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the
Orthopaedic
forum
The Role of the Subacromial Bursa in Rotator
Cuff Healing
Friend or Foe?
Brittany P. Marshall, PhD, William N. Levine, MD, and Stavros Thomopoulos, PhD

Investigation performed at Columbia University, New York, NY

Clinical Burden of Rotator Cuff Disease
The rotator cuff comprises the set of tendons that stabilize the
glenohumeral joint (Fig. 1). Rotator cuff degeneration is a
common pathology that results in pain, disability, lost produc-
tivity, and limitations to recreational activities1. Rotator cuff
pathology carries a large clinical burden: in the United States,
>4.5 million individuals suffer from rotator cuff tendinopathy,
and >17 million individuals have a rotator cuff injury2. The
incidence of rotator cuff pathology is high, with approximately
50% of the population who are ‡65 years of age experiencing a
rotator cuff tear3-5. These injuries result in >500,000 rotator cuff
repairs annually in the U.S.1,3,6-8. Despite being one of the most
common orthopaedic shoulder procedures, outcomes after
rotator cuff repair are unpredictable and depend on factors
such as tendon length, bone quality, and muscle quality, with
failure rates ranging from 20% to 94%9-12. Repairs are typically
performed arthroscopically and rely on sutures that are passed
through the torn cuff tendon(s) and fixed to the humerus via
suture anchors13. This serves to reapproximate the tendon to its
native footprint in order to promote healing of the tendon to
the bone. When the tendon is deemed irreparable due to irre-
versible degeneration and/or retraction, reconstruction may be
recommended14.
Before completing either repair or reconstruction, suba-
cromial decompression often is performed (Fig. 1). This in-
cludes broadening of the subacromial space by resecting the
subacromial bursa (subsequently referred to as the “bursa”),
the coracoacromial ligament, and the inferior side of the acro-
mion to varying degrees depending on the diagnosis and clini-
cian preference15,16. Decompression is indicated in shoulders
with or without refractory subacromial bursitis or subacromial
impingement because it also improves visualization of the rota-
tor cuff repair site15,17,18. However, decompression that includes
subacromial bursectomy with acromioplasty has recently been
shown to have no benefit over bursectomy alone, calling into
question the necessity of acromioplasty19. Similarly, a systematic
review of subacromial impingement treatment strategies revealed
that bursectomy without acromioplasty is sufficient for treating
symptoms of impingement20. Interestingly, subacromial decom-
pression has been shown to impart no clinically meaningful
improvement in patient outcomes21,22. Bursectomy has even been
shown to be less effective in patients with subacromial pain syn-
drome if they also had degeneration in the shoulder23. Despite the
judicious use of bursectomy, the impact that this procedure has
on tendon-healing has not been established. Hence, investigating
the involvement of the bursa in the tendon-healing response is
critical for defining best surgical repair practices.
Historical Perspective
The bursa was first discussed in the literature in 1906 when
Codman reported its involvement in “stiff and painful shoul-
ders.”24 The bursa, a reportedly “delicate” and “complicated

Disclosure: The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article (http://links.lww.com/JBJS/H307).

J Bone Joint Surg Am. 2023;105:417-25 d http://dx.doi.org/10.2106/JBJS.22.00680

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Fig. 1
Shoulder anatomy before (Fig. 1-A) and after (Fig. 1-B) a subacromial decompression procedure that includes bursectomy (removal of the bursa), ac-
romioplasty (removal of bone from the underside of the acromion), and resection of the coracoacromial ligament.
