Decellularized Tissue Hydrogels via Apoptosis-Based Processing

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Solution Overview

Problem

Conventional decellularization methods for tissue scaffolds often require harsh chemicals and cell lysis, leading to tissue disruption and loss of desired extracellular matrix components, which complicates tissue regeneration and repair.

Innovation Solution

The development of apoptosis-based and chemical decellularization methods that induce apoptosis in tissues to remove cellular components without harsh chemicals, preserving extracellular matrix proteins and enabling the formation of decellularized tissue hydrogels for tissue engineering applications.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Quantity of substance

If conventional decellularization methods using harsh chemicals and cell lysis are used, then cellular components are removed effectively, but tissue integrity is disrupted and extracellular matrix components are lost

Engineering Contradiction:

Improvecellular component removalVSAvoidtissue integrity

Core Design Contradiction:

Quantity of substanceVSStability of the object's composition

Solution Approach 1:

The patent changes the chemical parameters of the decellularization process by using mild detergents (Triton X-100, Tween 20) instead of harsh chemicals, and controls pH levels (6.5-7.5) to maintain tissue integrity while removing cellular components. This parameter optimization allows effective decellularization without compromising the extracellular matrix structure

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent replaces mechanical cell lysis methods with chemical detergent-based approaches that gently solubilize cell membranes without disrupting the tissue architecture. This substitution enables cellular removal while preserving the structural integrity of the extracellular matrix

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

2Quantity of substance

If harsh chemicals are used for decellularization, then cellular content is removed, but extracellular matrix proteins are damaged or lost

Engineering Contradiction:

Improvecellular content removalVSAvoidextracellular matrix proteins

Core Design Contradiction:

Quantity of substanceVSLoss of substance

Solution Approach 1:

The patent uses mild, biocompatible detergents like Triton X-100 and Tween 20 that can be easily removed and do not leave harmful residues. These gentle chemicals effectively remove cellular components while being safe for the extracellular matrix, replacing the need for harsh, protein-damaging chemicals

Inventive Principle:

Principle #27Cheap short-living objects (Disposable)

Solution Approach 2:

The patent employs detergent molecules as intermediaries that selectively interact with and solubilize cell membranes while leaving extracellular matrix proteins intact. These detergents act as mediators between the decellularization goal and the preservation requirement, enabling selective removal of cellular material

Inventive Principle:

Principle #24Intermediary (Mediator)

3Quantity of substance

If tissue decellularization is performed to create scaffolds, then cellular components are removed, but the process becomes complex and time-consuming

Engineering Contradiction:

Improvecellular component removalVSAvoiddecellularization process complexity

Core Design Contradiction:

Quantity of substanceVSDevice complexity

Solution Approach 1:

The patent combines multiple decellularization steps into a streamlined protocol using sequential detergent treatments followed by controlled crosslinking. This merged approach integrates cellular removal and matrix stabilization into a cohesive process, reducing overall complexity compared to multiple separate treatment steps

Inventive Principle:

Principle #5Merging (Combining)

Solution Approach 2:

The patent performs preliminary optimization of detergent concentrations, pH levels, and incubation times to establish a standardized protocol. This preliminary characterization allows the development of a predictable, repeatable process that reduces complexity in subsequent applications

Inventive Principle:

Principle #10Preliminary action

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

These methods effectively remove cellular content while maintaining tissue integrity, allowing for the creation of tissue scaffolds that support tissue regeneration and can be used for various injuries and diseases, including nerve injuries and spinal cord damage, by forming injectable hydrogels that promote cellular growth and matrix preservation.

Implementation Method 1

inducing widespread apoptosis in the tissue

Methodology Applied

Scientific EffectApoptosis:

Implementation Method 2

removing DNA by exposing the tissue from (c) to DNase

Methodology Applied

Scientific EffectEnzymatic digestion: Enzyme

Implementation Method 3

enzymatically digesting the tissue from (d)

Methodology Applied

Scientific EffectEnzymatic digestion: Enzyme

Implementation Method 4

the decellularized tissue is cross-linked to form the hydrogel

Methodology Applied

Scientific EffectHydrogel formation: Hydrogel

Data Source

PatentUS20210046125A1Decellularized tissues, hydrogels thereof, and uses thereof

Publication Date: 2021.02.18 UNIV OF FLORIDA RESEARCH FOUNDATION INC

AI summary

Described herein are methods of producing decellularized tissue hydrogels. In some aspects, the decellularized tissue hydrogels can contain one or more extracellular matrix proteins. Also described herein are methods of making the decellularized tissue hydrogels. Also described herein are methods of using the decellularized tissue hydrogels. In some aspects, the decellularized tissue hydrogels or a pre-gel solution can be administered to a subject.