ArticleLiterature Review

The biology of rotator cuff healing

Authors:
  • Sonnenhof Orthopaedics Sportsclinicnumber1 Inselspital
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Abstract

Despite advances in surgical reconstruction of chronic rotator cuff (RC) tears leading to improved clinical outcomes, failure rates of 13-94% have been reported. Reasons for this rather high failure rate include compromised healing at the bone-tendon interface, as well as the musculo-tendinous changes that occur after RC tears, namely retraction and muscle atrophy, as well as fatty infiltration. Significant research efforts have focused on gaining a better understanding of these pathological changes in order to design effective therapeutic solutions. Biological augmentation, including the application of different growth factors, platelet concentrates, cells, scaffolds and various drugs, or a combination of the above have been studied. It is important to note that instead of a physiological enthesis, an abundance of scar tissue is formed. Even though cytokines have demonstrated the potential to improve rotator cuff healing in animal models, there is little information about the correct concentration and timing of the more than 1500 cytokines that interact during the healing process. There is only minimal evidence that platelet concentrates may lead to improvement in radiographic, but not clinical outcome. Using stem cells to biologically augment the reconstruction of the tears might have a great potential since these cells can differentiate into various cell types that are integral for healing. However, further studies are necessary to understand how to enhance the potential of these stem cells in a safe and efficient way. This article intends to give an overview of the biological augmentation options found in the literature.

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... D espite the advancements in arthroscopic surgery with procedure-specific devices, variable healing rates between 13% and 94% prevail for rotator cuff repairs. [1][2][3] This is due to poor tendon quality with degenerative changes, massive rotator cuff tears, and chronic tears with fatty infiltration of the muscle and concomitant muscle atrophy. 1,3,4 Age, smoking, diabetes mellitus, and hypercholesterolemia are important biological factors and comorbidities, respectively. ...
... [1][2][3] This is due to poor tendon quality with degenerative changes, massive rotator cuff tears, and chronic tears with fatty infiltration of the muscle and concomitant muscle atrophy. 1,3,4 Age, smoking, diabetes mellitus, and hypercholesterolemia are important biological factors and comorbidities, respectively. 3 One fundamental factor of rotator cuff healing is that instead of a physiological enthesis, scar tissue is formed. ...
... 1,3,4 Age, smoking, diabetes mellitus, and hypercholesterolemia are important biological factors and comorbidities, respectively. 3 One fundamental factor of rotator cuff healing is that instead of a physiological enthesis, scar tissue is formed. 1,3 The scar tissue formation during healing results in an inferior construct compared to normal tendon tissue. ...
Article
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Purpose To report the clinical outcomes after biologically augmented rotator cuff repair (RCR) with a fibrin scaffold derived from autologous whole blood and supplemented with concentrated bone marrow aspirate (cBMA) harvested at the proximal humerus. Methods Patients who underwent arthroscopic RCR with biologic augmentation using a fibrin clot scaffold (“Mega- Clot”) containing progenitor cells and growth factors from proximal humerus BMA and autologous whole blood between April 2015 and January 2018 were prospectively followed. Only high-risk patients in primary and revision cases that possessed relevant comorbidities or physically demanding occupation were included. Minimum follow-up for inclusion was 1 year. The visual analog score for pain (VAS), American Shoulder and Elbow Surgeons (ASES), Simple Shoulder Test (SST), Single Assessment Numerical Evaluation (SANE), and Constant-Murley scores were collected preoperatively and at final follow-up. In vitro analyses of the cBMA and fibrin clot using nucleated cell count, colony forming units, and live/dead assays were used to quantify the substrates. Results Thirteen patients (56.9 ± 7.7 years) were included. The mean follow-up was 26.9 ± 17.7 months (n = 13). There were significant improvements in all outcome scores from the preoperative to the postoperative state: VAS (5.6 ± 2.5 to 3.1 ± 3.2; P < .001), ASES (42.0 ± 17.1 to 65.5 ± 30.6; P < .001), SST (3.2 ± 2.8 to 6.5 ± 4.7; P = .002), SANE (11.5 ± 15.6 to 50.3 ± 36.5; P < .001), and Constant-Murley (38.9 ± 17.5 to 58.1 ± 26.3; P < .001). Six patients (46%) had retears on postoperative MRI, despite all having improvements in pain and function except one. All failures were chronic rotator cuff tears, and all were revision cases except one (1.6 ± 0.5 previous RCRs). The representative sample of harvested cBMA showed an average of 28.5 ± 9.1 × 10⁶ nucleated cells per mL. Conclusion Arthroscopic rotator cuff repairs that are biologically augmented with a fibrin scaffold containing growth factors and autologous progenitor cells derived from autologous whole blood and humeral cBMA can improve clinical outcomes in primary, as well as revision cases in high-risk patients. However, the incidence of retears remains a concern in this population, demanding further improvements in biologic augmentation. Level of Evidence: IV, therapeutic case series.
... Surgical repair of RCT is one of the most commonly performed procedures because of its positive outcomes. However, previous studies have reported high retear rates following RC repair, accounting for 26-94% [3][4][5]. The re-tear of RC repair negatively affects long-term clinical outcomes. ...
... Tendon-bone healing (TBH) is vital to the ultimate success. Facilitate the quality of TBH is the core of repair and functional rehabilitation [4]. Therefore, new biologic strategies that enhance the TBH response are subjects of interest in sports medicine [4][5][6][7]. ...
... Facilitate the quality of TBH is the core of repair and functional rehabilitation [4]. Therefore, new biologic strategies that enhance the TBH response are subjects of interest in sports medicine [4][5][6][7]. ...
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Background: Application of platelet-rich plasma (PRP) can improve tendon-bone healing (TBH) after rotator cuff surgical repair. Graphene Oxide (GO) is a steady, controlled, and sustained carrier. The purpose of this study is to determine whether GO/PRP Composite Scaffold enhances the TBH after RC surgical repair in a rabbit model. Methods: A full-thickness tear of the supraspinatus tendon was created and repaired in 36 adult male New Zealand rabbits. They were divided into three groups: Control group, PRP group, and GO/PRP Composite Scaffold group (GO group). The effect of GO/PRP Composite Scaffold on TBH was assessed using histological and biomechanical evaluations at 8 and 12 weeks postoperatively. Results: Histological analysis showed that greater continuity, better orientation, and more density of collagen fiber were detected in the GO group than PRP and Control groups at 8 and 12 weeks, respectively. Results of biomechanical evaluations showed that the load to failure and stiffness of the GO group were statistically higher than those of PRP and Control groups at both 8 and 12 weeks (P<0.05). Compared with 8 weeks in the GO group, there was no significant difference in load to failure at 12 weeks (P>0.05), while the stiffness at 12 weeks was higher than that at 8 weeks (P<0.05). Conclusions: These results demonstrated that GO/PRP Composite Scaffold enhanced the TBH following rotator cuff surgical repair in a rabbit model. The GO may be an effective carrier for PRP into repair sites.
... 3. Consumo de tabaco: la nicotina actúa como vasoconstrictor, disminuyendo el aporte de oxígeno a los tejidos, lo cual afecta en especial a la zona hipovascular tanto del supraespinoso como del infraespinoso (8,(28)(29)(30) . ...
... En las roturas del manguito rotador se produce la retracción del vientre muscular y su tendón, que modifica el ángulo de penación de las fibras musculares (30) . A consecuencia de ello, se genera un proceso de atrofia de las fibras musculares, fibrosis y acumulación grasa alrededor de los músculos conocido como degeneración grasa. ...
... Como comentamos previamente, la rotura de los tendones del manguito rotador se produce a consecuencia de múltiples factores, entre los que destacaremos el envejecimiento, el sobreuso y las alteraciones vasculares, que provocan cambios patológicos en la microestructura del tendón (30) . ...
... Some tendons such as the Achilles tendon can also undergo rupture following treatment with some antibiotics (75,76) or statins (77-79) but this again is a rare event and some aspects have been called into question (80)(81)(82). Partial tears of the rotator cuff tendon often occur very near the enthesis of the tendon-bone interface, a site very difficult to repair and have a high rate of re-injury (83)(84)(85), likely as the enthesis is a unique structure (86,87). As tendons can have three sites for incurring a tear (myotendinous junction, mid-substance, or the insertion into bone), this further complicates the repair process. ...
... Endogenous repair following either conservative care (no surgery) or following surgery leads to scar formation with the risk for functional compromise due to the inferior biochemical and biomechanical properties of the scar tissue (84,85,92). However, recently Chen et al. (23,93) have reported that some patients who have had their Achilles tendon ruptures surgically repaired had very good functional outcomes by 1-year post-surgery while others had less optimal outcomes. ...
Article
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Tendons are dense connective tissues of the musculoskeletal system that link bones with muscles to foster mobility. They have complex structures and exist in varying biomechanical, metabolic and biological environments. In addition, tendon composition and mechanical properties can change over the lifespan as an individual ages. Many tendons function in high stress conditions with a low vascular and neuronal supply, conditions often leading to development of chronic tendinopathies, and in some cases, overt rupture of the tissues. Given their essential nature for human mobility and navigation through the environment, the effective repair and regeneration of different tendons after injury or damage is critical for quality of life, and for elite athletes, the return to sport participation at a high level. However, for mainly unknown reasons, the outcomes following injury are not always successful and lead to functional compromise and risk for re-injury. Thus, there is a need to identify those patients who are at risk for developing tendon problems, as well those at risk for poor outcomes after injury and to design interventions to improve outcomes after injury or rupture to specific tendons. This review will discuss recent advances in the identification of biomarkers prognostic for successful and less successful outcomes after tendon injury, and the mechanistic implications of such biomarkers, as well as the potential for specific biologic interventions to enhance outcomes to improve both quality of life and a return to participation in sports. In addition, the implication of these biomarkers for clinical trial design is discussed, as is the issue of whether such biomarkers for successful healing of one tendon can be extended to all tendons or are valid only for tendons in specific biomechanical and biological environments. As maintaining an active lifestyle is critical for health, the successful implementation of these advances will benefit the large number of individuals at risk.
... In general, the recommended method of treating this disease is surgery. However, the failure rate of this procedure is as high as 94% [69]. After a rupture, the muscle recedes less than the tendons. ...
... At the tendon-bone interface, macrophages cause the formation of scar tissue, but not normal tendon tissue, by secreting myogenic regulatory factors [71]. The complex mechanism of interaction at the molecular and cellular level leads to further scar tissue formation and permanent irreversible changes in the RC structure [69]. ...
Article
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Vitamin D takes part in the functioning of many processes that ensure the homeostasis of the body. In orthopedics, it is indicated as an inseparable element ensuring proper bone growth and functioning, and its deficiencies are indicated in various diseases, mainly in the proper structure and function of the skeleton. In this review, we focus on the most important components of the vitamin D metabolic pathway, in correlation with selected orthopedic conditions. Records were obtained from the PubMed database in a timeline of 2010–2022. The keywords were as follows: vitamin D/cholesterol/vitamin D binding protein/ VDBP/Cytochrome/CYP24A1/CYP 27B1/Vitamin D receptor/VDR/ + diseases (ACL reconstruction, rotator cuff, arthroplasty knee/hip/shoulder). The recent original studies were analyzed, discussed, and the most important data were shown. The vast majority of articles concern the metabolite of vitamin D (25(OH)D), which is measured as a standard in diagnostic laboratories. Even though there is a lot of valuable information in the literature, we believe that the other elements of the vitamin D pathway also deserve attention and suggest their research in correlation with orthopedic disorders to supplement the missing knowledge on this topic.
... 1,16,22 Biologic augmentation is also a strategy that has been developed and is considered relevant for improving the rate and quality of healing. [9][10][11]18,19,32 The use of platelet-rich plasma, growth factor, patches, and bone marrow stimulation are procedures that promote biologic processes in the healing response. 4,7,9,13 The crimson duvet procedure (CDP) was proposed to be applied in shoulder rotator cuff repair by Snyder in 2009, with the objective of providing mesenchymal stem cells through microfracture of the footprint. ...
... Unfortunately, many of them have not resulted in predictable clinical or radiologic improvement, and some of them are complex and expensive procedures. 1 Ideal healing should reproduce the normal transition of the tendon, cartilage, and bone zones. 32 Improvements in surgical materials should not change the fibroblastic scar tissue that is observed in rotator cuff tears postoperatively. Improvements by biologic augmentation may be a solution not only to diminish nonhealing but also to obtain higher-quality healing. ...
Article
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Background Rotator cuff tears are one of the more frequent pathologies of the shoulder. Arthroscopic techniques and biological augmentation have been developed to improve the rate and quality of healing. The crimson duvet procedure (CDP) theoretically provides mesenchymal stem cells (MSCs) through microfracture treatment of the footprint. The aim of this research was to evaluate the effect of the CDP in patients who underwent arthroscopic surgery for complete rotator cuff repair. Methods A prospective randomized clinical trial was performed in a total of 123 patients, consisting of 59 women and 64 men, with a mean age of 58 years. We included patients with a clinical and radiological diagnosis of a complete rotator cuff tear. All patients were treated with arthroscopic rotator cuff repair. In group I, the surface of the footprint was débrided; in group II, the footprint underwent microfracture. The primary outcome was the nonhealing rate, which was detected by magnetic resonance imaging (MRI) or ultrasound (US), and the secondary outcome was the functional result. A Sugaya classification of I to III was considered to indicate healing. 20,28 For clinical evaluation, the ASES and Constant scores were evaluated, along with the range of motion. The functional evaluation was performed preoperatively and at 6 months and one year postoperatively. The radiological (MRI or ultrasound) evaluation was performed at 6 months. Neither the patients nor the radiologists and physical therapists who performed the postoperative evaluations were informed of the random selection. Results We observed a healing rate of 85.11% in the control group and 93.7% in the CDP group without statistical significance (p=0.19). A significant improvement in function was observed in all patients. The ASES score improved from 68.9 (SD: 13.8) preoperatively to 92.2 at sixth months and 96.4 (SD: 6,2) at twelve months (p<0.05), but no difference was observed between the groups. A similar amount of improvement was observed in the Constant score. Conclusion The arthroscopic repair of complete rotator cuff tears presents good and excellent clinical results in most patients. Nevertheless, nonhealing occurs at a rate that depends mainly on the age of the patient and the size of the tear. The addition of the CDP did not improve the functional results, neither the healing rate.
