3D Fibroblast Construct for Cardiac Cell Engraftment

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Solution Overview

Problem

Current treatments for chronic heart failure and related cardiac disorders, such as ischemic and non-ischemic cardiac conditions, have shown disappointing results with stem cell injections due to poor cell survival and integration in the hostile myocardial environment lacking adequate blood supply and matrix support.

Innovation Solution

Development of three-dimensional fibroblast constructs (3DFC) seeded with muscle cells, including cardiomyocytes or cardiac stem cells, which are adhered to the construct using centrifugal force and cultured to enhance cell adhesion and synchronization, providing a pro-angiogenic matrix for improved cell survival and integration.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If stem cells are injected directly into the heart, then cell delivery is achieved, but cell survival and integration are poor due to hostile myocardial environment

Engineering Contradiction:

Improvecell survivalVSAvoidhostile myocardial environment

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

A three-dimensional fibroblast construct serves as an intermediary between the injected stem cells and the hostile myocardial environment. The construct provides a supportive matrix with pro-angiogenic factors that protect transplanted cells from the harsh cardiac environment, improving cell survival and integration while mediating the interaction between cells and host tissue.

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The fibroblast construct is prepared in advance with pro-angiogenic factors and extracellular matrix components before cell transplantation. This preliminary preparation creates a pre-conditioned, cell-friendly environment that immediately supports transplanted cells upon injection, rather than exposing them directly to the hostile myocardial environment.

Inventive Principle:

Principle #10Preliminary action

2Manufacturing precision

If cell density is increased to improve tissue formation, then functional integration improves, but cell aggregation and poor distribution occur

Engineering Contradiction:

Improvecell distributionVSAvoidcell density

Core Design Contradiction:

Manufacturing precisionVSQuantity of substance

Solution Approach 1:

The three-dimensional fibroblast construct provides a spatially distributed matrix with varying local properties that guide cell distribution. The construct's architecture creates specific microenvironments at different locations, allowing cells to disperse uniformly throughout the tissue rather than aggregating, while maintaining appropriate local cell densities for functional integration.

Inventive Principle:

Principle #3Local quality

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 3DFC constructs promote cell engraftment and functional integration into the myocardium, improving cardiac function by enhancing blood vessel formation and providing a supportive matrix for cardiomyocytes, leading to improved ejection fraction, cardiac output, and reduced end-diastolic pressure.

Implementation Method 1

subjecting the cells within the suspension to a force that causes said cells to contact the 3DFC

Methodology Applied

Scientific EffectCentrifugal force: Centrifugal Force

Data Source

PatentUS11345894B2Cellular seeding and co-culture of a three dimensional fibroblast construct

Publication Date: 2022.05.31 THE ARIZONA BOARD OF REGENTS ON BEHALF OF THE UNIV OF ARIZONA

AI summary

The present invention provides methods for cellular seeding onto three-dimensional fibroblast constructs, three-dimensional fibroblast constructs seeded with muscle cells, and uses therefore.