3D Microphysiologic System for Female Reproductive Tract Modeling

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Solution Overview

Problem

Current three-dimensional cell and tissue culture systems for the female reproductive tract lack a robust, physiologically relevant model that mimics the in vivo biology of the human reproductive system, particularly for long-term processes like the menstrual cycle, and often use non-human cells or fail to maintain viability and hormonal responsiveness.

Innovation Solution

A microfluidic microphysiologic system integrating individual three-dimensional cultures of ovarian follicles, fallopian tubes, uterus, and cervix, where hormones and factors secreted by ovarian follicles stimulate downstream tissues, maintaining viability for at least one menstrual cycle and mimicking hormonal fluctuations, using human cells and microfluidics for fluid communication between cultures.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If traditional three-dimensional cell and tissue culture systems are used, then the structural complexity is reduced, but the physiological relevance and hormonal responsiveness are insufficient

Engineering Contradiction:
Improvephysiological relevanceVSAvoidsystem complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The system divides the reproductive tract into separate three-dimensional tissue modules (ovary, fallopian tube, uterus, cervix) that can be cultured independently and then integrated through microfluidic connections, allowing each module to maintain its physiological characteristics while forming a complete functional system

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

Microfluidic channels serve as intermediaries that connect the separate tissue modules, enabling hormonal and chemical factor exchange between organs while maintaining physical separation, thus preserving physiological relevance without requiring direct tissue integration

Inventive Principle:
Principle #24Intermediary (Mediator)

2Reliability

If non-human cells are used in culture systems, then the ease of manufacture is improved, but the human physiological relevance is reduced

Engineering Contradiction:
Improvehuman physiological relevanceVSAvoidculture system establishment
Core Design Contradiction:
ReliabilityVSEase of manufacture

Solution Approach 1:

The system uses human primary cells obtained from minimally invasive procedures (such as endometrial biopsies) to maintain human-specific physiological responses, while the microfluidic platform provides standardized culture conditions that facilitate reproducibility

Inventive Principle:
Principle #3Local quality

3Duration of action of stationary object

If static culture systems are used, then the device complexity is reduced, but the duration of viability and hormonal responsiveness deteriorate

Engineering Contradiction:
Improvetissue viability durationVSAvoidculture system complexity
Core Design Contradiction:
Duration of action of stationary objectVSDevice complexity

Solution Approach 1:

The microfluidic system establishes continuous flow of culture media and hormonal factors through the tissue modules, mimicking the continuous physiological environment in vivo and maintaining tissue viability and responsiveness over extended periods (at least one menstrual cycle)

Inventive Principle:
Principle #20Continuity of useful action

Solution Approach 2:

The system incorporates feedback mechanisms where hormones secreted by one tissue module (e.g., ovarian follicles secreting estrogen and progesterone) flow to downstream modules (fallopian tube, uterus, cervix) and regulate their function, creating a self-sustaining hormonal cycle that maintains long-term viability

Inventive Principle:
Principle #23Feedback

4Reliability

If integrated multi-organ systems are created, then the physiological relevance is improved, but the difficulty of detecting and measuring increases

Engineering Contradiction:
Improvephysiological relevanceVSAvoidmeasurement complexity
Core Design Contradiction:
ReliabilityVSDifficulty of detecting and measuring

Solution Approach 1:

The microfluidic channels act as controlled intermediaries that direct hormonal flow between organs in a defined sequence, allowing researchers to measure hormone concentrations at specific points and understand inter-organ communication without the complexity of simultaneous multi-point measurements

Inventive Principle:
Principle #24Intermediary (Mediator)

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 system maintains the viability and hormonal responsiveness of human reproductive tissues for an extended period, allowing for the simulation of the female menstrual cycle and enabling the assessment of therapeutic agents and environmental toxins' effects, providing a physiologically relevant model for reproductive biology studies.

Implementation Method 1

the first 3D cell culture subsystem and the second 3D cell culture subsystem are in unidirectional fluid communication such that factors secreted from said first cell type flow downstream to the second 3D cell culture subsystem

Methodology Applied
Scientific EffectFluid flow:

Data Source

PatentUS11542475B23D microphysiologic system
Publication Date: 2023.01.03 NORTHWESTERN UNIV
  • US11542475B2 patent drawing
  • US11542475B2 patent drawing
  • US11542475B2 patent drawing

AI summary

The present invention relates generally to a three-dimensional cell and tissue culture system for the female reproductive tract. In particular provided herein the system includes individual female reproductive cultures in a dynamic microfluidic setting or integrated using a microfluidic microphysiologic system. In some embodiments, the present invention provides ex-vivo female reproductive tract integration in a three dimensional (3D) microphysiologic system.