ECFC Vascularization via Collagen Matrix Stiffness Control

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Solution Overview

Problem

Current tissue engineering strategies face challenges in promoting the growth of new vasculature for treating diseases and injuries due to impaired vascular perfusion, particularly in developing functional vascular networks for clinical-scale tissue replacements, where existing methods lack control over the size, shape, and properties of developing tissues and fail to effectively guide vessel formation in vivo.

Innovation Solution

The use of endothelial colony forming cells (ECFCs) seeded into collagen matrices composed of acid-soluble Type I collagen fractions with varying molecular weights, specifically monomers and oligomers, to create a controlled microenvironment that supports vessel formation by modulating matrix stiffness, fibril density, and cross-link composition, thereby influencing endothelial cell behavior and vascular network development.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If ECFCs are transplanted to promote new vasculature growth, then vascularization is improved, but control over vessel formation and tissue properties is insufficient

Engineering Contradiction:

Improvevascularization efficacyVSAvoidcontrol over vessel formation

Core Design Contradiction:

ReliabilityVSEase of operation

Solution Approach 1:

The patent applies parameter changes by systematically varying collagen matrix properties including stiffness (through concentration and crosslinking), fibril density, and composition (Type I vs Type III collagen ratios) to optimize ECFC behavior and vessel formation control

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The collagen matrix serves as an intermediary between the transplanted ECFCs and the host tissue, providing a controlled microenvironment that guides vessel formation while mediating cell-matrix interactions through specific biochemical and biophysical cues

Inventive Principle:

Principle #24Intermediary (Mediator)

2Reliability

If tissue engineering strategies are used for clinical-scale replacements, then tissue regeneration is improved, but functional vascular network development is limited

Engineering Contradiction:

Improvetissue regeneration capabilityVSAvoidvascular network development efficiency

Core Design Contradiction:

ReliabilityVSProductivity

Solution Approach 1:

The patent applies preliminary action by pre-forming vascular networks within collagen matrices in vitro before implantation, allowing vessels to develop and mature in a controlled environment prior to in vivo deployment, thereby improving overall vascular network development efficiency

Inventive Principle:

Principle #10Preliminary action

Solution Approach 2:

The patent applies local quality by creating spatially heterogeneous collagen matrices with varying stiffness, composition, and fibril density in different regions to guide localized vessel formation and tissue differentiation, enabling functional vascular networks to develop in specific areas as needed

Inventive Principle:

Principle #3Local quality

3Ease of operation

If collagen matrix properties are modified to guide ECFC behavior, then vessel formation control is improved, but matrix design complexity increases

Engineering Contradiction:

Improvevessel formation controlVSAvoidmatrix design complexity

Core Design Contradiction:

Ease of operationVSDevice complexity

Solution Approach 1:

The patent applies segmentation by dividing the collagen matrix into distinct functional zones with different properties (e.g., varying collagen concentrations, crosslinking densities, or compositions) to independently control ECFC behavior in different regions without requiring complete redesign of the entire matrix

Inventive Principle:

Principle #1Segmentation

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

This approach enables the formation of functional vascular structures with increased vacuole density and area, supporting the development of long-lasting vessels and improving the efficacy of vascularized tissue constructs for therapeutic applications by regulating the biophysical properties of the collagen matrix.

Implementation Method 1

modulating matrix stiffness, fibril density, and cross-link composition, thereby influencing endothelial cell behavior and vascular network development

Methodology Applied

Scientific EffectMatrix stiffness modulation:

Implementation Method 2

collagen matrices composed of acid-soluble Type I collagen fractions with varying molecular weights, specifically monomers and oligomers

Methodology Applied

Scientific EffectCollagen polymerization:

Implementation Method 3

modulating matrix stiffness, fibril density, and cross-link composition

Methodology Applied

Scientific EffectCross-linking:

Data Source

PatentUS10828337B2Materials and methods for controlling vasculogenesis from endothelial colony forming cells

Publication Date: 2020.11.10 PURDUE RES FOUND

AI summary

Materials and methods are disclosed for controlling vasculogenesis using building blocks of a collagen matrix and endothelial colony forming cells (ECFC). The building blocks may be isolated by fractionating an acid soluble Type I collagen. The building blocks comprising monomers and/or oligomers may be recombined in desired ratios to alter the matrix microenvironment and to influence ECFC behavior.