Can Exosomes Help With Rotator Cuff & Tendon Injuries? What the Research Says

Rotator cuff tears and other tendon injuries can be frustrating because tendons don't always heal quickly—or return to their original strength and structure after an injury.

That's one reason extracellular vesicles and exosomes have attracted attention in orthopedic research.

Scientists are investigating whether the biological signals carried by extracellular vesicles may influence inflammation, collagen organization, tendon cells and the difficult transition where tendon attaches to bone.

The findings so far are encouraging.

A systematic review examining 46 preclinical studies reported favorable findings involving tendon and tendon-to-bone healing across histological, biomechanical and morphological outcomes.

More recent studies have specifically investigated chronic rotator cuff tears.

So what exactly is the research finding?

What Does the Research Show?

Researchers have investigated exosomes and other extracellular vesicles across several types of tendon injury, including:

• rotator cuff tears
• Achilles tendon injuries
• tendon-to-bone healing
• tendon degeneration
• surgical tendon repair

Across this research, investigators have reported findings involving collagen organization, inflammation, extracellular-matrix remodeling, biomechanical strength and healing at the tendon-to-bone interface.

A large 2023 systematic review found positive tendon or tendon-to-bone findings across the 46 preclinical studies it evaluated. Proposed mechanisms included regulation of inflammatory responses and macrophage polarization, remodeling of the extracellular matrix and effects on angiogenesis.

A separate systematic review focused specifically on Achilles tendon research identified 18 in-vivo animal studies involving 800 subjects. All but one reported that EVs augmented aspects of the healing process.

These findings help explain why researchers are continuing to investigate EVs for tendon repair.

But there is an important distinction:

Why Are Exosomes Being Studied for Tendon Injuries?

Tendons are strong connective tissues designed to transfer force between muscle and bone.

When they're damaged, restoring the original tissue architecture can be difficult.

The problem becomes particularly interesting with the rotator cuff because successful repair involves more than simply reconnecting torn tissue.

Researchers are interested in the bone-to-tendon interface, sometimes called the enthesis—the specialized region where tendon transitions into bone.

Extracellular vesicles participate in cell-to-cell communication and can carry proteins, lipids and nucleic acids. For background on the particles themselves, see where exosomes come from.

Researchers have therefore investigated whether EV signaling could influence some of the biological processes involved in tendon healing.

Rather than thinking of exosomes as simply “building new tendon,” it is more useful to understand the research question as:

That is what much of the current research is attempting to answer.

Research Highlight: Chronic Rotator Cuff Tear in a Rabbit Model

Han et al., 2025 — Arthroscopy

A particularly interesting 2025 study investigated dermal fibroblast-derived exosomes in a chronic rotator cuff tear model.

Researchers used 48 rabbits, randomly assigning them to three groups of 16.

To create a chronic injury rather than an immediately repaired tear, the researchers transected the rotator cuff tendon and left it untreated for six weeks before surgically repairing it.

The groups then received:

• saline
• fibrin glue alone
• dermal fibroblast-derived exosomes delivered with fibrin glue

This design allowed researchers to compare the exosome-containing preparation with both saline and its delivery material.

How were the exosomes characterized?

The researchers reported positive expression of the exosomal markers CD9, CD63 and ALIX, while the negative-control marker calnexin was nearly absent.

That provides more information than simply labeling the material “exosomes.” For more on what characterization involves, see extracellular vesicle characterization and testing.

What did researchers find?

At four weeks following surgery, the exosome group had the highest reported expression of several genes associated with the developing tendon-to-bone interface, including COL1A1, COL3A1 and ACAN.

Researchers also reported greater preliminary fibrocartilaginous matrix formation.

By 12 weeks, the exosome group showed:

• better collagen-fiber continuity and orientation
• denser collagen fibers
• a more mature bone-to-tendon junction
• greater fibrocartilage-layer formation

The researchers also performed biomechanical testing.

The exosome group demonstrated a greater load-to-failure value, reported as 53.3 ± 6.1 N/kg.

The authors concluded that dermal fibroblast-derived exosome administration promoted bone-to-tendon-interface healing in their chronic rabbit rotator-cuff model.

What is the important limitation?

These were rabbits, not human patients.

The study gives researchers useful information about tissue structure, gene expression and biomechanical properties under controlled experimental conditions.

It does not establish that dermal fibroblast-derived exosomes improve rotator cuff healing in people.

What Does the Larger Tendon Research Show?

One individual experiment becomes more meaningful when we can compare it with the larger body of research.

Zou and colleagues conducted a systematic review specifically examining exosomes in tendon and tendon-to-bone healing.

The researchers initially reviewed 1,794 articles and ultimately included 46 preclinical studies.

Together, those studies included:

• 1,481 rats
• 416 mice
• 330 rabbits
• 48 dogs
• 12 sheep

Across the included research, the authors reported improved histological, biomechanical and morphological outcomes associated with exosome treatment.

The review identified several recurring biological themes.

Researchers investigated EV effects involving inflammatory responses and macrophage polarization, changes in gene expression and the cellular environment, extracellular-matrix reconstruction and angiogenesis.

That's a much broader foundation than a single positive animal experiment.

At the same time, the review identified an important challenge: researchers still had not established the optimal EV source, isolation method, concentration or administration frequency.

That variability matters when comparing studies.

Research Highlight: A Different Approach to Chronic Rotator Cuff Repair

Xu et al., 2025 — International Journal of Biological Macromolecules

Another 2025 study approached rotator cuff healing differently.

