3D Tissue-Engineered Bone Marrow for Personalized Drug Screening

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Solution Overview

Problem

Current drug screening models for multiple myeloma, particularly 2D cultures, fail to accurately predict drug sensitivity and resistance due to their inability to mimic the complex 3D bone marrow microenvironment, which includes oxygen and drug gradients, and do not account for the genetic and epigenetic variability of individual patients.

Innovation Solution

A tissue-engineered bone marrow model using an autologous fibrin scaffold with patient-derived cells and a gradient of oxygen and drugs, which recreates the bone marrow microenvironment, allowing for personalized drug screening and prediction of therapeutic responses.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If 2D tissue culture systems are used for drug screening, then the model is simple and easy to operate, but the prediction accuracy of drug sensitivity is poor due to inability to mimic oxygen and drug gradients

Engineering Contradiction:

Improveprediction accuracy of drug sensitivityVSAvoidcomplexity of culture system

Core Design Contradiction:

Measurement precisionVSDevice complexity

Solution Approach 1:

The patent transitions from 2D tissue culture to 3D tissue-engineered bone marrow models. This dimensional change enables the creation of oxygen and drug concentration gradients that mimic the physiological bone marrow microenvironment, thereby improving prediction accuracy of drug sensitivity while accounting for the complexity through systematic design of the 3D structure with controlled gradients

Inventive Principle:

Principle #17Another dimension (Dimensionality change)

2Reliability

If classic tissue culture models are used, then the manufacturing process is simple, but the model reliability is poor due to neglect of bone marrow microenvironment role in drug resistance

Engineering Contradiction:

Improvemodel reliability for predicting drug resistanceVSAvoidcomplexity of microenvironment reconstruction

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The patent creates distinct microenvironments within the 3D bone marrow model, including vascular niches with high oxygenation and endosteal niches with hypoxia. Each niche has localized properties (oxygen concentration, drug penetration, cell types) that mimic the physiological bone marrow, improving reliability for predicting drug resistance without requiring uniform complexity throughout the entire system

Inventive Principle:

Principle #3Local quality

3Reliability

If 3D models with foreign materials like Matrigel are used, then the structural support is provided, but the physiological accuracy is reduced due to non-physiological material interactions

Engineering Contradiction:

Improvephysiological accuracy of cell-matrix interactionsVSAvoidease of scaffold preparation

Core Design Contradiction:

ReliabilityVSEase of manufacture

Solution Approach 1:

The patent changes the material parameters by using decellularized bone marrow matrix instead of foreign materials like Matrigel. This native matrix provides physiological cell-matrix interactions while maintaining manufacturability through established decellularization protocols. The material composition is optimized to retain biochemical cues essential for accurate drug response prediction

Inventive Principle:

Principle #35Parameter changes

4Measurement precision

If patient-specific 3D models are created, then the personalized prediction accuracy is improved, but the manufacturing time and complexity increase significantly

Engineering Contradiction:

Improvepersonalized prediction accuracy of drug responseVSAvoidtime required for model preparation

Core Design Contradiction:

Measurement precisionVSLoss of time

Solution Approach 1:

The patent performs preliminary actions by isolating and cryopreserving patient-specific bone marrow cells and matrix components at the time of bone marrow aspiration. These pre-prepared cellular and acellular components can be rapidly expanded and assembled into 3D models when needed, significantly reducing the turnaround time from patient sample to personalized drug response prediction while maintaining high accuracy

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

This model provides a more accurate prediction of drug responses and resistance by recreating the 3D bone marrow microenvironment, enabling personalized therapeutic strategies and improving the effectiveness of drug testing by accounting for individual patient variability.

Implementation Method 1

The autologous fibrin scaffold may include fibrinogen isolated from the patient's bone marrow

Methodology Applied

Scientific EffectFibrin polymerization: Coagulation

Data Source

PatentUS10463764B23D tissue-engineered bone marrow for personalized therapy and drug development

Publication Date: 2019.11.05 WASHINGTON UNIV IN SAINT LOUIS

AI summary

A tissue-engineered bone marrow for personalized therapy of a patient is described. The tissue-engineered bone marrow includes an autologous fibrin scaffold and a plurality of patient-derived cells isolated from the patient's bone marrow. The autologous fibrin scaffold is made using fibrinogen isolated from the patient's bone marrow. The plurality of patient-derived cells may include cells associated with a hematological or metastatic malignancy, bone marrow stromal cells, and endothelial cells. The patient-derived cells are cultured on the autologous fibrin scaffold to create the tissue-engineered bone marrow. The tissue-engineered bone marrow may be used for personalized drug screening.