# Increased Blood Flow and Tendon Swelling Precedes Vascular Expansion and Tissue Matrix Changes In Early Human Tendinopathy: A Potential Window for Superior Treatment Response

## TL;DR

Early tendinopathy is marked by increased blood flow and swelling, while chronic tendinopathy involves vascular and tissue changes, suggesting early treatment may be more effective.

## Contribution

The study identifies distinct early and chronic phases of tendinopathy using advanced imaging and proteomics, revealing a potential window for superior treatment response.

## Key findings

- Early tendinopathy features tendon swelling and hyperperfusion without vascular expansion.
- Chronic tendinopathy is characterized by neovascularization and extracellular matrix changes.
- Early tissue changes may be more receptive to treatment than later stages.

## Abstract

Tendinopathy represents a major musculoskeletal health problem, yet its pathogenesis remains poorly understood. Tendinopathy development is studied in humans with early (< 3 months of symptoms, n = 14) (ET) or chronic (> 3 months, n = 16) (CT) patellar tendinopathy and in healthy subjects (n = 15) (CTRL). Pain increases, and function declines with tendinopathy duration and correlated with tendon size (3T and 7T MRI). Tendon blood flow (Doppler ultrasonography) increases gradually in ET and CT, while peritendinous blood flow only rose in CT. Microscopy‐based mapping (immunofluorescence microscopy and Cell DIVE) of vasculature shows marked changes in CT only, indicating flow increases in existing vessels early in tendinopathy, whereas angiogenesis is a late phenomenon. Cell DIVE indicates perivascular cell recruitment and potential lymphatic expansion in tendinopathy. Further, proteomics reveals that most matrix regulation occurs late in tendinopathy. Data from a previous study from the lab demonstrate faster treatment effect in tendinopathy with shorter symptom duration, supporting that early tissue changes may be more receptive to treatment. It is concluded that early tendinopathy is dominated by pain correlating with tendon swelling and hyperperfusion, whereas chronic tendinopathy is characterized by neovascularization and matrisome changes. These findings suggest that targeting early tissue changes can lead to superior treatment effects in tendinopathy.

Human participants with early‐ or chronic‐stage tendinopathy and healthy controls are investigated using ultrasound Doppler, 3T and 7T MRI, and tendon biopsies. Tendon swelling and hyperperfusion are evident early, while vascular growth and extracellular matrix changes are most pronounced in chronic tendinopathy. Early intervention may provide superior treatment outcomes before persistent tissue changes manifest in chronic tendinopathy.