... [1][2][3] Although the complexity of the healing process is not yet fully understood, both osteoblasts and tenocytes have been reported to be important for sufficient boneeenthesis healing. 4,5 Further, recent in vitro studies suggested human subacromial bursal tissue (SBT) as an easily accessible, inexpensive, and viable biologic augment for arthroscopic rotator cuff repair in an attempt to support the endogenous healing potential of the repaired tendon. [6][7][8][9][10][11][12][13] Previous in vitro studies demonstrated that osteoblasts and tenocytes have the ability to adhere and proliferate on suture material used in rotator cuff surgery, which may aid in the tendon-to-bone incorporation process critical for rotator cuff healing. ...
... Although the complexity of the healing process is yet to be fully understood, both osteoblasts and tenocytes have been reported to be important for sufficient boneeenthesis healing. 4,5 Further, previous in vitro studies demonstrated that osteoblasts and tenocytes have the ability to adhere and proliferate on suture material used in rotator cuff surgery. 4,14 Similarly, the present study found that osteoblasts and tenocytes were able to adhere to and proliferate on suture tape, which may aid in the tendon-to-bone incorporation process critical for rotator cuff healing. ...
Article
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Purpose To evaluate the effect of magnesium on cellular adhesion and proliferation of human subacromial bursal tissue (SBT), osteoblasts, and tenocytes on nonabsorbable suture tape commonly used in rotator cuff surgery. Methods Human SBT cells, primary human osteoblasts (HOBs), and primary human tenocytes were isolated from tissue samples and cultured in growth media. Commercially available collagen-coated nonabsorbable suture tape was cut into one-inch pieces, placed into 48-well culture dishes, sterilized under ultraviolet light, and treated with (+) or without (–) magnesium. For the (+) magnesium group, a one-time dose of 5 mM sterile magnesium chloride was added. Subsequently, cells were plated at a density of 20,000 cells/cm². For each cell source (SBT, HOBs, tenocytes) cellular proliferation and adhesion assays on suture tape treated (+) or (–) magnesium were performed. Results SBT, HOBs, and tenocytes each demonstrated the ability to adhere and proliferate on suture tape. Augmenting suture tape with magnesium resulted in a significantly increased cellular adhesion of SBT compared with nonaugmented sutures (P = .001), whereas no significant differences were observed for HOBs (P = .081) and tenocytes (P = .907). Augmentation with magnesium demonstrated no significant difference in cellular proliferation of SBT (P = .856), HOBs (P = .672), and tenocytes (P = .251) compared with nonaugmented sutures. Conclusions SBT, osteoblasts, and tenocytes each demonstrated the ability to adhere and proliferate on suture tape. In addition, augmenting the suture with magnesium resulted in a significantly increased cellular adhesion of SBT compared with nonaugmented sutures, whereas no significant differences were observed for osteoblasts and tenocytes. Further, magnesium did not impair the proliferative activity of SBT, osteoblasts, and tenocytes on suture tape used in rotator cuff surgery. Clinical Relevance Modifying the surface of the suture used for repair with application of magnesium may be an inexpensive and technically feasible option to improve the use of SBT for biologic augmentation of rotator cuff repair.
... Based on closeness to the bone surface, enthesis tissue is divided into the fibrous region (Zone I), unmineralized fibrocartilagenous region (Zone II), mineralized fibrocartilagenous region (Zone III), and bony region (Zone IV) 40,42,46 (Figure 2(a)-(d)). ...
Article
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Enthesis, the interfacial tissue between a tendon/ligament and bone, exhibits a complex histological transition from soft to hard tissue, which significantly complicates its repair and regeneration after injury. Because traditional surgical treatments for enthesis injury are not satisfactory, tissue engineering has emerged as a strategy for improving treatment success. Rapid advances in enthesis tissue engineering have led to the development of several strategies for promoting enthesis tissue regeneration, including biological scaffolds, cells, growth factors, and biophysical modulation. In this review, we discuss recent advances in enthesis tissue engineering, particularly the use of biological scaffolds, as well as perspectives on the future directions in enthesis tissue engineering.
... Furthermore, the production of IL-6 will stimulate T-cell and macrophage activation with an emphasis on inflammation in the presence of TNF -α. TNF-α and IL-6 stimulate apoptosis of myocytes, catabolism of intramyocellular proteins, and dysregulation of the regeneration pathway [54,55]. In RCI patients, IL-6 gene expression and cytokine production correlate with the extent of degeneration and joint stiffness [56]. ...
Article
Rotator Cuff Injuries (RCI) are prevalent cause of shoulder pain affecting over 20% of the population in the USA. Surgical repair of the torn rotator cuff helps in relieving the pressure on the rotator cuff tendon and from symptoms, however tendon-to-bone healing after rotator cuff surgery still has a high failure rate. Hyperlipidemia has been strongly associated with RCI although the cellular and molecular mechanisms are largely unknown. The focus of this critical review is to further explore the role of hyperlipidemia in RCI and rotator cuff tissue repair to determine its implication as a risk factor for tears, repair, and retears. A literature review was conducted to elucidate the role of hyperlipidemia as an inflammatory mediator and catalyst for structural instability within the shoulder. The results from various studies were critically reviewed to summarize the relationship between hyperlipidemia and rotator cuff pathology. Hyperlipidemia induces LDL-particle entrapment within the dense regular collagen of rotator cuff tendons resulting in foam cell aggregation and macrophage recruitment. Subsequent inflammatory pathways including the JAK2/STAT3 pathway and NLRP3 inflammasome pathway led to persistent inflammation and Extracellular Matrix (ECM) degradation within the rotator cuff. While arthroscopic repair remains the most common treatment modality, nonsurgical treatment including statins, vitamin D, and targeting miRNA are also of therapeutic benefit. Hyperlipidemia interferes with arthroscopic repairs by inducing inflammation and stiffness within tendons and increases the risk of retears. Most notably, targeting underlying mechanisms influencing inflammation has large therapeutic value as a novel treatment strategy for the management of rotator cuff pathology.
... In addition to acute trauma, intrinsic factors such as age and health status play a role in the pathogenesis, as do extrinsic factors, such as smoking and nutrition [2]. If these tendon injuries are not treated immediately or adequately, long-term damage, such as fatty degeneration, extensive retraction and the formation of scar tissue may occur [3]. Especially for ruptures of large tendons, surgical treatment is often unavoidable. ...
Article
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Chronic tendon ruptures are common disorders in orthopedics. The conventional surgical methods used to treat them often require the support of implants. Due to the non-availability of suitable materials, 3D-printed polycaprolactone (PCL) scaffolds were designed from two different starting materials as suitable candidates for tendon-implant applications. For the characterization, mechanical testing was performed. To increase their biocompatibility, the PCL-scaffolds were plasma-treated and coated with fibronectin and collagen I. Cytocompatibility testing was performed using L929 mouse fibroblasts and human-bone-marrow-derived mesenchymal stem cells. The mechanical testing showed that the design adaptions enhanced the mechanical stability. Cell attachment was increased in the plasma-treated specimens compared to the control specimens, although not significantly, in the viability tests. Coating with fibronectin significantly increased the cellular viability compared to the untreated controls. Collagen I treatment showed an increasing trend. The desired cell alignment and spread between the pores of the construct was most prominent on the collagen-I-coated specimens. In conclusion, 3D-printed scaffolds are possible candidates for the development of tendon implants. Enhanced cytocompatibility was achieved through surface modifications. Although adaptions in mechanical strength still require alterations in order to be applied to human-tendon ruptures, we are optimistic that a suitable implant can be designed.
... It is necessary to reconstruct the tendon-bone interface once the tendon is injured in many clinical cases, but the regenerated interface is often composed of scar tissue with poor biomechanical properties [47]. On the other hand, affected by many negative factors, such as aging and stress shielding caused by suture, the quality of patients' tendon is always poor, which may lead to tendon re-tear [48]. Therefore, in this study, two RCT models were utilized to investigate the therapeutic effect of CS-FS scaffolds in tendon injury repair: a rat RCT model and a rabbit RCT model. ...
Article
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Tendon-bone healing is essential for an effective rotator cuff tendon repair surgery, however, this remains a significant challenge due to the lack of biomaterials with high strength and bioactivity. Inspired by the high-performance exoskeleton of natural organisms, we set out to apply natural fish scale (FS) modified by calcium silicate nanoparticles (CS NPs) as a new biomaterial (CS-FS) to overcome the challenge. Benefit from its “Bouligand” microstructure, such FS-based scaffold maintained excellent tensile strength (125.05 MPa) and toughness (14.16 MJ/m³), which are 1.93 and 2.72 times that of natural tendon respectively, allowing it to well meet the requirements for rotator cuff tendon repair. Additionally, CS-FS showed diverse bioactivities by stimulating the differentiation and phenotypic maintenance of multiple types of cells participated into the composition of tendon-bone junction, (e.g. bone marrow mesenchymal stem cells (BMSCs), chondrocyte, and tendon stem/progenitor cells (TSPCs)). In both rat and rabbit rotator cuff tear (RCT) models, CS-FS played a key role in the tendon-bone interface regeneration and biomechanical function, which may be achieved by activating BMP-2/Smad/Runx2 pathway in BMSCs. Therefore, natural fish scale -based biomaterials are the promising candidate for clinical tendon repair due to their outstanding strength and bioactivity.
... The rotator cuff tendonto-bone interface is a typical transition zone, a fibrocartilaginous zone connecting the compliant tendon properly with the hard bone, which serves a critical function in alleviating stress concentration during load transfer from the tendon to the bone [40]. Some previous studies have already demonstrated that, instead of regenerating fibrocartilage, the healing process is usually achieved by the formation of scar tissue, resulting in a high rate of failed surgery repairs [41,42]. Hence, it is still a significant challenge to produce an advanced biomaterial that functionally fulfills the criteria for use in rotator cuff tendon-to-bone interface regeneration. ...
Article
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Fibrocartilaginous regeneration at the tendon-to-bone interface is a major challenge for rotator cuff tear repair. We fabricated a decellularized umbilical cord Wharton’s jelly (DUCWJ) scaffold by decellularization method and performed histological and proteomic analyses. We then synthesized a kartogenin-conjugated DUCWJ (DUCWJ-KGN) scaffold using an EDC/NHS catalyst. 1H NMR, Fluorescence staining, and FTIR confirmed that the carboxyl group of KGN was covalently coupled with the free amine groups in the Wharton’s jelly (WJ) matrix, and the in vitro release profiles of KGN from the DUCWJ-KGN scaffold showed sustained release for 6 weeks. Both the DUCWJ and DUCWJ-KGN scaffolds had excellent biocompatibility and biofunctionality, supporting cell attachment, migration, and proliferation, and DUCWJ-KGN scaffolds the KGN-loaded scaffold could induce higher chondrogenic markers expression. The DUCWJ-KGN scaffold could also promote fibrocartilaginous regeneration at the rotator cuff tendon-to-bone interface, which indicates that the DUCWJ-KGN scaffold is a promising enthesis to enhance fibrocartilaginous interface regeneration.
... Furthermore, onlay graft options do not reliably address the core issue of inability to recapitulate the architecture of the transition zoneduniquely adept at transitioning stress from the soft tissue of the rotator cuff to the hard tissue of the greater tuberosity bone. 8 Other options include graft augmentation under the tendon repair in an attempt to augment the healing of this critical area. Platelet-rich plasma and bone marrow aspirate concentrate have been used with some success to augment the biology in this region. ...
Article
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Rotator cuff repair in the setting of a chronic tear or poor tissue quality presents a surgical challenge because of the high risk of structural failure. Patients with an increased risk of retear may be candidates for enthesis augmentation with a novel, biphasic allograft, composed of a demineralized cancellous matrix with a layer of mineralized bone. This interpositional graft was designed with the intention to promote both soft-tissue and osseous integration into the matrix, thereby conferring greater stability and regeneration of the transitional zone of the rotator cuff enthesis. Here, we describe a technique for a transosseous-equivalent supraspinatus repair with placement of a biphasic interpositional allograft.
... Biologic augmentation of rotator cuff repairs provides a means to address the poor healing rates associated with this pathology [1][2][3][4][5][6]. Recent research has investigated the utility of different types of biologic augmentation such as platelet concentrates, connective tissue progenitor (CTP) cells, and growth factors [2,[7][8][9][10]. ...
Article
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The purpose of this study is to determine if arthroscopic shavers can effectively collect and process connective tissue progenitor (CTP) cells from subacromial bursal tissue for utilization in rotator cuff repair augmentation. Subacromial bursal tissue was collected and processed using two arthroscopic shavers, Shaver A and Shaver B, in 10 patients undergoing arthroscopic rotator cuff repair. Each shaver was used in a random order for the same patient. Tissue samples underwent testing for cellular proliferation, cellular concentration, number of colony-forming units (CFU), live/dead assay, fluorescence-activated cells sorting (FACS) analysis, cytokine analysis, and growth factor analysis. Shaver A produced more CFUs compared to Shaver B (210.3 vs. 125.9; p < 0.001). At 3 weeks, cells collected via Shaver A had greater cellular proliferation (0.35 vs. 0.51; p < 0.001) as well as more viable cells (214,773 vs. 132,356 cells/gram; p < 0.001). Tissue collected with Shaver B had greater amounts of the cytokines MMP-1 (3741 vs. 5500 pg/mL; p < 0.001), MMP-3 (1131 vs. 1871 pg/mL; p < 0.001), and MMP-13 (179 vs. 401 pg/mL; p < 0.001), while those collected with Shaver A had greater vascular endothelial growth factor (VEGF) (47.8 vs. 9.0 pg/mL; p < 0.05). Arthroscopic shavers are capable of harvesting and processing CTP cells from subacromial bursal tissue. Different shavers may produce different yields of viable CTP cells.
... The tendon-bone healing process after the surgery is dynamic, involving inflammation, restoration and tissue remodeling, and the outcome depends on the interaction between the fibroblasts in the tendon tissue layers and the osteoblasts and collagens in the bone layers [10]. For patients with symptoms and large-area rotator cuff injury, since non-surgical treatment cannot achieve satisfactory results [11], surgery has become the first choice. ...
Article
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Based on the published animal studies, we systematically evaluated the outcomes of various materials for rotator cuff repair in animal models and the potentials of their clinical translation. 74 animal studies were finally included, of which naturally derived biomaterials were applied the most widely (50.0%), rats were the most commonly used animal model (47.0%), and autologous tissue demonstrated the best outcomes in all animal models. The biomechanical properties of naturally derived biomaterials (maximum failure load: WMD 18.68 [95%CI 7.71–29.66]; P = 0.001, and stiffness: WMD 1.30 [95%CI 0.01–2.60]; P = 0.048) was statistically significant in the rabbit model. The rabbit model showed better outcomes even though the injury was severer compared with the rat model.
