Pulsed electromagnetic field therapy improves tendon‐to‐bone healing in a rat rotator cuff repair model

Rotator cuff tears are common musculoskeletal injuries often requiring surgical intervention with high failure rates. Currently, pulsed electromagnetic fields (PEMFs) are used for treatment of long‐bone fracture and lumbar and cervical spine fusion surgery. Clinical studies examining the effects of PEMF on soft tissue healing show promising results. Therefore, we investigated the role of PEMF on rotator cuff healing using a rat rotator cuff repair model. We hypothesized that PEMF exposure following rotator cuff repair would improve tendon mechanical properties, tissue morphology, and alter in vivo joint function. Seventy adult male Sprague–Dawley rats were assigned to three groups: bilateral repair with PEMF (n = 30), bilateral repair followed by cage activity (n = 30), and uninjured control with cage activity (n = 10). Rats in the surgical groups were sacrificed at 4, 8, and 16 weeks. Control group was sacrificed at 8 weeks. Passive joint mechanics and gait analysis were assessed over time. Biomechanical analysis and μCT was performed on left shoulders; histological analysis on right shoulders. Results indicate no differences in passive joint mechanics and ambulation. At 4 weeks the PEMF group had decreased cross‐sectional area and increased modulus and maximum stress. At 8 weeks the PEMF group had increased modulus and more rounded cells in the midsubstance. At 16 weeks the PEMF group had improved bone quality. Therefore, results indicate that PEMF improves early tendon healing and does not alter joint function in a rat rotator cuff repair model. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:902–909, 2017.

     

Effects of age and pathology on shear wave speed of the human rotator cuff

Rotator cuff tears are common and often repaired surgically, but post‐operative repair tissue healing, and shoulder function can be unpredictable. Tear chronicity is believed to influence clinical outcomes, but conventional clinical approaches for assessing tear chronicity are subjective. Shear wave elastography (SWE) is a promising technique for assessing soft tissue via estimates of shear wave speed (SWS), but this technique has not been used extensively on the rotator cuff. Specifically, the effects of age and pathology on rotator cuff SWS are not well known. The objectives of this study were to assess the association between SWS and age in healthy, asymptomatic subjects, and to compare measures of SWS between patients with a rotator cuff tear and healthy, asymptomatic subjects. SWE images of the supraspinatus muscle and intramuscular tendon were acquired from 19 asymptomatic subjects and 11 patients with a rotator cuff tear. Images were acquired with the supraspinatus under passive and active (i.e., minimal activation) conditions. Mean SWS was positively associated with age in the supraspinatus muscle and tendon under passive and active conditions (p ≤ 0.049). Compared to asymptomatic subjects, patients had a lower mean SWS in their muscle and tendon under active conditions (p ≤ 0.024), but no differences were detected under passive conditions (p ≥ 0.783). These findings identify the influences of age and pathology on SWS in the rotator cuff. These preliminary findings are an important step toward evaluating the clinical utility of SWE for assessing rotator cuff pathology. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:282–288, 2018.     

促进肩袖止点腱骨愈合的研究进展

肩袖修补术是肩袖撕裂常用的治疗方式,能有效缓解肩关节疼痛,改善肩关节的活动,但肩袖修补术后肩袖再撕裂的发生率依然很高,主要原因在于肩袖修补术后肩袖止点处腱—骨愈合差,不能恢复原有的组织学结构和生物力学性能。因此,如何有效提高肩袖止点处腱骨愈合是解决此类问题的关键。目前随着人们对于肩袖止点研究的不断深入,各类治疗方法在改善肩袖止点腱骨愈合方面取得了较大的进展。本文将从影响肩袖止点处腱骨愈合的因素、肩袖止点处腱骨界面的恢复以利于肩袖腱骨愈合以及组织工程学在腱骨愈合中的应用3个方面阐述近几年关于肩袖腱骨愈合的研究进展,以期为肩袖撕裂的临床治疗提供一定的指导。     

The effects of chronic unloading and gap formation on tendon‐to‐bone healing in a rat model of massive rotator cuff tears

