UNASSIGNED: We aimed to investigate the transcriptomic alterations that occur in the subacromial bursa (SAB) following degenerative or traumatic shoulder diseases.
UNASSIGNED: RNA sequencing was employed to evaluate the transcriptomic alterations of the SAB in individuals afflicted with degenerative rotator cuff tear (RCT), traumatic RCT and proximal humerus fracture (PHF). To gain insights into the biological significance of differentially expressed genes (DEGs), we conducted an enrichment analysis utilizing Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. We further utilized single-cell RNA sequencing datasets of SAB from a recently published study to explore the associated cellular dynamics and alterations.
UNASSIGNED: We detected 1,790 up-regulated and 1,964 down-regulated DEGs between degenerative RCT and PHF, 2,085 up-regulated and 1,919 down-regulated DEGs between degenerative RCT and traumatic RCT, and 20 up-regulated and 12 down-regulated DEGs between traumatic RCT and PHF. Given the similar expression pattern between traumatic RCT and PHF, they were integrated as the traumatic group. In comparison with the traumatic group, 1,983 up-regulated and 2,205 down-regulated DEGs were detected in degenerative SAB. Enrichment analysis of up-regulated DEGs uncovered an elevated inflammatory and immunologic responses in degenerative SAB. Single-cell transcriptomic analysis revealed macrophage represented the immune cell with the most DEGs between the degenerative and traumatic RCT.
UNASSIGNED: Our results revealed that the SAB in degenerative RCT exhibited a different transcriptional signature compared to that in traumatic RCT, and enrichment analysis showed immunologic and inflammatory activations. Macrophages may play a fundamental role in this process.

UNASSIGNED: Although adhesive capsulitis (AC) is a common condition, the pathological mechanisms remain understudied. The purpose of our research was to evaluate variations in gene expression across the entire genome in the subacromial bursa tissue of individuals with rotator cuff tears (RCT), with or without AC, and to explore the factors that may influence the occurrence and progression of AC.
UNASSIGNED: Transcription profiles of subacromial bursa samples from 12 RCT patients, of whom 6 had also AC, were evaluated. Data were generated using RNA-seq. DESeq2 was utilized to identify the differentially expressed genes (DEGs) in both groups. In order to conduct a more in-depth examination of the DEGs, we performed Gene Ontology (GO) functional enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. A network of interactions between proteins was built, and the central genes were determined using Cytoscape. The hub genes were confirmed through qRT-PCR and immunohistochemistry.
UNASSIGNED: 324 of the 16,251 detected genes were identified as DEGs. Analysis of GO functional enrichment showed that the DEGs were enriched in domains of biological process, molecule function and cellular component. Analysis of KEGG pathways revealed enrichment of DEGs in pathways like IL-17 signaling and ECM-receptor interaction. We verified that the association between AC and the increase in expression of the PPI network hub genes.
UNASSIGNED: This study investigated the transcriptome differences of subacromial bursa in RCT patients with or without AC. Using bioinformatics technology, we identified the DEGs and screened out the hub genes. The research enhanced the data on gene expression profiles of DEGs in the subacromial bursa tissue of patients with RCT, offering fresh perspectives on the regulation of gene transcription.

The subacromial bursa (SAB) plays an important role in the tendon healing process. Based on previous reports, co-culture of the rotator cuff (RC) and SAB have been shown to increase the tendon-related gene expressions, inflammatory cytokines, and tensile strength. However, the nature of the specific biochemical alterations during the inflammatory and repair phases of tendon healing with or without the SAB remain unknown. Using a full-thickness RC tear rat model, we determined how the presence or absence of the SAB alters the histological characteristics and gene expressions. After 3 and 6 weeks, tissues were collected for histological and real-time quantitative polymerase chain reaction (RT-qPCR) evaluations. Results showed greater cell density at 3 weeks, neovascularization and tendon thickening at 6 weeks with SAB preservation. Immunostaining revealed significant increases in type 3 collagen (COL3) expression at 6 weeks with SAB preservation. The RT-qPCR results showed that SAB preservation induced significant increases in the expression of scleraxis, matrix metalloproteinase-13 (MMP-13), interleukin-1β (IL-1β), and inducible nitric oxide synthase (iNOS) at 3 weeks and significant increases in COL3, IL-10, and arginase-1 (Arg-1) at 6 weeks. An RC tear undergoes more appropriate inflammatory and repair phases during the tendon healing process when the SAB is retained.

