# Tissue Chip Modeling of Synovial Joint Pathologies: Effects of Inflammation and Adipose-Mediated Diabetic Complications

> **NIH NIH UH3** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2021 · $1,109,539

## Abstract

Trauma, inflammation, infection, and aging can cause damages to joint tissues, ultimately leading to arthritic
disorders, such as osteoarthritis (OA), septic arthritis, and inflammatory arthritis, resulting in physical disabilities
that compromise quality of life; however, no efficacious therapies are currently available. The limited progress in
the development of disease-modifying medications (DMMs) is principally because of: (1) insufficient mechanistic
understanding of disease onset/progression; (2) inability to encompass the 3-dimensional (3D) and multi-tissue
nature of the synovial joint in early phase in vitro drug discovery; and (3) limited utility of pre-clinical animal
studies for early stage clinical efficacy and toxicity prediction (lacking “fail early/fail fast” capabilities), resulting in
unanticipated and costly clinical trial failures. Also, patient-specific etiology, progression, and drug sensitivity
profiles underscore the need for personalizable therapy development. To address these needs, we propose
engineering a 3D human micro-joint chip (mJoint), physiologically analogous to the native joint and capable of
modeling pathogenesis of joint diseases for DMM screening/development. UG3 - Aim 1: Engineering joint
components The osteochondral complex, synovium, and adipose, will be engineered using primary cells,
human mesenchymal stem cells (MSCs) or induced pluripotent stem cell (iPSC) derived MSCs encapsulated in a
photocrosslinked hydrogel scaffold, with macrophages included to evaluate their critical function in
mediating/regulating inflammation, and phenotype-characterized using molecular, biochemical and histological
analyses. Aim 2: Generating normal and diseased mJoint A bioreactor will be designed to house all of the
joint elements (mJoint), simulating the respective in vivo tissue conditions, and exposed to various pathogenic
agents and conditions to model OA, inflammatory arthritis, and adipose-mediated diabetic joint complications,
which will be assessed based on changes in histology and structure in each individual joint component as well as
biomarkers. UH3 - Aim 3: Investigating tissue interactions and developing specific biomarkers using
mJoint We will assess the contribution of and the interactions among the joint tissue components under normal
and diseased conditions. Joint diseases with different etiologies (see Aim 2) will be simulated, tissue interactions
analyzed, and potential biomarkers developed to predict joint health. Aim 4: Testing known drugs and
screening candidate DMMs We will assess the efficacy of known and candidate DMMs using the mJoint
disease models, including interleukin-4, NF-κB decoy oligonucleotides, statins, metalloproteinases inhibitors, and
others, focusing also on the applicability of biomarkers identified in Aim 3. Aim 5: Testing potential of cell-
based therapy The therapeutic efficacy of human MSCs and their products, such as exosomes and conditioned
media, and other biologics, will be ...

## Key facts

- **NIH application ID:** 10208992
- **Project number:** 5UH3TR002136-05
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Hang Lin
- **Activity code:** UH3 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $1,109,539
- **Award type:** 5
- **Project period:** 2017-08-20 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10208992

## Citation

> US National Institutes of Health, RePORTER application 10208992, Tissue Chip Modeling of Synovial Joint Pathologies: Effects of Inflammation and Adipose-Mediated Diabetic Complications (5UH3TR002136-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10208992. Licensed CC0.

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