The objective of this study was to understand the effect of pre‐repair rotator cuff chronicity on post‐repair healing outcomes using a chronic and acute multi‐tendon rat rotator cuff injury model. Full‐thickness dual tendon injuries (supra‐ and infraspinatus) were created unilaterally in adult male Sprague Dawley rats, and left chronically detached for 8 or 16 weeks. After chronic detachment, tears were repaired and acute dual tendon injuries were created and immediately repaired on contralateral shoulders. Tissue level outcomes for bone, tendon, and muscle were assessed 4 or 8 weeks after repair using histology, microcomputed tomography, biomechanical testing, and biochemical assays. Substantial gap formation was seen in 35% of acute repairs and 44% of chronic repairs. Gap formation negatively correlated with mechanical and structural outcomes for both healing time points regardless of injury duration. Bone and histomorphometry, as well as biomechanics, were similar between acute and chronic injury and repair regardless of chronicity and duration of healing. This study was the first to implement a multi‐tendon rotator cuff injury with surgical repair following both chronic and acute injuries. Massive tear in a rodent model resulted in gap formation regardless of injury duration which had detrimental effects on repair outcomes. © 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:439–447, 2014.     

Tissue‐engineered tendon constructs for rotator cuff repair in sheep

Current rotator cuff repair commonly involves the use of single or double row suture techniques, and despite successful outcomes, failure rates continue to range from 20 to 95%. Failure to regenerate native biomechanical properties at the enthesis is thought to contribute to failure rates. Thus, the need for technologies that improve structural healing of the enthesis after rotator cuff repair is imperative. To address this issue, our lab has previously demonstrated enthesis regeneration using a tissue‐engineered graft approach in a sheep anterior cruciate ligament (ACL) repair model. We hypothesized that our tissue‐engineered graft designed for ACL repair also will be effective in rotator cuff repair. The goal of this study was to test the efficacy of our Engineered Tissue Graft for Rotator Cuff (ETG‐RC) in a rotator cuff tear model in sheep and compare this novel graft technology to the commonly used double row suture repair technique. Following a 6‐month recovery, the grafted and contralateral shoulders were removed, imaged using X‐ray, and tested biomechanically. Additionally, the infraspinatus muscle, myotendinous junction, enthesis, and humeral head were preserved for histological analysis of muscle, tendon, and enthesis structure. Our results showed that our ETC‐RCs reached 31% of the native tendon tangent modulus, which was a modest, non‐significant, 11% increase over that of the suture‐only repairs. However, the histological analysis showed the regeneration of a native‐like enthesis in the ETG‐RC‐repaired animals. This advanced structural healing may improve over longer times and may diminish recurrence rates of rotator cuff tears and lead to better clinical outcomes. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:289–299, 2018.     

Cell‐based tissue engineering augments tendon‐to‐bone healing in a rat supraspinatus model

Rotator cuff pathology causes substantial pain/disability and health care costs. Cell‐based tissue engineering offers promise for improved outcomes in tendon to bone healing. Cells from the tendon‐bone interface were used here to amplify surgical defect healing in a rat model. Cells from tendon‐to‐bone interface of the rotator cuff were seeded in sponges and implanted into critical rotator cuff defects: Group I, control; II, surgical defect only; III, suture‐repaired defect; IV, surgical defect, repair with sponge only; V, surgical defect, repair with sponge with cells. Three, 6‐, and 12‐week results were assessed for histologic features. At 3 weeks, histologic indices in Group V were significantly increased versus other treatment groups. Group V (12 weeks) showed significantly improved collagen organization versus other treatment groups; there was no difference in collagen organization in Group I versus V. In summary, increased cellularity, inflammation, vascularity, and collagen organization were present at 3 weeks; increased collagen organization at 12 weeks in Group V provides evidence for improved healing with cells. Data further support the utility of tendon‐bone interface cells in rotator cuff healing. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 31: 407–412, 2013     

Molecular mechanism of fatty degeneration in rotator cuff muscle with tendon rupture

