Rotator Cuff Repair Healing Research Articles

Circadian Rhythm-Regulated ADSC-Derived sEVs and a Triphasic Microneedle Delivery System to Enhance Tendon-to-Bone Healing.

Modulating the inflammatory microenvironment to reconstruct the fibrocartilaginous layer while promoting tendon repair is crucial for enhancing tendon-to-bone healing in rotator cuff repair (RCR), a persistent challenge in orthopedics. Small extracellular vesicles (sEVs) hold significant potential to modulate inflammation, yet the efficient production of highly bioactive sEVs remains a substantial barrier to their clinical application. Moreover, achieving minimally invasive local delivery of sEVs to the tendon-to-bone interface presents significant technical difficulties. Herein, the circadian rhythm of adipose-derived stem cells is modulated to increase the yield and enhance the inflammatory regulatory capacity of sEVs. Circadian rhythm-regulated sEVs (CR-sEVs) enhance the cyclic adenosine monophosphate signaling pathway in macrophage (Mφ) via platelet factor 4 delivery, thereby inhibiting Mφ M1 polarization. Subsequently, a triphasic microneedle (MN) scaffold with a tip, stem, and base is designed for the local delivery of CR-sEVs (CR-sEVs/MN) at the tendon-to-bone junction, incorporating tendon-derived decellularized extracellular matrix in the base to facilitate tendon repair. CR-sEVs/MN mitigates inflammation, promotes fibrocartilage regeneration, and enhances tendon healing, thereby improving biomechanical strength and shoulder joint function in a rat RCR model. Combining CR-sEVs with this triphasic microneedle delivery system presents a promising strategy for enhancing tendon-to-bone healing in clinical settings.

Poster 112: Toxicity of Chlorhexidine and Povidone-Iodine to Rotator Cuff Tendon

Objectives: Antimicrobial wound lavages containing chlorhexidine gluconate (CHG) or povidone-iodine (PI) are commonly used to prevent periprosthetic infection during shoulder arthroplasty. However, the potential toxicity of these solutions to the native surrounding rotator cuff tendon is not well understood. In total shoulder arthroplasty, the rotator cuff tendon is often concomitantly repaired, and any toxic effects from antimicrobial wound lavage during surgery may be detrimental to postoperative rotator cuff tendon healing. The purpose of this study was to determine the in vitro effects of a 1-minute CHG exposure and a 3-minute 0.35% PI exposure on the viability and biochemical content of rotator cuff tendon. Methods: Infraspinatus tendons (n=6 per group) were isolated from shoulders of Nubian goats (n=3; 2 female and 1 male). Tendons were submerged in Irrisept (0.05% CHG in sterile water) for 1 minute or 0.35% Betadine (PI) for 3 minutes per manufacturer guidelines, followed by phosphate-buffered saline wash and culture in tissue culture medium. Control tendon specimens were similarly exposed to tissue culture medium, followed by phosphate-buffered saline wash and culture in tissue culture medium. After seven days of culture, isolates from both the tendinous and enthesis portions of the rotator cuff were analyzed for viability, collagen content (hydroxyproline assay), and glycosaminoglycan (GAG) content (dimethylmethylene blue assay). Statistical analyses were performed via one-way ANOVA with post hoc Tukey’s test. Results: Within the tendinous portion of the rotator cuff, CHG-treated specimens demonstrated a decrease in mean tenocyte viability compared to controls (p=0.045) (Fig.1). While PI-treated specimens exhibited lower mean viability compared to controls, this difference was not statistically significant. Within the enthesis portion of the rotator cuff, tenocyte viability decreased in both CHG- and PI-treated groups; however, these decreases were not statistically significant (Fig. 2). There were no significant differences in mean collagen content/wet weight or GAG/wet weight among groups within the tendinous and enthesis portion of the rotator cuff (Fig. 3). Conclusions: Due to the potential catastrophic consequences associated with periprosthetic infection, CHG and PI antimicrobial lavages are commonly used to reduce the risk of periprosthetic infection during shoulder arthroplasty. However, in this study, brief 0.05% CHG and 0.35% PI exposures to rotator cuff tendon resulted in lower tenocyte viability 7 days after treatment. These results are consistent with the toxicity reported with exposure of CHG and PI to other musculoskeletal tissues, including articular cartilage. The toxicity of antimicrobial irrigation to the surrounding native rotator cuff tendon may be detrimental to the postoperative healing of concomitant rotator cuff repair in the setting of shoulder arthroplasty.