... A s recurrent rotator cuff tears following primary repair remain a significant problem, improving healing potential using biologic adjuvants has become increasingly popular in recent years. 1 Platelet-rich plasma (PRP) is derived from autologous peripheral blood that is centrifuged to isolate a higher concentration of growth factors to promote healing. 2 Clinical outcomes following PRP application have been mixed; however, retear rates have been found to be significantly decreased. 3 Further, application of concentrated bone marrow aspirate (cBMA), 4 as the most common source of mesenchymal stem cells (MSCs) for biologic augmentation, has shown promising results in decreasing re-tear rates and improving healing outcomes. ...
Article
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As recurrent rotator cuff tears following repair remain a significant problem, improving healing potential using biologic adjuvants, including concentrated bone marrow aspirate (cBMA), platelet-rich plasma (PRP), or subacromial bursa tissue (SBT), has become increasingly popular in recent years. In an attempt to combine the benefits of these various biologic adjuvants and maximize the healing potential of the repaired tendon, an arthroscopic rotator cuff repair technique biologically augmented with autologous SBT, cBMA, PRP, platelet-poor plasma (PPP), and bovine thrombin has been developed. The created clot is used as a biologic scaffold for sufficient delivery, and it is stabilized using bovine thrombin in order to ensure maximum stability and retainment of the applied biologic augments at the repair site. Classifications I: shoulder; II: rotator cuff.
... The normal anatomy of the RC has four zones, from tendon to fibrocartilage to calcified fibrocartilage to bone. The ultimate goal of surgical repair is to replicate as much of this native enthesis as possible [26]. Su et al. reported that enthesis-preserving RC repair gave better histological and biomechanical results than enthesis-removal RC repair in a rabbit model [27]. ...
Article
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Background Some unusual rotator cuff (RC) tears are located in more proximal tendinous portions, with substantial remnant tissue attached to the footprint. The two options for surgical repair are sacrificing or preserving the remnant tissue. We introduce a surgical repair technique that preserves as much of the remnant footprint as possible. Surgical technique A double-loaded suture anchor is inserted into the subchondral bone at the medial portion of the RC footprint; the lateral remnant tissue is preserved. Each strand is shuttled and repassed through the medial portion of the tendon in a mattress fashion using a suture hook device. Then, multiple no. 1 PDS sutures are passed through the medial and lateral stumps and left untied. Strands from the suture anchor are first tied in a double mattress fashion. Then, the repair is completed by tying the remaining no. 1 PDS sutures. Conclusions We propose a remnant-preserving RC repair technique for transtendinous RC tears with sufficient tissue remaining within the RC footprint. This technique appears advantageous in terms of re-establishing an environment that promotes tendon healing after repair.
... This study was designed to examine whether there was an association between serum Vit B 12 levels and degenerative RC tear in adults 55 to 80 years of age. Factors found to affect degenerative RC tear include age, diabetes, hyperlipidemia, and Vit D deficiency [16]. Few studies have reported results on the relationship between Vit B 12 and RC tear. ...
Article
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Background Vitamin B 12 (Vit B 12 ) deficiency results in elevated homocysteine levels and interference with collagen cross-linking, which may affect tendon integrity. The purpose of this study was to investigate whether serum Vit B 12 levels were correlated with degenerative rotator cuff (RC) tear. Methods Eighty-seven consecutive patients with or without degenerative RC tear were enrolled as study participants. Possible risk factors (age, sex, medical history, bone mineral density, and serum chemistries including glucose, magnesium, calcium, phosphorus, zinc, homocysteine, Vitamin D, Vit B 12 , homocysteine, and folate) were assessed. Significant variables were selected based on the results of univariate analyses, and a logistic regression model (backward elimination) was constructed to predict the presence of degenerative RC tear. Results In the univariate analysis, the group of patients with degenerative RC tear had a mean concentration of 528.4 pg/mL Vit B 12 , which was significantly lower than the healthy control group (627.1 pg/mL). Logistic regression analysis using Vit B 12 as an independent variable revealed that Vit B 12 concentrations were significantly correlated with degenerative RC tear ( p = 0.044). However, Vit B 12 levels were not associated with tear size. Conclusion Low serum levels of Vit B 12 were independently related to degenerative RC tear. Further investigations are warranted to determine if Vit B 12 supplementation can decrease the risk of this condition.
... The current surgical approaches to repair torn rotator cuff tendons have unacceptably low success ratios [3]. Failure is ascribed to a lack of functional enthesis structure, consisting of tendon, non-calcified fibrocartilage, calcified fibrocartilage, and bone, and formation of fibrovascular scar tissue with inferior mechanical properties [4]. Various tissue engineering strategies Ivyspring International Publisher have been developed to promote tendon-to-bone healing and have demonstrated potential for functional re-integration of the injured rotator cuff [5][6][7][8]. ...
Article
Poor healing response after rotator cuff reconstruction is multifactorial, with the inflammatory microenvironment and deficiency of stem cell differentiation factors at the lesion site being most relevant. However, there is a lack of effective tissue engineering strategies that can simultaneously exert anti-inflammatory and pro-differentiation effects to promote rotator cuff healing. Methods: In this study, we synthesized and characterized a novel active drug delivery vector that successfully overcame the challenge of simultaneous high-efficiency loading and controlled release of Mg2+ and curcumin. The anti-inflammatory and pro-differentiation effects of the composite hydrogel were evaluated in vitro and in vivo. Moreover, healing of the rotator cuff tendon-to-bone interface was studied by histology, immunofluorescence, and biomechanical tests. Results: The composite hydrogel exhibited excellent biocompatibility and injectability, good adhesiveness, and rapid self-healing. The released curcumin showed obvious anti-inflammatory and antioxidation effects, which protected stem cells and tendon matrix. Furthermore, released Mg2+ promoted stem cell aggregation and chondrogenesis. Moreover, biomechanical tests and histological results of a rat rotator cuff tear model at 8 weeks after surgery indicated that the composite hydrogel significantly enhanced tendon-to-bone healing. Conclusions: The composite hydrogel mediated sustained in situ release of curcumin and Mg2+ to effectively promote rotator cuff tendon-to-bone healing via anti-inflammatory and pro-differentiation effects. Therefore, this composite hydrogel offers significant promise for rotator cuff repair.
... A s the high failure rates following rotator cuff repair remain a major concern in shoulder surgery, biologic adjuvants have been proposed in an attempt to support the endogenous healing potential of the repaired tendon as well as reduce retear rates. [1][2][3][4] Recent in vitro characterizations of human subacromial bursa tissue (SBT) have shown that these cells fulfill the characteristics of mesenchymal stem cells (MSCs), including similar surface antigen expression profiles and multilineage differentiation, along with superior proliferation potential compared with other tissues within the shoulder, suggesting its use as an easily accessible, inexpensive, and viable augment for arthroscopic rotator cuff repair. [5][6][7][8][9][10][11][12] In the setting of tendon injury, insulin-like growth factor 1 (IGF-1) has come to the forefront, as IGF-1 is active at different stages of the healing process. ...
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Purpose To evaluate the effect of a one-time dose of insulin or insulin-like growth factor 1 (IGF-1) on cellular proliferation and migration of subacromial bursa tissue (SBT) over time. Methods SBT was harvested from over the rotator cuff tendon in 4 consecutive patients undergoing primary arthroscopic rotator cuff repair. SBT was cultured for 3 weeks in complete media until reaching confluence. The culture dishes were stored in a humidified, low oxygen tension (5% CO2) incubator at 37°C. SBT of each patient underwent treatment with a one-time dose of insulin or IGF-1, whereas nontreated SBT served as a negative control. Cellular proliferation and migration were evaluated after 24, 48, 72, and 96 hours of incubation. SBT-derived cells migrated in the detection field were visualized using fluorescent microscopy. Results Cellular proliferation at 24, 48, 72, and 96 hours was 1.40 ± 0.27, 1.00 ± 0.20, 1.47 ± 0.31, and 1.68 ± 0.28 for IGF-1; 1.44 ± 0.24, 1.15 ± 0.27, 1.60 ± 0.36, and 1.61 ± 0.32 for insulin; and 1.51 ± 0.35, 1.29 ± 0.33, 1.53 ± 0.35, and 1.57 ± 0.38 for nontreated SBT. Untreated SBT demonstrated a significantly greater proliferation when compared with IGF-1 and insulin within the first 48 hours, although this effect was found to subside by 96 hours. Cellular migration at 24, 48, 72, and 96 hours was 575.7 ± 45.0, 641.6 ± 77.7, 728.3 ± 122.9, and 752.3 ± 114.5 for IGF-1; 528.4 ± 31.3, 592.5 ± 69.8, 664.2 ± 115.2, and 695.6 ± 148.2 for insulin; and 524.4 ± 41.9, 564.4 ± 49.8, 653.2 ± 81.5, and 685.7 ± 115.5 for nontreated SBT. Insulin showed no difference in migration at each timepoint compared to nontreated SBT (P > .05, respectively). Conclusions Insulin and IGF-1 initially inhibit cellular proliferation of human SBT, although this effect was found to subside by 96 hours. Further, neither insulin nor IGF-1 changed the slope of cellular migration over time. However, each treatment group demonstrated a significant increase in cellular proliferation and migration. Clinical Relevance In the setting of biologic augmentation of rotator cuff repair, the compatibility and synergistic effect of insulin on human SBT is highly limited.
... A systematic observation of MR images could help the surgeon to predict the impossibility to obtain a optimal repair of rotator cuff tear (RCT) and to consider different surgical approach, as shown in literature (5,6,7). ...
Article
Introduction / objectives Osteolytic-type reactions of the perianchor bone which in magnetic resonance are manifested as hyperintensity of the signal in T2 images are reported in many studies. T The objective of the present study is to evaluate and compare to the literature data the clinical and radiological results of a group of patients who underwent arthroscopic suture of a rotator cuff tear using polyetherketone (PEEK) suture anchors. Materials and methods Twenty patients, aged between 44 and 73 years, who underwent arthroscopic repair of the rotator cuff for lesions smaller than 4 cm considered reparaible between August 2017 and January 2019, were enrolled in the present study. Patients were evaluated clinically with clinical examination, Constant scale and ASES scale pre and post surgery. MRI either pre and post operation at one year were evaluated to obtain data about tendon healing and evaluate bone reaction to PEEK anchors. Results: MRI analysis showed a tendon signal according to Sugaya classification of type 1 in the 25% of patients, type 2 in the 60% of cases and type 3 in the remaining 15% . Osteolysis was grade 0 in 65%, grade 1 in 30 % and grade 2 in 5% of cases. No anchors pull out or mobilization were reported. Conclusions: The presence of a T2 hyperintense signal osteolysis like on MRI control using PEEK anchors for the sutur of rotator cuff lesions does not find correlation whit the final clinical result of the procedure.
Article
Retear rates after arthroscopic rotator cuff repair continue to be unacceptably high. Of the known risk factors for failure of rotator cuff repair, many are nonmodifiable. Poor glycemic control in patients with diabetes in the first 3 to 6 months after arthroscopic rotator cuff repair is associated with a lower healing rate. This represents a modifiable risk factor that we should routinely address in patients postoperative rotator cuff repair.
Article
Background: A pre-existing mood and anxiety disorder (MAD) is often present in patients with rotator cuff pathology, but its presumed negative effect on the outcomes has not been demonstrated. Aim of study and hypothesis: The primary objective of this study was to evaluate how a history of MAD affects the clinical outcomes 1 year after arthroscopic rotator cuff repair (RCR). The secondary objectives were to evaluate how a history of MAD affects tendon healing, analgesic consumption and the occurrence of complications. Materials and methods: The study population consisted of 219 patients (mean age 54.5 ± 6.6 years) who underwent arthroscopic repair for a distal supraspinatus tendon tear, with 17% (38/219) presenting an history of MAD (depression, unspecified mood disorder, anxiety, and bipolar disorder). Using univariate and multivariate analyses, the joint range of motion, Constant score, analgesic consumption, occurrence of complications during the first postoperative year and tendon healing at 1 year (MRI or CT arthrography) were compared between the two groups (with or without MAD). Results: The Constant score was lower preoperatively in patients with history of MAD (-4 points, p=.04) but there were no significant differences between the two groups at the various postoperative follow-up time points (p>.05). No significant difference was found between the two groups of patients in their analgesic consumption at the various postoperative time points (p>.05), tendon healing at 1 year (p=.17) or the occurrence of postoperative complications (p=.59). Discussion/conclusion: Pre-existing MAD had no effect on the clinical outcomes after arthroscopic RCR at 1 year and no effect on tendon healing, analgesic consumption or the occurrence of complications in our study population. Level of evidence: III; Retrospective case-control study.
Article
Technical considerations of the rotator cuff repair remain of great importance as retear rates remain high. The double-row (DR) rotator cuff repair was designed to better restore the native enthesis footprint to maximize healing. The DR repair features a medial and lateral row of suture anchors. Anatomical and cadaveric studies have demonstrated improved footprint restoration with DR repair. Biomechanically, the DR repair has a superior load to failure, decreased gap formation under cyclic loading, and greater contact areas and pressures. It is unclear whether the number of sutures per anchor may be more important than the number of rows and the row configuration. Medial row knots and suture tape constructs may improve the biomechanics of the repair, but the impact on clinical outcomes is unknown. High-quality clinical studies have shown that the DR repair in small to medium tears does not yield better clinical outcomes than the single-row (SR) and is not cost-effective. Healing rates seem to improve with the DR repair, and retear rates may be slightly reduced. However, in larger tears, the DR repair demonstrates favorable clinical outcomes with significant increases in functional scores, healing rates, and retear rates compared to SR repair. Although the DR repair has biomechanical advantages to SR constructs, clinical evidence suggests that the double-row repair should be reserved for large to massive tear patterns.
