Decellularized Urodele ECM Scaffolds for Xenotransplantation

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Solution Overview

Problem

Conventional biological and synthetic scaffolds for tissue regeneration face challenges such as donor site morbidity, disease transmission risk, intersample variation, cost, and limited availability, while mammalian-derived scaffolds are limited in effectiveness and availability for large-area applications.

Innovation Solution

Decellularized biomaterial derived from urodele (salamander) tissue, which includes extracellular matrix (ECM) components, is produced through a process that maintains structural and functional integrity while removing immunogenic cellular components, providing a suitable scaffold for xenotransplantation.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If mammalian-derived scaffolds are used for tissue regeneration, then structural support and cell adhesion are provided, but donor site morbidity, disease transmission risk, and limited availability occur

Engineering Contradiction:

Improvestructural support and cell adhesionVSAvoiddonor site morbidity, disease transmission risk

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The invention separates the beneficial ECM structural components from the harmful cellular components by using decellularization technology. This process segments the tissue into acellular ECM scaffold (retained) and cellular elements (removed), thereby maintaining structural support while eliminating donor site morbidity and disease transmission risks

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The invention extracts and removes immunogenic cellular components (nuclei, cytoplasm, organelles) from the tissue while retaining the ECM scaffold. This extraction process eliminates harmful factors such as donor-specific antigens and potential pathogens, while preserving the beneficial structural and biochemical framework for tissue regeneration

Inventive Principle:

Principle #2Taking out (Extraction)

2Reliability

If conventional biological scaffolds are used, then tissue regeneration is promoted, but intersample variation and high cost occur

Engineering Contradiction:

Improvetissue regeneration promotionVSAvoidintersample variation

Core Design Contradiction:

ReliabilityVSStability of the object's composition

Solution Approach 1:

The invention changes the source parameter from mammalian tissue to urodele tissue, which exhibits consistent scar-free healing properties across species. This parameter change results in reduced intersample variation while maintaining effective tissue regeneration promotion, as urodele ECM has standardized biochemical composition and structural characteristics

Inventive Principle:

Principle #35Parameter changes

3Reliability

If mammalian-derived scaffolds are used for large-area applications, then structural support is provided, but availability is limited

Engineering Contradiction:

Improvestructural supportVSAvoidavailability for large-area applications

Core Design Contradiction:

ReliabilityVSQuantity of substance

Solution Approach 1:

The invention makes the biomaterial universally applicable for large-area tissue regeneration by using urodele skin, which can be harvested in large continuous sheets. The decellularized urodele skin maintains its full-size structural integrity and can cover extensive wound areas, eliminating the limitation of scarce mammalian donor tissue while providing consistent structural support

Inventive Principle:

Principle #6Universality (Multi-functionality)

4Object-affected harmful factors

If decellularization process is applied to remove cellular components, then antigenicity is reduced, but structural integrity must be maintained

Engineering Contradiction:

Improveantigenicity reductionVSAvoidstructural and functional integrity

Core Design Contradiction:

Object-affected harmful factorsVSStrength

Solution Approach 1:

The invention converts the potential harm of aggressive decellularization (which could damage structure) into benefit by using optimized mild decellularization protocols. These protocols effectively remove immunogenic cellular components while simultaneously preserving or even enhancing ECM structural integrity and biochemical functionality, turning a risky process into a beneficial treatment

Inventive Principle:

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

Data Source

PatentUS20250256009A1Decellularized biomaterial from non-mammalian tissue

Publication Date: 2025.08.14 NEXTGEN BIOLOGICS INC

AI summary

The growth factor profile, connective tissue matrix constituents, and immunoprivileged status of urodele extracellular matrix (ECM) and accompanying cutaneous tissue, plus the presence of antimicrobial peptides there, render urodele-derived tissue an ideal source for biological scaffolds for xenotransplantation. In particular, a biological scaffold biomaterial can be obtained by a process that entails (A) obtaining a tissue sample from a urodele, where the tissue comprises ECM, inclusive of the basement membrane, and (B) subjecting the tissue sample to a decellularization process that maintains the structural and functional integrity of the extracellular matrix, by virtue of retaining its fibrous and on-fibrous proteins, glycoaminoglycans (GAGs) and proteoglycans, while removing sufficient cellular components of the sample to reduce or eliminate antigenicity and immunogenicity for xenograft purposes. The resultant urodele-derived biomaterial can be used to enhance restoration of skin homeostasis, to reduce the severity, durations and associated damage caused by post-surgical inflammation, and to promote progression of natural healing and regeneration processes. In addition, the biomaterial promotes the formation of remodeled tissue that is comparable in quality, function, and compliance to undamaged human tissue.