Rozprawy doktorskie na temat „Rotator cuff tear”

Shoulder pain is very common, affecting 14-21 % of the population at some time during their lifetime. The aims of this thesis were to improve the understanding of various aspects concerning the pathogenesis and treatment of subacromial pain and rotator cuff tears. Patients and healthy individuals were examined and compared in five studies: Study I) Seventy patients were retrospectively examined, clinically and with ultrasound, 15 years after arthroscopic subacromial decompression. All patients had an intact rotator cuff at surgery. Ultrasound showed significantly fewer rotator cuff tears compared to the prevalence of asymptomatic tears reported in the literature for the same age group. This indicates that arthroscopic subacromial decompression might protect the rotator cuff. Study II) Forty-two patients were retrospectively examined, clinically and with ultrasound, 39 months (mean) after an acute rotator cuff repair. All patients had pseudoparalysis after trauma, a full thickness tear and no previous history of shoulder symptoms. A delay in surgical treatment of three months and the number of tendons injured did not affect the outcome. Age affected outcome negatively. Study III) Plasma samples from 17 patients with cuff tears and 16 plasma samples from healthy age- and gender-matched controls were collected and analysed regarding the levels of matrix metalloproteinases and their inhibitors, TIMP1-4. Elevated levels of TIMP-1 were found in the patients with cuff tears compared to controls. Higher levels of TIMP-1, TIMP-3 and MMP-9 were found in patients with full-thickness tears compared to patients with partial-thickness tears. Study IV) Ninety-seven patients with longstanding subacromial pain, on the waiting-list for arthroscopic subacromial decompression, were prospectively randomised to specific shoulder exercises or control exercises for three months. Thereafter they were clinically examined and asked if they still wanted surgery. The specific shoulder exercises focusing on eccentric exercise for the rotator cuff and scapula stabilisers were found to be effective in reducing subacromial pain and improving shoulder function, thereby reducing the need for surgery. Study V) All patients including those operated, in Study IV were re-examined after one year using clinical assessment scores. The option of surgery was continuously available up to the one-year follow-up. Ultrasound and radiological examinations performed at inclusion were analysed in relation to the choice of surgery. The positive effects of the specific exercise programme were maintained after one year and significantly fewer patients in this group chose surgery. Surgery was significantly more often chosen by patients who had a low baseline shoulder score, and/or a full thickness rotator cuff tear.  All patients showed significant improvement in the clinical scores one year after inclusion or one year after surgery. These results support the concept that subacromial pain has a multifactorial aetiology and that the first line of treatment should be specific shoulder exercises. When conservative treatment fails, an acceptable result can be achieved with arthroscopic subacromial decompression. The rotator cuff status is important to consider when treating and studying these patients.

Rotator cuff disorders encompass a range of impairments from tendinopathy to partialor full-thickness rotator cuff tears, and represent the largest subgroup of shoulder pain. Rotator cuff tears, most of which are atraumatic, are common in adults with shoulder pain and are strongly associated with increasing age. Conservative treatment including physiotherapy is the first-line treatment, but some patients do not respond, and ultimately require surgery. Early predictions of response could allow individuals’ care pathways to be optimised, preventing unnecessary delays and suffering and benefiting patients and healthcare providers alike. My primary aim was to develop a prognostic model for the outcome of physiotherapy in adults with painful atraumatic partial-thickness tears (PTTs) of the rotator cuff. This was addressed by a prospective prognostic model study. The study was underpinned by a systematic review of prognostic models in adults undergoing physiotherapy for painful rotator cuff disorders and was further informed and complemented by the following work: the development and validation of the physiotherapy protocol for the prognostic study; the identification, selection and definition of the candidate prognostic factors for the prognostic study; the estimation of the Minimal Important Difference (MID) of the study’s primary outcome measure (the Western Ontario Rotator Cuff Index, WORC); and an exploratory responder analysis of the WORC outcome scores. The prognostic systematic review, prognostic study, MID analysis and responder analysis are original contributions to knowledge. The prognostic systematic review revealed important methodological deficiencies in the five included studies, and no clinically usable model. No study addressed a distinct PTT population. The process of identifying factors for my own prognostic model study revealed a lack of knowledge about the prognostic relevance of factors. All of the candidate models I explored in my prognostic study (n sample = 65, n analysed = 61) had low performance and precision. The estimated MID of the WORC was -300. The responder analysis resulted in different proportions of responders to treatment depending on the responder definition. My results highlight the difficulties involved in predicting outcomes in the field of shoulder pain and rotator cuff disorders, and the need for methodologically sound prognosis research.

Supraspinatus (SSP) tendon tear leads to intramuscular fat accumulation in the SSP muscle and the mechanisms are currently unknown. The purpose of this study was to investigate changes in vascularization of the SSP muscle and the relationship to intramuscular fat accumulation following SSP tendon detachment with or without reattachment. One hundred and six rabbits underwent SSP tendon detachment. In groups of ten, thirty rabbits were sacrificed 4, 8, and 12 weeks following detachment. Forty rabbits underwent detachment and immediate reattachment and were sacrificed in groups of ten following 0, 1, 2, and 6 weeks of healing. In groups of twelve, the remaining thirty-six rabbits underwent SSP tendon reattachment 4, 8, and 12 weeks after detachment and were sacrificed 12 weeks later. Vascularization was quantified in each specimen using CD31 immunohistochemistry. Four weeks after SSP tendon detachment, there was an increase in vascularization of the distal SSP muscle that reached significance after 12 weeks of detachment (p=0.024). We found that vascularization was positively correlated with intramuscular fat accumulation after detachment only (r=0.29; p=0.008). After SSP tendon reattachment, immediate or delayed, the correlation between vascularization and intramuscular fat accumulation was not observed. Microscopically, some SSP muscle vascular structures in the reattachment group had thicker vascular walls which were further quantified using αSMA immunohistochemistry. The delayed reattachment group showed an increase in vascular wall thickness in the distal portion of the SSP muscle at 4+12 (p=0.012) and 12+12 (p=0.012) weeks and in the proximal portion at 4+12 (p=0.024) weeks. Further investigation is required to demonstrate a cause/effect relationship between increased vascularization and intramuscular fat accumulation in the context of rotator cuff tear and success of surgical repair.

