Decellularized Lung Scaffold for 3D Tissue Engineering

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Solution Overview

Problem

Current methods for engineering lung tissue face challenges in replicating the complex structure and function of natural lungs, particularly in supporting endothelial, epithelial, and mesenchymal cell growth, and gas exchange, with limited progress in pulmonary progenitor and stem cell biology, and a lack of effective in vitro 3-dimensional lung culture models.

Innovation Solution

Development of a decellularized lung tissue scaffold that retains extracellular matrix components and immunogenic markers are removed, allowing for the growth of lung cells, including stem cells, and supporting differentiation, with a bioreactor system for ventilation and perfusion to mimic physiological conditions.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If decellularized tissue scaffold is used, then cell growth support and morphology retention are improved, but immunogenicity is reduced

Engineering Contradiction:
Improvecell growth supportVSAvoidimmunogenicity
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent applies extraction by removing cellular material and immunogenic components from the tissue while retaining the extracellular matrix scaffold. This process extracts the harmful immunogenic elements (cells, DNA, proteins) while preserving the beneficial structural framework that supports cell growth and maintains tissue morphology.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent applies local quality by differentiating between components that should be removed (immunogenic cellular material) and those that should be retained (extracellular matrix, structural framework). The decellularization process selectively removes specific components while preserving others, creating a scaffold with localized properties optimized for both immunocompatibility and cell support.

Inventive Principle:
Principle #3Local quality

2Reliability

If complex 3-dimensional lung structure is replicated, then gas exchange function is improved, but manufacturing complexity increases

Engineering Contradiction:
Improvegas exchange functionVSAvoidstructural complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent applies copying by using the native lung's own extracellular matrix as a template or mold. Instead of attempting to build a complex 3-dimensional structure from scratch, the method copies the existing natural architecture by preserving the decellularized lung scaffold, which already contains the intricate alveolar structures necessary for gas exchange.

Inventive Principle:
Principle #26Copying

Solution Approach 2:

The patent applies parameter changes by transforming the lung tissue from a cellular state to a decellularized scaffold state, then subsequently recellularizing it. This parameter transformation changes the physical and chemical properties of the tissue, converting it into a form that is both structurally intact and biologically active for supporting new cell growth.

Inventive Principle:
Principle #35Parameter changes

3Duration of action of stationary object

If immunosuppression is used to prevent rejection, then transplant survival is improved, but patient health deteriorates due to side effects

Engineering Contradiction:
Improvetransplant survivalVSAvoidinfection and malignancy risk
Core Design Contradiction:
Duration of action of stationary objectVSObject-affected harmful factors

Solution Approach 1:

The patent applies the blessing in disguise principle by converting the normally harmful immunogenic cellular material into a benefit through its selective removal. By eliminating the cellular components that cause immune rejection while preserving the acellular extracellular matrix, the method transforms the source of immunogenicity into an immunocompatible scaffold that does not trigger rejection, eliminating the need for immunosuppression.

Inventive Principle:
Principle #22Blessing in disguise (Convert harm into benefit)

Data Source

PatentUS20230310511A1Tissue engineering of lung
Publication Date: 2023.10.05 YALE UNIVERSITY
  • US20230310511A1 patent drawing
  • US20230310511A1 patent drawing
  • US20230310511A1 patent drawing

AI summary

The present invention relates to compositions comprising a decellularized tissue. The present invention also provides an engineered three dimensional lung tissue exhibiting characteristics of a natural lung tissue. The engineered tissue is useful for the study of lung developmental biology and pathology as well as drug discovery.