3D Bone Marrow Model With Anastomosed Vascular Channels

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Solution Overview

Problem

There is a challenge in recreating the complex, specialized microenvironment of the human bone marrow vasculature in vitro to study hematopoiesis and hematopoietic vascular niche processes, as existing methods primarily focus on the endosteal niche and fail to adequately mimic the human-specific hematopoietic vascular niche.

Innovation Solution

A microphysiological device comprising side channels with endothelial cells and a central channel with a cellularized scaffold containing hematopoietic stem cells, mesenchymal stromal cells, and endothelial cells, along with a multi-organ system, is developed to emulate the human bone marrow niche, allowing for the study of hematopoiesis and immune responses.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Manufacturing precision

If existing methods focus on the endosteal niche to study hematopoiesis, then the endosteal niche structure can be recreated, but the human-specific hematopoietic vascular niche cannot be adequately mimicked

Engineering Contradiction:

Improverecreation of endosteal niche structureVSAvoidability to mimic human-specific hematopoietic vascular niche

Core Design Contradiction:

Manufacturing precisionVSAdaptability or versatility

Solution Approach 1:

The device is divided into distinct functional zones: an endosteal niche region with porous scaffold for stromal cells, and a vascular niche region with channels lined by endothelial cells. This segmentation allows each region to be optimized for its specific physiological function while working together to recreate the complex bone marrow microenvironment.

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The invention transitions from two-dimensional cell culture to a three-dimensional microphysiological system with vertical layering. The scaffold extends vertically to create distinct compartments for different cell types, enabling realistic spatial organization of hematopoietic stem cells, stromal cells, and vascular structures.

Inventive Principle:

Principle #17Another dimension (Dimensionality change)

2Reliability

If a complex multicellular network is recreated to study hematopoiesis, then physiological processes can be better modeled, but the device complexity increases

Engineering Contradiction:

Improvemodeling of physiological processesVSAvoidstructure of microphysiological device

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The device integrates multiple physiological functions into a single platform: hematopoietic stem cell culture, vascular network formation, immune cell differentiation, and drug testing. This multi-functionality reduces the need for separate experimental systems while maintaining physiological relevance.

Inventive Principle:

Principle #6Universality (Multi-functionality)

Solution Approach 2:

Stromal cells are used as intermediary elements that mediate interactions between hematopoietic stem cells and the vascular niche. These cells secrete growth factors and cytokines that regulate hematopoiesis, creating a realistic signaling environment without requiring direct complex cell-cell contacts.

Inventive Principle:

Principle #24Intermediary (Mediator)

3Adaptability or versatility

If human cell-based in vitro models are used to study hematopoiesis, then human-specific processes can be investigated, but the difficulty of recreating the complex vascular microenvironment increases

Engineering Contradiction:

Improvestudy of human-specific hematopoietic processesVSAvoidrecreation of vascular microenvironment

Core Design Contradiction:

Adaptability or versatilityVSDevice complexity

Solution Approach 1:

The device incorporates microfluidic channels that simulate blood flow through the vascular niche. Controlled fluid flow delivers nutrients, oxygen, and signaling molecules to hematopoietic stem cells while removing waste products, recreating the dynamic vascular microenvironment without complex mechanical structures.

Inventive Principle:

Principle #29Pneumatics and hydraulics

Solution Approach 2:

A porous scaffold material is used to create the endosteal niche structure, allowing diffusion of signaling molecules and nutrients while providing structural support for stromal cells. The porous architecture mimics the natural extracellular matrix and facilitates cell-matrix interactions essential for hematopoiesis.

Inventive Principle:

Principle #31Porous materials

Data Source

PatentUS20250304892A1Apparatus, system, and method for forming a perturbable bone marrow model within a three-dimensional microphysiological system

Publication Date: 2025.10.02 THE CHILDRENS HOSPITAL OF PHILADELPHIA

AI summary

The present disclosure relates to a human bone marrow model. The present disclosure further relates to a microphysiological device comprising two or more side channels having endothelial cells therein and at least one central channel arranged therebetween, the at least one central channel having a cellularized scaffold formed therein, the cellularized scaffold of the at least one central channel including hematopoietic stem cells, mesenchymal stromal cells, and endothelial cells. In an embodiment, the device further comprises vasculature developed within and between the two or more side channels and the at least one central channel, wherein the vasculature developed within and between the two or more side channels and the at least one central channel includes anastomoses formed between vessels within the at least one central channel and an endothelium formed within the two or more side channels, the anastomoses permitting perfusion between the two or more side channels.