Background: la lesione di cuffia dei rotatori è la seconda patologia muscoloscheletrica più comune dopo la lombalgia ed è il disturbo di spalla più comune per il quale i pazienti necessitano di terapia. Per lesione o rottura di cuffia si intende lo strappo del tessuto tendineo con la parziale o totale disinserzione dalla superficie ossea che causa dolore alla spalla, perdita di movimento, debolezza e limitazioni nello svolgimento delle ADL. Il trattamento include la riparazione chirurgica e la fisioterapia, ma non è ancora presente un’opinione dominante su quale sia il trattamento più efficace per la risoluzione di questo quadro patologico. Obiettivo: analizzare studi di ricerca primaria che comparano l'efficacia della gestione chirurgica rispetto alla conservativa nel trattamento delle lesioni di cuffia degenerative, efficacia valutata in termini di miglioramento della sintomatologia dolorosa e disabilità (CMS). Disegno dello Studio: Revisione Sistematica costruita seguendo la traduzione italiana del PRISMA Statement (Fondazione GIMBE). Criteri di Eleggibilità: Studi Controllati Randomizzati (RCTs) con partecipanti affetti da lesione di cuffia degenerativa che indagano il miglioramento di dolore e disabilità rispettivamente nelle due tipologie di intervento. Fonti di ricerca: Gli studi primari sono stati reperiti nelle seguenti banche dati: PubMed, PEDro e Cochrane Library, cercando dall'incipit fino ad aprile 2020. Risultati: sono stati inclusi 3 studi. A tutti è stata applicata la PEDro Scale per la valutazione della validità interna. Tutti gli studi hanno riportato un punteggio ≥ 6, che riflette un’alta qualità metodologica. Conclusioni: gli studi inclusi non hanno dimostrato un chiaro beneficio in favore della chirurgia soprattutto nel breve termine dove si riscontrano minime differenze fra i due tipi di intervento. Sono dunque necessari ulteriori studi che determinino l’efficacia comparativa dei due interventi principalmente nel lungo termine.

Tyrimo objektas: Peties sąnario judesių amplitudės, raumenų jėgos, skausmo ir funkcinio pajėgumo pokyčiai taikant pratimus ir peties sąnario mobilizaciją po peties sąnario sukamosios manžetės plyšimo operacijos. Temos aktualumas. Peties sąnario sukamosios manžetės plyšimai dažnai lemia peties sąnario skausmus ir įvairaus pobūdžio negalią vyresniame amžiuje (Khair & Gulotta, 2011). Šią traumą patiria apie 25,0 proc. vyresnių nei 60 m žmonių ir apie 20,0 proc. vyresnių nei 20 m žmonių (Itoj, 2013). Lietuvoje yra atlikta nedaug tyrimų apie peties sąnario sukamosios manžetės plyšimus. Užsienio autoriai daugiau tyrinėja peties sąnario mobilizacijos ir pasyvių techninkų efektyvumą sergant peties ankšumo sindromu, artritu, artroze ir kitomis ligomis. Ypač trūksta informacijos apie gydymą, kuris leistų pacientams išvengti operacijos. Daugelis autorių nurodo, jog reikalingi išsamesni tyrimai šioje srityje. Tyrimo tikslas: įvertinti peties sąnario mobilizacijos ir pratimų efektyvumą gydant peties sąnario sukamosios manžetės plyšimus. Tyrimo uždaviniai: 1. Įvertinti pacientų po sukamosios manžetės plyšimo operacijos paties sąnario judesių amplitudę, raumenų jėgą, skausmą ir funkcinį pajėgumą prieš kineziterapiją. 2. Įvertinti peties sąnario mobilizacijos ir gydomųjų pratimų poveikį pacientų peties sąnario judesių amplitudei, raumenų jėgai, skausmui ir funkciniam pajėgumui po sukamosios manžetės plyšimo operacijos. 3. Įvertinti pacientų po sukamosios manžetės plyšimo operacijos judesių... [toliau žr. visą tekstą]
Object: The change of shoulder range of motion, muscle strength, pain and functional capacity after taking exercises and shoulder joint mobilization for patients after rotator cuff tear reconstruction surgery. Relevance of the topic. In elder age shoulder pain and various disabilities often occur because of the rotator cuff tears (Khair & Gulotta, 2011). 25,0 percent of population over 60 years and 20,0 percent of population over 20 years suffer from this injury (Itoj, 2013). Foreigner scientists more often make studies about the effectiveness of shoulder joint mobilization and other passive physical therapy techniques in curing other shoulder illnesses such as impingement syndrome, arthritis and ect. Especially there is lack of information about treatment that would prevent patients from surgery. Many scientists indicate that more studies are necessary about this topic. Task. The aim of this study was to evaluate the effectiveness of shoulder joint mobilization and therapeutic exercises curing rotator cuff tears. The main goals of this study were: 1. To evaluate range of motion, muscle strength, pain and functional capacity of operated shoulder for patients after rotator cuff tear arthroscopic reconstruction surgery. 2. To evaluate effectiveness of shoulder joint mobilization and therapeutic exercises for range of motion, muscle strength, pain and functional capacity of operated shoulder for patients after rotator cuff tear reconstruction surgery. 3. To evaluate how shoulder... [to full text]

The aim of this thesis was to study different aspects of the soft tissues of the shoulder joint. The variation in the quality of the tendons and ligaments can be explained by genetic factors. To test the hypothesis that collagen 1 α1 Sp1 polymorphism is related to the occurrence of cruciate ligament ruptures and shoulder dislocations, a total of 358 patients (233 patients with cruciate ligament ruptures and 126 with shoulder dislocations) were included in the study. We found a decreased risk of these injuries associated with collagen type 1 α1 Sp1 polymorphism. To study the mechanical properties of a better type of fixation of soft tissue to bone, 10 skeletally mature New Zealand white rabbits were operated bilaterally on the knees. The medial collateral ligaments were fixed by two types of plates one with a flat undersurface and the other with a pegged undersurface. After 4 weeks the force at failure, stiffness and energy uptake was almost double in the knees operated with the pegged plates. The prevalence and dysfunction of rotator cuff tears was investigated in 106 subjects who had never sought for their shoulder complaints, using Constant score, ultrasound and plain x-ray. The prevalence of full-thickness cuff tears was 30% (21% of all shoulders). The Constant score was lower in subjects with full-thickness tears. Partial-thickness tears and acromioclavicular joint osteoarthritis had no impact on shoulder complaints or Constant score. The subacromial index was lower for shoulders with full-thickness tears. Forty-eight patients with median age 56 years underwent subacromial decompression with or without acromioclavicular joint resection, investigated with MRI pre- and 3 months postoperatively. The Constant score and subjective shoulder value were measured preoperatively and at 3 and 6 months after surgery and even 2 years for subjective shoulder value. Two raters investigated the MRI. The results showed poor inter-rater reliability for MRI. However, both Constant score and subjective shoulder value improved over time. MRI is not a reliable method to study the capsular reaction after subacromial decompression due to high subjectivity of the radiologists.

To explore the potential mechanisms of tendon degeneration, we investigated the role of c-Jun N-terminal Kinase (JNK) activation and the regulation of matrix metalloproteinase 1 (MMP1) in tendon matrix degradation under oxidative stress. JNK and MMP1 activity in samples from normal and ruptured human supraspinatus tendons were evaluated by immunohistochemistry. Real-time quantitative PCR was utilized to evaluate MMP1 mRNA expression and western blotting for MMP1 and JNK protein detection. JNK activation and increased MMP1 activity were found in the torn human supraspinatus tendon tissue, as well as in human tendon cells under in vitro oxidative stress. Inhibition of JNK prevented MMP1 over-expression in oxidative stressed human tendon cells. Results from the current study indicated that stress activated JNK plays an important role in tendon matrix degradation, possibly through upregulating of MMP1.

