Copper Delivery via Microbubbles for Myocardial Ischemia Repair

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Solution Overview

Problem

Chronic myocardial ischemia leads to decreased capillary density and depressed angiogenesis, impairing the body's ability to regenerate damaged heart tissue due to persistent hypoxia and copper deficiency, which suppresses HIF-1 transcriptional activity and subsequent gene expression necessary for tissue repair.

Innovation Solution

Direct delivery of copper to the site of injury, either through microbubbles or direct injection, to restore HIF-1 transcription activity, promote stem cell migration, differentiation, and tissue regeneration, and enhance angiogenesis.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If direct copper delivery is implemented, then tissue repair and regeneration are enhanced, but delivery system complexity increases

Engineering Contradiction:
Improvetissue repair efficacyVSAvoiddelivery system complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent employs microbubbles as intermediary carriers to deliver copper to the injury site. These microbubbles serve as a mediator between the copper source and the target tissue, enabling controlled release through ultrasound-triggered cavitation. This resolves the contradiction by providing a reliable copper delivery mechanism while maintaining relatively simple system components that can be administered systemically rather than requiring complex localized delivery infrastructure.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Productivity

If copper delivery promotes angiogenesis and stem cell migration, then tissue regeneration improves, but treatment cost increases

Engineering Contradiction:
Improvetissue regeneration rateVSAvoidtreatment cost
Core Design Contradiction:
ProductivityVSEase of manufacture

Solution Approach 1:

The patent leverages the body's own repair mechanisms by delivering copper to enhance endogenous angiogenesis and stem cell migration. Rather than requiring expensive external scaffolds or complex biomaterial constructs, the treatment activates the body's intrinsic regenerative capacity. This resolves the contradiction by achieving improved tissue regeneration through a cost-effective approach that utilizes natural physiological processes enhanced by copper delivery.

Inventive Principle:
Principle #25Self-service

3Reliability

If copper is delivered to restore HIF-1 transcription activity, then ischemic damage is reversed, but measurement and monitoring difficulty increases

Engineering Contradiction:
Improveischemic damage reversalVSAvoidHIF-1 activity monitoring
Core Design Contradiction:
ReliabilityVSDifficulty of detecting and measuring

Solution Approach 1:

The patent employs ultrasound imaging to monitor microbubble distribution and cavitation activity at the injury site. This provides real-time feedback on copper delivery effectiveness and tissue response. While direct HIF-1 measurement remains challenging, the ultrasound feedback system allows indirect monitoring of treatment efficacy through observation of microbubble behavior and subsequent tissue changes, resolving the contradiction by providing a practical monitoring approach for ischemic damage reversal.

Inventive Principle:
Principle #23Feedback

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 delivery of copper to the injury site effectively reverses myocardial ischemic damage by enhancing stem cell homing, differentiation, and angiogenesis, improving cardiac function and reducing infarct size.

Implementation Method 1

persistent hypoxia and copper deficiency, which suppresses HIF-1 transcriptional activity and subsequent gene expression necessary for tissue repair

Methodology Applied
Scientific EffectHIF-1 transcriptional activity:

Implementation Method 2

promote stem cell migration, differentiation, and tissue regeneration

Methodology Applied
Scientific EffectStem cell homing:

Implementation Method 3

After homing to the injury site, stem cells or progenitor cells will differentiate into 'target' cells

Methodology Applied
Scientific EffectCell differentiation:

Implementation Method 4

enhance angiogenesis

Methodology Applied
Scientific EffectAngiogenesis:

Implementation Method 5

inducing blood vessel growth towards the site of brain injury

Methodology Applied
Scientific EffectBlood vessel growth:

Data Source

PatentEP3285782B1Methods of tissue repair and regeneration
Publication Date: 2021.09.08 INNOLIFE CO LTD
  • EP3285782B1 patent drawingFigure 1A~1D
  • EP3285782B1 patent drawingFigure 2A~2C
  • EP3285782B1 patent drawingFigure 3A~3I

AI summary

The disclosure provides local delivery of a trace element to a site of tissue injury, which triggers the body' inherent tissue repair mechanism. Local delivery of copper to the site of injury induces migration (i.e., homing) of stem cells to the site of injury, triggers differentiation of stem cells at the site of injury, induces tissue regeneration at the site of injury, induces signaling molecules that trigger tissue regeneration, reverses damage at the site of injury, and/or reconstructs the microenvironment of neurofibril cells and neurosecretory cells at the site of injury. In another aspect, delivering a trace element (for example, copper) directly to the site of injury and associated methods are disclosed.