Bursal Tissue Harvested During Rotator Cuff Repair Contains Viable Mesenchymal Stem Cells

PurposeThe purpose of this study was to evaluate the effect of intra operative ablation on the viability, distribution, phenotype, and potential for culture expansion of bursal cells harvested during arthroscopic rotator cuff surgery. MethodsTissue was collected during primary arthroscopic rotator cuff repair on six healthy, randomly selected patients from a fellowship-trained surgeon’s practice between September 2020 and January 2021. There were 3 females (age 60 ± 8 years) and 3 males (age 61 ± 10 years). At the time of surgery, subacromial bursal tissue was subjected to no ablation, one second, or three seconds of ablation. Tissues were collected by an autograft harvesting system connected to an arthroscopic shaver and a pituitary grasper. Tissue fragments from each condition were sampled for viability testing or cell isolation. A viability kit with confocal microscopy was used to assess live and dead cells. Cell isolation consisted of collagenase digestion or placing tissue fragments onto tissue culture treated plates that induced migration of cells out of the tissue. Cell proliferation rates were monitored and surface markers for mesenchymal stem cells (MSC) and pericytes were analyzed via multi-color flow cytometry. ResultsIncreased ablation time significantly reduced cell viability. The mean percentage of live cells was 55.2 ± 27.2% (range 26-90% live) in the control group, 46.8 ± 23.8% (range 9.6-69.6% p = 0.045) in the short, and 35.5 ± 19% (range 11-54% p = 0.03) in the long ablation group. No significant differences in population doubling level (1.6 ± 0.5 days) and population doubling time (6.7 ± 2.4 days) were observed in cells from any treatment. The surface marker profile indicated an MSC phenotype with absence of a pericyte population. Ablation or cell isolation procedure had no significant effect on the surface marker profile of isolated cells. ConclusionRadiofrequency ablation significantly reduced the overall tissue viability, but had no significant effect on cell proliferation, or expression of surface markers on isolated subacromial bursal cells harvested arthroscopically. Clinical RelevanceAnalysis of the viability and performance of cells harvested after the use of ablation devices using mechanical surgical collection during RCR surgery could further our understanding of subacromial bursal tissue and its potential role in augmenting rotator cuff repair healing.

A modified Patte classification system for rotator cuff tendon retraction to predict reparability and tendon healing in arthroscopic rotator cuff repair.

The purpose of this study was to propose a modified Patte classification system for tendon retraction, including the cut-off points for predicting reparability and rotator cuff healing after arthroscopic rotator cuff repair (ARCR) and assess its prediction accuracy and measurement reliability. This retrospective study included 463 consecutive patients scheduled to undergo ARCR for full-thickness supraspinatus tears. Receiver operating characteristic (ROC) curve analysis was used to determine the cut-off points for predicting reparability and tendon healing. The modified Patte classification system, in which these cut-off points were combined with the original Patte classification, classified the tendon retraction as stages I-V. The prediction accuracy of reparability and tendon healing was assessed using the area under the curve (AUC). Measurement reliability was determined using Cohen's κ statistics. Of the 402 included patients, 32 rotator cuff tears were irreparable and 71 of the remaining 370 were diagnosed with healing failure. ROC analysis determined the cut-off point of reparability at the medial one-fifth and that of tendon healing at the medial one-third of the humeral head. The AUC of the modified Patte classification for predicting reparability and tendon healing was 0.897 (excellent) and 0.768 (acceptable), respectively. Intra-rater reliability was almost perfect (mean κ value: 0.875), and inter-rater reliability was substantial (0.797). Diagnostic performance of the modified Patte classification system was excellent for reparability and acceptable for rotator cuff healing, with high measurement reliability. The modified Patte classification system can be easily implemented in clinical practice for planning surgical procedures and counselling patients in the day-by-day clinical work. Level III.

Effect of Polydeoxyribonucleotide on Tendon Healing and Fatty Degeneration in Arthroscopic Rotator Cuff Repair: A Randomized Controlled Trial

Effect of Polydeoxyribonucleotide on Tendon Healing and Fatty Degeneration in Arthroscopic Rotator Cuff Repair: A Randomized Controlled Trial

The Reverse Fragility Index: Interpreting the Evidence for Arthroscopic Rotator Cuff Repair Healing Associated With Early Versus Delayed Mobilization.