Zur Zeit gibt es keinen optimalen Sehnentransfer zur Behandlung von irreparablen Ruptur der Subscapularissehne. Obwohl der Pectoralis major Transfer als Therapie der Wahl gilt, bleibt der Kraftvektor der verlagerten Sehne-Muskeleinheit sehr unterschiedlich zum Kraftvektor des Subscapularismuskels. Das Ziel dieser Arbeit war, ein neues Konzept zur Behandlung von irreparablen Subscapularisrupturen zu definieren, bei dem die Subscapulariseinheit selektiv mittels Teres major(TM) und Pectoralis major (PM) wiederhergestellt wird. In den Kadaverstudien dieser Arbeit konnte gezeigt werden, dass sich der M. Teres major anatomisch-chirurgisch als Sehnentransfer zur Rekonstruktion der unteren Hälfte des M. Subscapularis eignet. Darüberhinaus wurde in einer dreidimensionalen Vektoranalyse gezeigt, dass der Kraftvektoren vom verlagerten Teres major sich nicht signifikant vom Kraftvektoir des unteren Anteils des Musculus subscapularis unterscheidet. Es wurde weiterhin gezeigt, dass Modifikationen des Pectoralis major transfer durch Reroutingmassnahmen zu einer deutlichen Verbesserung seines Kraftvektors im Vergleich zum oberen Amteil des Musculussubscapularis führt. Basierend auf den neuen anatomischen und biomechanischen Erkenntnissen wurde im letzten Teil dieser Schrift das neue Konzept klinisch angewandt. Dabei wurde bei 7 Patienten mit einer irreparablen Subscapularisruptur nach multiplen Voreingriffen eine selektive Rekonstruktion mittels kombinierten TM-PM Transfer durchgeführt. Es traten keine Komplikationen auf und alle Patienten hatten eine deutliche Linderung Ihrer Schmerzen und eine Verbesserung der Funktion. Somit erscheint diese neue Transferoperation eine sichere und effiziente Option zur Behandlung irreparabler Subscapularisrupturen darzustellen.
Currently there is no optimal tendon transfer procedure for the management of irreparable subscapularis lesions. Although the pectoralis major transfer is considered as the gold standard in the treatment of irreparable subscapularis tears, the force vector orientation of this transfer may not be optimal in comparision to the situation at the subscapularis muscle. Objective of this monograph was to establish the anatomical and biomechanical basis for a new concept of selective subscapularis reconstruction combining a teres major transfer to the pectoralis major transfer. In the cadaveric part of this work, it could be demonstrated that the teres major is a safe and biomechanically logical transfer for reconstruction of the lower part of the subscapularis. The analysis was carried on to define the optimal transfer for reconstruction of the upper part of the subscapularis. It was possible to determine the biomechanical effect of rerouting procedures of the pectoralis major transfer. Passing the tendon underneath the conjoined tendon appeared to be the most effective way to improve the direction of the pectoralis major transfer for subscapularis reconstruction. However this technique is demanding when the plane underneath the conjoined tendon is scarred and the pectoralis major is bulky. In such cases there is a risk to injure the musculocutaneous nerve. Therefore, rerouting the sternal part of the pectoralis major underneath its clavicular part (sPM tansfer) may be a safer option. Finally, based on the acquired anatomical and biomechanical data, early clinical experience in a series of 7 patients was reported. Although the clinical series was small, the combined TM-sPM transfer appeared to be a valuable and a safe alternative to treat irreparable subscapularis tears. An interesting observation in this study was that the transfer was able to recenter the statically subluxed humeral head in two cases. This could be attributed to the dynamic hammock built by the transferred teres major. The early promising subjective and objective results presented here encourage for further investigation.

The purpose of this study is to evaluate anatomical variations of the coracoacromial ligament (CAL) in relation to the etiology of subacromial impingement syndrome and rotator cuff tears. A knowledge and understanding of these variations will help to determine how such variations may influence the surrounding tissues and how the biomechanics of the shoulder works, as well as improving accurate diagnosis and subsequent treatment of shoulder impingement syndrome. The methodological approach involved the dissection of 220 cadaveric shoulders in the Centre for Anatomy and Human Identification (CAHID) with a mean age of 82 years (range 53 to 102 years). The CAL was classified according to its morphology and composed band number. The rotator cuff tendons were inspected for tears that were categorized into partial bursal and complete tears. Furthermore, the study inspected the CAL’s parameters and attachment sites: degenerative changes include acromial and coracoid spurs and attrition lesions at the undersurface of the acromion. Results: the multiple banded ligament was the most commonly observed type and was seen in 101 (46%) specimens. The attachment sites of the ligament varied as the size or number of bands of the ligament increased. An association was found between rotator cuff tears and shoulders which had three or more CAL bands (52%). In addition, shoulders with rotator cuff tears had wider attachments, thicker ligaments and larger subacromial insertions. Shoulders with rotator cuff tears also had a significant incidence and size of acromial spurs. The size of the spurs was correlated with the size of the CAL and attrition lesions on the undersurface of the acromion, and changes in morphology of the acromion. Attrition lesions at the subacromial insertion of the CAL were associated with tears in the rotator cuff tendons, and worsened as the size of the subacromial insertion increased. In conclusion, anatomical variations of the CAL showed a relationship with rotator cuff tears.

Questo progetto di tesi fa parte di un più ampio studio clinico condotto all’interno dell’azienda NCS Lab (Carpi,(MO)), in collaborazione con il Dr. Claudio Chillemi (ICOT, Latina (RM)) che mira ad eseguire un confronto tra diverse tecniche chirurgiche per la riparazione della cuffia dei rotatori. Lo studio clinico in questione durerà circa due anni: per questo motivo i dati analizzati in questo progetto di tesi provengono solo dal gruppo di pazienti acquisiti nella fase preoperatoria. Tutti i dati sono stati acquisiti utilizzando i sensori magneto-inerziali WISE (tecnologia proprietaria dell’azienda NCS Lab). Questo lavoro di tesi si propone, quindi, di valutare la ripetibilità del movimento in termini di coefficiente di correlazione multipla e di estrapolare alcuni parametri di interesse clinico come, ad esempio, i range di movimento (ROM) della scapola e dell’omero e il ritmo scapolo-omerale (SHR). Questi parametri sono stati poi caratterizzati da un punto di vista statistico al fine di valutare le differenze tra arto patologico e controlaterale. Sono state calcolate, inoltre, le prediction bands con lo scopo di descrivere le differenze tra arto patologico e controlaterale nella coordinazione scapolo-omerale dei pazienti. Per quanto riguarda la ripetibilità del movimento, i risultati ottenuti in questo lavoro di tesi mostrano che la rotazione medio-laterale è caratterizzata da un eccellente CMC sia per l'arto patologico che per il controlaterale. Inoltre, sono state riscontrate differenze significative dal punto di vista statistico tra le distribuzioni dei range di movimento dell'arto patologico e controlaterale. Tali differenze sono state trovate anche per quanto riguarda il ritmo scapolo-omerale.