structure,” was described anatomically as attached to the per-
iosteum beneath the clavicle, the coracoacromial ligament, the
acromion, and the deltoid muscle. Its base is formed by the
tuberosity of the humerus and the rotator cuff. Codman char-
acterized the bursa as “indispensable in abduction and rotation
of the humerus.” Later, he further emphasized the mechanical
role of the tissue when he described that nature provides bursae
across the body in regions of high range of motion between
osseous features where a cartilaginous joint is absent (e.g., the
subacromial, patellar, or olecranon bursa)25 (Fig. 2). This is
notable because the bursa had been overlooked up to this point
with regard to shoulder pathology, and one of its first mentions
in the literature posits it as essential for proper mechanical
function of the shoulder. Building on this mechanical empha-
sis, Codman noted that the bursa can become pathologically
inflamed in cases of trauma, fixation, or sepsis (Fig. 2). He
qualified this by stating that the bursa “is not a structure where
disease starts, so much as a structure which limits disease in
adjacent structures by temporary adhesions.”25 Codman also
asserted a form of crosstalk between the tendon and the bursa
when he distinguished one form of bursitis in which a complete
tendon tear permits synovial fluid escape from the joint into
the bursa, resulting in acute subacromial bursitis with classic
signs of inflammation25. This may have been the first descrip-
tion of bursa “activation” by a tendon injury. Contrary to this
example of crosstalk that progresses pathology, Codman dis-
cussed a common case of calcified deposits escaping the tendon
THE ROLE OF THE S U B AC R O M I A L B U R S A IN R O TAT O R C U F F H E A L I N G
and entering the bursa25. He asserted that leukocytes are likely
recruited to clear the deposits from the bursa in a pattern of
inflammatory response that is unique to the bursa. Using
radiographic imaging over time, Codman noted that, after rup-
ture of the calcified deposits from the tendon into the bursa,
pathological calcifications were cleared within 3 weeks. This
was the first mention of cellular crosstalk between the tendon
and the bursa that serves to resolve pathology.
It should be noted that the discussion of clinical care in
the 1906 report of bursal pathology made no indication for
bursectomy—it only recommended disruption of adhesions
and splinting of the arm to prevent mechanical irritation. For
years after the report by Codman, there was a persistent subset
in the field who insisted that removal of the bursa was objec-
tionable. Notably, in 1914, Littig conveyed that “the inflamed
bursa has been removed with very favorable results, but some of
the best surgeons in America object to this procedure, and the
objection is easy to understand when the extent of the bursa and
its function are considered.”26 The tone shifted in 1972 when
Charles Neer established anterior acromioplasty and subacro-
mial bursectomy, together now referred to as subacromial de-
compression, as the best course of care for chronic impingement
syndrome in patients with recalcitrant symptoms who required
surgery after unsuccessful nonoperative management16,27. This
approach hinged on Neer’s assertion of the mechanical (extrin-
sic) theory of impingement wherein impingement is caused by
compression of the rotator cuff20. This stands in contrast to the
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Fig. 2
The original depiction of the bursa by Codman during shoulder elevation (Fig. 2-A), where “A” is the deltoid insertion on the acromion and “B” is the
supraspinatus insertion on the humerus, and cellular changes to the pathological bursa (Fig. 2-B). Reproduced from: The shoulder: rupture of the
25
supraspinatus tendon and other lesions in or about the subacromial bursa/E.A. Codman. Wellcome Collection. In copyright .

degenerative (intrinsic) theory of impingement where symp-
toms are driven by degenerative changes in the rotator cuff
tendons. A role for impingement in rotator cuff pathology
was further supported in subsequent work by Bigliani and col-
leagues, which established a classification system and link be-
tween acromial morphology, age, and rotator cuff tears28,29. The
work by Neer, however, emphasized that decompression should
only be used when nonoperative treatments have been unsuc-
cessful. Despite this, the approach gained a vibrant following
and is widely cited as the motivation behind the now liberal use
of subacromial decompression in shoulder surgery. This shift
away from Codman’s declaration of the bursa as essential for
shoulder function and toward the regular practice of bursec-
tomy largely persisted until recent years, when uncertainty
about the efficacy of complete bursectomy resurfaced21,30-33. In
fact, the most recent reports appear to be swaying back toward a
Codman-like mindset, demonstrating improved long-term out-
comes for patients who undergo rotator cuff repair without
subacromial decompression34. In parallel with these discoveries
of the benefit of retaining the bursa, a connective tissue pro-
genitor (CTP) population within the bursa was discovered35-37.