Background: The American Academy of Orthopaedic Surgeons (AAOS) clinical practice guidelines (CPGs) note "strong" evidence that early and delayed mobilization protocols after small to medium arthroscopic rotator cuff repairs achieve similar rotator cuff healing rates. Purpose: We utilized the reverse fragility index (RFI) to assess the fragility of randomized controlled trials (RCTs) reporting no statistically significant difference in tendon re-tear rates after rotator cuff repair in those undergoing early versus delayed rehabilitation. Methods: Randomized controlled trials used in the most recent AAOS CPGs on the timing of postoperative mobilization after arthroscopic rotator cuff repairs were analyzed. Only RCTs with a reported P value ≥ .05 were included. The RFI at a threshold of P < .05 was calculated for each study. The reverse fragility quotient (RFQ) was calculated by dividing the RFI by the study sample size. Results: In 6 clinical trials with a total of 542 patients, the number of tendon re-tear events was 48. The median RFI at the P < .05 threshold was 4 (range: 3.25-4.75), and the median RFQ was .05 (range: 0.03-0.08). The median loss to follow-up was 6 patients. Of the 6 studies investigated, 3 reported a loss to follow-up greater than their respective RFI. Conclusion: The equivalence in rotator cuff repair healing rates associated with early and delayed mobilization protocols rests on fragile studies, as their statistical non-significance can be reversed by changing the outcome status of only a handful of patients. Consideration should be given to the routine reporting of RFI in clinical practice guidelines including RCTs with statistically non-significant results.

Prospective Randomized Trial of Biologic Augmentation With Bone Marrow Aspirate Concentrate in Patients Undergoing Arthroscopic Rotator Cuff Repair

Background: Although initial studies have demonstrated that concentrated bone marrow aspirate (cBMA) injections promote rotator cuff repair (RCR) healing, there are no randomized prospective studies investigating clinical efficacy. Hypothesis/Purpose: To compare outcomes after arthroscopic RCR (aRCR) with and without cBMA augmentation. It was hypothesized that cBMA augmentation would result in statistically significant improvements in clinical outcomes and rotator cuff structural integrity. Study Design: Randomized controlled trial; Level of evidence, 1. Methods: Patients indicated for aRCR of isolated 1- to 3-cm supraspinatus tendon tears were randomized to receive adjunctive cBMA injection or sham incision. Bone marrow was aspirated from the iliac crest, concentrated using a commercially available system, and injected at the aRCR site after repair. Patients were assessed preoperatively and serially until 2 years postoperatively via the following functional indices: American Shoulder and Elbow Surgeons (ASES), Single Assessment Numeric Evaluation (SANE), Simple Shoulder Test, 12-Item Short Form Health Survey, and Veterans RAND 12-Item Health Survey. Magnetic resonance imaging (MRI) was performed at 1 year to assess rotator cuff structural integrity according to Sugaya classification. Treatment failure was defined as decreased 1- or 2-year ASES or SANE scores as compared with preoperative baseline, the need for revision RCR, or conversion to total shoulder arthroplasty. Results: An overall 91 patients were enrolled (control, n = 45; cBMA, n = 46): 82 (90%) completed 2-year clinical follow-up and 75 (82%) completed 1-year MRI. Functional indices significantly improved in both groups by 6 months and were sustained at 1 and 2 years (all P < .05). The control group showed significantly greater evidence of rotator cuff retear according to Sugaya classification on 1-year MRI (57% vs 18%; P < .001). Treatment failed for 7 patients in each group (control, 16%; cBMA, 15%). Conclusion: cBMA-augmented aRCR of isolated supraspinatus tendon tears may result in a structurally superior repair but largely fails to significantly improve treatment failure rates and patient-reported clinical outcomes when compared with aRCR alone. Additional study is warranted to investigate the long-term benefits of improved repair quality on clinical outcomes and repair failure rates. Registration: NCT02484950 (ClinicalTrials.gov identifier).

Poster 130: Tendon-to-bone Healing in a CCR2 Knockout Mouse Model of Delayed Rotator Cuff Repair

Poster 130: Tendon-to-bone Healing in a CCR2 Knockout Mouse Model of Delayed Rotator Cuff Repair

Stem cell sheet interpositioned between the tendon and bone would be better for healing than stem cell sheet overlaid above the tendon-to-bone junction in rotator cuff repair of rats.