So far, tendon regeneration has mainly been analyzed independent from its adjacent tissues. However, the subacromial bursa in particular appears to influence the local inflammatory milieu in the shoulder. The resolution of local inflammation in the shoulder tissues is essential for tendon regeneration, and specialized pro-resolving mediators (SPMs) play a key role in regulating the resolution of inflammation. Here, we aimed to understand the influence of the bursa on disease-associated processes in neighboring tendon healing. Bursa tissue and bursa-derived cells from patients with intact, moderate and severe rotator cuff disease were investigated for the presence of pro-resolving and inflammatory mediators, as well as their effect on tenocytes and sensitivity to mechanical loading by altering SPM signaling mediators in bursa cells. SPM signal mediators were present in the bursae and altered depending on the severity of rotator cuff disease. SPMs were particularly released from the bursal tissue of patients with rotator cuff disease, and the addition of bursa-released factors to IL-1β-challenged tenocytes improved tenocyte characteristics. In addition, mechanical loading modulated pro-resolving processes in bursa cells. In particular, pathological high loading (8% strain) increased the expression and secretion of SPM signaling mediators. Overall, this study confirms the importance of bursae in regulating inflammatory processes in adjacent rotator cuff tendons.

UNASSIGNED: Connective tissue subacromial bursa-derived progenitor cells (SBDCs) have been suggested as a potent biologic augment to promote healing of the repaired rotator cuff tendon. Maximizing the amount of retained progenitor cells at the tendon repair site is essential for ensuring an optimal healing environment, warranting a search for proadhesive and proliferative adjuvants. The purpose was to evaluate the effect of magnesium (Mg), platelet-rich plasma (PRP), and a combination of both adjuvants on the in vitro cellular adhesion and proliferation potential of SBDCs on suture material commonly used in rotator cuff surgery.
UNASSIGNED: SBDCs were isolated from subacromial bursa samples harvested during rotator cuff repair and cultured in growth media. Commercially available collagen-coated nonabsorbable flat-braided suture was cut into 1-inch pieces, placed into 48-well culture dishes, and sterilized under ultraviolet light. Either a one-time dose of 5 mM sterile Mg, 0.2 mL of PRP, or a combination of both adjuvants was added, while a group without treatment served as a negative control. Cellular proliferation and adhesion assays on suture material were performed for each treatment condition.
UNASSIGNED: Augmenting the suture with Mg resulted in a significantly increased cellular adhesion (total number of attached cells) of SBDCs compared to PRP alone (31,527 ± 19,884 vs. 13,619 ± 8808; P < .001), no treatment (31,527 ± 19,884 vs. 21,643 ± 8194; P = .016), and combination of both adjuvants (31,527 ± 19,884 vs. 17,121 ± 11,935; P < .001). Further, augmentation with Mg achieved a significant increase in cellular proliferation (absorbance) of SBDCs on suture material when compared to the PRP (0.516 ± 0.207 vs. 0.424 ± 0.131; P = .001) and no treatment (0.516 ± 0.207 vs. 0.383 ± 0.094; P < .001) group. The combination of Mg and PRP showed a significantly higher proliferation potential compared to PRP alone (0.512 ± 0.194 vs. 0.424 ± 0.131; P = .001) and no treatment (0.512 ± 0.194 vs. 0.383 ± 0.094; P < .001). There were no significant differences in the remaining intergroup comparisons (P > .05, respectively).
UNASSIGNED: Augmenting suture material with Mg resulted in a significantly increased cellular adhesion of SBDCs compared to untreated suture material, as well as augmentation with PRP alone or a combination of both adjuvants. Further, Mg with or without PRP augmentation achieved a significant increase in the cellular proliferation of SBDCs on suture material compared to untreated sutures and augmentation with PRP alone. Application of Mg may be a clinically feasible approach to optimizing the use of SBDCs as a biological augment in rotator cuff repair, while combined augmentation with PRP may harness the full potential for optimized tissue recovery due to the high concentration of PRP-derived growth factors.

