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NIH grant 1F31AR088509-01: Crosstalk between the subacromial bursa and the rotator cuff during tendon healing
Institute: {'code': 'AR', 'abbreviation': 'NIAMS', 'name': 'National Institute of Arthritis and Musculoskeletal and Skin Diseases', 'admin_org_id': '12500006', 'admin_funding_url': ''}. PI: Jillian Smith. Award: $50114.
Start: 2026-09-30T00:00:00.
ABSTRACT
Rotator cuff tendon injuries are common, and the failure rate after surgical repair ranges from 20-90%. This is
due to the lack of regeneration of the tendon-to-bone attachment, which results in a mechanically weak scar
formation at the repair site. These injuries result in pain and disability, and there is a need for a better
understanding of tendon healing to develop therapeutics for improved healing. The subacromial bursa, a tissue
located on top of the supraspinatus tendon in the rotator cuff, has been implicated in rotator cuff tendon healing.
Although long thought to have an insubstantial role and typically removed during most shoulder surgical
procedures, the bursa becomes biologically activated in response to rotator cuff injuries and has a paracrine role
in regulating tendon healing. The bursa contains a niche of resident mesenchymal stem cells (MSCs) and
immune cells that may contribute to this activation and paracrine regulation. However, despite recent studies
implicating the bursa in rotator cuff tendon healing, there is much about the bursa that is not yet understood. For
example, the full cellular composition of the bursa and how these cells respond to injury and regulate tendon
healing is unclear. Although it is hypothesized that MSCs and immune cells in the bursa contribute to these
processes, the mechanisms of this have not been elucidated. Additionally, it is unknown whether inflammatory
pathways, such as the NF-κB pathway, which plays an important role in tendon healing, are necessary for the
bursa’s paracrine regulation of the tendons. Preliminary work has shown that bursa activation results in increased
expression of inflammatory genes and matrix metalloproteinases, which indicates that the NF-κB pathway is
likely involved in bursa activation. However, whether this pathway is necessary for the bursa to have an
immunomodulatory role in the healing tendons is not understood. Therefore, the overall objective of this study is
to identify the cellular and inflammatory pathways that contribute to bursa activation and paracrine modulation.
Aim 1 will investigate the cellular and biological response of the subacromial bursa to the rotator cuff tendon
injury inflammatory environment. Using a rat model of supraspinatus tendon injury to activate the bursa, we will
perform single cell RNA sequencing (scRNAseq) and single nuclei RNA sequencing (snRNAseq) to identify
changes in resident MSCs and immune cells and to examine the crosstalk between bursa cells and tendon cells.
In Aim 2, we will determine the necessity of the NF-κB pathway for bursa paracrine modulation of tendon healing.
We will use the rat model of supraspinatus tendon injury and inhibit the NF-κB pathway by delivering ACHP, an
inhibitor of IKKβ, locally to the bursa using microspheres at different timepoints after tendon injury and repair.
We will identify changes in bursa cell populations in response to NF-κB inhibition and use transcriptomics,
histology, and mechanics to examine changes in tendon healing. This work will provide a better understanding
of the cellular and inflammatory mechanisms for bursa activation and paracrine regulation, which could inform
on new therapeutic avenues for improving rotator cuff healing.document fetched 2026-10-15 02:48