Multi-Layered Drug-Eluting Stent Coating for Restenosis Prevention
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current drug-eluting stents face challenges with high rates of restenosis, particularly in diabetic patients and those with severe atherosclerosis, due to late thrombosis and inadequate endothelialization, despite the use of anti-thrombotic and anti-restenotic agents.
Innovation Solution
A multi-layered coating system comprising an anti-proliferative agent, an anti-inflammatory agent, and an anti-growth factor, along with a non-thrombogenic extracellular matrix molecule on a stent, for immediate and sustained release, promoting endothelial cell growth and reducing neovascularization.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If stents are coated with anti-thrombotic and anti-restenotic agents, then thrombosis and restenosis are reduced in the short term, but long-term restenosis prevention is inadequate due to late thrombosis and inadequate endothelialization
Solution Approach 1:
The coating system is divided into multiple functional layers: an inner layer containing anti-proliferative agents (paclitaxel, sirolimus) for sustained release over months to prevent restenosis, and an outer layer containing anti-thrombotic agents (heparin, phosphorylcholine) for immediate thrombosis prevention. This segmentation allows each layer to optimize its specific function over the appropriate time frame, with the inner layer providing long-term restenosis prevention and the outer layer providing immediate short-term thrombosis protection.
Solution Approach 2:
The stent coating is designed to promote preliminary endothelialization through the inclusion of endothelial cell-adhesive peptides (RGD sequences) and extracellular matrix proteins in the coating formulation. This preliminary action prepares the stent surface to facilitate rapid endothelial cell attachment and proliferation immediately after implantation, addressing the inadequate endothelialization problem before late thrombosis can occur.
2Object-affected harmful factors
If stents are coated with chemical agents such as heparin or phosphorylcholine, then thrombosis and restenosis are decreased in the short term, but sufficient therapeutically effective quantities cannot be loaded for practical long-term treatment
Solution Approach 1:
The coating system separates anti-thrombotic agents (heparin, phosphorylcholine) in the outer layer for immediate short-term effect from anti-proliferative agents (paclitaxel, sirolimus) in the inner layer for sustained long-term effect. This allows adequate loading of both agent types without compromising either function, as each agent type is optimized for its specific time frame and dosage requirements.
Solution Approach 2:
The coating formulation uses composite materials combining multiple polymers and active agents: the inner layer comprises paclitaxel and/or sirolimus embedded in a biodegradable polymer matrix (PLA, PLGA, polyorthoester), while the outer layer contains heparin and/or phosphorylcholine in a hydrophilic polymer matrix. This composite structure enables simultaneous delivery of multiple agents at therapeutically effective concentrations for their respective indications.
3Reliability
If multiple drug-eluting coatings are applied to the stent, then restenosis rates are reduced through enhanced endothelialization and suppressed neovascularization, but the device complexity increases
Solution Approach 1:
The patent combines multiple therapeutic functions into a single integrated multi-layer coating system applied to the stent surface. The inner layer delivers anti-proliferative agents for restenosis prevention, while the outer layer delivers anti-thrombotic agents for thrombosis prevention, and both layers incorporate endothelialization-promoting components. This merging of functions into one coating system simplifies the overall device structure compared to applying separate coatings or using multiple devices.
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 multi-layered coating system significantly reduces restenosis rates by enhancing endothelialization and suppressing neovascularization, providing improved long-term vascular patency and reduced thrombosis.
Implementation Method 1
The at least one additional bioactive material is an antibody or antibody fragment directed to platelet-derived growth factor (PDGF), PDGF receptor (PDGFR), basic fibroblast growth factor (bFGF), or FGF receptor (FGFR)
Implementation Method 2
The at least one layer of bioactive material comprises at least one non-thrombogenic extracellular matrix (ECM) molecule
Implementation Method 3
The at least one porous layer is composed of a biocompatible polymer and is of a thickness adequate to provide a controlled release of the bioactive materials
Implementation Method 4
The at least one porous layer is composed of a biocompatible polymer and is of a thickness adequate to provide a controlled release of the bioactive materials
Data Source
AI summary
The present invention relates to a combination of agents, including an anti-proliferative agent, an anti-inflammatory agent, an anti-growth factor, and an extracellular matrix (ECM) molecule coated on a stent to prevent acute and subacute thrombosis, enhance endothelial in-growth, and prevent neointimal hyperplasia, and/or suppress neovascularization, and thereby reduce restenosis rates for drug eluting stents. The present invention also relates to methods of using such multiple drug eluting stents for the treatment of heart disease and other vascular conditions.