This initiated a shift in the discussion around this tissue, from
a focus on its theorized detriment to rotator cuff healing to a
new focus on its potential supporting role in rotator cuff repair
and regeneration. As a result, there recently has been an increase
in studies characterizing the CTP population and/or delivering
CTPs to the rotator cuff tendon repair (e.g., via direct injec-
tion, cell-seeded scaffolds, and bursal tissue affixed to the
repair)35,36,38-45. CTPs derived from both human and murine
bursa have characteristics of mesenchymal stem cells (MSCs),
demonstrating their potential for integration into regenerating
tissues and immunomodulation, as has been shown in numer-
ous previously published studies using MSCs35,36,38,46. Recently,
clinical translation of bursa-derived CTP therapeutics has pro-
gressed, with several studies detailing techniques for isolating pro-
liferative CTPs that are superior to other common orthobiologic
treatments39-43. Bursal tissue itself has also been delivered to the
injured and repaired tendon in an animal model in order to
localize CTPs to the site of healing; however, biological evidence
of improved rotator cuff healing following this approach has not
yet been established44. This budding interest in bursa-derived cells
motivates additional investigation into whether the regenerative
potential of the bursa may be harnessed with in situ manipulation
in lieu of excision and ex vivo processing. Interestingly, as the
focus of the literature comes full circle to the original perspec-
tive on the bursa as functionally, and potentially biologically,
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important, it is pertinent that we establish what is currently
known of the biological role of the bursa.
Discoveries in Support of a Biological Role of the Bursa
The bursa, as noted above, has largely been known for provid-
ing cushioning and protecting from frictional wear24,47. In the
literature, the primary discussions of its other functions
include innervation and inflammation of the bursa, which
together cause pain-inducing bursitis and are indications for
bursectomy based on the current standard of care17,18. This con-
tinues to be a widely accepted practice, although there is no
evidence that decompression improves clinical outcomes for
rotator cuff repairs21,22. In fact, a reparative healing response
has been observed uniquely on the bursal side of torn rotator
cuff tendons, supporting a biological role of the bursa during
tendon-healing48. The cell populations in the bursa that contrib-
ute to this healing response are poorly understood, although it
has been proposed that resident mesenchymal progenitors are
involved31. These cells are also implicated in the regenerative
potential of the tissue following bursectomy36. A subpopulation
of aSMA1 (alpha-smooth muscle actin positive) cells in the
healing murine tendon has been suggested to originate from
the subacromial bursa, pointing to the essential nature of both
cellular crosstalk and integration between the bursa and the
rotator cuff49-51. Additionally, the subacromial space and the
bursa are highly vascularized, in stark contrast to the relatively
avascular supraspinatus tendon52-55. It is reasonable to speculate
that this vasculature is essential in cellular infiltration and debris
clearance during the inflammatory response to rotator cuff injury.
The bursa even undergoes observable phenotypic changes toward
fibrous, fatty, and/or vascular matrix that progress as rotator cuff
pathology advances to a full-thickness tear56. Taken together, these
observations of bothersome pain, inflammation, reparative heal-
ing, cellularity, regeneration, vascularity, and phenotypic changes
during pathogenesis suggest that this tissue may have a more
expansive role in rotator cuff pathology than we previously under-
stood (Fig. 3).
Building on the previously held belief that the bursa is of
limited benefit in its native location and state, the recent in vivo
investigations on this tissue involved removal of the bursa and
either delivery directly to the tendon repair site or expansion of
the resident CTP population for redelivery to the repair site39,40,44,57-60.
For example, Morikawa et al. identified the best preparation and
isolation techniques for retrieving cells from the bursa with favor-
able cellular potency for therapeutic redelivery39,40. Additionally,
these cells have been confirmed to have high proliferation rates
across demographics and rotator cuff disease states, as well as a
faster time to form colony units than traditionally sourced CTPs
from bone marrow57,60. One recent study created a midsubstance
tendon defect in a rat supraspinatus to demonstrate the thera-
peutic benefit of placing bursal tissue in the defect61. This surgical
model unfortunately has little clinical relevance because the only
midsubstance longitudinal tendon defects that have been re-
ported in the literature include transverse tear propagation with
enthesis unloading (L- or U-shaped), which the model lacks62,63.