Background The shoulder is the third most common site of musculoskeletal symptoms with an estimated 20% of the population reporting symptoms at any given time. Rotator cuff tears are the most common shoulder disorder, and the major debilitation patients seek help for is pain. Full thickness rotator cuff tears have an estimated prevalence of between 7 and 27%, but studies have shown that not all of these are symptomatic. Many case series have been set in shoulder clinics and may have drawn false causality between rotator cuff tears and pain. This study uses a community population-based cohort to determine the epidemiology of rotator cuff tears and test the association between rotator cuff tears, pain, and functional losses. Methods 463 consecutive subjects (926 shoulders) have undergone a multidisciplinary assessment of their shoulders including high-definition ultrasound, the Oxford shoulder score and myometric strength testing. Individuals were part of the Chingford 1000 women cohort, which is a 20-year-old longitudinal population study comprising 1003 women aged between 64 and 87, and is representative of the population of the UK. Results The population prevalence of full-thickness tears was 22.2%, of which 4.6% were bilateral which increased significantly with age. The prevalence was greater in the dominant arm with a 1.64 increase in relative risk. The population prevalence of all tendon abnormalities was 59.3%, of which 30.2% were bilateral, increasing with age. Although 48.4% of full-thickness tears were asymptomatic there was an association between rotator cuff tears and patient reported symptoms. The relative risk of symptoms compared to normal tendons was 1.97 for abnormal tendons, 2.20 for full-thickness tears<2.5cm, and 4.74 for full-thickness tears >2.5cm (p<0.001). Individuals with at least one full-thickness tear had a relative risk of symptoms 1.97 that of those with bilateral normal tendons (p<0.001). Quantitative shoulder strength reduced with age, (10.2-16.2%, p<0.001), the non-dominant arm (4.9%, p<0.001), and the presence of pain (10.8%, p<0.001). Rotator cuff tears had no independent effect, but a significant interaction with age. Strength was preserved in the under 70's irrespective of rotator cuff tear, but in the over 70's there was decrease in strength of between 33% and 39% irrespective of pain (p=0.004). Conclusions This study provides an epidemiological basis to the understanding of rotator cuff tears. The prevalence of full-thickness tears in a female population aged 64-87 was 22.2%. Although only half of all full-thickness tears are symptomatic there is a statistically significant increase in the likelihood of symptoms with increasing tear pathology. There is also an association with loss of strength but only in the over 70's.

Background: The ability of primary care Extended Scope Physiotherapists (ESPs) to refer appropriate patients to secondary care has not been adequately examined. Also referrals for shoulder surgery from secondary care ESPs have been shown to be misdirected in comparison to other specialties. Barriers to referral have not been investigated but the literature suggests that referral criteria may improve appropriate referrals. The high prevalence of rotator cuff disease, its impact on pain and disability, and the lack of agreement between surgeons about when to operate indicate that there is a strong case for the development of surgical referral criteria for rotator cuff tear pathology. Method: The thesis has three stages of study. First a national survey of 99 primary care ESPs was undertaken to determine conversion to surgery rates, barriers to referral and the use of referral criteria. Secondly a national Delphi study with 20 shoulder surgeons was undertaken and surgical referral criteria for rotator cuff tear were developed. Thirdly after development, the criteria were tested on a convenience sample of 9 ESPs using 3 vignette case studies. Results: Primary care ESPs have a mean conversion rate of 74%. There was not enough data to show differences between subspecialist groups. Most barriers to specialist referral were associated with commissioning rather than issues pertaining to the primary care environment. 50% of ESPs reported using referral criteria which may explain why barriers to referral were relatively low. Surgical referral criteria for rotator cuff tear were developed. Key areas of consensus were: severity of pain, functional limitation, identification of fat atrophy and agreement for a trial of physiotherapy before referral. When referral criteria were piloted on a surgical candidate 33% of the ESPs changed their referral behaviour appropriately. Conclusion: ESPs in primary care have shown mean conversion rates of 74%. Surgical referral criteria to improve the appropriateness of rotator cuff tear referrals have shown promising results when piloted. Implications: In future referral criteria may have the potential to improve the appropriateness of rotator cuff referrals and may be beneficial as a benchmark against which ESPs can independently demonstrate the appropriateness and quality of the care they provide.

This study compares a physiotherapy exercise regime with a control treatment for the physiotherapy management of patients with massive, irreparable rotator cuff tears of the shoulder. Following ethical approval and informed consent, eligible patients with radiologically confirmed massive rotator cuff tears were recruited to the investigation. The study design was a randomised placebo controlled trial of 60 patients evaluating the change from baseline to three months, six months and twelve months in the shoulder function of patients randomised into either an intervention arm (exercise, advice, pain relief and ultrasound) or a control group (advice, pain relief and ultrasound). Randomisation using group designation in sealed envelopes took place after the baseline assessment. The primary outcome measure was the Oxford shoulder score. Secondary outcome measures included Short Form 36, the Measure Yourself Medical Outcome Profile and measures of range of shoulder movement.

Includes bibliographical references
Aim: To assess the MRI pathoanatomical changes 10 years after unrepaired full thickness supraspinatus tears in a population of patients that had acromioplasty done for symptomatic impingement with a rotator cuff tear.

RERUME: Les modèles personnalisés 3D sont de plus en plus demandés pour la planification chirurgicale et les recherches en biomécanique. L’objectif principal de cette thèse cotutelle était d’améliorer la méthode de reconstruction 3D à partir des images radiographies biplanes proposée par Lagacé, Ohl et al., afin que celle-ci puisse être plus facilement utilisée en clinique et qu’elle puisse permettre d’aider à la planification chirurgicale et/ou l’évaluation post-chirurgicale. Le système de radiographie biplane EOS à faible dose d’irradiation est le résultat d’une collaboration entre la société EOS imaging, l’institut biomécanique humaine Georges Charpak d’Arts et Métiers ParisTech, le laboratoire de recherche en imagerie et orthopédie (LIO) de l’école de technologie supérieure de Montréal, Georges Charpak, Jean Dubousset et Gabriel Kalifa (Dubousset et al. 2010). Le principe du détecteur de rayon X est basé sur les travaux développés par le Prof. Charpak, qui réduit significativement la dose de rayonnement comparé à la radiographie standard (Dubousset et al. 2010) Quatorze indices cliniques utilisés plus ou moins couramment en clinique pour le diagnostic et le suivi des pathologies de l’épaule et pour la planification chirurgicale et son évaluation post-opératoire ont été calculé. La justesse est acceptable (biais <1 mm sauf la distance sous acrominale) et une reproductibilité (2 fois écart-type inférieur à 5 mm ou 5° sauf 2 paramètres) qui est similaire à ce qui est présenté dans la littérature. L’approche proposée apporte sur une amélioration de la reconstruction dans un contexte où il serait intéressant qu’elle devienne utilisable en routine clinique. Bien que les améliorations soient encore nécessaires, cette contribution apporte une pierre à l’analyse de l’articulation intacte et pathologique et est prometteuse quant à la possibilité de son implantation dans la routine clinique pour évaluer les interventions chirurgicales en pré- et post-opératoire
Three-dimensional subject-specific models are increasingly requested for surgical planning and research in biomechanics. The main objective of this cotutelle thesis was to improve the 3D reconstruction method using biplane radiography images proposed by Lagacé, Ohl et al., in order to facilitate its application in clinic, especially to assist surgical planning and/or post-surgical evaluation. The low-dose biplane radiography EOS was used and an improvement to the reconstruction method was proposed. Fourteen clinical indices used more or less routinely in clinical diagnosis for monitoring of shoulder disorders and for surgical planning and postoperative evaluation were calculated and evaluated. The accuracy is acceptable and reproducibility is similar to what is presented in the literature. The proposed approach brings an improvement of reconstruction in a context where it would be interesting for clinical routine use. Although improvements are required, this contribution brings a stone to the analysis of intact and pathological joint and is promising as to the possibility of its presence in the clinical routine for evaluating pre- and post-operative surgery

