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Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_18 | Pages 36 - 36
14 Nov 2024
Zderic I Kraus M Rossenberg LV Gueorguiev B Richards G Pape HC Pastor T Pastor T
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Introduction. Tendon ruptures are a common injury and often require surgical intervention to heal. A refixation is commonly performed with high-strength suture material. However, slipping of the thread is unavoidable even at 7 knots potentially leading to reduced compression of the sutured tendon at its footprint. This study aimed to evaluate the biomechanical properties and effectiveness of a novel dynamic high-strength suture, featuring self-tightening properties. Method. Distal biceps tendon rupture tenotomies and subsequent repairs were performed in sixteen paired human forearms using either conventional or the novel dynamic high-strength sutures in a paired design. Each tendon repair utilized an intramedullary biceps button for radial fixation. Biomechanical testing aimed to simulate an aggressive postoperative rehabilitation protocol stressing the repaired constructs. For that purpose, each specimen underwent in nine sequential days a daily mobilization over 300 cycles under 0-50 N loading, followed by a final destructive test. Result. After the ninth day of cyclic loading, specimens treated with the dynamic suture exhibited significantly less tendon elongation at both proximal and distal measurement sites (-0.569±2.734 mm and 0.681±1.871 mm) compared to the conventional suture group (4.506±2.169 mm and 3.575±1.716 mm), p=0.003/p<0.002. Gap formation at the bone-tendon interface was significantly lower following suturing using dynamic suture (2.0±1.6 mm) compared to conventional suture (4.5±2.2 mm), p=0.04. The maximum load at failure was similar in both treatment groups (dynamic suture: 374± 159 N; conventional suture: 379± 154 N), p=0.925. The predominant failure mechanism was breakout of the button from the bone (dynamic suture: 5/8; conventional suture: 6/8), followed by suture rupturing, suture unraveling and tendon cut-through. Conclusion. From a biomechanical perspective, the novel dynamic high-strength suture demonstrated higher resistance against gap formation at the bone tendon interface compared to the conventional suture, which may contribute to better postoperative tendon integrity and potentially quicker functional recovery in the clinical setting


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_18 | Pages 37 - 37
14 Nov 2024
Zderic I Kraus M Axente B Dhillon M Puls L Gueorguiev B Richards G Pape HC Pastor T Pastor T
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Introduction. Distal triceps tendon rupture is related to high complication rates with up to 25% failures. Elbow stiffness is another severe complication, as the traditional approach considers prolonged immobilization to ensure tendon healing. Recently a dynamic high-strength suture tape was designed, implementing a silicone-infused core for braid shortening and preventing repair elongation during mobilization, thus maintaining constant tissue approximation. The aim of this study was to biomechanically compare the novel dynamic tape versus a conventional high-strength suture tape in a human cadaveric distal triceps tendon rupture repair model. Method. Sixteen paired arms from eight donors were used. Distal triceps tendon rupture tenotomies and repairs were performed via the crossed transosseous locking Krackow stitch technique for anatomic footprint repair using either conventional suture tape (ST) or novel dynamic tape (DT). A postoperative protocol mimicking intense early rehabilitation was simulated, by a 9-day, 300-cycle daily mobilization under 120N pulling force followed by a final destructive test. Result. Significant differences were identified between the groups regarding the temporal progression of the displacement in the distal, intermediate, and proximal tendon aspects, p<0.001. DT demonstrated significantly less displacement compared to ST (4.6±1.2mm versus 7.8±2.1mm) and higher load to failure (637±113N versus 341±230N), p≤0.037. DT retracted 0.95±1.95mm after each 24-hour rest period and withstood the whole cyclic loading sequence without failure. In contrast, ST failed early in three specimens. Conclusion. From a biomechanical perspective, DT revealed lower tendon displacement and greater resistance in load to failure over ST during simulated daily mobilization, suggesting its potential for earlier elbow mobilization and prevention of postoperative elbow stiffness


