perivascularly applied collagen matrix (sealant) or hemostatic device. The hemostatic device may be biological, polymer based or mechanical. When placed at a site of vascular puncture or incision, the matrix, besides functioning as a sealant at the site of the vascular pucture site, incision site or site of vascular breach, allows for gradual elution of the therapeutic agent and serves as an extravascular source of drug delivery. Elution of the therapeutic agent such as rapamycin into and through the vascular wall occurs during the healing of anastamotic sites to prevent, suppress, or treat smooth muscle cell proliferation or other tissue responses to the vascular procedure.

Problems solved by technology

Such tissue response(s) may increase the morbidity of the vascular closure device, may render palpation of the arterial pulse (a helpful clinical pre-requisite for obtaining future vascular access) more difficult and make future percutaneous access at or through the placement of such matrices more difficult.

Images