碩士
國立成功大學
醫學工程研究所
83
Rotator cuff tear is a common disease in clinical practice and a goal of rehabilitation is to return the surgical extremity to its original strength. The purpose of this study was to determine the shoulder strength in patients who had undergone rotator cuff repair and acromioplasty surgery. Twenty-three male patients with average age 60.7 were tested bilaterally on the Kin-Corn 500H isokinetic dynamometer. Extemal rotation, internal rotation and flexion were tested in a velosity of 60 /sec. The results were compared in two groups devided in according to the tear size smaller or larger than 3 cm.The result showed that the large tear group had smaller strength than the small tear group especially in external and interal rotation which were statistically significant. The strength ratio of the operated and nonoperated shoulders showed 66%, 81% and 87% in external rotation, internal rotation and flexion. We also compared the strength ratio of external and internal rotation and it was 74% in nonoperated shoulders and 58% in operated shoulders. The result showed that the operated shoulder strength did not return to the level of the nonoperated and the tear size was related to the recovery. This finding may add information in estimating the prognosis and postsurgical rehabilitation.

Clinically it was observed that patients with decreased static resisted external rotation strength o f the arm (tested in neutral) often had rotator cuff tears. 'In addition, it was observed that the size of the rotator cuff tear seemed to be correlated with the amount of loss of muscle strength. The purpose of this study of the shoulder was to ascertain: l.If static resisted external rotation strength of the arm (tested in neutral) can be used as a diagnostic test to ascertain if a tear of the rotator cuff is present. 2.1f a relationship exists between the decrease of strength of the arm when testing static resisted external rotation (in neutral) and the size of the cuff tear. Thirty- two subjects who had been selected by an orthopaedic surgeon to have their rotator cuff artbroscopically examined, were used for the study. Certain exclusion criteria were applied and twelve subjects were excluded from the study. The pre-operative testing consisted of a routine shoulder examination, which was expanded to include the Constant score method. Isometric muscle testing of the rotator cuff muscles was undertaken using a Nicholas hand held dynamometer. The opposite unaffected arm was used as a control. The force production of the affected arm was then calculated as a percentage of the control arm, thus resulting in a dimensioniess relative measurement of the strength of the affected arm. The intra-operative results of the arthroscopic examinations were obtained and if a tear was present, the size was calculated by multiplying the length and breadth of the tear. The preoperative findings and intra-operative results were analysed using the Pearson's correlation coefficient test. The results show that an inverse relationship exists between the size of the tear and the strength o f static resisted external rotation force o f the arm ( r = 0.62) >.e. the larger the tear, the less the strength of the arm when testing static resisted external rotation in neutral. The results also show that if the relative streng th (%) of the affected arm is known, then in 62 % of the cases the tear size can be accurately calculated. The statistical tests were unable to demonstrate any relationships between the other parameters tested (i.e. pain, function, abduction strength, internal rotator strength) and tear size. In addition it was found that when using static resisted external rotation strength o f the arm (tested in neutral) as a diagnostic test in isolation, it is difficult to differentiate accurately between no tear and a small tear of the cuff. A large or massive tear is easier to diagnose.

碩士
國立雲林科技大學
全球運籌管理研究所碩士班
100
Rotator Cuff Tear is the common tendon injury of shoulder. Since it’s hard to diagnose the exact injured part and the problem on the injury of shoulder joint right away, it has to rely on clinical examination as well as imaging examination to diagnose. Sometimes it turns out that the patient doesn’t have Rotator Cuff Tear after the imaging examination. It causes not only the wastes of time and money to the patients but also increasing the cost of the human resource and imaging examination to the hospital. In order to use the medical resources appropriately, this research applies Naive Bayes Classifier, Arificial Neural Network, and Decision Tree to develop the predictive model. This will integrate the clinical examination to assist doctors’ diagnosis to know if the further imaging examination is needed. In addition, it also can help doctor to determine to do the surgery for the patient is diagnosed as Rotator Cuff Tear by the clinical examination and imaging examination to avoid the difference between the diagnosis and the surgery. This research will assist the doctors to determine the most appropriate treatment, and help to enhance the medical quality effectively as well. Keywords: Rotator Cuff Tear, Predictive Models, Naive Bayes, Artificial neural network, Decision Tree

