Bioartificial Heart via Decellularized Scaffold Recellularization

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Solution Overview

Problem

Current treatments for cardiovascular disease, particularly end-stage heart failure, are limited by the scarcity of donor organs, high costs, and the need for immunological matching in heart transplants, with existing pharmacological therapies ineffective for 50% of patients, and mechanical assist devices facing biocompatibility and integration issues.

Innovation Solution

Development of a bioartificial heart (BAH) fabricated using decellularized heart scaffolds recellularized with neonatal cardiac myocytes and fibrin gel, which are cultured in a perfusion system to mimic in vivo conditions, allowing for the creation of functional artificial heart muscle patches that can be implanted to replace damaged cardiac tissue.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If heart transplantation is performed, then effective treatment for end-stage heart failure is achieved, but donor organ shortage and immunological matching requirements limit availability

Engineering Contradiction:
Improvetreatment effectivenessVSAvoidorgan availability
Core Design Contradiction:
ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent creates a bioartificial heart by copying the structural and functional characteristics of a native heart using a decellularized extracellular matrix scaffold that is then recellularized with patient-specific cells, producing a functional heart organ without requiring a donor organ

Inventive Principle:
Principle #26Copying

Solution Approach 2:

The patent transforms the heart tissue by changing its cellular composition through decellularization and recellularization processes, while maintaining the structural integrity and functional parameters of the native heart tissue

Inventive Principle:
Principle #35Parameter changes

2Reliability

If mechanical assist devices are used, then heart failure is managed, but biocompatibility and integration issues arise

Engineering Contradiction:
Improveheart failure managementVSAvoidbiocompatibility issues
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent creates a composite tissue construct combining the structural framework of decellularized extracellular matrix with living patient-specific cells, producing a bioartificial heart that exhibits both mechanical support and biological functionality

Inventive Principle:
Principle #40Composite materials

Solution Approach 2:

The bioartificial heart uses the patient's own cells to populate and maintain the scaffold structure, enabling the construct to self-assemble and self-maintain without requiring external mechanical assistance or immunosuppression

Inventive Principle:
Principle #25Self-service

3Object-affected harmful factors

If decellularized scaffold is recellularized with patient-specific cells, then immunological rejection is avoided, but fabrication complexity increases

Engineering Contradiction:
Improveimmunological rejectionVSAvoidfabrication process
Core Design Contradiction:
Object-affected harmful factorsVSDevice complexity

Solution Approach 1:

The patent extracts all cellular material from the native heart tissue through decellularization, leaving only the acellular extracellular matrix scaffold that can be subsequently repopulated with patient-specific cells

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent performs decellularization as a preliminary step before recellularization, preparing the scaffold in advance to receive patient-specific cells and ensuring immunological compatibility before the actual tissue construction begins

Inventive Principle:
Principle #10Preliminary action

4Reliability

If perfusion culture system is used, then in vivo conditions are mimicked, but system complexity and cost increase

Engineering Contradiction:
Improvefunctional developmentVSAvoidculture system
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent employs a perfusion culture system that uses fluid flow to deliver nutrients and remove waste products from the bioartificial heart construct, mimicking the physiological blood flow conditions that would exist in vivo

Inventive Principle:
Principle #29Pneumatics and hydraulics

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 bioartificial heart demonstrates partial or complete replication of mammalian heart functions, showing structural and functional similarity to native heart tissue, with improved contractility and vascularization, offering a promising alternative to traditional heart transplants and pharmacological interventions.

Implementation Method 1

obtained by decellularization of a heart

Methodology Applied
Scientific EffectDecellularization:

Implementation Method 2

the scaffold is formed from fibrin gel

Methodology Applied
Scientific EffectGel formation: Gel

Implementation Method 3

the fibrin gel is mixed with saline and culture media containing thrombin

Methodology Applied
Scientific EffectCoagulation: Coagulation

Implementation Method 4

culturing the scaffold transplanted with the cells in a perfusion culture apparatus

Methodology Applied
Scientific EffectPerfusion:

Implementation Method 5

showing structural and functional similarity to native heart tissue, with improved contractility

Methodology Applied
Scientific EffectMuscle contraction:

Data Source

PatentUS10792145B2Two stage cellularization strategy for the fabrication of bioartificial hearts
Publication Date: 2020.10.06 UNIV HOUSTON SYST
  • US10792145B2 patent drawing
  • US10792145B2 patent drawing
  • US10792145B2 patent drawing

AI summary

In some embodiments, the present disclosure pertains to a method of fabricating an artificial heart muscle (AHM) patch. In some embodiments, the method includes obtaining and/or isolating cells from a subject. In some embodiments, the cells are primary cardiac cells. In some embodiments, the method further includes forming a scaffold. In some embodiments, the method includes seeding the cells in the fibrin gel scaffold. In some embodiments, the method includes culturing the cells seeded in the fibrin gel scaffold under conditions appropriate for the formation of an artificial heart muscle (AHM) patch.