ECM Particle Biomaterial Crosslinking for Layered Tissue Mimics

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Solution Overview

Problem

Existing tissue engineering methods struggle to replicate the complex layered structure and mechanical properties of biological tissues, particularly articular cartilage, using synthetic polymers, and natural polymers often require UV light for crosslinking, which disrupts the native tissue structure.

Innovation Solution

A biomaterial composed of decellularized and particulated extracellular matrix combined with thiolated polymers that crosslink via disulfide bonding, preserving the mechanical and biological properties of the tissue, allowing for 3D printing and injection into defects to create layered tissue mimics.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Strength

If synthetic polymers are used to create tissue scaffolds, then mechanical strength is improved, but biological compatibility and native tissue structure are compromised

Engineering Contradiction:
Improvemechanical strengthVSAvoidbiological compatibility
Core Design Contradiction:
StrengthVSObject-affected harmful factors

Solution Approach 1:

The patent combines synthetic polymer particles (提供机械强度) with natural extracellular matrix components (提供生物相容性), creating a composite biomaterial that achieves both mechanical strength and biological compatibility. The synthetic particles serve as structural reinforcement while the natural ECM provides cellular recognition sites and biochemical cues.

Inventive Principle:
Principle #40Composite materials

Solution Approach 2:

The invention creates scaffolds with spatially varying properties by controlling the distribution and concentration of synthetic polymer particles within the natural ECM framework. Different regions of the scaffold can have different particle densities to match the mechanical and biochemical gradients found in native tissues.

Inventive Principle:
Principle #3Local quality

2Stability of the object's composition

If UV light is used for crosslinking natural polymers, then structural stability is improved, but native tissue structure is disrupted

Engineering Contradiction:
Improvestructural stabilityVSAvoidtissue structure disruption
Core Design Contradiction:
Stability of the object's compositionVSObject-affected harmful factors

Solution Approach 1:

The patent replaces UV light crosslinking (optical/chemical method that damages tissue) with alternative crosslinking mechanisms such as enzymatic crosslinking, chemical crosslinking agents, or physical crosslinking (heat, pressure). This substitution maintains structural stability while avoiding the harmful effects of UV radiation on native tissue architecture.

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

3Manufacturing precision

If complex layered tissue structures are replicated, then functional accuracy is improved, but manufacturing complexity increases

Engineering Contradiction:
Improvestructural accuracyVSAvoidmanufacturing complexity
Core Design Contradiction:
Manufacturing precisionVSDevice complexity

Solution Approach 1:

The patent divides the complex tissue structure into discrete layers or zones, each containing synthetic polymer particles with specific properties (size, concentration, composition) tailored to replicate the mechanical and biochemical characteristics of different tissue regions. This segmentation allows independent optimization of each layer while simplifying the overall manufacturing process.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The invention controls the physical and chemical parameters of synthetic polymer particles (size distribution, concentration, crosslinking density, surface properties) to create distinct tissue zones with varying mechanical and biochemical properties, enabling accurate replication of complex layered structures through parameter optimization rather than complex processing.

Inventive Principle:
Principle #35Parameter changes

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 biomaterial effectively mimics the structure and function of native tissues, enabling robust tissue repair and regeneration by maintaining the native tissue architecture and promoting cellular integration and proliferation.

Implementation Method 1

The ECM-based particle bioink, pECM bioink, utilizes functionalized macromolecules combined or packed together with acellular tissue particles. When combined, the two materials crosslink via disulfide bonding to create stable tissue mimics or repair scaffolds.

Methodology Applied
Scientific EffectDisulfide bonding: Chemical Bonding

Data Source

PatentEP4259223B1Particulate materials for tissue mimics
Publication Date: 2026.04.01 THE REGENTS OF THE UNIVERSITY OF COLORADO
  • EP4259223B1 patent drawingFigure 1(A)
  • EP4259223B1 patent drawingFigure 1(B)
  • EP4259223B1 patent drawingFigure 1(C)~1(D)

AI summary

A two-component biomaterial and method that replicates both the structural complexity and diverse molecular composition necessary to create a tissue's form and function. It is an objective of the current invention to use the unique combination material and methods herein to provide a pharmaceutical composition, a medical device, a tissue regeneration scaffold, as well as a scaffold for 3D organ culture (tissue on a chip, lab grown meat, research stem cell differentiation) comprising a significant amount of acellular tissue particles packed tightly and held together via crosslinking between the acellular particles and a thiolated protein.