Article
A common postoperative complication after rotator cuff repair is re-tear requiring a secondary procedure. Double row and trans-osseous equivalent repair techniques have become increasingly popular in recent years, however repair failure remains a relatively common complication after primary rotator cuff repair. A retrospective observational study of 389 consecutive patients undergoing arthroscopic double-row rotator cuff repair from February 1, 2014 to March 31, 2020 was conducted. Univariate and multivariate statistics were used to assess differences in demographics, comorbidities, and tear characteristics between patients who experienced re-tear and those who did not. Repair failures were confirmed by plain MRI or intraoperatively during repeat surgical treatment. A subgroup analysis of patients who experienced re-tear due to medial row failure was conducted. The overall re-tear rate was 8.2% (32 patients). Six patients (1.5%) experienced medial row failure, while 26 patients (6.7%) experienced lateral row failure. The average time to re-tear was 279.3 ± 291.2 days. On multivariate analysis, patients with Goutallier Classification ≥3 (OR: 4.274, p = 0.046) and 3 anchor repair (OR: 5.387, p = 0.027) were at significantly increased risk for any re-tear after controlling for other tear characteristics. No statistically significant independent risk factors for medial row failure were identified after controlling for confounding variables. Goutallier classification greater than 3 and a primary repair with 3 anchors are significant risk factors for re-tear after double row rotator cuff repair, however they are not associated with increased occurrence of medial row failure. Further evaluation of risk factors for medial row failure is required to avoid this rare but serious re-tear pattern.
Article
Objective We assessed the relationship between early postoperative clinical outcomes of arthroscopic rotator cuff repair (ARCR) and observations obtained by postsurgical ultrasound (US) and strain elastography (SE) of repaired supraspinatus tendons (SSTs). Methods This retrospective study included 42 cases in which the patient underwent ARCR followed by postoperative US and SE. The Korean Shoulder Scoring (KSS) system was used to assess preoperative and postoperative conditions. The thickness of the repaired SST and subdeltoid fluid was measured by US. SE scores were classified into four grades (1 to 4) according to elasticity of repaired SST. In addition, SE scores were divided into two groups: soft (SE scores of 1 and 2) and hard (SE scores of 3 and 4). The relationship between clinical outcomes and US parameters and SE scores was determined by KSS. Results Postoperative SE scores observed by two readers correlated significantly with function (p = 0.021 and p = 0.021, respectively) and muscle strength (p = 0.008 and p = 0.015, respectively). SE scores were significantly correlated with a difference value of muscle strength of KSS scores (p = 0.002 and p = 0.014). In a comparison of hard and soft groups of repaired SSTs, function (p = 0.008 and p = 0.010, respectively) and muscle strength (p = 0.002 and p = 0.014, respectively) in postoperative KSS scores were statistically higher in the hard SE scores than the soft SE scores. The difference value of function (p = 0.021 and p = 0.021,) and muscle strength (p = 0.008 and p = 0.015) of KSS scores was significantly higher in the hard SE scores. Conclusions Postoperative SE scores of repaired tendons correlated significantly with muscle strength and function after ARCR. Postoperative US images including thickness of repaired tendon and subdeltoid fluid did not correlated with clinical outcome. Advances in knowledge SE evaluations of repaired SST may provide important information about postoperative muscle strength and function.
Article
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Repairing injured tendon or ligament attachments to bones (enthesis) remains costly and challenging. Despite superb surgical management, the disorganized enthesis newly formed after surgery accounts for high recurrence rates after operations. Tissue engineering offers efficient alternatives to promote healing and regeneration of the specialized enthesis tissue. Load-transmitting functions thus can be restored with appropriate biomaterials and engineering strategies. Interestingly, recent studies have focused more on microstructure especially the arrangement of fibers since Rossetti successfully demonstrated the variability of fiber under specific external force. In this review, we provide an important update on the current strategies for scaffold-based tissue engineering of enthesis when natural structure and properties are equally emphasized. We firstly described compositions, structures and features of natural enthesis with their special mechanical properties highlighted. Stimuli for growth, development and healing of enthesis widely used in popular strategies are systematically summarized. We discuss the fabrication of engineering scaffolds from the aspects of biomaterials, techniques and design strategies and comprehensively evaluate the advantages and disadvantages of each strategy. At last, this review pinpoints the remaining challenges and research directions to make breakthroughs in further studies.
Article
Background: Rotator cuff tears are one of the most common injuries of the shoulder joint in adults. Arthroscopic rotator cuff repair (ARCR) has become the gold standard for the treatment of rotator cuff injuries, but it still has a high rate of retear. Platelet-rich plasma (PRP) has been widely used as an adjunct to ARCR. However, the comparative efficacy of different PRP for ARCR remain unclear. In order to evaluate the relative efficacy of PRP for individuals with ARCR, we will conduct a systematic review and network meta-analysis of randomized controlled trials. Methods: A systematic literature search will be conducted in Embase, PubMed, Cochrane Library, Web of Science, China National Knowledge Infrastructure, Wanfang Database, and Chinese Biomedical Literature Database will be searched up to October 2022. The primary outcome will focus on the retear rate at the last follow-up. The secondary outcomes include the Visual Analogue Scale for postoperative pain and functional capacity scores. The risk of bias for individual studies will be assessed according to the revised Cochrane risk-of-bias tool for randomized trials (RoB 2.0). Data analysis will be performed using R 4.1.2. Publication bias will be examined using comparison-adjusted funnel plots and Egger's test using STATA 15.0. The quality of evidence will be assessed using the Grading of Recommendations, Assessment, Development and Evaluation approach. Results: The results of this study will be submitted to a peer-reviewed journal for publication. Conclusions: The review will compare the efficacy of different PRP for patients with ARCR. The result of the study will provide evidence-based medical evidence for ARCR with PRP augmentation.
Article
Introduction As rotator cuff repairs (RCRs) are among the most common procedures in upper extremity orthopedics, healing augmentation using pharmacologic enhancement of the repaired rotator cuff muscle is of particular interest. Objective The purpose of this study is to review the current understanding of Matrix Metalloproteinases (MMPs), Doxycycline, Testosterone, Estrogen, Growth hormone/ IGF-1, Vitamin D, and Vitamin C as a means to mitigate deleterious effects and propagate factors that support healing following RCR. Methods A review of English language articles in PubMed and Medline was conducted in December of 2020. All articles describing the current understanding of the aforementioned therapies were reviewed. Studies were excluded if they were non-English or reported incomplete results. Results Matrix metalloproteinases (MMP’s) are fundamental to the healing process after rotator cuff tears through a delicate balance of various proteases that can be modulated by doxycycline through inhibition. While testosterone has shown to induce replication and differentiation of the tendon stem-cells, estrogen agonists have been shown to decrease inflammation and muscle atrophy. Though growth hormone being associated with elevated collagen synthesis and decreased anoxic damage when present, clinical studies have shown inconclusive and adverse effects on rotator cuff healing. Patients with Vitamin D deficiency have shown to have increased fatty infiltration in rotator cuff muscle while Vitamin C functions as an antioxidant that increases collagen and fibroblast proliferation. Conclusion As manipulation of pharmacologic factors shows potential for enhancing healing following RCRs, future studies are needed to establish a viable augmentation strategy to improve patient outcomes
Article
Background High rates of structural failure are reported after rotator cuff repairs due to inability to recreate the native enthesis during healing. The development of biological augmentation methods that mitigate scar formation and regenerate the enthesis is still an unmet need. Since neonatal enthesis is capable of regeneration after injury, this study tested whether delivery of neonatal tendon progenitor cells (TPC) into the adult injured environment can enhance functional and structural supraspinatus enthesis and tendon healing. Methods TPCs were isolated from Ai14 Rosa26-TdTomato mouse Achilles tendons and labeled using Adenovirus-Cre. 52 CB57BL/6J mice underwent detachment and acute repair of the supraspinatus tendon and received either a fibrin-only or TPC-fibrin gel. Immunofluorescence analysis was carried out to determine cellularity (DAPI), fibrocartilage (SOX9), macrophages (F4/80), myofibroblasts (αSMA), and scar (laminin). Assays for function (gait and biomechanical testing) and structure (μCT imaging, Picrosirius Red/Alcian Blue staining, type I and III collagen staining) were carried out. Results Analysis of TdTomato cells after injury showed minimal retention of TPCs by d7 and d14, with detected cells localized near the bursa and deltoid rather than the enthesis/tendon. However, TPC delivery led to significantly increased %Sox9+ cells in the enthesis at d7 post-injury and decreased laminin intensity across almost all time points compared to fibrin-only. Similarly, TPC-treated mice showed gait recovery by d14 (paw area and stride length) and d28 (stance time) while fibrin-treated mice failed to recover gait parameters. Despite improved gait, biomechanical testing showed no differences between groups. Structural analysis by μCT suggests that TPC application improves cortical thickness after surgery compared to fibrin. Superior collagen alignment at the neo-enthesis was also observed in the TPC-augmented group at d28, but no difference detected in type I and III collagen intensity. Conclusion We found that neonatal TPCs improved and restored functional gait by reducing overall scar formation, improving enthesis collagen alignment and altering bony composition response after supraspinatus tendon repair. TPCs did not appear to integrate into the healing tissue, suggesting improved healing may be due to paracrine effects at early stages. Future work will determine the factors secreted by TPCs to develop translational targets.
Article
Background Mechanical stimulation and platelet-rich plasma (PRP) have been shown to be beneficial for healing of the bone-tendon interface (BTI), but few studies have explored the efficacy of a combination of these applications. We investigated the effect of mechanical stimulation combined with PRP on rotator cuff repair in mice. Hypothesis Mechanical stimulation combined with PRP can enhance BTI healing in a murine model of rotator cuff repair. Study Design Controlled laboratory study. Methods A total of 160 C57BL/6 mice were used. Overall, 40 mice were used to prepare PRP, while 120 mice underwent acute supraspinatus tendon (SST) repair. The animals were randomly assigned to 4 groups: control group, mechanical stimulation group, PRP group, and mechanical stimulation combined with PRP group (combination group). At 4 and 8 weeks postoperatively, animals were sacrificed, the eyeballs were removed to collect blood, and the SST–humeral complexes were collected. Histological, biomechanical, immunological, and bone morphometric tests were performed. Results Histologically, at 4 and 8 weeks after surgery, the area of the fibrocartilage layer at the BTI in the combination group was larger than in the other groups. The content and distribution of proteoglycans in this layer in the combination group were significantly greater than in the other groups. At 8 weeks postoperatively, trabecular number, and trabecular bone thickness of the subchondral bone area of interest at the BTI of the combination group were greater than those of the other groups, bone volume fraction of the combination group was greater than the control group. On biomechanical testing at 4 and 8 weeks after surgery, the failure load and ultimate strength of the SST–humeral complex in the combination group were higher than in the other groups. Enzyme-linked immunosorbent assay results showed that, at 4 weeks postoperatively, the serum concentrations of transforming growth factor beta 1 and platelet-derived growth factor (PDGF) in the combination group were significantly higher than in the other groups; at 8 weeks, the PDGF-AB concentration in the combination group was higher than in the control and mechanical stimulation groups. Conclusion Mechanical stimulation combined with PRP can effectively promote the early stage of healing after a rotator cuff injury. Clinical Relevance These findings imply that mechanical stimulation combined with PRP can serve as a potential therapeutic strategy for rotator cuff healing.
Chapter
Rotator cuff repair is one of the most commonly performed surgeries in orthopedics, yet rates of postoperative failure and retear remain relatively high. Poor biology and limited healing potential at the cuff insertion are frequently cited as potential confounders to otherwise technically successful surgeries. Over the past several years, ortho-biologics have been developed in an attempt to augment rotator cuff repairs. The following review will briefly cover normal biomechanics and histology of the rotator cuff and how this is altered in cuff tears, provide an in-depth summary of the available literature on various ortho-biologic agents, outline the limitations of each agent and give an idea on the future of ortho-biologics in rotator cuff.
Article
Background Rotator cuff (RC) tendon tear leads to impaired shoulder function and pain. The supraspinatus (SS) tendon is most often affected, but the biological response of the SS muscle to SS tendon tear is largely unknown. This study aimed to investigate time-dependent muscle inflammation, degeneration, fatty infiltration, and regeneration in experimental SS tear conditions. Methods Forty-five C57BL/6 mice were subjected to SS tendon tear and allowed to recover for 1, 3, 5, 7, 14, or 28 days. The extent of muscle damage was examined using histological, flow cytometry, proteomic, and chemiluminescence analyses. Results We found that muscle inflammation peaked around day 5 with increased monocyte infiltration and increased cytokine levels in the ipsilateral compared to the contralateral SS muscle. Bioinformatics analysis of proteomics on mice that survived 5 days after RC tendon tear revealed upregulated proteins involved in “neutrophil activation involved in immune response” and “extracellular matrix organization”, whereas “skeletal muscle tissue development and contraction” and “respiratory electron transport chain” were among the most downregulated. Histological analysis of collagen showed increased collagen accumulation and fatty infiltration of the ipsilateral SS over time. Finally, we observed time- and lesion-dependent changes in satellite cell and fibro-adipogenic progenitor populations. Conclusion Altogether, we demonstrate that the SS muscle shows severe signs of acute inflammation, early degeneration, and fatty infiltration, as well as reduced regenerative potential following SS tendon tear.
Article
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Purpose To clinically evaluate patients who underwent a biologic augmentation technique in revision arthroscopic rotator cuff repair using an autologous fibrin scaffold and concentrated stem cells isolated from bone marrow aspirate (BMA) obtained from the proximal humerus. Methods This is a retrospective review of prospectively collected data from patients who underwent biologic augmentation of revision arthroscopic rotator cuff repair using an autologous fibrin scaffold and BMA obtained from the proximal humerus between 2014 and 2015. Minimum follow-up was 12 months. Outcome measures were collected preoperatively and postoperatively including range of motion as well as American Shoulder and Elbow Surgeons Shoulder Form, Simple Shoulder Test, single assessment numeric evaluation, and visual analog score. In addition, BMA samples of each patient were assessed for the number of nucleated cells and colony-forming units. Regression analysis was performed to investigate whether the number of nucleated cells and colony-forming units had an influence on outcome and failure. Results Ten patients who underwent biologic augmentation of revision arthroscopic rotator cuff repair using an autologous fibrin scaffold and concentrated BMA obtained from the proximal humerus between 2014 and 2015 were included. The mean follow-up time was 30.7 (range: 12-49) months. Four patients were revised at final follow-up. Postoperative clinical scores improved significantly: American Shoulder and Elbow Surgeons (28.1 ± 5.4 to 60.9 ± 9.0; P < .01), single assessment numeric evaluation (6.6 ± 2.3 to 65.1 ± 10.9; P < .01), visual analog scale (7.2 ± 0.9 to 3.1 ± 0.9; P < .01), and Simple Shoulder Test (1.6 ± 0.5 to 10.3 ± 5.7; P < .01). Postoperative range of motion increased significantly with regard to flexion (97.0 ± 13.6 to 151.0 ± 12.2; P < .01) and abduction (88.0 ± 14.0 to 134.0 ± 15.1; P = .038) but not with external rotation (38.0 ± 5.7 to 50.5 ± 6.5; P = .16). Less pain was correlated to an increased number of nucleated cells (P = .026); however, there was no correlation between failure rate and number of nucleated cells (P = .430). Conclusions Patients who underwent biologic augmentation of revision arthroscopic rotator cuff repair using an autologous fibrin scaffold and concentrated BMA demonstrated a significant improvement in shoulder function along with reduction of pain. However, the overall revision rate for this procedure was 40%. Level of Evidence Level IV, therapeutic case series.