Instead of studying ordinary adipose-derived stem-cell exosomes alone, researchers isolated adipose-derived stem cells and selected chondrogenic stem/progenitor cells, then collected exosomes from those cells.

They compared these selected-cell exosomes with exosomes derived from unsorted adipose-derived stem cells.

The researchers then incorporated the exosomes into a GelMA/HA-NB hydrogel designed to retain them at the injury site.

The experiment used a chronic rotator cuff tear model involving 112 rats divided into four groups:

• control
• hydrogel alone
• unsorted-cell exosomes with hydrogel
• selected chondrogenic-cell exosomes with hydrogel

Healing was evaluated at four and eight weeks using micro-CT, histology and biomechanical testing.

What did researchers find?

The researchers reported that the selected-cell exosomes remained at the injury site for as long as 14 days when delivered through the hydrogel.

Compared with the other experimental groups, they reported improvements involving:

• histological scores
• bone mineral density
• bone volume relative to total volume
• trabecular thickness
• failure load
• stiffness

The selected-cell exosome group showed stronger findings than the unsorted adipose-derived exosome group in the chronic rotator-cuff model.

That comparison is especially interesting because it reinforces an important point:

What is the important limitation?

Again, this was preclinical research in rats, and the exosomes were delivered through a specialized hydrogel system.

We cannot separate those experimental conditions and assume that an entirely different exosome preparation or delivery approach would produce the same findings.

What About Achilles Tendon Research?

Rotator cuff research isn't the only tendon area where extracellular vesicles have been investigated.

A 2024 systematic review examined EV research specifically involving Achilles tendon repair.

The authors identified 18 in-vivo animal studies involving 800 subjects.

All but one study reported augmentation of Achilles-tendon wound-healing processes.

Recurring proposed mechanisms included:

• extracellular-matrix gene regulation
• macrophage polarization
• delivery of microRNAs to the injury environment

The authors also evaluated study quality. Approximately two-thirds of the included studies were assessed as having low overall risk of bias, with the remainder considered medium risk.

But the studies differed enough in sampling, outcomes and experimental design that the researchers determined a pooled meta-analysis would not be appropriate.

That's another reminder that “exosome research” isn't one standardized experiment repeated over and over.

Different researchers are studying different preparations under different conditions.

What Are Researchers Finding About Tendon Strength?

One advantage of animal tendon research is that researchers can perform measurements that would be difficult or impossible to perform routinely in people.

They can examine repaired tissue histologically and then physically test how much force the tendon-to-bone connection withstands before failure.

That's why biomechanical testing appears frequently in this research.

The 2023 systematic review reported improvements across biomechanical as well as histological and morphological outcomes in the included preclinical literature.

The Han rotator-cuff experiment likewise reported greater load-to-failure measurements in its dermal-fibroblast-exosome group.

And the Xu study reported improvements in failure load and stiffness in its selected-cell exosome/hydrogel group.

These are encouraging findings because researchers aren't looking only at what repaired tissue looks like under a microscope.

They're also investigating how the repaired tissue behaves mechanically.

But these remain measurements from experimental animal models.

Why EV Source and Preparation Matter

This research makes something particularly clear:

Not all extracellular-vesicle preparations are the same.

Even within the studies discussed on this page, researchers used very different materials.

One rotator-cuff study used dermal fibroblast-derived exosomes.

Another used exosomes from adipose-derived chondrogenic stem/progenitor cells and compared them with exosomes from unsorted adipose-derived stem cells.

Across the larger tendon literature, researchers have investigated EVs from numerous cellular sources.

Preparations can also differ in:

• culture conditions
• isolation methods
• purification
• particle concentration
• characterization
• formulation
• delivery method
• administration frequency

The 2023 systematic review specifically identified uncertainty around the most suitable source, isolation method, concentration and administration frequency.

So a positive finding involving one preparation should not automatically be generalized to every product described as containing exosomes—a point we explore further in are all exosome products the same?.

Why Results May Vary

As with many biologically active interventions, people may not respond identically. Individual genetics, age, underlying biology, disease severity and other person-specific factors may influence biological responses. The extracellular-vesicle preparation itself—including its source, manufacturing, characterization and formulation—may also matter. Researchers are still working to understand which factors may help predict how individuals respond.

For tendon research specifically, another major source of variability is simply what researchers are testing.

A recently repaired tendon, a chronic rotator cuff tear and an Achilles tendon injury aren't biologically identical situations.

Likewise, an EV preparation delivered in fibrin glue isn't necessarily equivalent to one retained inside an engineered hydrogel.

These differences are one reason careful comparison between studies matters. Researchers are investigating extracellular vesicles across other orthopedic areas as well—see what the research says about exosomes and knee pain.

The Bottom Line

Extracellular-vesicle research surrounding tendon healing has developed into a substantial preclinical field.

A systematic review encompassing 46 studies and thousands of experimental animals reported favorable histological, biomechanical and morphological findings across tendon and tendon-to-bone models.

More recent chronic rotator-cuff studies have reported encouraging findings involving collagen organization, fibrocartilage formation, tendon-to-bone structure and biomechanical strength.

Researchers are also beginning to investigate how EV source, formulation and delivery strategy may influence those results.

What the field still needs is human clinical research capable of determining whether these encouraging preclinical findings translate into meaningful outcomes for people with rotator-cuff and other tendon injuries. The rotator-cuff systematic review likewise concludes that further clinical trials are needed.