# Tendon TRAP: Targeted Therapeutic Delivery to Enhance Tendon Healing

> **NIH NIH R21** · UNIVERSITY OF ROCHESTER · 2022 · $169,400

## Abstract

Project Summary
Following injury, tendons heal via a fibrotic scar-tissue response that impedes full functional restoration.
Translation of pharmacotherapies to enhance tendon healing has been hampered by a combination of limited
tendon targeting of systemic treatments, and insufficient identification of biologically informed therapeutic
targets. In this high-risk high-reward study we will address both of these critical knowledge gaps. We have
recently identified genetic knockdown of S100a4 as a novel model of functionally-enhanced tendon healing,
thereby identifying S100a4 as a novel therapeutic target to improve tendon healing. Moreover, we have used
spatial transcriptomic profiling to define the spatially distinct molecular processes that dictate the fibrotic tendon
healing process. Using this approach we defined a macrophage-rich cluster located between the highly
reactive tendon stubs at the injury site. This cluster was defined by enriched expression of Acp5, the gene
encoding for TRAP (Tartrate resistant acid phosphatase). Our preliminary data further demonstrate regions of
robust TRAP activity in the healing tendon. Here, we will capitalize on this exciting finding by leveraging our
work using a TRAP binding peptide (TBP) conjugated nanoparticle (NP) drug delivery system. We have
demonstrated enhanced homing and retention of TBP-NPs at sites of high TRAP activity including the bone
fracture callus and during pathologic bone remodeling. Here, we will test the central hypothesis that TRAP
binding peptide loaded nanoparticles (TBP-NPs) efficiently home to the healing tendon, are taken up by
macrophages and that TBP-NP delivery of an S100a4 inhibitor enhances tendon regeneration compared to
control TBP-NPs. In Aim 1 we will track the systemic and tendon-specific localization and retention of
systemically administered fluorescently labelled TBP-NPs compared to scrambled control peptide-NPs. In
addition, we will use a combination of cell-type specific fluorescent reporter mouse models to define the
specific cell populations that uptake TBP-NPs during tendon healing. In Aim 2 we will define the loading and
release profile of an S100a4 inhibitor on TBP-NPs and define the efficacy of TBP-NP drug delivery, compared
to free drug and control NPs, to inhibit S100a4 expression and enhance the tendon healing process.
Successful completion of these studies will establish a novel nanoparticle-mediate delivery system to target the
healing tendon with high efficiency and efficacy, thereby substantially enhancing the translational feasibility of
pharmacologically mediating improved tendon healing.

## Key facts

- **NIH application ID:** 10461486
- **Project number:** 1R21AR081063-01
- **Recipient organization:** UNIVERSITY OF ROCHESTER
- **Principal Investigator:** Danielle S. Benoit
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $169,400
- **Award type:** 1
- **Project period:** 2022-04-20 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10461486

## Citation

> US National Institutes of Health, RePORTER application 10461486, Tendon TRAP: Targeted Therapeutic Delivery to Enhance Tendon Healing (1R21AR081063-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10461486. Licensed CC0.

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