BackgroundAlthough stem cells might enhance natural enthesis healing in surgical rotator cuff repair, not much attention has been given to the delivery and location of delivering stem cells. The purpose of this study to know where to locate those stem cells during repair.MethodsAnimal model of chronic rotator cuff tear was created in 24 rats. Adipose-derived stem cells were engineered as a sheet and transplanted 1) between a torn tendon and humerus (interposition group) or 2) over a repaired tendon-to-bone junction (overlay group) at the time of surgical repair. Tracking of stem cells with overexpression of green fluorescent protein (GFP) were carried out at the time of sacrifice in additional 4 shoulders in each group. Histological and Biomechanical evaluation was performed to compare the differences in tendon-to-bone healing.ResultsHistology showed increased fibrocartilage, a clear boundary at the mineralized fibrocartilage, abundant collagen type III, and higher total scores, especially in the interposition group. GFP-overexpression was observed at the transplanted site at 2 weeks after repair. Although two groups where stem cell sheets applied showed higher load to failure than the repair-only group, the load to failure was not different between the interposition and overlay group.ConclusionIn the chronic rotator cuff repair model, stem cell sheets enhanced regeneration of the tendon-to-bone junction. This regeneration was effective when the stem cell sheet was interpositioned at the tendon-to-bone interface.Level of evidenceBasic Science Study; In Vivo Animal Model; Histology and Biomechanics.

Effect of kartogenin-loaded gelatin methacryloyl hydrogel scaffold with bone marrow stimulation for enthesis healing in rotator cuff repair

Strategies involving microfracture, biomaterials, growth factors, and chemical agents have been evaluated for improving enthesis healing. Kartogenin (KGN) promotes selective differentiation of bone marrow mesenchymal stem cells (BMSCs) into chondrocytes. Gelatin methacryloyl (GelMA) is a promising biomaterial for engineering scaffolds and drug carriers. Herein, we investigated KGN-loaded GelMA hydrogel scaffolds with a bone marrow-stimulating technique for the repair of rotator cuff tear. KGN-loaded GelMA hydrogel scaffolds were obtained by ultraviolet GelMA crosslinking and vacuum freeze-drying. Fifty-four New Zealand rabbits were randomly divided into (1) repair only (control), (2) microfracture + repair (BMS), and (3) microfracture + repair augmentation with a KGN-loaded GelMA hydrogel scaffold (combined) groups. Tendons were repaired by transosseous sutures. The structure, degradation, and invitro KGN release of the scaffolds were characterized. Animals were euthanized 4, 8, and 12 weeks after repair. Enthesis healing was evaluated by macroscopy, microcomputed tomography, histology, and biomechanical tests. The KGN-loaded GelMA hydrogel scaffolds are porous with a 60.4 ± 28.2-μm average pore size, and they degrade quickly in 2.5 units/mL collagenase solution. Nearly 81% of KGN was released into phosphate-buffered saline within 12 hours, whereas the remaining KGN was released in 7 days. Macroscopically, the repaired tendons were attached to the footprint. No differences were detected postoperatively in microcomputed tomography analysis among groups. Fibrous scar tissue was the main component at the tendon-to-bone interface in the control group. Disorderly arranged cartilage formation was observed at the tendon-to-bone interface in the BMS and combined groups 4 weeks after repair; the combined group exhibited relatively more cartilage. The combined group showed improved cartilage regeneration 8 and 12 weeks after repair. Similar results were found in tendon maturation scores. The ultimate load to failure and stiffness of the repaired tendon increased in all 3 groups. At 4 weeks after repair, the BMS and combined groups exhibited greater ultimate load to failure than the control group, although there was no difference in stiffness among groups. The BMS and combined groups exhibited greater ultimate load to failure and stiffness than the control group, and the combined group exhibited better values than the BMS group at 8 and 12 weeks after repair. Compared with the bone marrow-stimulating technique, the KGN-loaded GelMA hydrogel scaffold with bone marrow stimulation improved enthesis healing by promoting fibrocartilage formation and improving the mechanical properties.

Acromial morphology is not associated with rotator cuff tearing or repair healing