Tamburini et al. conducted an in vitro assessment of bursa-
THE ROLE OF THE S U B AC R O M I A L B U R S A IN R O TAT O R C U F F H E A L I N G
tendon crosstalk using explanted human tissue samples from
biopsies and found that there was (1) a state of inflammation
induced in the bursa when it was co-cultured with biopsy samples
of torn tendon and (2) increased cellularity in the biopsy samples
of torn tendon when it was co-cultured with bursa64. Although
supportive of the idea of cellular crosstalk between the bursa and
the tendon, that study importantly lacked uninjured or nonin-
flamed controls. Central to the lack of thorough basic science
investigations is lack of a model system for clinically relevant
in vivo manipulation of the bursa. Therefore, much of the
focused investigation on the bursa uses human tissue biopsy
samples. This tissue source has biased our current understanding
of the bursa to that of pathological bursae from the inflamed
environment produced by the injured rotator cuff. However, the
bursa is uniquely positioned as a target for improving rotator cuff
healing as it sits immediately superior to the rotator cuff and
contains a depot of cells capable of responding to the injury
environment. Therefore, it is imperative that we comprehensively
establish the role that the bursa plays in the pathogenesis of
rotator cuff disease. In doing so, we can better understand the
consequence of its removal and the potential for targeting it
therapeutically.
Inflammation in the Rotator Cuff
Although it is the focus of long-standing debates, the tendon
field currently recognizes the existence of some level of inflam-
mation in all tendon injuries65,66. This inflammatory response
has been shown to include B and T cells in chronic Achilles
tendon injury67. Increased numbers of macrophages, mast cells,
and T cells have been observed in tendinopathic tendons when
compared with healthy controls, while reduced numbers of T
cells, macrophages, and mast cells have been observed in torn
tendons when compared with intact tendinopathic tendons68-71.
Infiltration of these cells, their phenotypes, and their signaling
patterns are known to be influenced by the paracrine environ-
ment at the injured site72. With preliminary support from the
literature for a biological role of the bursa, it is reasonable to
hypothesize that the bursa has the capacity to influence this
paracrine environment in which the infiltrating immune cells
reside.
The rotator cuff does not stand alone in undergoing a
robust inflammatory response in the injured shoulder environ-
ment. An inflammatory response within the bursa was first
described by Codman in the same body of work in which he
noted the necessity of the bursa for proper shoulder function24.
His claim that the bursa regularly became inflamed was based
on the thickening of the bursal wall, hypertrophic villi, and the
secretion of inflammatory fluids. However, Codman’s pro-
posed mechanisms of inflammation were largely speculative
and only described the inciting factor: mechanical impinge-
ment, adhesions of the bursa onto surrounding tissues, or
widespread infection24. This early report lacked any concrete
evidence of cell types or secreted factors that were present
during the inflammatory response to support this claim. This
predominantly descriptive type of discussion of inflammation
in the bursa pervaded the literature until the end of the
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Fig. 3
Although not yet overtly demonstrated, it is likely that the subacromial bursa has a biological role in rotator cuff pathology, given observations of bursal pain,
inflammation, cellularity, regeneration, vascularity, phenotypic changes, and bursal-sided reparative tendon-healing.