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_18 | Pages 87 - 87
14 Nov 2024
Savaş S Konya M Yılmaz BK Kağa S Kağa E Demirel HH
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Introduction. The Achilles tendon is the thickest and strongest tendon in the human body. Even though the tendon is so strong, it is one of the most frequently injured tendons. Treatment of patients after rupture is planned conservatively and surgically. Conservative treatment is generally applied to elderly patients with sedentary lives. If the treatment is surgical, it can be planned as open surgery or percutaneous surgery. In our study with rabbits, we wrapped a membrane made of plga (polylactic-co-glycolic acid) nanotubes impregnated with type 1 collagen around the tendon in rabbits that underwent open Achilles tendon repair surgery. After surgery, biomechanical and histological tests were performed on the tendons. Method. In the study consisting of 24 rabbits, 2 groups were created by random distribution. In the study group, after the Achilles tendon rupture was created, a type 1 collagen-impregnated plga-based membrane was placed around the tendon after the repair of 1 modified Kesslerr suture. In the control group, after the Achilles tendon rupture was created, 1 modified Kessler suture and Tendon repair was performed with the application of 3 primary sutures. At the end of the 6th week of the study, the rabbits in 2 groups were randomly distributed and histological examination was performed. Additionally, biomechanical testing was performed. Bonar and Movın scoring were used in histological examinations. Result. As a result of biomechanical tests, it was seen that the resistance of the tendon against rupture was higher in the study group than in the control group. In addition, it was observed that the tendon rupture time was longer in the study group than in the control group. Histological examinations gave supportive results from biomechanical tests. Conclusion. We think that the use of collagen-impregnated plga-based nanotubes in the surgical treatment of Achilles tendon ruptures has a positive healing effect. Although we think that the return to normal life after surgery may be faster, we believe that more clinical studies are needed


Bone & Joint 360
Vol. 13, Issue 5 | Pages 34 - 37
1 Oct 2024

The October 2024 Shoulder & Elbow Roundup360 looks at: Proximal humeral fractures with vascular compromise; Outcomes and challenges of revision arthroscopic rotator cuff repair: a systematic review; Evaluating treatment effectiveness for lateral elbow tendinopathy: a systematic review and network meta-analysis; Tendon transfer techniques for irreparable subscapularis tears: a comparative review; Impact of subscapularis repair in reverse shoulder arthroplasty; Isolated subscapularis tears strongly linked to shoulder pseudoparesis; Nexel and Coonrad-Morrey total elbow arthroplasties show comparable revision rates in New Zealand study; 3D MRI matches 3D CT in assessing bone loss and shoulder morphology in dislocation cases.


Bone & Joint Open
Vol. 5, Issue 9 | Pages 793 - 799
20 Sep 2024
Cederqvist S Flinkkilä T Tuominen A Sormaala M Ylinen J Kautiainen H Sirniö K Pamilo K Kiviranta I Paloneva J

Aims

Rotator cuff disease (RCD) can considerably decrease quality of life. Here, we investigated whether health-related quality of life (HRQoL) influences the need for surgery in patients with RCD.

Methods

We performed an analysis of 417 patients with symptomatic RCD who were recruited from two hospitals between June 2008 and December 2014 to be randomized to receive non-surgical or surgical treatment. After a three-month rehabilitation period, 36-Item Short-Form Health Survey questionnaire (SF-36), shoulder pain (visual analogue scale (VAS)), and shoulder function (Constant-Murley score) data were available from 191 still-symptomatic patients who were eligible for surgery. A control group was formed from 87 excluded patients who were no longer eligible for surgery due to relief of symptoms.


The Bone & Joint Journal
Vol. 106-B, Issue 9 | Pages 970 - 977
1 Sep 2024
De Rus Aznar I Ávila Lafuente JL Hachem A Díaz Heredia J Kany J Elhassan B Ruiz Ibán MÁ

Rotator cuff pathology is the main cause of shoulder pain and dysfunction in older adults. When a rotator cuff tear involves the subscapularis tendon, the symptoms are usually more severe and the prognosis after surgery must be guarded. Isolated subscapularis tears represent 18% of all rotator cuff tears and arthroscopic repair is a good alternative primary treatment. However, when the tendon is deemed irreparable, tendon transfers are the only option for younger or high-functioning patients. The aim of this review is to describe the indications, biomechanical principles, and outcomes which have been reported for tendon transfers, which are available for the treatment of irreparable subscapularis tears.

