Hypoxic ECM Compositions for Tissue Repair

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Solution Overview

Problem

Current materials for soft tissue repair and augmentation, such as collagen and ceramic particles, face challenges including immunogenic reactions, high production costs, and limited longevity, while treatments for coronary heart disease and osteochondral defects have limited success and require invasive surgical techniques.

Innovation Solution

ECM compositions are produced by culturing fibroblast cells under hypoxic conditions to generate pluripotent stem cells that secrete embryonic proteins, including Wnt factors and VEGF, which are used to create a bioabsorbable, long-lasting material for soft tissue repair and augmentation, and to promote vascularization and tissue regeneration.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If collagen compositions are used for soft tissue augmentation, then tissue repair is achieved, but immunogenic reactions and allergic responses occur

Engineering Contradiction:

Improvetissue repair effectivenessVSAvoidimmunogenic reactions

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent uses human fibroblast cells to produce and secrete human ECM proteins (collagen, elastin, fibronectin, laminin) that are identical to natural human tissue components. This copying approach ensures immunological compatibility by using the patient's own biochemical signature, eliminating rejection and allergic reactions while maintaining effective tissue repair.

Inventive Principle:

Principle #26Copying

2Reliability

If xenogeneic collagen materials are used for soft tissue repair, then tissue augmentation is achieved, but production cost increases due to complex processing requirements

Engineering Contradiction:

Improvesoft tissue repairVSAvoidproduction cost

Core Design Contradiction:

ReliabilityVSEase of manufacture

Solution Approach 1:

Human fibroblast cells are cultured to autonomously produce and secrete the ECM protein composition. The cells perform the manufacturing function themselves by synthesizing collagen, elastin, fibronectin, and laminin through their natural secretory mechanisms, eliminating the need for complex external processing, purification, and quality control steps required for xenogeneic materials.

Inventive Principle:

Principle #25Self-service

3Productivity

If conventional oxygen levels are used during cell culture, then cell growth is maintained, but embryonic protein secretion is reduced

Engineering Contradiction:

Improveembryonic protein secretionVSAvoidcell growth stability

Core Design Contradiction:

ProductivityVSReliability

Solution Approach 1:

The patent reduces the oxygen concentration during cell culture from conventional levels (20-21%) to hypoxic conditions (1-5%). This parameter change mimics the early embryonic environment and specifically triggers increased secretion of embryonic proteins including Wnt factors and VEGF by human fibroblast cells, while the cells remain viable and continue to grow.

Inventive Principle:

Principle #35Parameter changes

4Reliability

If invasive surgical techniques are used for coronary heart disease treatment, then blood flow improvement is achieved, but patient risk and recovery time increase

Engineering Contradiction:

Improveblood flow improvementVSAvoidsurgical risk

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent uses human fibroblast cells as intermediaries that secrete VEGF and other angiogenic factors into the target tissue. These biochemical mediators naturally stimulate blood vessel formation and improve blood flow without requiring direct surgical intervention, bypasses, or mechanical procedures, thereby eliminating surgical risks while achieving therapeutic blood flow improvement.

Inventive Principle:

Principle #24Intermediary (Mediator)

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 ECM compositions provide a safe, effective, and long-lasting solution for soft tissue repair, enhance hair growth, and improve blood flow in diseased hearts, offering a non-invasive alternative to current treatments by mimicking the early embryonic environment to stimulate tissue regeneration.

Implementation Method 1

culturing fibroblast cells under hypoxic conditions to generate pluripotent stem cells that secrete embryonic proteins, including Wnt factors and VEGF

Methodology Applied

Scientific EffectHypoxia-induced differentiation:

Implementation Method 2

stem cells produce and secrete into the medium and on the cell culture or surfaces, a soluble and non-soluble fraction

Methodology Applied

Scientific EffectParacrine signaling:

Data Source

PatentEP2451964B1Conditioned medium and extracellular matrix compositions from cells cultured under hypoxic conditions

Publication Date: 2018.01.24 HISTOGEN INC

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AI summary

Disclosed is a method of producing compositions including embryonic proteins The method includes culturing cells under hypoxic conditions on a biocompatible support in vitro The culturing method produces both soluble and non-soluble fractions, which may be used separately or in combination to obtain physiologically acceptable compositions useful in a variety of applications.