Scaffold-Free Microtissues with Gold Nanostructures for Cardiac Repair

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Solution Overview

Problem

Current treatments for heart failure, such as cell-based myocardial replacement therapy and scaffold-based approaches, face challenges like high cell loss, poor cell-cell coupling, and inadequate integration with the host myocardium, leading to inconsistent outcomes and potential complications.

Innovation Solution

Development of scaffold-free microtissues comprising gold nanostructures, specifically gold nanowires or nanorods, functionalized with cell adhesion motifs and vasculogenic peptides, to enhance electrical conductivity and integration with cardiac cells, allowing for minimally invasive injection into the infarcted myocardium.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If cell-based myocardial replacement therapy is used, then cell pool augmentation and endogenous regeneration are initiated, but high cell loss and poor cell-cell coupling occur

Engineering Contradiction:
Improvecell retentionVSAvoidcell loss rate
Core Design Contradiction:
ReliabilityVSProductivity

Solution Approach 1:

The patent uses composite microtissues combining cardiac cells with conductive nanomaterials (graphene oxide, carbon nanotubes, or gold nanowires) to create a hybrid structure that provides both biological functionality and electrical conductivity. This composite approach enables better cell-cell coupling while maintaining high cell retention, directly addressing the contradiction between reliability and productivity in cell-based therapy

Inventive Principle:
Principle #40Composite materials

2Strength

If scaffold-based approaches are used, then structural integrity is maintained, but electrical conductivity and electromechanical integration are inadequate

Engineering Contradiction:
Improvestructural integrityVSAvoidelectromechanical integration
Core Design Contradiction:
StrengthVSReliability

Solution Approach 1:

The patent fundamentally changes the electrical conductivity parameter of scaffolds by incorporating nanomaterials with high electrical conductivity (graphene oxide, carbon nanotubes, gold nanowires). This transforms the scaffold from an electrically insulating structure to one that supports electromechanical coupling, enabling synchronous contraction while maintaining structural integrity

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent creates composite scaffold materials by combining traditional scaffold components with conductive nanomaterials. This composite structure simultaneously provides mechanical support and electrical conductivity, resolving the contradiction between structural integrity and electromechanical integration

Inventive Principle:
Principle #40Composite materials

3Ease of manufacture

If conventional hydrogel scaffolds are used, then cell embedding is achieved, but electrical properties do not match native myocardium

Engineering Contradiction:
Improvecell embedding capabilityVSAvoidelectrical conductivity
Core Design Contradiction:
Ease of manufactureVSReliability

Solution Approach 1:

The patent transforms conventional hydrogel scaffolds into composite materials by integrating conductive nanomaterials (graphene oxide, carbon nanotubes, or gold nanowires) throughout the hydrogel matrix. This creates a composite structure that maintains the ease of cell embedding provided by hydrogels while adding the electrical conductivity needed to match native myocardium

Inventive Principle:
Principle #40Composite materials

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 scaffold-free, electrically conductive cardiac microtissues with gold nanostructures improves cell-cell coupling, electromechanical integration, and neovascularization, promoting effective regeneration and repair of infarcted myocardium with enhanced cell retention and functional integration.

Implementation Method 1

The use of scaffold-free, electrically conductive cardiac microtissues with gold nanostructures improves cell-cell coupling, electromechanical integration

Methodology Applied
Scientific EffectElectrical conduction: Conduction (electrical)

Implementation Method 2

gold nanostructures, specifically gold nanowires or nanorods, functionalized with cell adhesion motifs and vasculogenic peptides

Methodology Applied
Scientific EffectCell adhesion: Adhesive

Implementation Method 3

improves cell-cell coupling, electromechanical integration, and neovascularization, promoting effective regeneration and repair of infarcted myocardium

Methodology Applied
Scientific EffectNeovascularization:

Data Source

PatentUS11364321B2Nano scale decoration of scaffold-free microtissue using functionalised gold nanostructures
Publication Date: 2022.06.21 THE ARIZONA BOARD OF REGENTS ON BEHALF OF THE UNIV OF ARIZONA
  • US11364321B2 patent drawing
  • US11364321B2 patent drawing
  • US11364321B2 patent drawing

AI summary

A scaffold-free microtissue is disclosed that includes one or more gold nanostructures linked to a functional moiety, wherein the functional moiety is one or more vasculogenic peptides, one or more anti-inflammatory peptides, one or more antiapoptotic peptides, one or more antinecrotic peptides, one or more antioxidant peptides, one or more oligonucleotides, one or more lipid particles, one or more phospholipid particles, one or more liposomes, one or more nanoliposomes, one or more microRNAs, or one or more siRNAs. The scaffold-free microtissue further includes a plurality of cardiac myocytes or cardiac myoblasts, which are conjugated to the one or more gold nanostructures, wherein the plurality of cardiac myocytes or cardiac myoblasts are arranged in a cluster. The scaffold-free microtissue further includes a plurality of fibroblasts, wherein the fibroblasts are arranged in at least one layer of fibroblasts that substantially surrounds the cluster of gold-nanostructure-conjugated cardiac myocytes or gold-nanostructure-conjugated cardiac myoblasts.