3D Collagen Hydrogel for Matrix Vesicle Calcification Imaging

Resolve Bottlenecks,
Find Innovative Solutions
Generate Solutions

Solution Overview

Problem

Current research is hindered by the inability to identify and visualize early processes leading to micro-calcifications in atherosclerotic plaques, which contribute to plaque instability and thrombosis.

Innovation Solution

A controllable three-dimensional (3D) collagen hydrogel system is developed for in vitro imaging of cell-derived matrix vesicle calcification, where collagen is raised to a higher pH to form a network, and cell-derived matrix vesicles are added to induce micro and macro-calcifications, allowing for real-time imaging.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If traditional methods are used to study micro-calcifications, then research progress is hindered, but the ability to visualize early calcification processes remains unavailable

Engineering Contradiction:
Improvevisualization capabilityVSAvoidsystem complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent creates a simplified in vitro model that copies the essential features of in vivo calcification processes. By using purified collagen and matrix vesicles in a controlled environment, the system reproduces early calcification events that are difficult to observe in complex biological tissues, enabling visualization without requiring complex in vivo imaging systems

Inventive Principle:
Principle #26Copying

Solution Approach 2:

The patent introduces an intermediary imaging system that bridges the gap between the microscopic calcification processes and observable measurements. The use of specialized microscopy and imaging techniques allows researchers to visualize early calcification events that would otherwise be invisible, translating molecular-scale processes into detectable signals

Inventive Principle:
Principle #24Intermediary (Mediator)

2Adaptability or versatility

If in vitro systems are used to study calcification, then control over calcification processes is improved, but the ability to maintain physiological relevance deteriorates

Engineering Contradiction:
Improvecontrol over calcificationVSAvoidphysiological relevance
Core Design Contradiction:
Adaptability or versatilityVSReliability

Solution Approach 1:

The patent systematically varies key parameters such as collagen concentration, pH, calcium phosphate concentration, and matrix vesicle density to optimize the in vitro system. By controlling these parameters, the system achieves both physiological relevance and experimental control, allowing researchers to study calcification under conditions that mimic in vivo environments while maintaining reproducibility

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent uses composite materials combining purified collagen, matrix vesicles, and calcium phosphate to create an in vitro system that mimics the complexity of native tissue. This composite approach allows the system to maintain physiological relevance through the use of biologically derived components while enabling control through purification and isolation of specific elements

Inventive Principle:
Principle #40Composite materials

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

This method enables the visualization and study of calcification processes, facilitating the assessment of how reagents modulate micro-calcification growth, thereby providing insights into plaque stability and potential therapeutic interventions.

Implementation Method 1

raising the pH of collagen stored or prepared in an acidic solution, thereby causing the collagen to come out of the acidic solution to form a mesh-like network

Methodology Applied
Scientific EffectpH-induced precipitation: Precipitation

Implementation Method 2

adding matrix vesicles to the collagen network, resulting in calcification

Methodology Applied
Scientific EffectCalcification: Precipitation

Data Source

PatentUS10107823B2System and method for studying matrix vesicle calcification
Publication Date: 2018.10.23 THE BRIGHAM & WOMEN S HOSPITAL INC
  • US10107823B2 patent drawing
  • US10107823B2 patent drawing
  • US10107823B2 patent drawing

AI summary

Systems and methods for imaging of matrix vesicle-derived calcification are described. In one embodiment, the method comprises raising the pH of collagen stored in a solution, thereby causing the collagen to come out of the solution to form a network, adding matrix vesicles to the network, resulting in calcifications, and imaging the formation of the calcification. The calcification process can be imaged in real time by confocal or reflected light microscopy.