UNASSIGNED: The subacromial bursa has been found to be a rich, local, source of mesenchymal stem cells but is removed for visualization during rotator cuff repair. Reimplantation of this tissue may improve rotator cuff healing. The purpose of this study is to evaluate clinical outcomes of rotator cuff repair with and without subacromial bursa reimplantation.
UNASSIGNED: Patients aged 37-77 with a full-thickness or near full-thickness supraspinatus tears underwent arthroscopic transosseous-equivalent double row rotator cuff repair. In patients prior to July 2019, the subacromial bursa was resected for visualization, and discarded. In patients after July 2019, the subacromial bursa was collected using a filtration device connected to an arthroscopic shaver and reapplied to the bursal surface of the tendon at the completion of the rotator cuff repair. Rotator cuff integrity was evaluated via magnetic resonance imaging on bursa patients at 6 months postoperatively. Minimum 18-month clinical outcomes (Single Assessment Numeric Evaluation, American Shoulder and Elbow Surgeons, patient satisfaction) were compared between bursa and nonbursa cohorts.
UNASSIGNED: A total of 136 patients were included in the study (control n = 110, bursa n = 26). Preoperative demographics and tear characteristics were not different between groups. Average follow-up was significantly longer in the control group (control: 3.2 ± 0.7 years; bursa: 1.8 ± 0.3 years; P < .001). The control group showed a significantly higher Single Assessment Numeric Evaluation score (control: 87.9 ± 15.8, bursa: 83.6 ± 15.1, P = .037) that did not meet minimum clinically important difference. The American Shoulder and Elbow Surgeons and patient satisfaction scores were similar between the groups. Symptomatic retears were not significantly different between groups (control: 9.1%, bursa 7.7%, P = .86). Seven patients in the control group underwent reoperation (6.4%), compared to 0 patients in the bursa group (0%, P = .2). Six-month postoperative magnetic resonance images obtained on bursa patients demonstrated 85% rotator cuff continuity (n = 17/20) as defined via Sugaya classification.
UNASSIGNED: Augmentation of rotator cuff repair with bursal tissue does not appear to have negative effects, and given the accessibility and ease of harvest of this tissue, further research should be performed to evaluate its potential for improved tendon healing or clinical outcomes.

UNASSIGNED: Augmentation with subacromial bursa has not been fully established in bursal-sided partial-thickness rotator cuff tears (PT-RCTs).
UNASSIGNED: To compare the results of acromioplasty + arthroscopic debridement versus acromioplasty + augmentation with subacromial bursa for Ellman type 2 PT-RCTs involving 25% to 50% of the tendon surface area.
UNASSIGNED: Cohort study; Level of evidence, 3.
UNASSIGNED: Included were 40 patients (mean age, 47.8 years) with Ellman type 2 PT-RCTs whose symptoms did not regress despite 3 months of nonoperative treatment. The patients underwent either acromioplasty + debridement (group A; n = 18) or acromioplasty + augmentation (group B; n = 22). Outcome scores (visual analog scale [VAS] pain score, Constant-Murley score [CMS], and American Shoulder and Elbow Surgeons [ASES] score) were obtained preoperatively and at 6, 12, and 18 months postoperatively. Magnetic resonance imaging (MRI) scans performed at 6 months postoperatively were used to determine the integrity and state of healing.
UNASSIGNED: There were no significant differences between groups A and B in preoperative VAS, CMS, or ASES scores, and patients in both groups saw significant improvement at each follow-up time point on all 3 outcome scores (P = .001 for all). Scores on all 3 outcome measures were significantly better in group B than group A at each postoperative time point (P < .05 for all). Postoperative MRI scans revealed persistent partial tears in 5 of 18 patients in group A compared with 2 of 22 patients in group B (P < .05). Conversion to full-thickness tear (3/18 patients) was seen only in group A.
UNASSIGNED: Patients who underwent biological augmentation of their PT-RCTs had improved outcome scores compared with those treated with acromioplasty and debridement alone.