The purposes of this study were to determine whether acromial morphology (1) could be measured accurately on magnetic resonance images (MRIs) as compared to computed tomographs (CTs) as a gold standard, (2) could be measured reliably on MRIs, (3) differed between patients with rotator cuff tears (RCTs) and those without evidence of RCTsor glenohumeral osteoarthritis, and (4) differed between patients with rotator cuff repairs (RCRs) that healed and those that did not. This is a retrospective comparative study. We measured coronal, axial, and sagittal acromial tilt; acromial width, acromial anterior and posterior coverage, and glenoid version and inclination on MRI corrected into the plane of the glenoid. We determined accuracy by comparison with CT via intraclass correlation coefficients (ICCs). To determine reliability, these same measurements were made on MRI by 2 observers and ICCs calculated. We compared these measurements between patients with a full-thickness RCT and patients aged >50 years without evidence of an RCT or glenohumeral osteoarthritis. We then compared these measurements between those patients with healed RCRs and those with a retorn rotator cuff on MRI. In this portion, we only included patients with both a preoperative MRIand a postoperative MRI at least 1 year from RCR. Only those patients without tendon defects on postoperative MRIs were considered to be healed. In these patients, we also radiographically measured the critical shoulder angle. In a validation cohort of 30 patients with MRI and CT, all ICCs were greater than 0.86. In these patients, the inter-rater ICCs of the MRI measurements were >0.53. In our RCT group of 110 patients, there was greater acromial width [mean difference (95% confidence interval) = 0.1 (0, 0.2) mm, P = .012] and significantly less sagittal acromial tilt [9° (5°-12°), P < .001] than in our comparison group of 107 patients. A total of 110 RCRs were included. Postoperative MRI scans were obtained at a mean follow-up of 24.2 ± 15.8 months, showing 84 patients (76%) had healed RCRs. Aside from acromial width, which was 0.2 mm different and thus did not have clinical significance, there was no association between healing and any of the measured morphologic characteristics. Patients with healed repairs had significantly smaller tears in terms of both width (P < .001) and retraction (P < .001). Although the acromion is wider in RCTs, the difference of 0.1 mm likely has no clinical significance. The acromion is more steeply sloped from posteroinferior to anterosuperior in those with RCTs. These findings call into question subacromial impingement due to native acromial morphology as a cause of rotator cuff tearing. Acromial morphology, critical shoulder angle, and glenoid inclination were not associated with healing after RCR. This study does not support lateral acromioplasty.

The 3D-Printed PLGA Scaffolds Loaded with Bone Marrow-Derived Mesenchymal Stem Cells Augment the Healing of Rotator Cuff Repair in the Rabbits

The healing of tendon–bone in the rotator cuff is featured by the formation of the scar tissues in the interface after repair. This study aimed to determine if the 3D-printed poly lactic-co-glycolic acid (PLGA) scaffolds loaded with bone marrow-derived mesenchymal stem cells (BMSCs) could augment the rotator cuff repair in the rabbits. PLGA scaffolds were generated by the 3D-printed technology; Cell Counting Kit-8 assay evaluated the proliferation of BMSCs; the mRNA and protein expression levels were assessed by quantitative real-time polymerase chain reaction and western blot, respectively; immunohistology evaluated the rotator cuff repair; biomechanical characteristics of the repaired tissues were also assessed. 3D-printed PLGA scaffolds showed good biocompatibility without affecting the proliferative ability of BMSCs. BMSCs–PLGA scaffolds implantation enhanced the cell infiltration into the tendon-bone injunction at 4 weeks after implantation and improved the histology score in the tendon tissues after implantation. The mRNA expression levels of collagen I, III, tenascin, and biglycan were significantly higher in the scaffolds + BMSCs group at 4 weeks post-implantation than that in the scaffolds group. At 8 and 12 weeks after implantation, the biglycan mRNA expression level in the BMSCs–PLGA scaffolds group was significantly lower than that in the scaffolds group. BMSCs–PLGA scaffolds implantation enhanced collagen formation and increased collagen dimeter in the tendon–bone interface. The biomechanical analysis showed that BMSCs–PLGA scaffolds implantation improved the biomechanical properties of the regenerated tendon. The combination of 3D-printed PLGA scaffolds with BMSCs can augment the tendon–bone healing in the rabbit rotator cuff repair model.

Prospective Randomized Trial Of Biologic Augmentation With Mesenchymal Stem Cells In Patientsundergoing Arthroscopic Rotator Cuff Repair