碩士
國立成功大學
物理治療學系
104
Purpose: To examine the effect of compensatory strategies training for patients with massive rotator cuff tear (MRCT) Methods: Twenty-four subjects with MRCT were recruited from the department of Orthopedics in National Cheng Kung University Hospital to participate three times shoulder assessments and the 12 weeks of intervention. After initial assessment, the subjects were assigned randomly into two groups (CS-TE and TE-CS). CS-TE group was provided compensatory strategies (CS) training followed by the 6 weeks of traditional exercise (TE) training. In comparison, TE-CS group took 6 weeks TE training followed by CS. All the participants were arranged to attend the second assessments after completing the first 6 weeks of intervention, and the third assessment at the end of 12 weeks of intervention, including the measurements of visual analogue scale (VAS), the range of motion (ROM) of shoulder, shoulder pain and disability index(SPADI) questionnaire, shoulder and scapular muscle strength. In addition, scapular kinematics and related electromyography (EMG) analysis were performed at initial and 2nd assessments. The two-way repeated measures analysis of variance (ANOVA) was performed to assess the effect of CS training, with significant level of 0.05. Results: After completing the first 6 weeks training, CS-TE group showed significant improvement in motion pain measurement, SPADI score, AROM (except for extension) and the strength of local muscles at 6th week; however, TE-CS group only showed significant improvement in SPADI score and the flexion of shoulder. Moreover, after completing the 6 weeks of the CS training, TE-CS group showed significant improvement in VAS and the strength of compensatory muscles and scapular muscles. Furthermore, significant improvements in scapular control strategies were only found in CS-TE group after completing the 6 weeks of intervention, showing significantly increasing scapular external rotation (ER) and posterior tipping (PT) with significantly increased EMG activity in serratus anterior (SA)、lower trapezius (LT)、latissimus dorsi (LD) and pectoralis major (PM). Discussion: Our results have provided strong evidence for the enhancement of compensatory muscle strength by showing the significant increment of compensatory humeral head depressors (teres major, latissimus dorsi) after CS training for both group (CS-TE at 6th week, TE-CS at 12th week). In addition, our results also showed significant improvements at 6th week in LT and SA for CS-TE group, but only in SA for TE-CS group. It was not until completing additional 6 weeks CS training, the TE-CS group started to show significant improvements in LT strength. The results have again suggested that CS training is more effective in strengthening the compensatory humeral head depressors and scapular stabilizers. The improvements in compensatory and scapular muscles strength might provide a possible explanation for the preference of improvements found in the CS-TE group, since significant improvements in shoulder pain, and active ROM of shoulder joint (abduction, external rotation, and internal rotation) after completing the first 6 weeks training. In addition, significant improvement in shoulder pain was only found at 12th week for TE-CS group, after completing the final CS training with the significantly increased muscle strength for LT. The results have further supported the importance of compensatory strategy training protocol. To our knowledge, this study is the first study to report the effect on scapular control strategies for exercise intervention in patients with MRCT. We found that CS-TE group exhibited greater in posterior tipping (500~1200; 1200~600, p〈0.05) and lesser in internal rotation (500~1100, p〈0.05) during arm elevation and lowering after completing CS training. Also, the improvement of EMG (SA, LT, LD and PM) implied that CS training rebuild the better movement pattern to increase the AHD and depress the humeral head. Our results have supported that CS training is an effective treatment for establishing the compensatory strategies after MRCT and regaining the shoulder function.

La déchirure de la coiffe des rotateurs est une des causes les plus fréquentes de douleur et de dysfonctionnement de l'épaule. La réparation chirurgicale est couramment réalisée chez les patients symptomatiques et de nombreux efforts ont été faits pour améliorer les techniques chirurgicales. Cependant, le taux de re-déchirure est encore élevé ce qui affecte les stratégies de réhabilitation post-opératoire. Les recommandations post-chirurgicales doivent trouver un équilibre optimal entre le repos total afin de protéger le tendon réparé et les activités préconisées afin de restaurer l'amplitude articulaire et la force musculaire. Après une réparation de la coiffe, l'épaule est le plus souvent immobilisée grâce à une écharpe ou une orthèse. Cependant, cette immobilisation limite aussi la mobilité du coude et du poignet. Cette période qui peut durer de 4 à 6 semaines où seuls des mouvements passifs peuvent être réalisés. Ensuite, les patients sont incités à réaliser les exercices actifs assistés et des exercices actifs dans toute la mobilité articulaire pour récupérer respectivement l’amplitude complète de mouvement actif et se préparer aux exercices de résistance réalisés dans la phase suivante de la réadaptation. L’analyse électromyographique des muscles de l'épaule a fourni des évidences scientifiques pour la recommandation de beaucoup d'exercices de réadaptation au cours de cette période. Les activités sollicitant les muscles de la coiffe des rotateurs à moins de 20% de leur activation maximale volontaire sont considérés sécuritaires pour les premières phases de la réhabilitation. À partir de ce concept, l'objectif de cette thèse a été d'évaluer des activités musculaires de l'épaule pendant des mouvements et exercices qui peuvent théoriquement être effectués au cours des premières phases de la réhabilitation. Les trois questions principales de cette thèse sont : 1) Est-ce que la mobilisation du coude et du poignet produisent une grande activité des muscles de la coiffe? 2) Est-ce que les exercices de renforcement musculaire du bras, de l’avant-bras et du torse produisent une grande activité dans les muscles de la coiffe? 3) Au cours d'élévations actives du bras, est-ce que le plan d'élévation affecte l'activité de la coiffe des rotateurs? Dans notre première étude, nous avons évalué 15 muscles de l'épaule chez 14 sujets sains par électromyographie de surface et intramusculaire. Nos résultats ont montré qu’avec une orthèse d’épaule, les mouvements du coude et du poignet et même quelques exercices de renforcement impliquant ces deux articulations, activent de manière sécuritaire les muscles de ii la coiffe. Nous avons également introduit des tâches de la vie quotidienne qui peuvent être effectuées en toute sécurité pendant la période d'immobilisation. Ces résultats peuvent aider à modifier la conception d'orthèses de l’épaule. Dans notre deuxième étude, nous avons montré que l'adduction du bras réalisée contre une mousse à faible densité, positionnée pour remplacer le triangle d’une orthèse, produit des activations des muscles de la coiffe sécuritaires. Dans notre troisième étude, nous avons évalué l'électromyographie des muscles de l’épaule pendant les tâches d'élévation du bras chez 8 patients symptomatiques avec la déchirure de coiffe des rotateurs. Nous avons constaté que l'activité du supra-épineux était significativement plus élevée pendant l’abduction que pendant la scaption et la flexion. Ce résultat suggère une séquence de plan d’élévation active pendant la rééducation. Les résultats présentés dans cette thèse, suggèrent quelques modifications dans les protocoles de réadaptation de l’épaule pendant les 12 premières semaines après la réparation de la coiffe. Ces suggestions fournissent également des évidences scientifiques pour la production d'orthèses plus dynamiques et fonctionnelles à l’articulation de l’épaule.
Rotator cuff tear is one of the most common causes of shoulder pain and dysfunction. The operative repair has been widely performed for symptomatic patients and many efforts have been done to improve the surgical techniques. However, the re-tear rate is still high and this affects post-repair rehabilitation strategies. Post-surgical care should balance between the restriction imposed to protect the repaired tendon and the activities prescribed to restore range of motion and muscle strength. Frequently, early after rotator cuff repair, shoulder is immobilized in a sling or abduction orthosis, but this immobilization includes elbow and wrist joints as well. In this period that may last 4-6 weeks, only passive range of motion exercises are performed. After removing the immobilizer, patients are encouraged to do active assisted and active range of motion exercises respectively to regain the full active range of motion and be prepared for the resistance exercises in the following phase of rehabilitation. Electromyography of shoulder muscles has provided scientific basis for many of rehabilitation exercises during this period. Anecdotally, the activities of less than 20% of the maximal voluntary contraction of rotator cuff muscles are considered safe for the first phases of rehabilitation after rotator cuff repair. Using this concept, the aim of this dissertation is to evaluate the activity of shoulder musculature during some movements and exercises that can theoretically be performed during the early phases of rehabilitation. Three main questions of this thesis are: 1) Do elbow and wrist mobilizations highly activate rotator cuff muscles? 2) Do some resistance exercises of arm, forearm and chest muscles produce high activity in rotator cuff muscles? 3) During active arm elevation, does the plane of elevation affect rotator cuff activity? In our first study, we evaluated 15 shoulder muscles in 14 healthy subjects with both surface and indwelling EMG. Our results showed that while wearing a shoulder orthosis, elbow and wrist movements and even some resistance training involving these two joints, would minimally activate the rotator cuff muscles and can be considered safe. We also introduced some daily living tasks that can be performed safely during immobilization period. These findings may help to modify the design of current shoulder orthoses. In the second study, we also showed that resisted arm adduction against a low-density foam that replaced the hard wedge of orthosis would not highly activate the cuff muscles. In our final study, we evaluated the EMG of shoulder musculature during arm elevation tasks in 8 symptomatic patients with rotator cuff tears. We found that supraspinatus activity during arm elevation is significantly higher in abduction plane than in scaption and flexion planes in patients with rotator cuff tears. This suggested a plane sequences for active range of motion exercises during rehabilitation. The findings that are presented in this dissertation, suggest some modifications in the rehabilitation protocols during the first 12 weeks after rotator cuff repair. These suggestions also provide a scientific basis for producing more dynamic and functional shoulder orthoses.

