# Microphysiological joint-on-chip platform for the study of arthritic diseases

> **NIH NIH R01** · UNIVERSITY OF COLORADO · 2024 · $618,629

## Abstract

PROJECT SUMMARY / ABSTRACT
The objective of this proposal is to establish a new microphysiological ‘joint-on-chip’ system, with structural
biomimicry and biomechanical function, that can support mechanistic study of arthritic diseases and rapidly test
candidate treatments. Recent advances in the development of on-chip technologies have shown potential to
miniaturize musculoskeletal tissues and emulate key aspects of a healthy joint. One primary goal of on-chip
technologies is to create robust and reliable human models of the joint so that the study of disease pathogenesis
and screening of promising drug treatment candidates is possible with high throughput. No disease modifying
treatments are available to address osteoarthritis (OA), a health burden that afflicts millions of people in the
United States. With the development of on-chip technologies, pharmaceutical companies would be positioned to
‘fail fast’, and advance or accelerate only the most promising candidate drug therapies toward clinical trials.
Unfortunately, realistic joint-on-chip models currently lack minimal essential functionality that is necessary for
the study of arthritic diseases and evaluation of treatment candidates. Challenges include the need for human-
derived biomaterial inks that support tissue-specific mechanical and cellular responses, and the need to
recapitulate the complexity of the human joint, including crosstalk between multiple tissue types, and movement-
induced biomechanical stimuli like frictional sliding that mimics the in vivo environment. To improve realistic joint-
on-chip models, our lab has developed human-derived biomaterial inks – particulated allograft extracellular
matrix with a unique crosslinking technology – to enable 3D bioprinting of tissues that more closely mimic the
natural structure of cartilage, bone, and synovium. We have additionally demonstrated that differential
biomechanical stimuli (e.g., compression and frictional sliding) promote distinct cellular responses that are
characteristic of healthy tissue and needed in the engineering of a miniaturized version of the human joint. We
now plan to develop a joint-on-chip with minimal essential functionality using human-sourced tissues and cells
to study arthritic diseases and drug treatment candidates. We will optimize human biomaterials to recreate
essential tissue structure and function, and engineer necessary biomechanical stimulation that is currently
lacking in on-chip technology. We will pursue three related specific aims. In Aim 1, we will optimize a library of
particulated and human-derived biomaterial inks for 3D joint-on-chip printing. In Aim 2, we will establish a human
joint-on-chip platform with minimal essential functionality. In Aim 3, we will quantify the joint-on-chip pathogenic
response to biomechanical injury and inflammatory challenge. If successful, we will for the first time create a
realistic joint-on-chip model with essential functionality that is useful to study art...

## Key facts

- **NIH application ID:** 10976945
- **Project number:** 1R01AR083379-01A1
- **Recipient organization:** UNIVERSITY OF COLORADO
- **Principal Investigator:** Corey P Neu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $618,629
- **Award type:** 1
- **Project period:** 2024-08-15 → 2029-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10976945

## Citation

> US National Institutes of Health, RePORTER application 10976945, Microphysiological joint-on-chip platform for the study of arthritic diseases (1R01AR083379-01A1). Retrieved via AI Analytics 2026-06-12 from https://api.ai-analytics.org/grant/nih/10976945. Licensed CC0.

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