The best tendon to be transferred remains controversial. Pectoralis major transfer was described more than 30 years ago to treat patients with failed surgery for instability of the shoulder. It has subsequently been used extensively to manage irreparable subscapularis tendon tears in many clinical settings. Although pectoralis major reproduces the position and orientation of the subscapularis in the coronal plane, its position in the axial plane – anterior to the rib cage – is clearly different and does not allow it to function as an ideal transfer. Consistent relief of pain and moderate recovery of strength and function have been reported following the use of this transfer. In an attempt to improve on these results, latissimus dorsi tendon transfer was proposed as an alternative and the technique has evolved from an open to an arthroscopic procedure. Satisfactory relief of pain and improvements in functional shoulder scores have recently been reported following its use. Both pectoralis minor and upper trapezius transfers have also been used in these patients, but the outcomes that have been reported do not support their widespread use.

Cite this article: Bone Joint J 2024;106-B(9):970–977.


The Bone & Joint Journal
Vol. 106-B, Issue 9 | Pages 957 - 963
1 Sep 2024
Baek CH Kim JG Kim BT

Aims

Favourable short-term outcomes have been reported following latissimus dorsi tendon transfer for patients with an irreparable subscapularis (SSC) tendon tear. The aim of this study was to investigate the long-term outcomes of this transfer in these patients.

Methods

This was a retrospective study involving 30 patients with an irreparable SSC tear and those with a SSC tear combined with a reparable supraspinatus tear, who underwent a latissimus dorsi tendon transfer. Clinical scores and active range of motion (aROM), SSC-specific physical examination and the rate of return to work were assessed. Radiological assessment included recording the acromiohumeral distance (AHD), the Hamada grade of cuff tear arthropathy and the integrity of the transferred tendon. Statistical analysis compared preoperative, short-term (two years), and final follow-up at a mean of 8.7 years (7 to 10).


The Bone & Joint Journal
Vol. 106-B, Issue 9 | Pages 978 - 985
1 Sep 2024
Savoie III FH Delvadia BP Tate JP Winter JE Williams GH Sherman WF O’Brien MJ

Rotator cuff tears are common in middle-aged and elderly patients. Despite advances in the surgical repair of rotator cuff tears, the rates of recurrent tear remain high. This may be due to the complexity of the tendons of the rotator cuff, which contributes to an inherently hostile healing environment. During the past 20 years, there has been an increased interest in the use of biologics to complement the healing environment in the shoulder, in order to improve rotator cuff healing and reduce the rate of recurrent tears. The aim of this review is to provide a summary of the current evidence for the use of forms of biological augmentation when repairing rotator cuff tears.

Cite this article: Bone Joint J 2024;106-B(9):978–985.


Bone & Joint Open
Vol. 5, Issue 7 | Pages 534 - 542
1 Jul 2024
Woods A Howard A Peckham N Rombach I Saleh A Achten J Appelbe D Thamattore P Gwilym SE

Aims

The primary aim of this study was to assess the feasibility of recruiting and retaining patients to a patient-blinded randomized controlled trial comparing corticosteroid injection (CSI) to autologous protein solution (APS) injection for the treatment of subacromial shoulder pain in a community care setting. The study focused on recruitment rates and retention of participants throughout, and collected data on the interventions’ safety and efficacy.

Methods

Participants were recruited from two community musculoskeletal treatment centres in the UK. Patients were eligible if aged 18 years or older, and had a clinical diagnosis of subacromial impingement syndrome which the treating clinician thought was suitable for treatment with a subacromial injection. Consenting patients were randomly allocated 1:1 to a patient-blinded subacromial injection of CSI (standard care) or APS. The primary outcome measures of this study relate to rates of recruitment, retention, and compliance with intervention and follow-up to determine feasibility. Secondary outcome measures relate to the safety and efficacy of the interventions.