Objectives: To compare the clinical outcome of arthroscopic rotator cuff repair with and without augmentation with MSCs and to identify the incidence of persistent structural defects in the tendon following surgery Methods: Patients aged 18-70 undergoing repair of a full-thickness supraspinatus tear or partial thickness converted to full thickness tear determined by MRI were identified and prospectively enrolled. Exclusion criteria included involvement of the subscapularis tendon, revision surgery or irreparable tear. In the injection group, 60 cc of bone marrow aspirate was drawn from the iliac crest and processed to bone marrow aspirate concentrate (BMAC) using the Arthrex Angel System (Arthrex, Naples, FL). After completion of the rotator cuff repair, half of the BMAC was injected into the tendon at the junction of the bone and tendon while the other half was injected at the site of the footprint. The control group received a small 0.5 cm incision on the hip to maintain blinding. All patients underwent a shoulder exam pre-operatively as well as at 3 months, 6 months, 1 year and 2 years post-operatively. All patients completed the Standardized Shoulder Test (SST), ASES, Constant, SANE, and VR/SF-12 questionnaires preoperatively as well as 3 months, 6 months, 12 months, 18 months and 24 months postoperatively. Baseline questionnaire scores were subtracted from scores at each timepoint to find the improvement and unpaired T-tests were performed between the two groups. Additionally, all patients underwent an MRI at 12 months postoperatively to evaluate the rotator cuff. MRIs were read by a board-certified orthopaedic surgeon and graded using the Sugaya classification system. Results: 34 patients were randomized to the control group and 28 were randomized to the receive the injection. Average BMA MSC concentration (#/uL) was 2.63 compared to 14.95 for the BMAC MSC concentration. As a result, the BMAC was on average 5.68 times as concentrated with respect to MSC per ul when compared to the BMA. Patients received an average BMAC volume of 2.7 mL, equating to 50410.79 +/- 25375.45 mesenchymal stem cells. There were no differences across improvement in patient reported outcomes from baseline between the control group and the group randomized to receive the injection, except for the Standardized Shoulder Test at 6 months. The mean SST score at 12 months was 87.50 in the BMAC group compared with 85.32 in the control (p=0.18). The mean ASES score at 12 months was 87.38 in the BMAC group and 89.96 in the control group (0.67). Mean Sugaya score for the control group was 3.25±1.12 (range 2-5). Mean Sugaya score for the injection group was 2.60±0.91 (range 2-5). Sugaya scores showed statistical significance with Chi-squared test at 1 year postoperative MRI (p=0.0012), and approached statistical significance with independent t test (p=0.067). Conclusion: MSCs injected into the shoulder at the time of rotator cuff repair show improved tendon quality on post-operative MRI at 1-year post-op, based on the Sugaya scoring system, with the difference in mean Sugaya score approaching significance. Further investigation is needed into this new and evolving treatment; however, it shows promise for improving the rate of rotator cuff repair healing and overall functional outcome.

Effect of a poloxamer-based thermosensitive gel on rotator cuff repair in a rabbit model: a controlled laboratory study

BackgroundA common complication after rotator cuff repair is postoperative stiffness, which can be reduced by a simple application of an anti-adhesive agent. However, anti-adhesive agents may affect rotator cuff healing by preventing fibrosis. This experimental animal study evaluated the effect of the application of a poloxamer-based thermosensitive anti-adhesive gel and its influence on the healing of an acute rotator cuff repair in a rabbit model.MethodsAcute rotator cuff repair (supraspinatus tendon) was performed using a transosseous suturing method. One shoulder on a randomly selected side was treated with a local application of the anti-adhesive agent (applied side), and saline was applied to the contralateral side (control side). Biomechanical testing and histological analyses were performed at 4 and 8 weeks postoperatively. Eight rabbits were included for each testing and time point, for a total of 32 rabbits.ResultsThe failure load at 4 weeks was lower in the experimental group (95.2 ± 19.6 N vs. 110.0 ± 20.5 N; P = 0.017). Conversely, at 8 weeks, the failure load was higher in the experimental group (148.3 ± 16.2 N) than in the control group (122.4 ± 16.9 N; P = 0.002). Histological analyses revealed no statistically significant differences in the tendon maturing scores at 4 and 8 weeks between the two groups (all P > 0.05). The thickness of the fibrosis between the rotator cuff tendon and deltoid was thinner in the experimental group at both time points (0.50 ± 0.25 vs. 1.27 ± 0.47; P = 0.002 at 4 weeks, and 0.37 ± 0.35 vs. 1.39 ± 0.50; P = 0.003 at 8 weeks).ConclusionsApplication of an anti-adhesive agent in this rotator cuff model confirmed the agent’s effectiveness at reducing fibrosis in the subacromial space. The healing of the tendon showed interesting results, as the experimental group had poorer biomechanical strength at 4 weeks but superior strength at 8 weeks.

Effects of Perioperative Nonsteroidal Anti-inflammatory Drug Administration on Soft Tissue Healing: A Systematic Review of Clinical Outcomes After Sports Medicine Orthopaedic Surgery Procedures.

