ATRA-Eluting Vascular Implants for Neointimal Hyperplasia
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current prosthetic vascular grafts face challenges with thrombosis and neointimal hyperplasia, leading to poor patency rates and systemic side effects from surface modification strategies like heparin, necessitating an improved method to inhibit these issues without toxic effects.
Innovation Solution
Controlled release vascular implants using a biocompatible polymer matrix with all-trans retinoic acid (ATRA) or its derivatives to inhibit neointimal hyperplasia and thrombosis, providing localized and predictable ATRA delivery to prevent smooth muscle cell proliferation and enhance antithrombotic gene expression.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If heparin is used to modify the surface of vascular grafts to reduce thrombus formation and neointimalhyperplasia, then thrombosis and neointimalhyperplasia are reduced, but antiplatelet antibodies and heparin-induced thrombocytopenia occur
Solution Approach 1:
The patent applies local quality by delivering ATRA specifically at the graft site through localized release mechanisms (such as coating the graft surface or incorporating it into the graft material), rather than systemic administration. This localized delivery provides antithrombotic and antiproliferative effects at the graft site while avoiding systemic exposure and its associated toxicities like antiplatelet antibody formation and thrombocytopenia.
Solution Approach 2:
The patent uses an intermediary approach by employing a delivery system (such as a polymer coating or graft material matrix) that facilitates controlled release of ATRA from the graft surface into the local environment. This intermediary delivery mechanism ensures therapeutic concentrations of ATRA are provided locally while preventing systemic absorption and associated harmful effects.
2Adaptability or versatility
If ePTFE grafts are used for bypass grafting, then graft availability is improved, but thrombosis and neointimalhyperplasia increase
Solution Approach 1:
The patent applies preliminary action by pre-modifying the ePTFE graft surface with ATRA or ATRA-containing materials before implantation. This preliminary surface modification creates an antithrombotic and antiproliferative environment that actively prevents thrombus formation and neointimalhyperplasia from the outset, thereby improving graft patency while maintaining the availability and versatility of ePTFE grafts.
Solution Approach 2:
The patent uses composite materials by combining ePTFE graft material with ATRA or ATRA-containing polymers to create a composite graft structure. This composite approach maintains the mechanical properties and availability of ePTFE while adding the biological activity of ATRA to prevent thrombosis and neointimalhyperplasia, thus improving overall graft reliability.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The use of ATRA in biocompatible polymer matrices effectively reduces neointimal hyperplasia and thrombosis, improving graft patency and safety by localizing therapeutic effects and minimizing systemic toxicity.
Implementation Method 1
the vascular implant releases a therapeutically effective amount of ATRA sufficient to inhibit or prevent neointimal hyperplasia
Data Source
AI summary
Controlled release vascular implants, such as vascular grafts, stents, wraps, and gels comprising a biocompatible polymer and all trans retinoic acid (ATRA), or its derivatives, can be used to treat, prevent, or inhibit thrombosis and/or neointimal hyperplasia which may otherwise be induced by prosthetic implantation. In particular, the implants herein can inhibit smooth muscle cell proliferation, neointimal hyperplasia, and upregulate antithrombotic genes and nitric oxide production in the vasculature. Further, the implants are capable of delivering controlled and predictable localized concentrations of ATRA.