BACKGROUND: It has been shown that subacromial bursa (SAB) harbors connective tissue progenitor cells (CTPCs). The purpose of this study was to evaluate the effects of implantation of subacromial bursa-derived cells (SBCs) suspended in a fibrin sealant bead and implantation of SAB tissue at rotator cuff repair site on biomechanical properties of the repair in a mouse (C57Bl/6) model of supraspinatus tendon (ST) detachment and repair.
METHODS: Part One: Murine SAB tissue was harvested and cultured. Viability of SBCs suspended in 10μl of fibrin sealant beads was confirmed in vitro and in vivo. Eighty mice underwent right ST detachment and repair augmented with either fibrin sealant bead (control group) or fibrin sealant bead with 100,000 SBCs (study group) applied at the repair site. Part Two: 120 mice underwent right ST detachment and repair and were randomized equally into 4 groups: 1) tissue group received a piece of freshly harvested SA tissue; 2) cell group received SBCs suspended in fibrin sealant bead; 3) fibrin sealant group received plain fibrin sealant bead without cells; and 4) control group received nothing at ST repair site. An equal number of mice in each group were sacrificed at 2- and 4-weeks. Specimens underwent biomechanical testing to evaluate failure force (Part One and Two) and histologic analysis of the repair site (Part One only).
RESULTS: Part One: The mean failure force in the study group was statistically higher than controls at 2- and 4-weeks (3.25 ± 1.03 N vs 2.43 ± 0.56 N, p = 0.01 and 4.08 ± 0.99 N vs 3.02 ± 0.8 N, p = 0.004, respectively). Mean cell density of the ST at the repair site was significantly lower in the study group at 2 weeks than in controls (18292.13 ± 1706.41 vs 29501.90 ± 3627.49, p = 0.001). Study group specimens had lower proteoglycan contents than controls but this difference was not statistically significant. Part Two: There was no difference in failure force between cell and tissue groups at 2- and 4-week time points (p = 0.994 and p =0.603, respectively). There was no difference in failure force between fibrin sealant bead and control groups at 2- and 4-week time points (p = 0.978 and p =0.752, respectively).
CONCLUSIONS: This study shows that the application of SBCs and SAB tissue at the rotator cuff repair site increases the strength of repair in a murine model of rotator cuff detachment and repair.

The subacromial bursa has long been demolded as friction-reducing tissue, which is often linked to shoulder pain and, therefore, partially removed during shoulder surgery. Currently, the discovery of the stem cell potential of resident bursa-derived cells shed a new light on the subacromial bursa. In the meanwhile, this neglected tissue is gaining more attention as to how it can augment the regenerative properties of adjacent tissues such as rotator cuff tendons. Specifically, the tight fibrovascular network, a high growth factor content, and the large progenitor potential of bursa-derived cells could complement the deficits that a nearby rotator cuff injury might experience due to the fact of its low endogenous regeneration potential. This review deals with the question of whether bursal inflammation is only a pain generator or could also be an initiator of healing. Furthermore, several experimental models highlight potential therapeutic targets to overcome bursal inflammation and, thus, pain. More evidence is needed to fully elucidate a direct interplay between subacromial bursa and rotator cuff tendons. Increasing attention to tendon repair will help to guide future research and answer open questions such that novel treatment strategies could harvest the subacromial bursa\'s potential to support healing of nearby rotator cuff injuries.

BACKGROUND: The role of the subacromial bursa in the development or healing of shoulder pathologies is unclear. Due to this limited knowledge, we aimed to understand specific reactions of the subacromial bursa according to rotator cuff (RC) pathologies compared to non-tendon defects of the shoulder. We hypothesized that the tissue composition and inflammatory status of the bursa are likely to vary between shoulder pathologies depending on the presence and the extent of RC lesion.
METHODS: Bursa samples from patients with either 1) shoulder instability with intact RC (healthy bursa, control), 2) osteochondral pathology with intact RC, 3) partial supraspinatus (SSP) tendon tear, or 4) full-thickness SSP tear were investigated histologically and on gene expression level.
RESULTS: Bursae from SSP tears differed from non-tendon pathologies by exhibiting increased chondral metaplasia and TGFβ1 expression. MMP1 was not expressed in healthy bursa controls, but strongly increased with full-thickness SSP tears. Additionally, the expression of the inflammatory mediators IL1β, IL6, and COX2 increased with the extent of SSP tear as shown by correlation analysis. In contrast, increased angiogenesis and nerve fibers as well as significantly upregulated IL6 and COX2 expression were features of bursae from patients with osteochondral pathology. Using immunohistochemistry, CD45+ leukocytes were observed in all examined groups, which were identified in particular as CD68+ monocytes/macrophages.
CONCLUSIONS: In summary, besides the strong increase in MMP1 expression with SSP tear, molecular changes were minor between the investigated groups. However, expression of pro-inflammatory cytokines correlated with the severity of the SSP tear. Most pronounced tissue alterations occurred for the osteochondral pathology and full-thickness SSP tear group, which demonstrates that the bursal reaction is not exclusively dependent on the occurrence of an SSP tear rather than longstanding degenerative changes. The present bursa characterization contributes to the understanding of specific tissue alterations related to RC tears or non-tendon shoulder pathologies. This pilot study provides the basis for future studies elucidating the role of the subacromial bursa in the development or healing of shoulder pathologies.