Chapter
Despite advances in surgical techniques, recurrent tears of the rotator cuff following repair remain a major challenge. As the endogenous healing potential of the repaired tendon appears to be limited, augmentation techniques using biologic adjuvants have garnered recent attention, including the application of growth factors, platelet-rich plasma (PRP), or mesenchymal stem cells (MSCs). Although bone marrow still remains the traditional source for MSCs used for biologic augmentation of rotator cuff repair, recent studies have highlighted subacromial bursal tissue to be an alternative, easily accessible, inexpensive source of MSCs. Despite strong in vitro results regarding the stimulating effects of PRP on tenocytes and myocytes, clinical outcomes following PRP application have been inconsistent. Additionally, reported clinical outcomes of concentrated bone marrow aspirate (BMAC) applications should be interpreted with caution, with the actual clinical efficacy of BMAC still remaining a matter of debate. In vitro studies of human subacromial bursa-derived cells (SBDCs) have shown strong results, demonstrating superior differentiation and proliferation potential compared to BMAC. Thus, SBDCs may be a promising biological augment for rotator cuff surgery, however, clinical outcomes following repair augmentation are yet to be reported.
Article
Background Tenocytes derived from tendons have been reported to be effective in the treatment of rotator cuff tears through the expression of extracellular matrix proteins. Human dermal fibroblasts, known to express collagen types I and III as tenocytes do, may likely be substitutes for tenocytes to enhance healing rotator cuff tears. Purpose To demonstrate the capability of human dermal fibroblasts to enhance healing of rotator cuff tears. Study Design Controlled laboratory study. Methods The cellular properties and expression profiles of growth factors were compared between human dermal fibroblasts and tenocytes. In both cell types, a series of extracellular matrix proteins were analyzed along with matrix metalloproteinases and tissue inhibitors of metalloproteinases involved in the collagenolytic system. A total of 35 rabbits were divided into 5 groups: normal (n = 2), saline control (n = 9), fibrin control (n = 9), low dose of human fibroblasts (HF-LD; n = 9), and high dose of human fibroblasts (HF-HD; n = 6). Cells were injected into the sutured lesions at 6 weeks after creation of bilateral rotator cuff tears, followed by histological and biomechanical analyses at 12 weeks. Results Human dermal fibroblasts exhibited a protein expression pattern similar to that of tenocytes. More specifically, the expression levels of collagen types I and III were comparable between fibroblasts and tenocytes. The histological analysis of 30 surviving rabbits showed that collagen fibers were more continuous and better oriented with a more mature interface between the tendon and bone in the sutured lesions in the HF-LD and HF-HD groups. Most importantly, biomechanical strength, measured using the load to failure at the injection site, was 58.8 ± 8.9 N/kg in the HF-HD group, increasing by approximately 2-fold ( P = .0003) over the saline control group. Conclusion Human dermal fibroblasts, showing cellular properties comparable with tenocytes, effectively enhanced healing of chronic rotator cuff tears in rabbits. Clinical Relevance Human dermal fibroblasts can be used in place of tenocytes to enhance healing of rotator cuff tears.
Article
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The treatment of rotator cuff tear is one of the major challenges for orthopedic surgeons. The key to treatment is the reconstruction of the tendon-bone interface (TBI). Autologous platelet-rich plasma (PRP) is used as a therapeutic agent to accelerate the healing of tendons, as it contains a variety of growth factors (GFs) and is easy to prepare. Graphene oxide (GO) is known to improve the physical properties of biomaterials and promote tissue repair. In this study, PRP gels containing various concentrations of GO were prepared to promote TBI healing and supraspinatus tendon reconstruction in a rabbit model. The incorporation of GO improved the ultrastructure and mechanical properties of the PRP gels. The gels containing 0.5 mg/mL GO (0.5GO/PRP) continuously released TGF-β1 and PDGF-AB, and the released TGF-β1 and PDGF-AB were still at high concentrations, ∼1063.451 pg/ml and ∼814.217 pg/ml, respectively, on the 14th day. In vitro assays showed that the 0.5GO/PRP gels had good biocompatibility and promoted BMSCs proliferation and osteogenic and chondrogenic differentiation. After 12 weeks of implantation, the MRI, μCT, and histological results indicated that the newly regenerated tendons in the 0.5GO/PRP group had a similar structure to natural tendons. Moreover, the biomechanical results showed that the newly formed tendons in the 0.5GO/PRP group had better biomechanical properties compared to those in the other groups, and had more stable TBI tissue. Therefore, the combination of PRP and GO has the potential to be a powerful advancement in the treatment of rotator cuff injuries.
Chapter
This chapter presents a case scenario of a 63‐year‐old man who complains of three days of shoulder pain after overexertion when lifting a weight. He describes the pain as mostly mechanic, with progressive worsening throughout the day. When deciding on the management of a rotator cuff tear, the patient’s age is an important variable to assess. The size of the tear is closely related to a risk of re‐rupture following rotator cuff repair. Making a distinction between an acute rupture, acute symptoms of a chronic rupture or the acute extension of an existing chronic rupture are very difficult. Single row, double row, transosseous, and bridged repairs are some of the options currently in the therapeutic arsenal and are applied depending on the surgeon’s preference. The chapter provides recommendations for implementing evidence‐based practice in the clinical setting.
Article
Background Recurrent tears after arthroscopic rotator cuff repair (ARCR) remain a significant clinical problem. Oxidative stress contributes to the degeneration of the rotator cuff, and a degenerative rotator cuff can lead to recurrent tear after ARCR. However, the correlation between oxidative stress and retear after ARCR is unclear. Purpose To investigate the correlation between superoxide-induced oxidative stress and recurrent tear after ARCR. Study Design Case-control study; Level of evidence, 3. Methods A total of 68 patients who underwent ARCR using a suture-bridge technique participated in this study. Specimens were collected from the edge of the torn tendon during surgery. The modified Bonar score was used to evaluate degeneration of the rotator cuff on histological specimens, and fluorescence intensity on dihydroethidium (DHE) staining was used to detect oxidative stress. Superoxide dismutase (SOD) enzyme activity was also measured. The following were used for clinical evaluation: age, tear size on magnetic resonance imaging (MRI) before surgery, Goutallier classification on MRI before surgery, and Japanese Orthopaedic Association score before and 6 months after surgery. After the repaired rotator cuffs were evaluated on MRI 6 months after surgery, the patients were divided into groups: those with a healed rotator cuff (healed group; n = 46) and those with a recurrent tear (retear group; n = 22). The significant differences between the groups were determined with regard to clinical evaluation, modified Bonar score, DHE intensity, and SOD activity. In addition, multivariate logistic regression analysis was performed to investigate risk factors for recurrent tear. Results Age, tear size, Goutallier classification, modified Bonar score, DHE intensity, and SOD activity were significantly greater in the retear group than in the healed group, although the Japanese Orthopaedic Association score was not significantly different. Multiple logistic regression analysis demonstrated that age, tear size, and SOD activity were significantly correlated with recurrent tear. Conclusion In addition to tear size and age, superoxide-induced oxidative stress may be an exacerbating factor for retear after ARCR.
Article
Background: Follow-up magnetic resonance imaging (MRI) after rotator cuff repair can sometimes demonstrate healing with non-tendinous tissue that extends from the footprint to the retracted tendon end, which is inferred as fibrous tissue formation. The aim was to investigate this particular finding and its significance. Methods: There were 494 eligible cases of healed superior medium- to massive-sized rotator cuff repairs, after the exclusion of re-tears. A retrospective review was performed for the three groups that were divided according to their MRI appearances of healing: Type I described the direct 'healing' of the tendon to the footprint, while Types II demonstrated the distinctive continuity of non-tendinous tissue from the footprint to the retracted tendinous portion, and the Type III also showed the similar appearance but with obvious thinning of the tissue, without any evidence of defect confirmed on the routine outpatient ultrasonography. Results: Only 108 of 494 patients (21.9%) demonstrated Type I healing while the signs of 'non-tendinous' healing were evident for the rest, with the 116 patients (23.5%) being classified as Type III with attenuation. Comparing the preoperative tendon retraction, 34.8% and 37.2% of the Patte stages 2 and 3, respectively, resulted in Type III healing, which were significantly higher compared to that of the stage 1 (15.3%, P<0.001). The Type III had the highest average preoperative Goutallier grades. The average postoperative VAS and the ASES scores have improved significantly for all three groups (P<0.05), with the ASES being 86.1±15.9 for Type I, 93.7±36.1 for Type 2, and 87.8±15.1 for Type 3 without significant differences between the groups (P=0.03). Conclusions: Only a fifth of the rotator cuff repairs led to the direct 'healing' to the footprint, and the rest healed with the MRI appearances of non-tendinous tissue formation bridging between the retracted tendinous portions and the footprints. These MRI appearances did not represent the true tendinous tissue formation between the torn end of the tendon and the bone after healing. Such appearances did not seem to affect the clinical outcomes. Level of evidence: Level IV; Case Series; Treatment Study.
Article
Purpose: The purpose of this study was to evaluate long-term patient-reported outcomes and revision surgery after arthroscopic rotator cuff repair with or without acromioplasty. Methods: Between 2007-2011, prospectively enrolled patients undergoing arthroscopic repair for full-thickness rotator cuff tears, with any acromial morphology, were randomized into either acromioplasty or non-acromioplasty groups. Patients with revision surgery, subscapularis involvement, advanced neurologic conditions, or death were excluded. Baseline and long-term follow-up questionnaires, including the American Shoulder and Elbow Surgeons (ASES), Simple Shoulder Test (SST), University of California-Los Angeles (UCLA), Visual Analog Scale (VAS) for pain, and Constant scores were obtained. Rates of symptomatic retear, revision rotator cuff surgery, or secondary reoperation were recorded. Averages with standard deviation (SD) were calculated, and t-tests were utilized to compare outcomes of interest between cohorts. Results: In total, 69 of 90 patients (76.7%) were available at 92.4 months (±10.5). There were 23/32 patients in the acromioplasty cohort and 24/37 patients in the non-acromioplasty cohort. Mean age for the non-acromioplasty cohort was 56.9 (± 7.6) while acromioplasty was 59.6 (±6.8). Comparison of baseline demographics and intraoperative information revealed no significant differences, including age, gender, workers compensation, acute mechanism of injury, tear size, degree of retraction, and surgical technique (e.g. single- vs. double-row). At final follow-up, there were no statistically significant differences according to ASES (p=0.33), VAS pain (p=0.79), Constant (p=0.17), SST (p=0.05), UCLA (p=0.19), and SF-12 (p=0.79) in patients with and without acromioplasty. Two patients with acromioplasty (5.6%) and three patients without acromioplasty (9.1%) sustained atraumatic recurrent rotator cuff tear with secondary repair (p=0.99), and there was no significant difference in retear rates or patient-reported outcome measures by acromial morphology. Conclusion: This randomized trial, with mean 7.5-year follow-up, found no difference in validated patient-reported outcomes, retear rate, or revision surgery rate between subjects undergoing rotator cuff repair with or without acromioplasty.
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Introduction: In the field of arthroscopic rotator cuff repair (ARCR), reporting standards of published studies differ dramatically, notably concerning adverse events (AEs). In addition, prognostic studies are overall methodologically poor, based on small data sets and explore only limited numbers of influencing factors. We aim to develop prognostic models for individual ARCR patients, primarily for the patient-reported assessment of shoulder function (Oxford Shoulder Score (OSS)) and the occurrence of shoulder stiffness 6 months after surgery. We also aim to evaluate the use of a consensus core event set (CES) for AEs and validate a severity classification for these events, considering the patient's perspective. Methods and analysis: A cohort of 970 primary ARCR patients will be prospectively documented from several Swiss and German orthopaedic clinics up to 24 months postoperatively. Patient clinical examinations at 6 and 12 months will include shoulder range of motion and strength (Constant Score). Tendon repair integrity status will be assessed by ultrasound at 12 months. Patient-reported questionnaires at 6, 12 and 24 months will determine functional scores (subjective shoulder value, OSS), anxiety and depression scores, working status, sports activities, and quality of life (European Quality of Life 5 Dimensions 5 Level questionnaire). AEs will be documented according to a CES. Prognostic models will be developed using an internationally supported regression methodology. Multiple prognostic factors, including patient baseline demographics, psychological, socioeconomic and clinical factors, rotator cuff integrity, concomitant local findings, and (post)operative management factors, will be investigated. Ethics and dissemination: This project contributes to the development of personalised risk predictions for supporting the surgical decision process in ARCR. The consensus CES may become an international reference for the reporting of complications in clinical studies and registries. Ethical approval was obtained on 1 April 2020 from the lead ethics committee (EKNZ, Basel, Switzerland; ID: 2019-02076). All participants will provide informed written consent before enrolment in the study. Trial registration number: NCT04321005. Protocol version: Version 2 (13 December 2019).
Article
Rotator cuff anchor repair is an increasingly common surgical procedure but the failure rate remains high. In order to improve surgical outcomes, a better understanding of post‐repair histological and cellular responses at the tendon‐bone attachment site (enthesis) is needed. We examined operated shoulders from 42 New Zealand female white rabbit. The animals underwent unilateral supraspinatus detachment followed by anchor repair a week later. To assess enthesis reformation, fibrocartilage staining area and the number of chondrocytes or non‐chondrocytes were quantified at 0, 1, 2, and 4 weeks post‐repair. Using linear regression, we correlated these results with the load to failure and stiffness recorded during mechanical testing of the tendons. Fibrocartilage staining and chondrocyte number increased during the first 2 weeks of enthesis formation. Between 2‐4 weeks, fibrocartilage staining plateaued while chondrocyte number decreased. The presence of non‐chondrocytes remained similar between 0‐ and 1‐week post‐repair but then decreased abruptly at 2 weeks. There was a linear correlation between fibrocartilage staining area and load to failure as well as stiffness. Non‐chondrocyte number negatively correlated with stiffness. Early plateau of fibrocartilage staining and decrease in chondrocytes between 2‐4 weeks post‐repair suggest a blunted enthesis formation response in our animal model. This article is protected by copyright. All rights reserved.