twentieth century, when Santavirta et al. defined a number of
immune cells present in pathological bursae from patients with
tendinitis73. For the first time, the pathological bursa was shown
to possess 50% to 80% CD21 T cells, 10% to 40% CD11b1
macrophages, and very few PCA11 plasma cells. These find-
ings were used to characterize the biological response more
formally as an inflammatory reaction. Furthermore, substance
P in the bursa was shown to correlate with patient pain caused
by rotator cuff disease17. Soon after, a negative correlation was
determined between the relative ratio of 2 forms of interleukin
(IL)-1 receptor antagonist and IL-1 in subacromial synovitis,
although a lack of healthy controls was a predominant weakness
of the study18. Upregulation of vascular endothelial growth factor
expression was also demonstrated within the bursa and was
associated with synovial proliferation, vascularity, and shoulder
pain74. Expanding on this, a broader array of factors was shown
to be upregulated in tissues from patients with subacromial bur-
sitis, including inflammatory cytokines (tumor necrosis factor-a
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[TNF-a], IL-1a, IL-1b, and IL-6), matrix metalloproteinases
(MMP-1 and MMP-9), and cyclooxygenases (COX-1 and
COX-2)75-77. These studies confirmed that an inflammatory
reaction persists in the bursa and motivated the use of anti-
inflammatory agents as therapeutic treatment for painful shoul-
der pathologies. Unfortunately, these years of emphasis in the
literature on the markers for inflammation in the bursa also
solidified the surgical practice of bursectomy for removing what
was now presumed to be the primary source of shoulder inflam-
mation and pain. This steered the field away from outlining the
complete story within which the bursa, as Codman put it, “limits
disease in adjacent structures25.” Instead, the focus of the litera-
ture became, in part, ways in which to use the bursa (now sur-
gical waste), such as isolating and redelivering bursa-derived
CTPs for enhanced rotator cuff repair. Thus, the field is currently
without a comprehensive understanding of the role that the
bursa, a tissue that is certainly capable of a complex inflamma-
tory response, may play in the progression or resolution of rota-
tor cuff pathology. Therefore, identification of the mechanism(s)
by which the bursa may influence the shoulder paracrine envi-
ronment is essential for understanding how the rotator cuff
responds to injury (Fig. 4).
Therapeutically Targeting the Bursa
There is a substantial body of evidence that supports biological
strategies for improved tendon-healing, including inflammation
modulation78. Among the many approaches to tendon inflam-
mation modulation are growth factor delivery or inhibition,
immune cell phenotype modulation, inflammatory cytokine
inhibition, and MSC exosome therapies79-88. Importantly, few
studies have considered the therapeutic potential of the bursa
for improving tendon-healing and regeneration. In 1 recent
animal-model study, bursa-derived stem cells were isolated
and delivered to rotator cuff repairs in an effort to improve
healing89. Reasons for the lack of work in this area include (1)
the lack of a model system for experimental testing in preclinical
Fig. 4
Pathological rotator cuff tendons and the subacromial bursa have been shown to possess diverse populations of immune cells and express upregulated
proinflammatory cytokines. Paracrine communication between cells in the tendons and the bursa, and modulation of the inflammatory response in
particular, is unknown. MSC = mesenchymal stem cells.
THE ROLE OF THE S U B AC R O M I A L B U R S A IN R O TAT O R C U F F H E A L I N G
models, (2) the widely held belief that the bursa is detrimental to
the health of the pathological rotator cuff, and (3) the need to
remove the bursa for visualization during rotator cuff repair.
However, there is good cause to believe that the bursa is ripe
with potential for supporting improved tendon-healing. For
one, it is highly cellular and thereby responsive to and involved
in directing the healing environment of the underlying tendon.
Additionally, the bursa offers a physical depot for drug delivery,
which has already been demonstrated in clinical reports of cor-
ticosteroids delivered to bursae across the body90-92. The depot
nature of the bursa has only been used for drugs intended to
manage impingement-related or generalized joint pain, but the
principle holds for therapeutics aiming to improve tendon-
healing by modulation of the paracrine environment in the
shoulder. An important advantage to this biologically built-in
depot for localized drug delivery is the removal of any need to
immobilize a therapy in a complex, and less easily clinically
adoptable, system, such as with use of a hydrogel or scaffolds.
Having established the hypothetical advantage of targeting the
bursa for improved tendon-healing, it is appropriate that we
consider candidate drugs that may modulate the inflammatory
environment in the rotator cuff when they are delivered directly
to the bursa.
One treatment approach for painful shoulder patholo-
gies that has spread rapidly throughout orthopaedic care is
inflammation modulation with corticosteroid or glucocorti-
coid (steroid) therapy. This treatment approach has been used
for innumerable pathologies, including tendinopathy, bursitis,
osteoarthritis, and neuropathy93. Hydrocortisone injection into
the bursa, along with injection into the joint space and the long
head of the biceps, was first reported in 1955 as a treatment
strategy for periarthritis (frozen shoulder)94. Corticosteroid
injection into the subacromial space has been reported many
times since, often as a treatment for general shoulder pain but
largely irrespective of the underlying pathology95. One study
compared pain scores and range of motion in patients who
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were given subacromial platelet-rich plasma (PRP) or steroid
injections; there were better pain scores in the steroid group
compared with the PRP group at 6 months96. The focus of
these studies has been on patient-reported outcomes such as
pain and clinically measurable outcomes such as range of
motion, without addressing the biological consequences of
these therapies (e.g., inflammatory protein levels). These
studies, which have focused only on the reduction of gener-
alized pain rather than tendon-healing, have applied these
treatments when surgical repair of the rotator cuff has not
been indicated.
