Heart Slice Culture System with Electrical Stimulation

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Solution Overview

Problem

Current culture systems for human heart tissue are limited by the inability to maintain functional and structurally viable heart slices for more than 24 hours, which hinders the validation of heart failure therapies and cardiotoxicity testing.

Innovation Solution

A medium-throughput culture system for heart slices that utilizes electrical stimulation and an optimized culture medium containing fetal bovine serum, vascular endothelial cell growth factor, and fibroblast growth factor, which supports the metabolic demands of cardiac tissue and maintains electromechanical properties.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of manufacture

If standard simplified medium (M199/ITS) is used for culturing heart slices, then the culture system is simple and accessible, but the heart slices lose over 90% of their contractile ability within 24 hours

Engineering Contradiction:

Improveculture system simplicityVSAvoidheart slice contractile function duration

Core Design Contradiction:

Ease of manufactureVSDuration of action of moving object

Solution Approach 1:

The culture medium composition was fundamentally changed from standard M199/ITS to a specialized formulation containing high glucose (25mM), insulin (10μg/mL), transferrin (10μg/mL), selenium (5ng/mL), and antibiotics. This parameter change in medium composition enabled the heart slices to maintain contractile function for extended periods while preserving culture accessibility

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The culture medium was formulated as a composite solution combining multiple essential components: high glucose for energy, insulin for metabolism regulation, transferrin for iron transport, selenium for antioxidant defense, and antibiotics for contamination prevention. This composite medium provides comprehensive support for heart slice viability and function

Inventive Principle:

Principle #40Composite materials

2Reliability

If highly sophisticated bioengineered devices are used for electromechanical stimulation, then heart slice viability is maintained, but the device complexity increases and limits adoption by other laboratories

Engineering Contradiction:

Improveheart slice viabilityVSAvoidstimulation device complexity

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The patent employs disposable, inexpensive stimulation devices rather than complex, expensive bioengineered systems. These simple devices can be easily replaced and distributed to multiple laboratories, maintaining heart slice viability through electromechanical stimulation while ensuring broad accessibility and ease of adoption

Inventive Principle:

Principle #27Cheap short-living objects (Disposable)

Solution Approach 2:

The patent replaces complex bioengineered mechanical stimulation systems with simpler electrical stimulation devices. This substitution maintains the essential electromechanical function needed for heart slice viability while dramatically reducing device complexity and improving accessibility

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

3Productivity

If culture systems are designed for medium-throughput, then productivity increases for drug testing, but the complexity of maintaining optimal culture conditions increases

Engineering Contradiction:

Improvedrug testing throughputVSAvoidculture condition control complexity

Core Design Contradiction:

ProductivityVSDevice complexity

Solution Approach 1:

The culture system was designed with universal components and standardized protocols that can be applied across multiple culture wells simultaneously. The optimized medium formulation and simple stimulation protocol can be used across the entire culture plate, enabling medium-throughput experimentation without requiring separate complex control systems for each well

Inventive Principle:

Principle #6Universality (Multi-functionality)

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 culture system effectively maintains the viability and functionality of heart slices for up to 6 days, as evidenced by preserved calcium homeostasis, contractile force generation, and gene expression profiles, enabling reliable testing of therapeutic agents for cardiotoxicity and efficacy.

Implementation Method 1

the culture medium comprises fetal bovine serum (FBS), vascular endothelial cell growth factor (VEGF), and fibroblast growth factor (FGF)

Methodology Applied

Scientific EffectDiffusion: Diffusion

Implementation Method 2

applying electrical stimulation to the slice while the heart slice is in culture. In some embodiments, the electrical stimulation has a frequency of 0.5 to 2 HZ

Methodology Applied

Scientific EffectElectrical stimulation: Electric Field

Data Source

PatentUS20250136943A1Physiological biomimetic culture system for heart slices

Publication Date: 2025.05.01 UNIVERSITY OF LOUISVILLE RESEARCH FOUNDATION INC

AI summary

A method for culturing heart tissue by culturing a slice of the heart tissue in a culture medium, wherein the culture medium comprises fetal bovine serum (FBS), vascular endothelial cell growth factor (VEGF), and fibroblast growth factor (FGF); and applying electrical stimulation to the slice while the heart slice is in culture is provided. Methods of screening candidate therapeutic agents for therapeutic effect or cardiotoxicity using the culture system are also provided.