# A microphysiological system of tendon inflammation and fibrosis for drug screening and efficacy testing: MPS Database Engagement

> **NIH NIH UG3** · UNIVERSITY OF ROCHESTER · 2021 · $75,416

## Abstract

Abstract
The continued advancement of microphysiological systems (MPS) as pre-clinical research tools is vital to
overcome the low throughput and inaccuracies inherent in animal models of human disease. The limitations of
pre-clinical animal models, most commonly mice, are particularly apparent in inflammatory diseases which are
known to have distinct genetic and cytokine responses to inflammation. The establishment of MPS alternatives,
however, will require scientific consensus on the protocols and systems best suited to address particular
diseases. As the current MPS era is characterized by a proliferation of approaches, the Microphysiological
System Data Base (MPS-db) created by the University of Pittsburgh is a valuable tool to hasten the
development of MPS standards. Because the success of the MPS-db requires the active participation by MPS
developers and users, we seek supplemental funding to contribute the designs, protocols and results for an
MPS system that models the interplay between inflammation and fibrosis in tendon healing (UG3TR00287).
Importantly, the injury and repair of connective tissue injury is not represented in the current MPS-db but
accounts for more than 8.5 million clinical procedures annually, including 2 million major surgeries. Our human
tendon-on-a-chip (hToC) model focuses on the early inflammatory stages of tendon repair, where timely
interventions may promote scarless healing. The hToC features vascular and collagen compartments which
exchange soluble and cellular factors in a simulation of the neovascularized microenvironment established
shortly after blood clotting. Monocyte infiltration is hypothesized to play an essential role in the generation of
contractile myofibroblasts which progress to senescence and release monocyte activating factors in a positive
feedback loop that causes scar tissue. The model uses iPSCs derived from primary human tenocytes to create
vascular endothelial cells and monocytes in an isogenic, patient-centric triculture. With supplemental funding we
will share: 1) descriptions of the mechanisms of the tendon injury and fibroinflammatory repair process; 2)
design details for the hToC including device components and modules for both flow and integrated photonic-
based sensing; 3) cell culture and device protocols including phenotypic characteristics and operational
parameters such as flow rates for priming of ECs and the introduction of immune cells; 4) The design and
rationale for studies under baseline and inflammation/repair conditions; and 5) Results including an analysis of
intra-study reproducibility.

## Key facts

- **NIH application ID:** 10430792
- **Project number:** 3UG3TR003281-02S1
- **Recipient organization:** UNIVERSITY OF ROCHESTER
- **Principal Investigator:** Hani A Awad
- **Activity code:** UG3 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $75,416
- **Award type:** 3
- **Project period:** 2020-08-15 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10430792

## Citation

> US National Institutes of Health, RePORTER application 10430792, A microphysiological system of tendon inflammation and fibrosis for drug screening and efficacy testing: MPS Database Engagement (3UG3TR003281-02S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10430792. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*