Partial reduction of inflammation has previously been
demonstrated to benefit tendon-healing97. Additionally, low-
dose dexamethasone, a glucocorticoid, has been shown to (1)
prevent cell death and tissue degeneration in a tendon explant
model of a stress-deprived joint injury and (2) support a chon-
droprotective proanabolic environment that limits IL-1-induced
degradation in a canine model of osteochondral repair98,99. This
begs the question of whether low-dose and slow-release cortico-
steroids may also benefit rotator cuff healing, in addition to
providing the pain relief that has been widely reported in the
literature. The tendinopathic inflammatory response is notably
complex, involving multiple cell types and a myriad of tempo-
rally regulated cytokines. Therefore, control of inflammation
with drugs such as corticosteroids must be approached cau-
tiously since our understanding of inflammatory processes dur-
ing rotator cuff disease is incomplete. In particular, the dosage
and timing of corticosteroid administration are critical as com-
plete ablation of inflammation is known to have an inhibitory
effect on tendon-healing. It is also timely to note that delivery of
corticosteroids, especially at high doses, to the pathological ten-
don has been reported to have detrimental effects on tendon-
healing100-102. Therefore, low-dose corticosteroid delivery to the
bursa, which we have recently learned is responsive to and
involved in the response of the rotator cuff to injury and healing,
offers a novel therapeutic target for improved rotator cuff repair.
This proposed therapeutic direction is rooted in prior literature
on corticosteroid delivery to the bursa; however, alternative
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THE ROLE OF THE S U B AC R O M I A L B U R S A IN R O TAT O R C U F F H E A L I N G
inflammation-modulating treatments (e.g., pharmacologic cyto-
kine inhibition) are also prime candidates for achieving a similar
therapeutic goal.
Conclusions
Evolving from the age-old characterization of the bursa as a means
of cushioning and protection against friction, this article posits
that the subacromial bursa, due to its proximity to the rotator cuff,
is a depot of cells that can respond to rotator cuff pathology. The
response driven by these cells can be beneficial or detrimental to
rotator cuff healing, depending on which cells are involved and
what paracrine factors they secrete. Due to the complex biology
that drives the progression of rotator cuff disease, the specific
involvement of these cells and their secreted factors is likely
dependent on the stage of disease. Therefore, this tissue is un-
iquely positioned for introducing disease-state-appropriate ther-
apeutics that can direct a cellular response to mitigate rotator cuff
pathology and improve healing. If this is accomplished, clinical
practice may pivot toward retention, redelivery, or therapeutic
modification of some part of the bursa that is beneficial to healing.
Moving forward, focused basic science investigations into the role
the bursa plays in the response to tendon injury and during
tendon-healing are needed to define best clinical practices.
Source of Funding
The paper was supported by funds from the National Institutes
of Health (R01 AR057836) and the National Science Founda-
tion (DGE–1644869). n
Brittany P. Marshall, PhD1
1
William N. Levine, MD
1
Stavros Thomopoulos, PhD
1
Columbia University, New York, NY
Email for corresponding author: sat2@columbia.edu
7. Jain NB, Higgins LD, Losina E, Collins J, Blazar PE, Katz JN. Epidemiology of
musculoskeletal upper extremity ambulatory surgery in the United States. BMC
Musculoskelet Disord. 2014 Jan 8;15(1):4.
8. Vitale MA, Vitale MG, Zivin JG, Braman JP, Bigliani LU, Flatow EL. Rotator cuff
repair: an analysis of utility scores and cost-effectiveness. Journal of Shoulder and
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