碩士
國立雲林科技大學
健康產業管理研究所碩士班
101
Rotator cuff tears was the most common disorder of the shoulder joint Magnetic Resonance Image was the diagnostic gold standard of rotator cuff tears. However, there were some dilemmas in the rotator cuff tears treatment. Clinically, surgical results of rotator cuff tears were sometimes different from MRI results of rotator cuff tears. So the study provided two models to predict pre-operative diagnosis of rotator cuff tears. Model 1 was the full thickener rotator cuff tears. The charts of 158 patients were completely reviewed and the collected datas were analyzed with logistic regression and artificial neural network to build up a predictive model of pre-operative diagnosis. Model 2 was the partial-thickener ears of rotator cuff tears. The charts of 158 patients were completely reviewed and the collected datas were analyzed with logistic regression and artificial neural network to build up a predictive model of pre-operative diagnosis. The results showed that the predictive accuracy of artificial neural networks was higher than the predictive accuracy of logistic regression. The application of this study could assist doctors to increase the accuracy rate of pre-operative diagnosis and to decrease the legal problems.

The purpose of the study was to investigate the static and dynamic architecture of supraspinatus throughout its volume in the normal and pathological state. The architecture was first investigated in cadaveric specimens free of any tendon pathology. Using a serial dissection and digitization method tailored for supraspinatus, the musculotendinous architecture was modeled in situ. The 3D model reconstructed in Autodesk MayaTM allowed for visualization and quantification of the fiber bundle architecture i.e. fiber bundle length (FBL), pennation angle (PA), muscle volume (MV) and tendon dimensions. Based on attachment sites and architectural parameters, the supraspinatus was found to have two architecturally distinct regions, anterior and posterior, each with three subdivisions. The findings from the cadaveric investigation served as a map and platform for the development of an ultrasound (US) protocol that allowed for the dynamic fiber bundle architecture to be quantified in vivo in normal subjects and subjects with a full-thickness supraspinatus tendon tear. The architecture was studied in the relaxed state and in three contracted states (60º abduction with either neutral rotation, 80º external rotation, or 80º internal rotation). The dynamic changes in the architecture within the distinct regions of the muscle were not uniform and varied as a function of joint position. Mean FBL in the anterior region shortened significantly with contraction (p<0.05) but not in the posterior. In the anterior region, mean PA was significantly smaller in the middle part compared to the deep (p<0.05). Comparison of the normal and pathological muscle found large differences in the percentage change of FBL and PA with contraction. The architectural parameter that showed the largest changes with tendon pathology was PA. In sum, the results showed that the static and dynamic fiber bundle architecture of supraspinatus is heterogeneous throughout the muscle volume and may influence tendon stresses. The architectural data collected in this study and the 3D muscle model can be used to develop future contractile models. The US protocol may serve as an assessment tool to predict the functional outcome of rehabilitative exercises and surgery.

博士
國立臺灣大學
生醫電子與資訊學研究所
107
The lifetime prevalence of shoulder pain approaches 70%, which is mostly attributable to rotator cuff lesions such as inflammation, calcific tendinitis, and tears. On clinical examination, shoulder ultrasound is recommended to detect lesions. However, inter-operator variability of diagnostic accuracy exists due to the operator’ experience and expertise. In this study, a computer-aided diagnosis (CAD) system was developed to assist ultrasound operators in diagnosing rotator cuff lesions and to improve practicality of ultrasound examination. The collected cases included 43 inflammations, 30 calcific tendinitis, and 26 tears. For each case, the lesion area and texture features were extracted from the entire lesions and combined in a multinomial logistic regression classifier for lesion classification. The proposed CAD achieved an accuracy of 87.9%. The individual accuracy of this CAD system was 88.4% for inflammation, 83.3% for calcific tendinitis, and 92.3% for tear groups. The k value of Cohen’s Kappa was 0.798. In another part of this study, a computer-aided tear classification (CTC) system was developed to identify supraspinatus tears in ultrasound examinations and reduce inter-operator variability. The observed cases included 89 ultrasound images of supraspinatus tendinopathy and 102 of supraspinatus tear from 136 patients. For each case, intensity and texture features were extracted from the entire lesion and combined in a binary logistic regression classifier for lesion classification. The proposed CTC system achieved an accuracy rate of 92% (176/191) and an area under receiver operating characteristic curve (Az) of 0.9694. Based on diagnostic performance, the CAD and CTC systems have promise for clinical use.