Article
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Rotator cuff (RC) disease is a common musculoskeletal disorder of the shoulder entailing pain, with reduced functionality and quality of life. The main objective of this study was to present a perspective of the current scientific evidence about personalized, predictive, participatory, precision, and preventive approaches in the management of RC diseases. The personalized, predictive, participatory, precision and preventive (P5) medicine model is an interdisciplinary and multidisciplinary approach that will provide researchers and clinicians with a comprehensive patrimony of knowledge in the management of RC diseases. The ability to define genetic predispositions in conjunction with the evaluation of lifestyle and environmental factors may boost the tailoring of diagnosis and therapy in patients suffering from RC diseases.
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Background Some unusual rotator cuff (RC) tears are located in more proximal tendinous portions, with substantial remnant tissue attached to the footprint. The two options for surgical repair are sacrificing or preserving the remnant tissue. We introduce a surgical repair technique that preserves as much of the remnant footprint as possible. Surgical technique : A double-loaded suture anchor is inserted into the subchondral bone at the medial portion of the RC footprint; the lateral remnant tissue is preserved. Each strand is shuttled and repassed through the medial portion of the tendon in a mattress fashion using a suture hook device. Then, multiple no. 1 PDS sutures are passed through the medial and lateral stumps and left untied. Strands from the suture anchor are first tied in a double mattress fashion. Then, the repair is completed by tying the remaining no. 1 PDS sutures. Conclusions We propose a remnant-preserving RC repair technique for transtendinous RC tears with sufficient tissue remaining within the RC footprint. This technique appears advantageous in terms of re-establishing an environment that promotes tendon healing after repair.
Article
Background The purpose of this study was to evaluate the relationship between preoperative subscapularis (SSc) status as well as radiographic factors with internal rotation (IR) following reverse shoulder arthroplasty (RSA). Our hypothesis was that increased glenosphere lateralization and SSc insertion lateralization and the absence of a preoperative SSc tear would be associated with improved postoperative IR (IRF). Methods A retrospective review was performed of primary RSAs (n = 132) by a single surgeon using a 135° inlay prosthesis. Range of motion including forward flexion (FFF), external rotation (ERF) and IRF were evaluated at one year postoperative. IRF was divided into high (≥ L4) and low (≤ L4) groups. Preoperative subscapularis (SSc) status, glenosphere size, and postoperative positions of the glenosphere and humerus were assessed. Novel radiographic factors were used to assess lateralization including the lesser tuberosity scapula (LTS) and lateral glenosphere scapula (LGS) ratios. Results Only 32% of patients achieved IRF ≥ L4 postoperatively. Patients who achieved high IRF had a lower incidence of preoperative SSc tear compared to those who had an IRF < L4 (9% vs. 47%; p = 0.002). Higher LTS and LGS ratios were associated with improved IRF (p < 0.001). The chance of having IRF ≥ L4 increased by 86% (p = 0.049) and by 62% (p = 0.038) for every 0.1 increase in LGS ratio and LTS ratios, respectively. Conclusion With a 135° inlay prosthesis design, an intact SSc preoperatively, as well as increased lateralization parameters, LTS and LGS ratios are associated with increased postoperative IR following RSA.
Article
Purpose To evaluate if nucleated cell count (NCC) could serve as an approximation for the number of colony-forming units (CFUs) in concentrated bone marrow aspirate (cBMA) obtained from the proximal humerus. Methods Bone marrow aspirate (BMA) was harvested from the proximal humerus in 96 patients (mean age: 56.2±7.0 years) during arthroscopic rotator cuff repair. Following concentration of the aspirate, nucleated cells of each sample were counted. The total number of CFUs was evaluated under the microscope at their first appearance, usually after 5-10 days in culture. Fluorescence-activated cell sorting analysis and assays for osteogenic, adipogenic, and chondrogenic differentiation were performed. Linear regression was assessed to predict the number of CFUs by using NCC. Age, sex and body mass index (BMI) were evaluated as independent variables. Results The average volume of the obtained BMA was 86.7 ± 35.2 ml. Concentrated BMA contained a mean of 26.3 ± 6.8 × 10⁶ nucleated cells per cc, which yielded a mean of 1421.7 ± 802.7 CFUs in cell culture. There were no significant differences in NCC or number of CFUs, when sex, volume of BMA, age, or BMI were examined independently (P>0.05, respectively). Linear regression found that NCC was of limited predictive value for the total number of CFUs being yielded following cell culture (r²=0.28 with a root mean square error of 679.4). Conclusion NCC was of negligible predictive value for the total number of CFUs for connective tissue progenitor cells in bone marrow aspirate harvested from the proximal humerus during arthroscopic rotator cuff repair. Clinical Relevance NCC is often used to assess the quality of cBMA samples for biological augmentation during surgery. The limited predictive value of this measurement tool is of clinical importance, as effectiveness of BMA applications has been suggested to depend on the concentration of progenitor cells within the sample.
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Background: Use of anti-inflammatory medications (NSAIDs) is an important component of multimodal pain control after orthopedic procedures to avoid opioid overutilization and abuse. However, the deleterious effects of NSAIDs on tendon healing are of particular concern in rotator cuff repair (RCR). The purpose of this study was to evaluate the effect of celecoxib or placebo on healing rates after RCR when administered in the perioperative and immediate postoperative period using MRI evaluation at one year postoperatively. A secondary aim was to determine whether clinical differences existed between patients with intact or non-intact repairs. Methods: Patients aged ≤65 years with partial- or full-thickness rotator cuff tear (<25x25 mm) were randomized to receive celecoxib 400 mg or placebo 1 hour before the procedure and 200mg bid for 3 weeks postoperatively. All patients were treated as clinically indicated at the time of surgery and followed standard postoperative protocol. Repair integrity was evaluated with MRI using the Sugaya classification for repair integrity. Data were analyzed using multivariable logistic regression by intent to treat. Results: Seventy-nine patients were enrolled; 21 were lost to follow-up, 6 did not have cuff repair, 5 were revised, and 2 declined follow-up, leaving 45 patients with one-year follow-up. Five of these patients did not complete MRI, leaving 40 patients for review. Eighteen of 20 patients (90%) who received celecoxib completed all doses of study medication as did 15 of 20 patients (75%) who received placebo. The patient groups were similar for demographics, clinical results, and healing rate. After adjusting for tear size, no statistically significant difference in healing rate was found between groups, with 10 of 20 celecoxib patients (50%) having intact repair at 1 year compared with 14 of 20 placebo patients (70%) (OR = 0.53, 95% CI: 0.14, 2.08, P = 0.35). Conclusion: Half of the patients who received celecoxib had an intact repair compared with 70% intact repair for patients receiving placebo. Although not statistically significant in this small study, larger studies are needed to clarify this important clinical concern. The authors do not recommend use of celecoxib for postoperative pain control after RCR.
Article
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Background: Tendon pain occurs in individuals with extreme cholesterol levels (familial hypercholesterolaemia). It is unclear whether the association with tendon pain is strong with less extreme elevations of cholesterol. Objective: To determine whether lipid levels are associated with abnormal tendon structure or the presence of tendon pain. Methods: We conducted a systematic review and meta-analysis. Relevant articles were found through an electronic search of 6 medical databases-MEDLINE, Cochrane, AMED, EMBASE, Web of Science and Scopus. We included all case-control or cross-sectional studies with data describing (1) lipid levels or use of lipid-lowering drugs and (2) tendon structure or tendon pain. Results: 17 studies (2612 participants) were eligible for inclusion in the review. People with altered tendon structure or tendon pain had significantly higher total cholesterol, low-density lipoprotein cholesterol and triglycerides, as well as lower high-density lipoprotein cholesterol; with mean difference values of 0.66, 1.00, 0.33, and -0.19 mmol/L, respectively. Conclusions: The results of this review indicate that a relationship exists between an individual's lipid profile and tendon health. However, further longitudinal studies are required to determine whether a cause and effect relationship exists between tendon structure and lipid levels. This could lead to advancement in the understanding of the pathoaetiology and thus treatment of tendinopathy.
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While the use of bone marrow concentrate (BMC) has been described in the treatment of rotator cuff tears, the impact of a rotator cuff injury on the mesenchymal stem cells (MSCs) content present in the human shoulder has not been determined, especially with regard to changes in the levels of MSCs at the tendon-bone interface. With the hypothesis that there was a decreased level of MSCs at the tendon-bone interface tuberosity in patients with rotator cuff tear, we assessed the level of MSCs in the tuberosity of the shoulder of patients undergoing a rotator cuff repair. We analysed the data of 125 patients with symptomatic rotator cuff tears and of 75 control patients without rotator cuff injury. We recorded the following data: size of tear, number of torn tendons, aetiology of the tear, lag time between onset of shoulder symptoms/injury and repair, and also fatty infiltration of muscles. Mesenchymal stem cell content at the tendon-bone interface tuberosity was evaluated by bone marrow aspiration collected in the humeral tuberosities of patients at the beginning of surgery. A significant reduction in MSC content (from moderate, 30-50 %, to severe >70 %) at the tendon-bone interface tuberosity relative to the MSC content of the control was observed in all rotator cuff repair study patients. Severity of the decrease was statistically correlated to a number of factors, including the delay between onset of symptoms and surgery, number of involved tendons, fatty infiltration stage and increasing patient age. This study demonstrates that the level of MSCs present in the greater tuberosity of patients with a rotator cuff tear decreases as a function of a number of clinical factors, including lag time from tear onset to treatment, tear size, number of tears and stage of fatty infiltration, among others. This information may help the practices in using biologic augmentation of a rotator cuff repair.
Article
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Adult stem cell therapy for the treatment of tendon injuries is a growing area of research. This study is aimed to investigate the efficacy of human adipose-derived stem cell (hADSC) injection on the tendon during its healing process in a rat model of rotator cuff injury. Human ADSCs were injected 3 days after collagenase induced rotator cuff injuries in experimental groups while the control group received saline as a placebo. Histological and biomechanical analyses were performed on 7, 14, 21 and 28 days after collagenase injection. Compared to the control group, it was found that inflammatory cells were significantly decreased in the hADSC-treated group after collagenase injection for 7 days and 14 days. In the hADSC-injected group, the fiber arrangement and tendon organization had also been improved. On the 7th day after collagenase injection, the load-to-failure of the hADSC-injected group (15.87±2.20N) was notably higher than that of the saline-injected group (11.20±1.35N). It is suggested that the tensile strength of the supraspinatus tendon was significantly enhanced. Local administration of hADSCs might have the possibility to restore the tensile strength and attenuate the progression of tendinitis. Taken together, these findings demonstrate that the recovery processes in damaged tendons can be facilitated architecturally and functionally after hADSC injection.
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Background: Although platelet-rich plasma (PRP) has been used in rotator cuff repair, most authors have been unable to report the advantages of this method in clinical trials. Hypothesis: The use of PRP promotes better functional and structural results in arthroscopic rotator cuff repair. Study design: Randomized controlled trial; Level of evidence, 1. Methods: This was a prospective, randomized, double-blind study with 2 groups of 27 patients each (PRP group and control group). Complete supraspinatus tears with retraction of less than 3 cm were subjected to arthroscopic single-row repair; at the end of the surgical procedure, liquid PRP prepared by apheresis was given to the patients in the PRP group with autologous thrombin. The outcomes were assessed by the University of California at Los Angeles (UCLA) and Constant scales, visual analog scale (VAS) for pain, and magnetic resonance imaging (MRI) before and 3, 6, 12, and 24 months after surgery. The significance level was 5%. Results: The 2 groups of patients exhibited significant clinical improvement (P < .001). Between the preoperative assessment and 24-month follow-up, the mean UCLA score increased from 13.63 ± 3.639 to 32.70 ± 3.635 and from 13.93 ± 4.649 to 32.44 ± 4.318 in the control and PRP groups, respectively (P = .916). The mean Constant score increased from 47.37 ± 11.088 to 85.15 ± 9.879 in the control group and from 46.96 ± 11.937 to 84.78 ± 14.048 in the PRP group (P = .498). The mean VAS score varied from 7.00 ± 1.939 and 6.67 ± 1.617 before surgery to 1.15 ± 1.916 and 0.96 ± 2.244 at the 24-month assessment in the control and PRP groups, respectively (P = .418). The only difference was in the mean UCLA score at 12 months, with 30.04 ± 4.528 in the control group and 32.30 ± 3.506 in the PRP group (P = .046). The control group exhibited 1 case of a complete retear and 4 partial retears, and the PRP group exhibited 2 cases of partial retears (P = .42). Conclusion: Platelet-rich plasma prepared by apheresis and applied in the liquid state with thrombin did not promote better clinical results at 24-month follow-up. Given the numbers available for analysis, the retear rate also did not change.
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Purpose: The purpose of this study was to evaluate the efficiency of biologic augmentation of rotator cuff repair with iliac crest bone marrow-derived mesenchymal stem cells (MSCs). The prevalence of healing and prevention of re-tears were correlated with the number of MSCs received at the tendon-to-bone interface. Methods: Forty-five patients in the study group received concentrated bone marrow-derived MSCs as an adjunct to single-row rotator cuff repair at the time of arthroscopy. The average number of MSCs returned to the patient was 51,000 ± 25,000. Outcomes of patients receiving MSCs during their repair were compared to those of a matched control group of 45 patients who did not receive MSCs. All patients underwent imaging studies of the shoulder with iterative ultrasound performed every month from the first postoperative month to the 24th month. The rotator cuff healing or re-tear was confirmed with MRI postoperatively at three and six months, one and two years and at the most recent follow up MRI (minimum ten-year follow-up). Results: Bone marrow-derived MSC injection as an adjunctive therapy during rotator cuff repair enhanced the healing rate and improved the quality of the repaired surface as determined by ultrasound and MRI. Forty-five (100 %) of the 45 repairs with MSC augmentation had healed by six months, versus 30 (67 %) of the 45 repairs without MSC treatment by six months. Bone marrow concentrate (BMC) injection also prevented further ruptures during the next ten years. At the most recent follow-up of ten years, intact rotator cuffs were found in 39 (87 %) of the 45 patients in the MSC-treated group, but just 20 (44 %) of the 45 patients in the control group. The number of transplanted MSCs was determined to be the most relevant to the outcome in the study group, since patients with a loss of tendon integrity at any time up to the ten-year follow-up milestone received fewer MSCs as compared with those who had maintained a successful repair during the same interval. Conclusion: This study showed that significant improvement in healing outcomes could be achieved by the use of BMC containing MSC as an adjunct therapy in standard of care rotator cuff repair. Furthermore, our study showed a substantial improvement in the level of tendon integrity present at the ten-year milestone between the MSC-treated group and the control patients. These results support the use of bone marrow-derived MSC augmentation in rotator cuff repair, especially due to the enhanced rate of healing and the reduced number of re-tears observed over time in the MSC-treated patients.