Background:The effects of perioperative nonsteroidal anti-inflammatory drugs (NSAIDs) on soft tissue healing in humans have yet to be established.Purpose:To systematically review the literature addressing the effects of perioperative NSAID administration on soft tissue healing and clinical patient outcomes.Study Design:Systematic review; Level of evidence, 3.Methods:This review study was conducted in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement. A review of the literature regarding the existing evidence for clinical effects of NSAID use on soft tissue healing was performed through use of the Cochrane Database of Systematic Reviews, the Cochrane Central Register of Controlled Trials, PubMed (1980 to present), and MEDLINE. Inclusion criteria for articles were as follows: outcome studies after soft tissue (ligament, meniscus, tendon, muscle) healing after surgical procedure with perioperative NSAID administration, at least 1 year of follow-up, English language, and human participants.Results:A total of 466 studies were initially retrieved, with 4 studies satisfying all inclusion criteria. Among the surgical procedures reported, 93% of the patients (4144/4451) underwent anterior cruciate ligament (ACL) reconstruction, 3% (120/4451) underwent rotator cuff repair, 3% (155/4451) underwent Bankart shoulder repair, and 1% (32/4451) underwent meniscal repair. The reported surgical failure rate among patients administered NSAIDs was 3.6% (157/4360). The reported surgical failure rate among control participants not given NSAIDs was 3.7% (147/3996). NSAID use showed no statistically significant effect on need for reoperation in meniscal repair (P = .99), ACL reconstruction (P = .8), and Bankart repair (P = .8) compared with no NSAID administration. Celecoxib administration had a significantly higher rate of retear (37%) after rotator cuff repair compared with ibuprofen (7%) (P = .009).Conclusion:Insufficient data are available to definitively state the effects of perioperative NSAIDs on soft tissue healing. Use of NSAIDs should be considered on a case-by-case basis and may not affect healing rates following either meniscal, ACL, rotator cuff, or Bankart repair. However, celecoxib (a selective COX-2 inhibitor) may inhibit tendon-to-bone healing in rotator cuff repair. Further research through clinical trials is required to fully determine whether NSAIDs have an adverse effect on soft tissue healing.

Biomarkers of Rotator Cuff Disease Severity and Repair Healing.

* Identifying biomarkers of disease severity and prognostic factors for healing after rotator cuff repair would allow improved clinical decision-making about the treatment of patients with rotator cuff pathologies and possibly identify targets for therapeutic intervention to promote healing.* The state of investigations to identify biomarkers of disease severity or repair success has been neither systematic nor standardized. Clinical studies to date have been largely exploratory, with small sample sizes and univariate analyses.* Current evidence shows that inflammatory biomarkers (interleukin 1 [IL-1β], interleukin 1 receptor antagonist [IL-1ra], tumor necrosis factor alpha [TNF-α], cyclooxygenase-2 [COX-2], inducible nitric oxide synthase [iNOS]) and matrix remodeling biomarkers (biglycan, aggrecan, and members of the collagen and matrix metalloproteinase [MMP] families) were found to be significantly associated with rotator cuff disease severity. Similarly, inflammatory biomarker COX-2 and matrix remodeling biomarkers (biglycan, tissue inhibitor of metalloproteinase [TIMP]-1, and members of the collagen and MMP families) were found to be significantly associated with rotator cuff retears.* Future studies investigating biomarkers of rotator cuff disease severity and healing should be standardized and should employ sample sizes large enough to allow for adequate power and multivariate analyses. Genetic and cellular biomarkers should be investigated, in addition to the more typical biochemical and structural factors. Progress would be greatly facilitated by forming a consortium of experts to define a strategic approach to biomarker research in rotator cuff disease and repair.

Augmentation with a reinforced acellular fascia lata strip graft limits cyclic gapping of supraspinatus repairs in a human cadaveric model

A reinforced biologic strip graft was designed to mechanically augment the repair of rotator cuff tears that are fully reparable by arthroscopic techniques yet have a likelihood of failure. This study assessed the extent to which augmentation of human supraspinatus repairs with a reinforced fascia strip can reduce gap formation during in vitro cyclic loading. The supraspinatus tendon was sharply released from the proximal humerus and repaired back to its insertion with anchors in 9 matched pairs of human cadaveric shoulders. One repair from each pair was also augmented with a reinforced fascia strip. All repairs were subjected to cyclic mechanical loading of 5 to 180 N for 1000 cycles. All augmented and nonaugmented repair constructs completed 1000 cycles of loading. Augmentation with a reinforced fascia strip graft significantly decreased the amount of gap formation compared with nonaugmented repairs. The average gap formation of augmented repairs was 1.5 ± 0.7 mm after the first cycle vs. 3.0 ± 1.2 mm for nonaugmented repairs (P = .003) and 5.0 ± 1.5 mm after 1000 cycles of loading, which averaged 24% ± 21% less than the gap formation of nonaugmented repairs (7.0 ± 2.8 mm, P = .014). Cadaveric human supraspinatus repairs augmented with a reinforced fascia strip have significantly less initial stroke elongation and gap formation than repairs without augmentation. Augmentation limited gap formation to the greatest extent early in the testing protocol. Human studies are necessary to confirm the appropriate indications and effectiveness of augmentation scaffolds for rotator cuff repair healing in the clinical setting.