Tese de Doutoramento em Medicina
Massive rotator cuff tears (MRCTs) are very large tears that are difficult to repair and often associated to an uncertain prognosis. These lesions are usually degenerative and may be associated with chronic pain and severe functional impairments. They are extremely frequent with advancing age, leading to great suffering and limitations in affected patients. The musculo-tendinous degenerative changes associated to chronic MRCTs and, the low natural healing and regeneration potential of the rotator cuff Tendon-Bone interface (TBi) represents a difficult challenge, thereby imposing the development of new therapeutic strategies. Several clinical solutions (e.g. surgical repair, tendon transfers, reverse shoulder arthroplasty and, superior capsule reconstruction) have been addressed to tackle this problem. However, none of them have been, so far, satisfactory, imposing the need for innovative therapeutical approaches. Several studies have proposed the use of stem cells as a possible tool for tendon healing and regeneration, and within it, human mesenchymal stem cells (hMSCs) have emerged as a valid therapeutic option. Most of their therapeutic effects are attributed to their capacity of secreting a wide panel of trophic factors (secretome) capable of inducing modulation and regenerative processes in the affected regions. Having this in mind the present thesis aimed at developing innovative strategies for MRCT regenerative medicine based on hMSCs, their secretome and the combination of them with nanopatterned based biodegradable biomaterials. For this purpose a MRCT rat model was initially established by sectioning bilaterally the supraspinatus and infraspinatus tendons. Interestingly, with the use of a bilateral lesion, our results demonstrated that the degenerative changes were aggravated in a more accurate way, resembling those observed in human tissues. Consequently, the described animal model represented a key step for the assessment of therapeutic strategies aiming at preventing/reverting chronic musculo-tendinous changes and/or enhancing the potential healing of TBi. After this, considering the importance of muscle quality on TBi healing and surgical outcomes when repair is attempted, the effect of hMSCs secretome on the prevention of muscle degeneration after inflicting a MRCT was analyzed. It was observed that the injection of hMSCs secretome immediately after the lesion was established, could decrease the development of muscle degeneration in a rodent model of MRCT. In addition, both precise intramuscular local injection and multiple systemic secretome injections shown to be promising delivery forms for preventing muscle degeneration. This strategy is particularly important for patients whose tendon healing after later surgical repair could be compromised by the progressing degenerative changes. Finally, the impact of a Tissue Engineering (TE) strategy based on the combination of an electrospun keratin scaffold seeded with hMSCs secretome-preconditioned human tendon cells (hTCs) to improve rotator cuff TBi healing, without surgical repair, was assessed. Initial in vitro data revealed that hMSCs secretome increased hTCs phenotype, particularly the expression of extracellular matrix associated molecules, as well as their cell densities, and viability. A proteomic characterization of hMSCs secretome, revealed the presence of specific proteins (e.g. Follistatin, Pigment epithelium-derived factor (PEDF), IL-6, decorin, and biglycan) involved in muscle homeostasis and TBi healing, which are most likely linked to these phenomena. Subsequent experiments performed in a MRCT rat animal model (previously described and discussed) revealed that preconditioning hTCs with the hMSCs secretome in a TE strategy yielded improved rotator cuff TBi healing. In summary, the present work indicates that hMSCs, and their secretome, could represent a potential tool to help treating and improve MRCT outcomes. Nevertheless, we should keep in mind that its application in the future should be combined with other different approaches, particularly those that use TE concepts. These findings are of clinical and social relevance as they bring a new perspective for the prevention and treatment of MRCT aiming to improve the quality of life of these patients.
As roturas massivas da coifa dos rotadores (RMCR) são roturas grandes, difíceis de reparar e muitas vezes associadas a um prognóstico incerto. Estas lesões são geralmente degenerativas e podem causar dor crónica e incapacidade funcional graves. As RMCR são mais frequentes com o avançar da idade, levando a um aumento da sintomatologia e limitação funcional. As alterações degenerativas músculo-tendinosas associadas às RMCR crónicas e o baixo potencial natural de cicatrização e regeneração da interface Osso-Tendão (iOT) da coifa dos rotadores representam um desafio difícil, impondo assim o desenvolvimento de novas estratégias terapêuticas. Várias soluções clínicas (e.g. reparação cirúrgica, transferências tendinosas, artroplastia invertida do ombro e reconstrução da cápsula superior) têm sido usadas para tentar resolver este problema. No entanto, nenhuma destas opções tem sido satisfatória, até agora, impondo a necessidade de terapêuticas inovadoras. Vários estudos têm proposto o uso de células-estaminais como uma possível ferramenta para a cicatrização e regeneração do tendão e, dentro destas, as células-estaminais mesenquimatosas humanas (CEMh) emergiram como uma opção terapêutica válida. A maior parte dos seus efeitos terapêuticos é atribuída à sua capacidade de segregar um vasto painel de fatores tróficos (secretoma) que são capazes de induzir modulação e processos regenerativos nas regiões afetadas. Tendo isto em mente, a presente tese teve como objetivos o desenvolvimento de estratégias inovadoras para a medicina regenerativa das RMCR baseada em CEMh, o seu secretoma e a combinação deles com biomateriais biodegradáveis baseados em nanopartículas. Para este propósito, um modelo de rato de RMCR foi inicialmente estabelecido através da secção bilateral dos tendões supra-espinhoso e infra-espinhoso. Curiosamente, os nossos resultados demonstraram que usando a lesão bilateral, as alterações degenerativas foram agravadas de forma mais consistente e semelhante aquelas observadas nos tecidos humanos. Consequentemente, o modelo animal descrito representou um passo chave para a avaliação de estratégias terapêuticas visando a prevenção/reversão de alterações músculo-tendinosas crónicas e/ou o aumento do potencial de cicatrização da iOT. Depois disso, e considerando a importância da qualidade do músculo na cicatrização da iOT e dos resultados cirúrgicos quando a reparação é tentada, foi analisado o efeito do secretoma das CEMh sobre a prevenção de degeneração muscular após induzir uma RMCR. Os resultados demonstraram que a injeção de secretoma das CEMh, imediatamente após a lesão ser estabelecida, poderia diminuir o desenvolvimento de degeneração muscular num modelo de rato de RMCR. Além disso, tanto a injeção local precisa intramuscular quanto as injeções sistémicas múltiplas de secretoma mostraram ser formas de administração promissoras para prevenir a degeneração muscular. Esta estratégia é particularmente importante para os pacientes cuja cicatrização do tendão após a posterior reparação cirúrgica poderia ser comprometida pelas alterações degenerativas progressivas. Por fim, avaliou-se o impacto de uma estratégia de Engenharia de Tecidos (ET) baseada na combinação de uma matriz de queratina electroalinhada semeada com células tendinosas humanas (CTh) pré-condicionadas pelo secretoma das CEMh para melhorar a cicatrização da iOT da coifa dos rotadores, sem reparação cirúrgica associada. Os dados iniciais in vitro revelaram que o secretoma das CEMh aumentaram o fenótipo das CTh, particularmente a expressão de moléculas associadas à matriz extracelular, bem como a sua viabilidade e densidades celulares. A caracterização proteómica do secretoma das CEMh, revelou a presença de proteínas específicas (e.g. Follistatina, fator derivado do epitélio pigmentado (FDEP); IL-6, decorina, and biglycano) envolvidos na homeostasia muscular e cicatrização da iOT, e que estão muito provavelmente ligados a estas ações. Experiências subsequentes realizadas no modelo animal de rato de RMCR (anteriormente descrito e discutido) revelaram que o pré-condicionamento de CTh com o secretoma das CEMh, numa estratégia de ET, proporcionou uma melhoria da cicatrização da iOT da coifa dos rotadores. Em resumo, o presente trabalho indica que as CEMh, e o seu secretoma, podem representar um instrumento potencial para ajudar a tratar e melhorar os resultados clínicos das RMCR. No entanto, devemos ter em mente que a sua aplicação futura deve ser combinada com outras abordagens diferentes, particularmente aquelas que utilizam conceitos de ET. Estes achados são de relevância clínica e social, uma vez que trazem uma nova perspetiva para a prevenção e tratamento das RMCR visando melhorar a qualidade de vida desses pacientes.
The work presented in this thesis was performed in the Life and Health Sciences Research Institute (ICVS), Minho University. Financial support was provided by FEDER funds through the Operational Programme Competitiveness Factors - COMPETE and National Funds through FCT - Foundation for Science and Technology under the project POCI-01-0145-FEDER-007038; and by the project NORTE-01-0145-FEDER- 000013, supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF).