Joint Organ Chip With Differential Perfusion for Disease Modeling
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Solution Overview
Problem
Current therapies for joint diseases like osteoarthritis are inadequate due to insufficient mechanistic understanding of disease onset and progression, limited utility of pre-clinical animal studies, and the inability to model the three-dimensional and multi-tissue nature of synovial joints in vitro drug discovery.
Innovation Solution
Development of cell-based microphysiological joint (mJoint) tissue bioreactors that include the osteochondral complex, synovium, and adipose tissue, replicating the stratifications and physiologic conditions of human joints to study disease progression and develop personalized therapies.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If pre-clinical animal studies are used for drug discovery, then some disease modeling capability is provided, but the model fails to accurately predict clinical efficacy and toxicity due to species differences and inability to replicate human joint physiology
Solution Approach 1:
The patent creates a human joint organ chip that copies and replicates human joint physiology, cartilage structure, and tissue organization in vitro, replacing animal models to accurately predict human clinical responses without species differences
Solution Approach 2:
The patent changes the fundamental parameter of model species from animal to human by using human-derived cells and tissues in the organ chip, thereby achieving human-specific physiological responses and eliminating interspecies variability
2Device complexity
If traditional in vitro models focus on single tissue types (cartilage or bone), then simplified experimentation is enabled, but the three-dimensional and multi-tissue nature of synovial joints cannot be encompassed
Solution Approach 1:
The patent merges multiple joint tissues including cartilage, bone, synovium, and adipose tissue into a single integrated organ chip system, enabling comprehensive modeling of joint disease while maintaining a relatively simple microdevice structure
Solution Approach 2:
The patent nests multiple tissue types within a hierarchical microstructure where different tissues are organized in anatomically relevant configurations, with cartilage, bone, synovium, and adipose tissue arranged to mimic native joint architecture
3Ease of operation
If current therapies focus on symptom relief rather than disease modification, then patient comfort is improved, but no effective treatment addresses the underlying pathogenesis of joint diseases
Solution Approach 1:
The organ chip enables self-service disease modeling where researchers can independently study disease mechanisms, test disease-modifying therapies, and evaluate treatments without relying on complex animal studies or clinical trials, thereby accelerating DMMOAD development
Data Source
AI summary
Disclosed herein are various bioreactor devices that mimic the mammalian joint. The bioreactor device can include a series of bioreactor chambers that contain different components of the joint, such as bone, cartilage, synovium, nerve and ligament. At least two different nutrient fluid circulation systems connect subsets of the bioreactor chambers to differentially supply nutrient fluids at concentrations optimized for the tissue that the fluid nourishes. For example, relatively hypoxic fluid can be supplied to synovium and cartilage to mimic oxygenation in the joint compartment, but normoxic fluid can be supplied to the bone and other components that have an arterial supply that provides higher oxygen concentrations. One or more or all of the bioreactor chambers can be supplied with separate inlets through which perturbation agents (such as drugs or other agents) can be introduced to model the effect of the perturbations on different components of the system. In some cases, the system can include a well plate having a plurality of wells and a bioreactor situated in each well of the well plate.