Aptamer Copolymer Implant Coating for Controlled Explantation

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Solution Overview

Problem

Current implantable devices face challenges in controlled degradation, particularly during explantation, due to sensitivity to pH, ionic strength, and temperature changes in the human body, and the limitations of using electromagnetic radiation or electric/magnetic fields for triggering degradation.

Innovation Solution

An implantable object with a copolymer layer containing an aptamer that degrades upon a binding event, allowing for targeted and controlled degradation, facilitated by systemically supplied compounds, enabling easier explantation without tissue damage.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Duration of action of stationary object

If constant degradation polymers are used under physiological conditions, then degradation rate can be controlled from a few days to several months, but the degradation behavior is inadequate for differentiated control particularly when implant removal is needed

Engineering Contradiction:
Improvedegradation time controlVSAvoiddifferentiated degradation control
Core Design Contradiction:
Duration of action of stationary objectVSAdaptability or versatility

Solution Approach 1:

The patent changes the degradation trigger from passive physiological parameters (pH, temperature, ionic strength) to an active, controllable parameter system using aptamer-ligand binding events. By incorporating aptamers that respond to specific triggers (glucose, theophylline, adenosine, etc.), the degradation timing and rate can be precisely controlled and differentiated based on physiological conditions or external administration, resolving the contradiction between duration control and adaptability.

Inventive Principle:
Principle #35Parameter changes

2Stability of the object's composition

If implant coatings are designed to be stable after ingrowth process completion, then implant stability is ensured, but explantation becomes considerably more difficult due to firm contact between tissue and implant surface

Engineering Contradiction:
Improveimplant stabilityVSAvoidexplantation ease
Core Design Contradiction:
Stability of the object's compositionVSEase of operation

Solution Approach 1:

The patent applies dynamics by creating a coating that transitions from a stable state during implant operation to a degradable state during explantation. The aptamer-containing copolymer coating remains stable and promotes tissue ingrowth during normal function, but can be dynamically triggered to degrade when explantation is needed, allowing the implant to change its interaction with tissue based on operational phase.

Inventive Principle:
Principle #15Dynamics

Solution Approach 2:

The patent prepares the implant coating in advance with aptamer sequences that will respond to specific triggers. Before explantation, the triggering compound can be administered systemically, and the coating is pre-configured to degrade upon binding event, weakening the tissue-implant connection before removal begins, thus facilitating easier explantation.

Inventive Principle:
Principle #10Preliminary action

3Adaptability or versatility

If polymers are used that change degradation behavior through targeted external influence (pH, ionic strength, temperature), then degradation can be controlled, but these influences are very difficult to carry out in vivo since the human organism reacts sensitively to changes

Engineering Contradiction:
Improvedegradation controlVSAvoidphysiological sensitivity to parameter changes
Core Design Contradiction:
Adaptability or versatilityVSObject-affected harmful factors

Solution Approach 1:

The patent uses aptamers as intermediaries between the implant coating and the triggering compounds. Instead of directly exposing the coating to harsh physiological changes (pH, temperature, ionic strength), the aptamer selectively binds to specific trigger molecules (glucose, theophylline, adenosine) under mild physiological conditions, initiating degradation through a benign binding event rather than extreme parameter changes.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent replaces the mechanical/physical degradation control system (pH, temperature, ionic strength changes) with a biochemical recognition system based on aptamer-ligand binding. This substitution allows degradation control to occur under mild physiological conditions through specific molecular recognition rather than extreme environmental changes, eliminating the harmful effects on the organism.

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

4Adaptability or versatility

If electromagnetic radiation or electric/magnetic fields are used to trigger degradation, then degradation can be triggered, but these methods require considerable equipment and make quick automatic reaction difficult

Engineering Contradiction:
Improvedegradation triggeringVSAvoidequipment requirement
Core Design Contradiction:
Adaptability or versatilityVSDevice complexity

Solution Approach 1:

The patent enables the implant system to trigger its own degradation through biochemical self-recognition. The aptamer sequences in the coating automatically recognize and bind to their specific trigger compounds when administered, initiating degradation without requiring external equipment or complex control systems. The system serves itself through the inherent specificity of the aptamer-ligand interaction.

Inventive Principle:
Principle #25Self-service

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 aptamer-containing copolymer layer allows for precise control over degradation, simplifying the removal of implants by weakening the connection between the implant and tissue, reducing tissue damage during explantation.

Implementation Method 1

aptamers, which show the property of binding to organic molecules with a change in conformation

Methodology Applied
Scientific EffectAptamer binding event:

Implementation Method 2

most of these polymers are subject to general hydrolysis under physiological conditions and thus are degraded after contact with water over a long period of time

Methodology Applied
Scientific EffectHydrolysis: Hydrolysis

Implementation Method 3

show a constant rate of degradation under the influence of enzymes (e.g. esterases, lipases, dehydrogenases or oxygenases)

Methodology Applied
Scientific EffectEnzymatic degradation: Enzyme

Data Source

PatentEP2777723B1Implantable object comprising selectively degradable copolymers for improved explantability
Publication Date: 2017.12.20 BIOTRONIK AG
  • EP2777723B1 patent drawingFigure 1
  • EP2777723B1 patent drawingFigure 2
  • EP2777723B1 patent drawing

AI summary

Implantable object comprising a layer comprising a copolymer containing an aptamer, wherein, depending on a binding event to the aptamer, bonds in the copolymer can be broken, resulting in degradation of the copolymer.