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_6 | Pages 25 - 25
2 May 2024
Ajula R Mayne A Cecchi S Ebert J Edwards P Davies P Ricciardo B Annear P D'Alessandro P
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Proximal hamstring tendon avulsion from the ischial tuberosity is a significant injury, with surgical repair shown to have superior functional outcomes compared to non-surgical treatment. However, limited data exists regarding the optimal rehabilitation regime following surgical repair. The aim of this study was to investigate patient outcomes following repair of proximal hamstring tendon avulsions between a conservative (CR) versus an accelerated rehabilitation (AR) regimen. This prospective randomized controlled trial (RCT) randomised 50 patients undergoing proximal hamstring tendon repair to either a braced, partial weight-bearing rehabilitation regime (CR=25) or an accelerated, unbraced regime, that permitted full weight-bearing as tolerated (AR=25). Patients were evaluated pre-operatively and at 3 and 6 months post-surgery, via patient-reported outcome measures (PROMs) including the Lower Extremity Functional Scale (LEFS), Perth Hamstring Assessment Tool (PHAT) and 12-item Short Form Health Survey (SF-12). Primary analysis was per protocol and based on linear mixed models. Both groups were matched at baseline with respect to patient characteristics. All PROMs improved (p>0.05) and, while the AR group reported a significantly better Physical Component Score for the SF-12 at 3 months (p=0.022), there were no other group differences. Peak isometric hamstrings strength and peak isokinetic quadriceps and hamstrings torque symmetry were all comparable between groups (p>0.05). Three re-injuries have been observed (CR=2, AR=1). After proximal hamstring repair surgery, post-operative outcomes following an accelerated rehabilitation regimen demonstrate comparable outcomes to a traditionally conservative rehabilitation pathway, albeit demonstrating better early physical health-related quality of life scores, without an increased incidence of early re-injury


Bone & Joint Research
Vol. 13, Issue 4 | Pages 169 - 183
15 Apr 2024
Gil-Melgosa L Llombart-Blanco R Extramiana L Lacave I Abizanda G Miranda E Agirre X Prósper F Pineda-Lucena A Pons-Villanueva J Pérez-Ruiz A

Aims. Rotator cuff (RC) injuries are characterized by tendon rupture, muscle atrophy, retraction, and fatty infiltration, which increase injury severity and jeopardize adequate tendon repair. Epigenetic drugs, such as histone deacetylase inhibitors (HDACis), possess the capacity to redefine the molecular signature of cells, and they may have the potential to inhibit the transformation of the fibro-adipogenic progenitors (FAPs) within the skeletal muscle into adipocyte-like cells, concurrently enhancing the myogenic potential of the satellite cells. Methods. HDACis were added to FAPs and satellite cell cultures isolated from mice. The HDACi vorinostat was additionally administered into a RC injury animal model. Histological analysis was carried out on the isolated supra- and infraspinatus muscles to assess vorinostat anti-muscle degeneration potential. Results. Vorinostat, a HDACi compound, blocked the adipogenic transformation of muscle-associated FAPs in culture, promoting myogenic progression of the satellite cells. Furthermore, it protected muscle from degeneration after acute RC in mice in the earlier muscle degenerative stage after tenotomy. Conclusion. The HDACi vorinostat may be a candidate to prevent early muscular degeneration after RC injury. Cite this article: Bone Joint Res 2024;13(4):169–183


Bone & Joint Open
Vol. 5, Issue 3 | Pages 252 - 259
28 Mar 2024
Syziu A Aamir J Mason LW

Aims

Posterior malleolar (PM) fractures are commonly associated with ankle fractures, pilon fractures, and to a lesser extent tibial shaft fractures. The tibialis posterior (TP) tendon entrapment is a rare complication associated with PM fractures. If undiagnosed, TP entrapment is associated with complications, ranging from reduced range of ankle movement to instability and pes planus deformities, which require further surgeries including radical treatments such as arthrodesis.

Methods

The inclusion criteria applied in PubMed, Scopus, and Medline database searches were: all adult studies published between 2012 and 2022; and studies written in English. Outcome of TP entrapment in patients with ankle injuries was assessed by two reviewers independently.


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_1 | Pages 91 - 91
2 Jan 2024
Graça A Rodrigues M Domingues R Gomes M Gomez-Florit M
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Macrophages play a critical role in innate immunity by promoting or inhibiting tissue inflammation and repair. Classically, macrophages can differentiate into either pro-inflammatory (M1) or pro-reparative (M2) phenotypes in response to various stimuli. Therefore, this study aimed to address how extracellular vesicles (EVs) derived from polarized macrophages can affect the inflammatory response of tendon cells. For that purpose, human THP-1 cells were stimulated with lipopolysaccharide (LPS), and interleukins -4 and -13 (IL- 4, IL-13), to induce macrophages polarization into M1, M2, and hybrid M1/M2 phenotypes. Subsequently, the EVs were isolated from the culture medium by ultracentrifugation. The impact of these nanovesicles on the inflammation and injury scenarios of human tendon-derived cells (hTDCs), which had previously been stimulated with interleukin- 1 beta (IL-1ß) to mimic an inflammatory scenario, was assessed. We were able to isolate three different nanovesicles populations, showing the typical shape, size and surface markers of EVs. By extensively analyzing the proteomic expression profiles of M1, M2, and M1/M2, distinct proteins that were upregulated in each type of macrophage-derived EVs were identified. Notably, most of the detected pro- inflammatory cytokines and chemokines had higher expression levels in M1-derived EVs and were mostly absent in M2-derived EVs. Hence, by acting as a biological cue, we observed that M2 macrophage-derived EVs increased the expression of the tendon-related marker tenomodulin (TNMD) and tended to reduce the presence of pro-inflammatory markers in hTDCs. Overall, these preliminary results show that EVs derived from polarized macrophages might be a potential tool to modulate the immune system responses becoming a valuable asset in the tendon repair and regeneration fields worthy to be further explored