Growth factor delivery strategies for rotator cuff repair and regeneration

The high incidence of degenerative tears and prevalence of retears (20–95%) after surgical repair makes rotator cuff injuries a significant health problem. This high retear rate is attributed to the failure of the repaired tissue to regenerate the native tendon-to-bone insertion (enthesis). Biological augmentation of surgical repair such as autografts, allografts, and xenografts are confounded by donor site morbidity, immunogenicity, and disease transmission, respectively. In contrast, these risks may be alleviated via growth factor therapy, which can actively influence the healing environment to promote functional repair. Several challenges have to be overcome before growth factor delivery can translate into clinical practice such as the selection of optimal growth factor(s) or combination, identification of the most efficient stage and duration of delivery, and the design considerations for the delivery device. Emerging insight into the injury-repair microenvironment and our understanding of growth factor mechanisms in healing are informing the design of advanced delivery scaffolds to effectively treat rotator cuff tears. Here, we review potential growth factor candidates, design parameters and material selection for growth factor delivery, innovative and dynamic delivery scaffolds, and novel therapeutic targets from tendon and developmental biology for the structural and functional healing of rotator cuff repair.

Management of Failed Rotator Cuff Repair in Young Patients.

Management of failed rotator cuff repair may be difficult, especially in young patients. Various nonmodifiable and modifiable patient factors, including age, tendon quality, rotator cuff tear characteristics, acute or chronic rotator cuff tear, bone quality, tobacco use, and medications, affect rotator cuff repair healing. Surgical variables, such as the technique, timing, tension on the repair, the biomechanical construct, and fixation, as well as the postoperative rehabilitation strategy also affect rotator cuff repair healing. Variable outcomes have been reported in patients who undergo revision rotator cuff repair; however, a systematic surgical approach may increase the likelihood of a successful outcome. Numerous cellular and mechanical biologic augments, including platelet-rich plasma, platelet-rich fibrin matrix, mesenchymal stem cells, and acellular dermal matrix grafts, have been used in rotator cuff repair; however, conflicting or inconclusive outcomes have been reported in patients who undergo revision rotator cuff repair with the use of these augments. A variety of tendon transfer options, including latissimus dorsi, teres major, lower trapezius, pectoralis minor, pectoralis major, combined pectoralis major and latissimus dorsi, and combined latissimus dorsi and teres major, are available for the management of massive irreparable rotator cuff tears. Ultimately, the optimization of surgical techniques and the use of appropriate biologic/tendon transfer techniques, if indicated, is the best method for the management of failed rotator cuff repair.

Increasing age and tear size reduce rotator cuff repair healing rate at 1 year

Background and purpose — There is a need to understand the reasons why a high proportion of rotator cuff repairs fail to heal. Using data from a large randomized clinical trial, we evaluated age and tear size as risk factors for failure of rotator cuff repair.Patients and methods — Between 2007 and 2014, 65 surgeons from 47 hospitals in the National Health Service (NHS) recruited 447 patients with atraumatic rotator cuff tendon tears to the United Kingdom Rotator Cuff Trial (UKUFF) and 256 underwent rotator cuff repair. Cuff integrity was assessed by imaging in 217 patients, at 12 months post-operation. Logistic regression analysis was used to determine the influence of age and intra-operative tear size on healing. Hand dominance, sex, and previous steroid injections were controlled for.Results — The overall healing rate was 122/217 (56%) at 12 months. Healing rate decreased with increasing tear size (small tears 66%, medium tears 68%, large tears 47%, and massive tears 27% healed). The mean age of patients with a healed repair was 61 years compared with 64 years for those with a non-healed repair. Mean age increased with larger tear sizes (small tears 59 years, medium tears 62 years, large tears 64 years, and massive tears 66 years). Increasing age was an independent factor that negatively influenced healing, even after controlling for tear size. Only massive tears were an independent predictor of non-healing, after controlling for age.Interpretation — Although increasing age and larger tear size are both risks for failure of rotator cuff repair healing, age is the dominant risk factor.