Fatty degeneration often occurs in rotator cuff muscle with tendon rupture. However, the molecular mechanism underlying this change has not been fully clarified yet. We investigated the gene expression of Wnt10b and adipogenic marker gene, PPARγ and C/EBPα in C2C12 myogenic cell line under inhibition of Wnt10b by adipogenic induction medium, isobutylmethylxanthine, dexamethasone, and insulin (MDI). The role of Wnt‐signal was confirmed by adding Lithium chloride (LiCl), which mimics Wnt signaling to the cultured cell with MDI. We also assessed the expression profiles of same genes in the rat rotator cuff tear model in vivo. MDI induced Oil red‐O staining positive adipocytes and upregulated PPARγ and C/EBPα expression. LiCl inhibited adipogenic induction of MDI. Rotator cuff muscle with tendon rupture showed positive staining for Oil red‐O. Real‐time polymerase chain reaction analyses revealed decreased expression of Wnt10b followed by increased PPARγ and C/EBPα gene expression in the supraspinatus muscle. Fatty degeneration and its molecular events were remarkably seen in the distal one‐third of the detached supraspinatus muscle versus control. Wnt signaling may regulate adipogenic differentiation both in the myoblasts in vitro and the muscle in vivo. Our results indicate that the reduction of Wnt10b in muscle with a rotator cuff tear is a key signal in fatty degeneration of the muscle. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 29:861–866     

Editorial Commentary: Monitoring Tendon and Muscle Recovery After Rotator Cuff Repair Using Diagnostic Ultrasound Demonstrates that Early Repair is Beneficial for Many Patients With Reparable Tears

Rotator cuff repair is performed to effect healing of the enthesis; to restore shoulder comfort, strength, and function; to prevent tear propagation; and to prevent progression of atrophic muscle changes (fatty degeneration, fatty infiltration, and fatty atrophy) that eventually occur. Non-retracted and moderately retracted rotator cuff tears usually heal after repair, and muscle atrophy may recover over time. It follows that early rotator cuff repair is beneficial for many patients with chronic but reparable rotator cuff tears. Diagnostic ultrasound can provide quantitative information about the recovery of both muscle and tendon and represents a viable alternative to magnetic resonance imaging for evaluating healing after rotator cuff repair.     

Early pullout of lateral row knotless anchor in rotator cuff repair

Use of lateral row anchors in rotator cuff repair as a means of enhancing the strength of the repair; and improving footprint tendon contact, thus promoting healing, is becoming more popular in current arthroscopic practice. In our knowledge, failures of lateral row knotless anchors have not yet been reported. We present a case of double row rotator cuff repair using a Swivelock anchor (Arthrex) as a lateral row anchor that failed two weeks after surgery.     

Effects of lidocaine on torn rotator cuff tendons

We determined lidocaine's action on torn rotator cuff tendons in vitro and in vivo. For in vitro experiments, cell proliferation and viability assays were performed using tenocytes derived from human torn rotator cuff tendons. For in vivo experiments, acute rotator cuff tears were made on the supraspinatus tendons in the rats’ bilateral shoulders; before closure, lidocaine was injected into the shoulder and saline into the contralateral shoulder (control). After sacrifice, the specimens underwent biomechanical testing or histological analysis at 24 h and at 2, 4, and 8 weeks after surgery. The extent of collagen organization and apoptosis were semi‐quantitatively evaluated using collagen picrosirius red staining. Apoptosis was examined using TUNEL staining and electron microscopy. Cell proliferation decreased dose‐dependently. After exposure to 0.1% lidocaine for 24 h, cell viability decreased. Two and 4 weeks after surgery, the ultimate load to failure decreased more in the lidocaine group than in the control group, with significantly reduced stiffness in the lidocaine group 2 weeks after surgery. Collagen organization significantly decreased in the lidocaine group by 4 weeks after surgery but returned to baseline at 8 weeks. TUNEL staining detected numerous apoptotic tenocytes at the torn tendon edge exposed to lidocaine 24 h after surgery; electron microscopy confirmed the condensed cell nuclei. These changes were not observed in controls. Lidocaine caused cytotoxicity to tenocytes under both conditions, decreased biomechanical properties, and induced apoptosis and delay of collagen organization in this model. Subacromial lidocaine injections in patients with rotator cuff tears should be performed carefully. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1620–1627, 2016.     

Effects of Pulsed Electromagnetic Field Therapy on Rat Achilles Tendon Healing

The Achilles tendon is frequently injured. Data to support specific treatment strategies for complete and partial tears is inconclusive. Regardless of treatment, patients risk re-rupture and typically have long-term functional deficits. We previously showed that pulsed electromagnetic field (PEMF) therapy improved tendon-to-bone healing in a rat rotator cuff model. This study investigated the effects of PEMF on rat ankle function and Achilles tendon properties after (i) complete Achilles tendon tear and repair with immobilization, (ii) partial Achilles tendon tear without repair and with immobilization, and (iii) partial Achilles tendon tear without repair and without immobilization. We hypothesized that PEMF would improve tendon properties, increase collagen organization, and improve joint function, regardless of injury type. After surgical injury, animals were assigned to a treatment group: (i) no treatment control, (ii) 1 h of PEMF per day, or (iii) 3 h of PEMF per day. Animals were euthanized at 1, 3, and 6 weeks post-injury. Joint mechanics and gait analysis were assessed over time, and fatigue testing and histology were performed at each time point. Results indicate no clear differences in Achilles healing with PEMF treatment. Some decreases in tendon mechanical properties and ankle function suggest PEMF may be detrimental after complete tear. Some early improvements were seen with PEMF after partial tear with immobilization; however, immobilization was found to be a confounding factor. This body of work emphasizes the distinct effects of PEMF on tendon-to-bone healing and supports trialing potential treatment strategies pre-clinically across tendons before applying them clinically. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:70–81, 2020     

Autologous tendon‐derived cell‐seeded nanofibrous scaffolds improve rotator cuff repair in an age‐dependent fashion

Rotator cuff tendon tears are one of the most common shoulder pathologies, especially in the aging population. Due to a poor healing response and degenerative changes associated with aging, rotator cuff repair failure remains common. Although cell‐based therapies to augment rotator cuff repair appear promising, it is unknown whether the success of such a therapy is age‐dependent. We hypothesized that autologous cell therapy would improve tendon‐to‐bone healing across age groups, with autologous juvenile cells realizing the greatest benefit. In this study, juvenile, adult, and aged rats underwent bilateral supraspinatus tendon repair with augmentation of one shoulder with autologous tendon‐derived cell‐seeded polycaprolactone scaffolds. At 8 weeks, shoulders treated with cells in both juvenile and aged animals exhibited increased cellularity, increased collagen organization, and improved mechanical properties. No changes between treated and control limbs were seen in adult rats. These findings suggest that cell delivery during supraspinatus repair initiates earlier matrix remodeling in juvenile and aged animals. This may be due to the relative “equilibrium” of adult tendon tissue with regards to catabolic and anabolic processes, contrasted with actively growing juvenile tendons and degenerative aged tendons. This study demonstrates the potential for autologous cell‐seeded scaffolds to improve repairs in both the juvenile and aged population. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1250–1257, 2017.

     

Editorial Commentary: Long Head Biceps Tendon Can Be Used Like a Split Skin Graft: Mesh It and Augment Rotator Cuff Repairs

Full-thickness tears of the rotator cuff are common, and surgical treatment is indicated in most cases. Arthroscopic repair has become the standard technique, but despite improved surgical techniques, instrumentations, and implants, failure rates continue to be high and can reach 40% and more. Augmented repairs with allograft patches or autograft tissue, such as long head biceps tendon or fascia lata, have been used with mixed results. However, autograft augmentation seems to be resulting in superior outcomes and higher healing rates. Treating skin defects with split-skin grafts is the gold standard in burns and soft-tissue surgery. Given the limited supply of autograft, meshing autograft tendon and using it similar to a split-skin graft is a novel idea. When using a 2:1 expansion ratio, the long head biceps tendon can be formed into a porous scaffold with the in situ tenocytes, producing cytokines and promoting tenogenic differentiation. However, the scaffolds exhibited reduced tensile properties. The results are encouraging, and it will be interesting whether the clinical trials will demonstrate higher healing rates and better functional outcomes when compared to primary repair and allograft patch augmentation.     

Rotator cuff repair with a novel mesh suture: An ex vivo assessment of mechanical properties

Surgical repair is a common treatment for rotator cuff tear; however, the retear rate is high. A high degree of suture repair strength is important to ensure rotator cuff integrity for healing. The purpose of this study was to compare the mechanical performance of rotator cuffs repaired with a mesh suture versus traditional polydioxanone suture II and FiberWire sutures in a canine in vitro model. Seventy‐two canine shoulders were harvested. An infraspinatus tendon tear was created in each shoulder. Two suture techniques—simple interrupted sutures and two‐row suture bridge—were used to reconnect the infraspinatus tendon to the greater tuberosity, using three different suture types: Mesh suture, polydioxanone suture II, or FiberWire. Shoulders were loaded to failure under displacement control at a rate of 20 mm/min. Failure load was compared between suture types and techniques. Ultimate failure load was significantly higher in the specimens repaired with mesh suture than with polydioxanone suture II or FiberWire, regardless of suture technique. There was no significant difference in stiffness among the six groups, with the exception that FiberWire repairs were stiffer than polydioxanone suture II repairs with the simple interrupted technique. All specimens failed by suture pull‐out from the tendon. Based on our biomechanical findings, rotator cuff repair with the mesh suture might provide superior initial strength against failure compared with the traditional polydioxanone suture II or FiberWire sutures. Use of the mesh suture may provide increased initial fixation strength and decrease gap formation, which could result in improved healing and lower re‐tear rates following rotator cuff repair. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:987–992, 2018.

     

Lysophosphatidic acid‐induced RhoA signaling and prolonged macrophage infiltration worsens fibrosis and fatty infiltration following rotator cuff tears

Previous studies have suggested that macrophage‐mediated chronic inflammation is involved in the development of rotator cuff muscle atrophy and degeneration following massive tendon tears. Increased RhoA signaling has been reported in chronic muscle degeneration, such as muscular dystrophy. However, the role of RhoA signaling in macrophage infiltration and rotator muscle degeneration remains unknown. Using a previously established rat model of massive rotator cuff tears, we found RhoA signaling is upregulated in rotator cuff muscle following a massive tendon‐nerve injury. This increase in RhoA expression is greatly potentiated by the administration of a potent RhoA activator, lysophosphatidic acid (LPA), and is accompanied by increased TNFα and TGF‐β1 expression in rotator cuff muscle. Boosting RhoA signaling with LPA significantly worsened rotator cuff muscle atrophy, fibrosis, and fatty infiltration, accompanied with massive monocytic infiltration of rotator cuff muscles. Co‐staining of RhoA and the tissue macrophage marker CD68 showed that CD68+ tissue macrophages are the dominant cell source of increased RhoA signaling in rotator cuff muscles after tendon tears. Taken together, our findings suggest that LPA‐mediated RhoA signaling in injured muscle worsens the outcomes of atrophy, fibrosis, and fatty infiltration by increasing macrophage infiltraion in rotator cuff muscle. Clinically, inhibiting RhoA signaling may represent a future direction for developing new treatments to improve muscle quality following massive rotator cuff tears. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1539–1547, 2017.

     

Editorial Commentary: Allogenic Dermal Fibroblasts in Collagen Matrix Scaffold Enhance Rotator Cuff Repair in an Animal Model

There has been a recent surge of interest on the use of biologic supplements to facilitate rotator cuff repair healing. Experimental evidence appears to support use of allogenic dermal fibroblasts (ADFs), either in the form of local injection or tenocytes embedded in collagen matrix scaffold, to enhance healing of a repaired rotator cuff tendon tear in an animal model. When compared with the ADFs, the platelet-rich plasma (PRP)-induced response seems to be limited in terms of the specific increases in local collagen 1 concentration, thus resulting in a bone-tendon healing response that is inferior in both biology and biomechanical behavior under the same laboratory conditions. While on the one hand, there is pilot data supporting use of dermal fibroblast in the clinical setting, thus reinforcing the animal study findings, on the other hand, we are also aware of the encouraging biologic changes that occurred in the retrieved acellular dermal matrix (ADM) allograft that was used for superior capsular reconstruction as a treatment of irreparable rotator cuff tears. In theory, ADFs locally instilled as an injection should further enhance the healing response compared to the ADM. However, this needs to be further studied to be able to be widely applicable clinically.     

Editorial Commentary: Platelet-Rich Plasma Shows Promise for Improving Shoulder Tendinopathy

Platelet-rich plasma (PRP) injections continue to be used at increasing rates to treat common musculoskeletal conditions. PRP has a low-risk profile and emerging in vitro evidence to support its positive effects on soft-tissue healing. PRP has been shown to be of benefit for knee osteoarthritis, but less has been published regarding the shoulder. PRP delivers a high concentration of growth factors, cytokines, and other important inflammatory modulators. Its use is appealing for treating partial-thickness rotator cuff tears, subacromial bursitis, and rotator cuff tendinopathy since rotator cuff tendons often have poor healing capacity due to intrinsic degeneration. PRP has been shown to increase cell proliferation and matrix synthesis in tenocytes, which may aid tendon regeneration and healing. Adult tendons also contain a small amount of tendon progenitor cells, which can be induced to an active state by PRP. In addition, PRP is an autologous biologic agent and easy to acquire and administer in an outpatient clinical setting. Clinical studies continue to lag and are often heterogenous in quality and in results. PRP can vary widely based on multiple intrinsic and extrinsic factors, including patient age, sex, activity level, centrifugation speed, and number of centrifugation cycles. Thus, quality research methods should include reporting using the PAW (platelets/activation/white blood cells) system. Clinicians should remain cautiously optimistic about the future role of PRP injections in the shoulder.     

Effect of platelet‐rich plasma on degeneration change of rotator cuff muscles: In vitro and in vivo evaluations

Atrophy with fatty degeneration is often seen in rotator cuff muscles with torn tendons. PRP has been reported to enhance tissue repair processes after tendon ruptures. However, the effect of PRP on atrophy and fatty degeneration of the muscle is not yet known. The aim of this study is to examine the effect of PRP on degeneration change of rotator cuff muscles in vitro and in vivo. A murine myogenic cell line and a rat rotator cuff tear model were used in this study and PRP was administrated into subacromial space which is widely used in clinical practice. In in vitro study, administration of PRP to C2C12 cells stimulated cell proliferation while inhibited both myogenic and adipogenic differentiation. In in vivo study, administration of PRP suppressed Oil Red‐O positive lipid droplet formation. The expression of adipogenic genes was also decreased by PRP administration. In conclusion, PRP promoted proliferation of myoblast cells, while inhibiting adipogenic differentiation of myoblast cells and suppressing fatty degeneration change in rat torn rotator cuff muscles. Further investigations are needed to determine the clinical applicability of the PRP. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1806–1815, 2017.

     

Allogenous tendon stem/progenitor cells in silk scaffold for functional shoulder repair

Tendon stem/progenitor cells (TSPCs) were recently identified within tendon tissues. The aim of this study was to investigate TSPC-seeded knitted silk-collagen sponge scaffold for functional shoulder repair. The multidifferentiation potential, proliferation, and immune properties of TSPCs were investigated in vitro, while the efficacy of TSPC-seeded knitted silk-collagen sponge scaffolds in promoting rotator cuff regeneration was evaluated in vivo within a rabbit model. TSPCs, which exhibited universal stem cell characteristics (i.e., clonogenicity, high proliferative capacity, and multidifferentiation potential), nonimmunogenicity, and immunosuppression, proliferated well on our scaffold in vitro. Implantation of allogenous TSPC-seeded scaffolds within a rabbit rotator cuff injury model did not elicit an immunological reaction, but instead increased fibroblastic cell ingrowth and reduced infiltration of lymphocytes within the implantation sites at 4 and 8 weeks postsurgery. After 12 weeks, the allogenous TSPC-treated group exhibited increased collagen deposition and had better structural and biomechanical properties compared to the control group. This study thus demonstrated that the allogenous TSPC-seeded knitted silk-collagen sponge scaffold enhanced the efficacy of rotator cuff tendon regeneration by differentiating into tenocytes, and by secreting anti-inflammatory cytokines that prevent immunological rejection. Hence, allogenous TSPC-seeded knitted silk-collagen sponge scaffolds can be a clinically useful application for tendon tissue engineering.