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_1 | Pages 94 - 94
2 Jan 2024
Graça A Domingues R Docheva D Gomez-Florit M Gomes M
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Worldwide, tendon disorders are one of the main causes of disability that decrease the quality of life of individuals and represent a substantial economic burden on society. Currently, the main therapies used for tendon injuries are not able to restore tendon functionality, and due to tendons' hypovascular and hypocellular nature, they present a reduced healing capacity, which also limits the success of the available therapies. In order to discover new therapies, extracellular vesicles (EVs), key players in cell-cell communication, have been widely explored for tissue engineering and regenerative medicine applications. Thus, the aim of this study is to assess the role of EVs derived from platelets in stem cell tenogenic commitment using a bioengineered tendon in vitro model for potential use as tendon therapeutic agents. Biomimetic platelet-derived EVs were produced by freeze-thaw cycles of platelets and isolation at different centrifugation speed. To recreate the architecture of tendons, a 3D system consisting of electrospun anisotropic nanofiber scaffolds coated with collagen encapsulating human adipose stem cells (hASCs) and different types of platelet-derived EVs, were produced. Then, the influence of the tendon-mimetic constructs and the distinct EVs populations in the hASCs tenogenic differentiation were assessed over culture time. We observed that the hASCs on the nanofibrous tendon scaffolds, show high cytoskeleton anisotropic organization that is characteristic of tenocytes. Moreover, acting as biological cues, platelet-derived EVs boosted hASCs tenogenic commitment, supported by the increased gene expression of tendon-related markers (SCX and TNMD). Additionally, EVs enhanced the deposition of tendon like extracellular matrix (ECM), as evidenced by the increased gene expression of ECM-related markers such as COL1, COL3, DCN, TNC, and MMP-3, which are fundamental for ECM synthesis and degradation balance. Moreover, EVs induced lower collagen matrix contraction on hASCs, which has been related with lower myofibroblast differentiation. Overall, the results revealed that EVs are capable of modulating stem cells' behavior boosting their tenogenic commitment, through the increased expression of healthy tendon cell markers, potentiating ECM deposition and decreasing cell contractility. Therefore, platelet EVs are a promising biochemical tool, worthy to be further explored, as paracrine signaling that might potentiate tendon repair and regeneration


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_2 | Pages 30 - 30
2 Jan 2024
Park H Kim R
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Glutamate regulates the expression of apoptosis-related genes and triggers the apoptosis of fibroblasts in rotator cuff tendons. Subacromial bursitis is always accompanied by symptomatic rotator cuff tear (RCT). However, no study has been reported on the presence of glutamate in subacromial bursa and on its involvement of shoulder pain in patients who had RCT. The purposes of this study were to determine whether the glutamate expression in subacromial bursa is associated with the presence of RCT and with the severity of shoulder pain accompanying RCT. Subacromial bursal tissues were harvested from patients who underwent arthroscopic rotator cuff tendon repair or glenoid labral repair with intact rotator cuff tendon. Glutamate tissue concentrations were measured, using a glutamate assay kit. Expressions of glutamate and its receptors in subacromial bursae were histologically determined. The sizes of RCT were determined by arthroscopic findings, using the DeOrio and Cofield classification. The severity of shoulder pain was determined, using visual analog scale (VAS). Any associations between glutamate concentrations and the size of RCT were evaluated, using logistic regression analysis. The correlation between glutamate concentrations and the severity of pain was determined, using the Pearson correlation coefficient. Differences with a probability <0.05 were considered statistically significant. Glutamate concentrations showed significant differences between the torn tendon group and the intact tendon group (P = 0.009). Concentrations of glutamate significantly increased according to increases in tear size (P < 0.001). In histological studies, the expressions of glutamate and of its ionotropic and metabotropic receptors have been confirmed in subacromial bursa. Glutamate concentrations were significantly correlated with pain on VAS (Rho=0.56 and P =0.01). The expression of glutamate in subacromial bursa is significantly associated with the presence of RCT and significantly correlated with its accompanying shoulder pain. Acknowledgements: This research was supported by the Basic Science Research Program, through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (NRF-2015R1D1A3A01018955 and 2017R1D1A1B03035232)


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_2 | Pages 129 - 129
2 Jan 2024
Gehwolf R
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Tendons are characterised by an inferior healing capacity when compared to other tissues, ultimately resulting in the formation of a pathologically altered extracellular matrix structure. Although our understanding of the underlying causes for the development and progression of tendinopathies remains incomplete, mounting evidence indicates a coordinated interplay between tendon-resident cells and the ECM is critical. Our recent results demonstrate that the matricellular protein SPARC (Secreted protein acidic and rich in cysteine) is essential for regulating tendon tissue homeostasis and maturation by modulating the tissue mechanical properties and aiding in collagen fibrillogenesis [1,2]. Consequently, we speculate that SPARC may also be relevant for tendon healing. In a rat patellar tendon window defect model, we investigated whether the administration of recombinant SPARC protein can modulate tendon healing. Besides the increased mRNA expression of collagen type 1 and the downregulation of collagen type 3, a robust increase in the expression of pro-regenerative fibroblast markers in the repair tissue after a single treatment with rSPARC protein was observed. Additionally, pro-fibrotic markers were significantly decreased by the administration of rSPARC. Determination of structural characteristics was also assessed, indicating that the ECM structure can be improved by the application of rSPARC protein. Therefore, we believe that SPARC plays an important role for tendon healing and the application of recombinant SPARC to tendon defects has great potential to improve functional tendon repair


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_2 | Pages 11 - 11
2 Jan 2024
Ciardulli M Giudice V Oliva F Selleri C Maffulli N Della Porta G
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Poor tendon repair is an unsolved issue in clinical practice, due to complex tendon structure. Tendon stem/progenitor cells (TSPCs) play key roles in homeostasis, regeneration, and inflammation regulation in acute tendon injuries, and rely on TGF-β signaling for recruitment into degenerative tendons. In this study, we aimed to develop an in vitro model for tenogenesis adopting a dynamic culture of a fibrin 3D scaffold, bioengineered with human TSPCs collected from both healthy and tendinopathic surgery explants (Review Board prot./SCCE n.151, 29 October 2020). 3D culture was maintained for 21 days under perfusion provided by a custom-made bioreactor, in a medium supplemented with hTGF-β1 at 20 ng/mL. The data collected suggested that the 3D in vitro model well supported survival of both pathological and healthy cells, and that hTGF-β signaling, coupled to a dynamic environment, promoted differentiation events. However, pathological hTSPCs showed a different expression pattern of tendon-related genes throughout the culture and an impaired balance of pro-inflammatory and anti-inflammatory cytokines, compared to healthy hTSPCs, as indicated by qRT-PCT and immunofluorescence analyses. Additionally, the expression of both tenogenic and cytokine genes in hTSPCs was influenced by hTGF-β1, indicating that the environment assembled was suitable for studying tendon stem cells differentiation. The study offers insights into the use of 3D cultures of hTSPCs as an in vitro model for investigating their behavior during tenogenic events and opens perspectives for following the potential impact on resident stem cells during regeneration and healing events


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_1 | Pages 75 - 75
2 Jan 2024
Marr N Zamboulis D Beaumont R Tatarczyk Z Meeson R Thorpe C
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Tendon injuries occur frequently in athletes and the general population, with inferior healing leading to deposition of fibrotic scar tissue. New treatments are essential to limit fibrosis and enable tendon regeneration post-injury. In this study, we tested the hypothesis that rapamycin improves tendon repair and limits fibrosis by inhibiting the mTOR pathway. The left hindlimb of female adult Wistar rats was injured by needle puncture and animals were either given daily injections of rapamycin (2mg/kg) or vehicle. Animals were euthanized 1 week or 3 weeks post-injury (n=6/group). Left and right Achilles tendons were harvested, with the right limbs acting as controls. Tendon sections were stained with haematoxylin & eosin, and scored by 2 blinded scorers, assessing alterations in cellularity, cell morphology, vascularity, extracellular matrix (ECM) organization and peritendinous fibrosis. Immunohistochemistry was performed for the tendon pan-vascular marker CD146 and the autophagy marker LC3. Injury resulted in significantly altered ECM organization, cell morphology and cellularity in both rapamycin and vehicle-treated groups, but no alterations in vascularity compared to uninjured tendons. Rapamycin had a limited effect on tendon repair, with a significant reduction in peritendinous fibrosis 3 weeks after injury (p=0.028) but no change in cell morphology, cellularity or ECM organization compared to vehicle treated tendons at either 1 week or 3 weeks post injury. CD146 labelling was increased at the site of injury, but there was no apparent difference in CD146 or LC3 labelling in rapamycin and vehicle treated tendons. The decrease in peritendinous fibrosis post-injury observed in rapamycin treated tendons indicates rapamycin as a potential therapy for tendon adhesions. However, the lack of improvement of other morphological parameters in response to rapamycin treatment indicates that rapamycin is not an effective therapy for injuries to the tendon core. Acknowledgements: This study was funded by Versus Arthritis (22607)


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_1 | Pages 32 - 32
2 Jan 2024
Traweger A
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Approximately 30% of general practice consultations for musculoskeletal pain are related to tendon disorders, causing substantial personal suffering and enormous related healthcare costs. Treatments are often prone to long rehabilitation times, incomplete functional recovery, and secondary complications following surgical repair. Overall, due to their hypocellular and hypovascular nature, the regenerative capacity of tendons is very poor and intrinsically a disorganized scar tissue with inferior biomechanical properties forms after injury. Therefore, advanced therapeutic modalities need to be developed to enable functional tissue regeneration within a degenerative environment, moving beyond pure mechanical repair and overcoming the natural biological limits of tendon healing. Our recent studies have focused on developing biologically augmented treatment strategies for tendon injuries, aiming at restoring a physiological microenvironment and boosting endogenous tissue repair. Along these lines, we have demonstrated that the local application of mesenchymal stromal cell-derived small extracellular vesicles (sEVs) has the potential to improve rotator cuff tendon repair by modulating local inflammation and reduce fibrotic scarring. In another approach, we investigated if the local delivery of the tendon ECM protein SPARC, which we previously demonstrated to be essential for tendon maturation and tissue homeostasis, has the potential to enhance tendon healing. Finally, I will present results demonstrating the utility of nanoparticle-delivered, chemically modified mRNAs (cmRNA) to improve tendon repair


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_2 | Pages 48 - 48
2 Jan 2024
Faydaver M Russo V Di Giacinto O El Khatib M Rigamonti M Rosati G Raspa M Scavizzi F Santos H Mauro A Barboni B
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Digital Ventilated Cages (DVC) offer an innovative technology to obtain accurate movement data from a single mouse over time [1]. Thus, they could be used to determine the occurrence of a tendon damage event as well as inform on tissue regeneration [2,3]. Therefore, using the mouse model of tendon experimental damage, in this study it has been tested whether the recovery of tissue microarchitecture and of extracellular matrix (ECM) correlates with the motion data collected through this technology.

Mice models were used to induce acute injury in Achilles tendons (ATs), while healthy ones were used as control. During the healing process, the mice were housed in DVC cages (Tecniplast) to monitor animal welfare and to study biomechanics assessing movement activity, an indicator of the recovery of tendon tissue functionality. After 28 days, the AT were harvested and assessed for their histological and immunohistochemical properties to obtain a total histological score (TSH) that was then correlated to the movement data.

DVC cages showed the capacity to distinguish activity patterns in groups from the two different conditions. The data collected showed that the mice with access to the mouse wheel had a higher activity as compared to the blocked wheel group, which suggests that the extra movement during tendon healing improved motion ability. The histological results showed a clear difference between different analyzed groups. The bilateral free wheel group showed the best histological recovery, offering the highest TSH score, thus confirming the results of the DVC cages and the correlation between movement activity and structural recovery.

Data obtained showed a correlation between TSH and the DVC cages, displaying structural and movement differences between the tested groups. This successful correlation allows the usage of DVC type cages as a non-invasive method to predict tissue regeneration and recovery.

Acknowledgements: This research is part of the P4FIT project ESR13, funded by the H2020-ITN-EJD MSCA grant agreement No.955685.