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Purpose To evaluate the clinical and magnetic resonance imaging (MRI) outcome of arthroscopic rotator cuff repair with the use of leukocyte-platelet–rich plasma (L-PRP) in patients with large or massive rotator cuff tears. Methods A comparative cohort of patients with large or massive rotator cuff tears undergoing arthroscopic repair was studied. Two consecutive groups of patients were included: rotator cuff repairs with L-PRP injection (group 1, n = 35) and rotator cuff repairs without L-PRP injection (group 2, n = 35). A double-row cross-suture cuff repair was performed by a single surgeon with the same rehabilitation protocol. Patients were clinically evaluated with the Constant score; Simple Shoulder Test score; University of California, Los Angeles (UCLA) score; and strength measurements by use of a handheld dynamometer. Rotator cuff healing was evaluated by postoperative MRI using the Sugaya classification (type 1 to type 5). Results We prospectively evaluated the 2 groups at a minimum 2-year follow-up. The results did not show differences in cuff healing between the 2 groups (P = .16). The size of recurrent tears (type 4 v type 5), however, was significantly smaller in group 1 (P = .008). There was no statistically significant difference in the recurrent tear rate (types 4 and 5) between the 2 groups (P = .65). There was no significant difference between group 1 and group 2 in terms of University of California, Los Angeles score (29.1 and 30.3, respectively; P = .90); Simple Shoulder Test score (9.9 and 10.2, respectively; P = .94); Constant score (77.3 and 78.1, respectively; P = .82); and strength (7.5 and 7.0, respectively; P = .51). Conclusions In our study the use of autologous L-PRP did not improve the quality of tendon healing in patients undergoing arthroscopic repair of large or massive rotator cuff tears based on postoperative MRI evaluation. The only significant advantage was that the L-PRP patients had smaller iterative tears. However, the functional outcome was similar in the 2 groups of patients. Level of Evidence Level III, case-control study.
Article
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Assess platelet rich plasma (PRP) injection for rotator cuff tendinopathy (RCT). Prospective open label study with 1-year follow-up. Participants recruited from an outpatient sports medicine clinic had clinically and magnetic resonance image (MRI)-demonstrated RCT refractory to physical therapy and corticosteroid injection. They received one ultrasound-guided injection of 3.0 mL of 1% xylocaine followed by 3.5 mL of PRP at the lesion and surrounding tendon. Primary outcome: 0-10 visual analog scale (VAS; baseline, 8, 12, and 52 weeks). Secondary outcomes: functional shoulder tests assessing rotator cuff strength and endurance (at baseline and 8 and 12 weeks), MRI severity (1-5 points [at baseline and 4 and 8 weeks]), and patient satisfaction (52 weeks). Eighteen participants with 19 assessed shoulders reported VAS pain score improvement from 7.5 ± 0.3 points to 0.5 ± 0.3 points by week 12 and 0.4 ± 0.2 (P = .0001) points at week 52. Functional outcomes significantly improved; the largest effect was seen in the external rotation test: 33.5 ± 5.7 seconds to 62.6 ± 7.2 seconds at week 12 (P = .0001). MRI appearance improved by 1 to 3 points in 16 of 18 assessed shoulders. Seventeen participants were "completely satisfied" (12) or "satisfied" (5). One participant was "unsatisfied." A single ultrasound-guided, intralesional injection of PRP resulted in safe, significant, sustained improvement of pain, function, and MRI outcomes in participants with refractory RCT. Randomized multidisciplinary effectiveness trials that add ultrasound and validated clinical outcome measures are needed to further assess PRP for RCT.
Article
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Background: Few studies have considered hormonal influences, particularly vitamin D, on healing. Hypothesis: Vitamin D deficiency would have a negative effect on the structure of the healing tendon-bone interface in a rat model and would result in decreased tendon attachment strength. Study design: Controlled laboratory study. Methods: Vitamin D deficiency was induced in 28 male Sprague-Dawley rats using a specialized vitamin D-deficient diet and ultraviolet light restriction. Serum levels of vitamin D were measured after 6 weeks. These vitamin D-deficient animals (experimental group) plus 32 rats with normal vitamin D levels (controls) underwent unilateral detachment of the right supraspinatus tendon from the greater tuberosity of the humerus, followed by immediate repair using bone tunnel suture fixation. The animals were sacrificed at 2- and 4-week intervals after surgery for biomechanical analysis. A paired t test was used to compare serum vitamin D levels at day 0 and at 6 weeks. A nonparametric Mann-Whitney U test was used to compare load-to-failure and stiffness values between the experimental group and controls. Bone density and new bone formation at the tendon insertion site on the greater tuberosity were assessed with micro-computed tomography (CT). The organization of collagen tissue, new bone formation, vascularity at the tendon-bone interface, fibrocartilage at the tendon-bone interface, and collagen fiber continuity between the tendon and bone tissue were evaluated with safranin O and picrosirius red staining. Results: Blood draws confirmed vitamin D deficiency at 6 weeks compared with time zero/baseline for rats in the experimental group (10.9 ng/mL vs 6.5 ng/mL, respectively; P < .001). Biomechanical testing demonstrated a significant decrease in load to failure in the experimental group compared with controls at 2 weeks (5.8 ± 2.0 N vs 10.5 ± 4.4 N, respectively; P < .006). There was no difference in stiffness at 2 weeks between the control and experimental groups. At 4 weeks, there was no significant difference in load to failure or stiffness between the control and experimental groups. Histological analysis showed less bone formation and less collagen fiber organization in the vitamin D-deficient specimens at 4 weeks as compared with controls. Micro-CT analysis showed no significant difference between groups for total mineral density and bone volume fraction of cortical, whole, or trabecular bone at 4 weeks. Conclusion: The biomechanical and histological data from this study suggest that low vitamin D levels may negatively affect early healing at the rotator cuff repair site. Clinical relevance: It is estimated that 1 billion people worldwide are vitamin D deficient. In the deficient state, acutely injured rotator cuffs may have a reduced ability for tendon healing. Further studies are needed to determine the exact mechanism by which vitamin D affects tendon healing and whether vitamin D supplementation can improve rotator cuff tendon healing and reduce the incidence of retears.
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Platelet-rich plasma is being used more frequently to promote healing of muscle injuries. The growth factors contained in platelet-rich plasma accelerate physiological healing processes and the use of these factors is simple and minimally invasive. The aim of this study was to demonstrate the efficacy of ultrasound-guided injection of platelet-rich plasma in muscle strains and the absence of side effects. Fifty-three recreational athletes were enrolled in the study. The patients were recruited from the Emergency Room in the University Hospital at Parma according to a pre-defined protocol. Every patient was assessed by ultrasound imaging to evaluate the extent and degree of muscle injuries. Only grade II lesions were treated with three ultrasound-guided injections of autologous platelet-rich plasma every 7 days. Platelet concentrate was produced according to standard methods, with a 10% variability in platelet count. The platelet gel for clinical use was obtained by adding thrombin to the concentrates under standardised conditions. Outcomes assessed were: pain reduction, muscle function recovery and return to sports activity, ultrasound-imaging tissue healing, relapses, local infections, and any side effect during the treatment. In all cases muscle lesions healed fully on ultrasound-imaging, the pain disappeared, and muscle function recovery was documented with a return to sports activity. A single patient had a relapse 1 year after treatment. Platelet-rich plasma injected into the injury site is one of the most important factors rendering the treatment effective. To maximise its efficacy the preliminary ultrasound must be done accurately to localise the lesion and guide the needle into the corresponding lesion. According to the current results, which document full muscle recovery and no relapse except for one case, platelet-rich plasma ultrasound-guided injection represents a valid mini-invasive treatment for muscle injuries.
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Aim: Professional athletes require faster recovery after trauma. The aim of our study was to evaluate the efficacy of ultrasound guided platelets rich plasma (PRP) treatment for acute muscle injury comparing with traditional conservative therapy. Materials and methods: Thirty consecutive men (mean age 24 years old) professional athletes with acute local muscle injury were enrolled. All patients underwent US and sonoelastography examination. Patients were randomly assigned to 2 groups: group A received targeted PRP injection under US guidance and additionally conservative treatment and group B received conventional conservative treatment only. The pain was assessed according to visual analogue scale (0 to 10), muscle function according to pain on resisted flexion or strength, and range of motion. Both groups were further evaluated in the days 1, 7, 14, 21, and 28 after treatment starting. US criteria for regeneration were considered to be the disappearance of hypoechoic areas of muscle damage, fibrous tissue more stiff on sonoelastography, and neovascularity appearances. Results: The pain relief was more important in group A compared to group B starting from day 1 and continuing in the next 3 evaluation sessions (p<0.05). At the end of observation (28 day), 93 % of pain regression was declared by patients in group A vs 80 % of regression of pain in group B (p>0.05). Assessing the physical evolution in the 7th and 14th days significant changes in strength (p<0.05) and range of motion (p<0.05) for PRP treatment group was observed. After 28 days no significant differences between groups were observed concerning the pain on resisted flexion and strength (p>0.05) but the range of movement improved better in group A compared with group B (p< 0.05). Subjective global function scores improved significantly in group A compared with group B on the 28th day (p<0.05). The mean time for the physical recovery movement volume and the ability to practice sport was 10+/-1.2 days in group A and 22+/-1.5 days in group B. Conclusions: Injections of PRP under ultrasound guidance had asignificantly higher level of pain relief, physical recovery, and faster regeneration compared with conventional conservative treatment in acute muscle trauma in professional athletes.
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Background: Recent studies report a relatively high failure rate for tendon-bone healing after rotator cuff repair. Several studies have investigated biologically augmented rotator cuff repair; however, none has shown the application of synovial mesenchymal stem cells for such repair. Purpose: To demonstrate whether cells derived from shoulder tissues have mesenchymal stem cell properties and to identify which tissue is the best source of the mesenchymal stem cells. Study design: Controlled laboratory study. Methods: Forty-two patients with a diagnosed rotator cuff tear preoperatively were enrolled in this study. Human mesenchymal tissues were obtained during arthroscopic surgery for rotator cuff tears from 19 donors who met the inclusion criteria and had investigable amounts of tissue. Colony-forming units, yield obtained, expandability, differentiation potential, epitope profile, and gene expression were compared among the cells from 4 shoulder tissues: synovium of the glenohumeral joint, subacromial bursa, margin of the ruptured supraspinatus tendon, and residual tendon stump on the greater tuberosity (enthesis). Results: The number of live passage 0 cells from whole tissue was significantly higher in cells derived from the subacromial bursa (P < .05). Subacromial bursa-derived cells retained their expandability even at passage 10. In adipogenesis experiments, the frequency of Oil Red O-positive colonies was significantly higher for synovium- and subacromial bursa-derived cells than for tendon- and enthesis-derived cells (P < .0001). In studies of osteogenesis, the rate of von Kossa- and alkaline phosphatase-positive colonies was highest in subacromial bursa-derived cells (P < .0001). The chondrogenic potential was highest in cells derived from the enthesis. For epitope profiling, 11 surface antigens were measured, and most had similar epitope profiles, irrespective of cell source. Conclusion: The findings indicate that the subacromial bursa is a good candidate for the source of mesenchymal stem cells in rotator cuff tears. Clinical relevance: Synovial cells from the subacromial bursa in patients with rotator cuff tears are a superior cell source in vitro, suggesting that mesenchymal stem cells from this tissue could be good candidates for biological augmentation of rotator cuff repair.
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Background: Arthroscopic rotator cuff repair has a high rate of patient satisfaction. However, multiple studies have shown significant rates of anatomic failure. Biological augmentation would seem to be a reasonable technique to improve clinical outcomes and healing rates. Purpose: To represent a prospective, double-blinded, randomized study to assess the use of platelet-rich fibrin matrix (PRFM) in rotator cuff surgery. Study design: Randomized controlled trial; level of evidence, 1. Methods: Prestudy power analysis demonstrated that a sample size of 30 patients in each group (PRFM vs control) would allow recognition of a 20% difference in perioperative pain scores. Sixty consecutive patients were randomized to either receive a commercially available PRFM product or not. Preoperative and postoperative range of motion (ROM), University of California-Los Angeles (UCLA), and simple shoulder test (SST) scores were recorded. Surgery was performed using an arthroscopic single-row technique. Visual analog scale (VAS) pain scores were obtained upon arrival to the recovery room and 1 hour postoperatively, and narcotic consumption was recorded and converted to standard narcotic equivalents. The SST and ROM measurements were taken at 3, 6, 9, and 12 weeks postoperatively, and final (1 year) American shoulder and elbow surgeons (ASES) shoulder and UCLA shoulder scores were assessed. Results: There were no complications. Randomization created comparable groups except that the PRFM group was younger than the control group (mean ± SD, 59.67 ± 8.16 y vs 64.50 ± 8.59 y, respectively; P < .05). Mean surgery time was longer for the PRFM group than for the control group (83.28 ± 17.13 min vs 73.28 ± 17.18 min, respectively; P < .02). There was no significant difference in VAS scores or narcotic use between groups and no statistically significant differences in recovery of motion, SST, or ASES scores. Mean ASES scores were 82.48 ± 8.77 (PRFM group) and 82.52 ± 12.45 (controls) (F(1,56) = 0.00, P > .98). Mean UCLA shoulder scores were 27.94 ± 4.98 for the PRFM group versus 29.59 ± 1.68 for the controls (P < .046). Structural results correlated with age and size of the tear and did not differ between the groups. Conclusion: Platelet-rich fibrin matrix was not shown to significantly improve perioperative morbidity, clinical outcomes, or structural integrity. While longer term follow-up or different platelet-rich plasma formulations may show differences, early follow-up does not show significant improvement in perioperative morbidity, structural integrity, or clinical outcome.
