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

Inhibitory Effect of Different Antiproliferative Agents

Prefabricated collagen matrices were placed in different antiproliferative drug solutions until complete saturation occurred. The antiproliferative drugs were chosen to represent the more active compounds capable of smooth muscle cell and fibroblast inhibition without inhibiting collagenase and elastase, which enzymatically inhibit collagen accumulation—one cause of restenosis. The collagen matrices were saturated with these compounds at a concentration of 25 μg/ml lyophilized, washed with 0.066 M phosphate buffer of pH 7.4 at 37° C. for 24 hours and cut in the shape of a disc with density of compound of about 5 μg/cm2. After washing, sterile discs 15 mm in diameter were placed in a 24-well culture plate, and cells were seeded at a density of 5,000/cm2. Five days later, cell number was counted and enzymatic activity evaluated in the aliquots of media by chromogenic substrate hydrolysis and spec

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-requ

Images