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Mesenchymal stem cells (MSCs) hold promise for cell-based therapy in regenerative medicine. To date, MSCs have been obtained from conventional bone marrow via a highly invasive procedure. Therefore, MSCs are now also isolated from sources such as adipose tissue, cord blood and cord stroma, a subject of growing interest. As the characterization and differentiation potential of adipose-derived MSCs (AD-MSCs) and bone-marrow-derived MSCs (BM-MSCs) have not been documented, we have evaluated and compared the characteristics of both MSC types by qualitative and quantitative analyses. Both cell types show similar morphology and surface protein expression, being positive for stromal-associated markers and negative for hematopoietic and endothelial markers. The colony-forming potential of AD-MSCs is distinctly higher than that of BM-MSCs. Nonetheless, similar adipogenic and osteogenic differentiation is observed in both groups of MSCs. Cytochemical qualitative analysis and calcium mineralization demonstrate higher levels toward osteogenic differentiation in BM-MSCs than in AD-MSCs. On the contrary, the percentage of Nile red oil staining for differentiated adipocytes is higher in AD-MSCs than in BM-MSCs. Quantitative real-time polymerase chain reaction shows similar patterns of osteogenic- and adipogenic-associated gene expression in both cell types. Each of theMSCs respond in functional analysis by exhibiting unique properties at the differentiation level according to their micro-environmental niche. Thus, quantitative analysis might be a valuable means of describing stem cell multipotency, in addition to qualitative investigation.
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Platelet concentrates such as platelet-rich plasma (PRP) have gained popularity in sports medicine and orthopaedics to promote accelerated physiologic healing and return to function. Each PRP product varies depending on patient factors and the system used to generate it. Blood from some patients may fail to make PRP, and most clinicians use PRP without performing cell counts on either the blood or the preparation to confirm that the solution is truly PRP. Components in this milieu have bioactive functions that affect musculoskeletal tissue regeneration and healing. Platelets are activated by collagen or other molecules and release growth factors from alpha granules. Additional substances are released from dense bodies and lysosomes. Soluble proteins also present in PRP function in hemostasis, whereas others serve as biomarkers of musculoskeletal injury. Electrolytes and soluble plasma hormones are required for cellular signaling and regulation. Leukocytes and erythrocytes are present in PRP and function in inflammation, immunity, and additional cellular signaling pathways. This article supports the emerging paradigm that more than just platelets are playing a role in clinical responses to PRP. Depending on the specific constituents of a PRP preparation, the clinical use can theoretically be matched to the pathology being treated in an effort to improve clinical efficacy.
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Musculotendinous retraction is a limiting factor for repair of long-standing rotator cuff tears. However, it is currently unknown to what extent the muscle and tendon contribute to the degree of total retraction. Further understanding of this may possibly influence the strategy of musculotendinous reconstruction. To analyze the contribution of muscle and tendon to the process of myotendinous retraction. Cross-sectional study; Level of evidence, 3. Magnetic resonance imaging of 130 shoulders with intact (n = 20) or completely torn supraspinatus tendons was analyzed. Fatty infiltration of the supraspinatus muscle was graded according to Goutallier stages. The degree of retraction of the tendon stump and of the musculotendinous junction was assessed. There were 30 shoulders without evidence of supraspinatus fatty infiltration, 25 with stage 1, 23 with stage 2, 25 with stage 3, and 15 with stage 4 changes. The corresponding tear sizes (distance of tendon end from greater tuberosity) were 4, 21, 27, 37, and 41 mm; the distance of the myotendinous junction from the greater tuberosity was 22, 33, 39, 48, and 48 mm; and the length of the tendons (distance of tendon end to myotendinous junction) was 19, 13, 12, 11, and 8 mm, respectively. In Goutallier stage 3 and above, and in case of a positive tangent sign, the musculotendinous junction was, in 90% of the cases, retracted to or beyond the glenoid. Musculotendinous retraction in chronic rotator cuff tears results mainly from shortening of the muscle fibers but in advanced stages results also from shortening of the tendon tissue itself. The present data demonstrate, for the first time, that the residual tendon stump in a tendon tear does not have the length of the original tendon and is further shortened over time. Therefore, direct anatomic tendon reinsertion will result in lengthening of the supraspinatus muscle greater than what it would have been before the tear.
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Increased age, larger tear size, and more advanced fatty degeneration of the rotator cuff musculature have been correlated with poorer healing rates after rotator cuff repair. Platelets are an endogenous source of growth factors present during rotator cuff healing. Augmentation of rotator cuff repairs with platelet-rich fibrin matrix (PRFM) may improve the biology of rotator cuff healing and thus improve functional outcome scores and retear rates after repair. Cohort study; Level of evidence, 3. Rotator cuff tears at risk for retear were prospectively identified using an algorithm; points were assigned for age (50-59 years = 1; 60-69 years = 2; >70 years = 3), anterior-to-posterior tear size (2-2.9 cm = 0; 3-3.9 cm = 1; >4 cm = 2), and fatty atrophy (Goutallier score 0-2 = 0; Goutallier score 3-4 = 1). Three points were required for enrollment. Arthroscopic rotator cuff repair was performed with the addition of PRFM. Preoperative and 1-year postoperative magnetic resonance imaging (MRI) and functional outcome scores were obtained. Imaging and functional outcomes were compared with historical controls meeting the same enrollment criteria. Sixteen and 21 patients were enrolled in the PRFM and control groups, respectively. Mean age (65 ± 7 and 65 ± 9 years; P = .89), tear size (3.8 ± 1.1 and 3.9 ± 1.1 cm; P = .79), and median Goutallier scores (2 and 3; P = .18) were similar between the PRFM and control groups, respectively. Retear rates (56.2% vs 38.1%) were statistically significantly higher (P = .024) in the PRFM group compared with controls. Functional outcome scores postoperatively were not significantly improved compared with controls. Complications included 2 infections in the PRFM group. The augmentation of at-risk rotator cuff tears with PRFM did not result in improved retear rates or functional outcome scores compared with controls.
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To investigate the behavior of rotator cuff tears treated with conventional repair technique with the aid of autologous bone marrow mononuclear cells (BMMC). Fourteen consecutive patients (9 women, 5 men, mean age of 59.2 years) with complete rotator cuff tears (mean preoperative UCLA score of 12 ± 3.0) were fixed by transosseous stitches through mini-open incision, with subsequent injection of BMMC into the tendon borders, obtained from the iliac crest just prior to surgery. Magnetic resonance images (MRI) were acquired before and after surgery and evaluated by two musculoskeletal radiologists regarding new postoperative findings of patients treated with BMMC. After a minimum 12-month follow-up period, the UCLA score increased from 12 ± 3.0 to 31 ± 3.2. Clinical findings remained unaltered in the following year in all but one patient (13/14). MRI analysis after a 12-month follow-up period demonstrated tendon integrity in all cases (14/14), presence of low-signal intensity areas along the supraspinatus tendon and distal muscle belly in 8 cases (8/14), and high-intensity blooming small round artifact at the bursal and tendon topography in 11 cases (11/14). Six patients (6/14) showed formation of a high-signal intensity zone at the critical zone. Clinical findings remained unaltered in the following year in all but one patient, who relapsed into loss of strength and pain, being considered a bad result. Implantation of BMMC in rotator cuff sutures appears to be a safe and promising alternative to other biological approaches currently used to enhance tissue quality in affected tendons.
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Surgical repair of the rotator cuff repair is one of the most common procedures in orthopedic surgery. Despite it being the focus of much research, the physiological tendon-bone insertion is not recreated following repair and there is an anatomic non-healing rate of up to 94%. During the healing phase, several growth factors are upregulated that induce cellular proliferation and matrix deposition. Subsequently, this provisional matrix is replaced by the definitive matrix. Leukocyte- and platelet-rich fibrin (L-PRF) contain growth factors and has a stable dense fibrin matrix. Therefore, use of LPRF in rotator cuff repair is theoretically attractive. The aim of the present study was to determine 1) the optimal protocol to achieve the highest leukocyte content; 2) whether L-PRF releases growth factors in a sustained manner over 28 days; 3) whether standard/gelatinous or dry/compressed matrix preparation methods result in higher growth factor concentrations. 1) The standard L-PRF centrifugation protocol with 400 x g showed the highest concentration of platelets and leukocytes. 2) The L-PRF clots cultured in medium showed a continuous slow release with an increase in the absolute release of growth factors TGF-β1, VEGF and MPO in the first 7 days, and for IGF1, PDGF-AB and platelet activity (PF4=CXCL4) in the first 8 hours, followed by a decrease to close to zero at 28 days. Significantly higher levels of growth factor were expressed relative to the control values of normal blood at each culture time point. 3) Except for MPO and the TGFβ-1, there was always a tendency towards higher release of growth factors (i.e., CXCL4, IGF-1, PDGF-AB, and VEGF) in the standard/gelatinous- compared to the dry/compressed group. L-PRF in its optimal standard/gelatinous-type matrix can store and deliver locally specific healing growth factors for up to 28 days and may be a useful adjunct in rotator cuff repair.
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Tendon augmentation grafts have the potential to facilitate the repair of massive or otherwise unrepairable rotator cuff tears. In our clinic, between 2009 and 2013, 25 patients underwent surgery to treat massive symptomatic rotator cuff tears with porcine dermal collagen patch. This study is a clinical and instrumental assessment of 9 patients with the longest follow-up. These patients were evaluated with Constant score, the American Shoulder and Elbow Surgeons Evaluation Form, ultrasound imaging, magnetic resonance imaging, and electromyography. The clinical evaluations have shown good outcomes. The magnetic resonance imaging results were comparable with those of the ultrasound scan. In all cases, we found covering of humeral head, centering of the humeral head, maintenance of the tropism of the supraspinatus, no appearance of fatty degeneration, no worse in cases with fatty degeneration. With the electromyographic examination a complete functional recovery was observed with the possibility of performing maximal contraction against resistance in all cases. We believe that porcine dermal collagen is effective as an augmentation graft in the treatment of chronic extensive rotator cuff tears, providing excellent pain relief with an improvement in active ranges of motion and strength.
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Background: Platelet-rich plasma (PRP) has been proposed to augment tendon healing through improving tissue structure during the initial repair phase. Purpose: To investigate both the clinical and tissue effects of the coapplication of PRP injection with arthroscopic acromioplasty (AA) in patients with chronic rotator cuff tendinopathy. Design: Randomized controlled trial; Level of evidence, 1. Methods: The study comprised 60 randomized patients diagnosed with rotator cuff tendinopathy (55% women) aged between 35 and 75 years. Patients were randomized to AA alone or in combination with an injection of autologous PRP into the subacromial bursa (AA + PRP). Efficacy of treatment was assessed by analysis of patient-reported outcomes up to 2 years after treatment (Oxford Shoulder Score [OSS]) and by analysis of tendon biopsy specimens taken 12 weeks after treatment. Results: There was no significant difference in the OSS between AA alone and AA + PRP at any time point in the study. From 12 weeks onward, there was a significant increase in the OSS for both groups compared with their baseline scores (P < .001). Bonar scoring determined no significant change in tissue structure with the coapplication of PRP compared with surgery alone. The number of blood vessels and tendon cellularity were significantly decreased in tissue biopsy specimens taken from PRP-treated patients. The expression of p53-positive apoptotic cells increased after AA + PRP but decreased after AA alone. Conclusion: Arthroscopic acromioplasty significantly improves long-term clinical outcomes up to 2 years. The coapplication of PRP did not affect clinical outcomes. PRP significantly alters the tissue characteristics in tendons after surgery with reduced cellularity and vascularity and increased levels of apoptosis. Clinical relevance: The coapplication of PRP did not improve clinical outcomes and may have potential deleterious effects on healing tendons. Registry number: ISRCTN 10464365.
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Chronic rotator cuff tendon tearing is associated with irreversible atrophy, fatty infiltration, and interstitial fibrosis of the corresponding muscle. Anabolic steroids can prevent musculotendinous degeneration during retraction and/or can reverse these changes after operative repair of the retracted musculotendinous unit in sheep. Controlled laboratory study. The infraspinatus tendon was released in 18 alpine sheep. All sheep underwent repair of the retracted musculotendinous unit after 16 weeks and were sacrificed after 22 weeks; 6 sheep served as controls, 6 sheep were treated with weekly intramuscular injection of 150 mg of nandrolone decanoate after infraspinatus (ISP) repair (group N6W), and 6 sheep were treated with 150 mg of nandrolone decanoate immediately after tendon release (group N22W). Muscle biopsy specimens were taken before tendon release and after 16 and 22 weeks. Muscle volume and fatty infiltration (on MRI), myotendinous retraction, and muscle density (on computed tomography) were measured immediately after ISP release, after 6 weeks, and before ISP repair and sacrifice. Muscle volume on MRI decreased to a mean (±SD) of 80% ± 8% of the original volume after 6 weeks, remained stable at 78% ± 11% after 16 weeks, and decreased further to 69% ± 9% after 22 weeks in the control group. These findings were no different from those in group N22W (72% ± 9% at 6 weeks, 73% ± 6% at 16 weeks, and 67% ± 5% at 22 weeks). Conversely, the N6W group did not show a decrease in ISP volume after repair; this finding differed significantly from the response in the control and N22W groups. Fatty infiltration (on MRI) continuously increased in the control group (12% ± 4% at tendon release, 17% ± 4% after 6 weeks, 50% ± 9% after 16 weeks, and 60% ± 8% after 22 weeks) and the N6W group. However, application of anabolic steroids at the time of tendon release (N22W group) significantly reduced fatty infiltration after 16 (16% ± 5%; P < .001) and 22 weeks (22% ± 7%; P < .001). In a sheep model of rotator cuff tendon tear, further muscle atrophy can be prevented with the application of anabolic steroids starting immediately after tendon repair. In addition, fatty muscle infiltration can largely be prevented if the steroids are applied immediately after tendon release. Study findings may lead to the development of treatment strategies to prevent or reduce muscle degeneration caused by rotator cuff tendon tearing. © 2015 The Author(s).
Article
Two main questions about the use of platelet-rich plasma (PRP) for regeneration purposes are its effect on the speed of healing and the quality of healing. Despite recent numerous studies, evidence is still lacking in this area, especially in a representative patient population with medium to large rotator cuff tears. To assess the efficacy of PRP augmentation on the speed and quality of healing in patients undergoing arthroscopic repair for medium to large rotator cuff tears. Randomized controlled trial; Level of evidence, 1. A total