Purpose: To explore perceptions and initial outcomes of patients with rotator cuff-related pain to a pain education session. Materials and Methods: Ten individuals with persistent rotator cuff-related pain (≥3 months duration) attended an individual pain education session. They completed patient-reported outcomes measures on a weekly basis, three weeks prior and three weeks following the session. Individual semi-structured interviews were conducted three weeks following the pain education. Interviews were recorded, transcribed verbatim, and analyzed using the General Inductive Approach. Results: There were two over-arching key themes: firstly, ‘Participants’ Perspectives’ of the session generated four themes: Improved understanding of ‘the whole’; Mindful self-awareness; Taking charge; “The pain is still there”. Their understanding of pain was reconceptualised, evident by their ability to describe the role of neurophysiological mechanisms, stress and general well-being towards their pain. The second over-arching key theme, ‘Participants’ Recommendations’, had two themes: Integrating neuroscience with pathoanatomical knowledge and Educating other health professionals. Pain levels decreased post-pain education compared to pre-pain education. Conclusions: Following the pain education session, participants had greater understanding of factors influencing their shoulder pain. Pain education, in addition to pathoanatomical information may be useful as part of treatment for persistent rotator cuff-related pain.

The glenohumeral (GH) joint is the most mobile joint in the human body, but its mobility inherently increases the risk of instability. The humeral head sits in a shallow glenoid in the scapula like a golf ball sitting on a tee. The stability in this joint is provided by the rotator cuff muscles and tendons that actively pull the humerus back into the socket to prevent dislocation, especially during overhead motions. However, the rotator cuff is prone to tears, resulting in pain, loss of mobility, and recreational limitations. Surgical reattachment of the tendon to the bone is challenging due to the mechanical disparity between the two tissues, resulting in stress concentrations and a high risk of retear. Notably, the specialized tissue at the tendon-to-bone attachment, which facilitates stress transfer between tendon and bone in healthy joints, does not regenerate after surgical reattachment and healing, making tendon-to-bone repairs prone to re-tears. A comprehensive understanding of GH joint biomechanics is essential for developing early interventions to prevent rotator cuff injuries. Furthermore, improving tendon-to-bone fixation during rotator cuff repair is critical to improve post-surgery outcomes. In the last decade, bioinspired solutions have shown considerable promise for addressing several biomedical problems. This thesis draws bioinspiration from two animals that have evolved unique mechanical functions: (i) the bat shoulder joint, which facilitates repetitive overhead motions during flight and may offer insights into rotator cuff pathology and (ii) the curvature of python snake teeth, which enables secure grasping of prey without soft tissue tearing. In the first part of the thesis, the bat shoulder was studied for its unique characteristics relative to mice. Overhead motions in humans often lead to shoulder injuries, partly because the bony anatomy of the unstable GH joint places greater stress on the joint's surrounding soft tissues to stabilize these motions. Traditional animal models used to study shoulder pathology are quadrupeds, which lack the capacity for overhead motion. In contrast, bats consistently engage in overhead motion during flight, subjecting their shoulders to substantial loading throughout their relatively long lifespan. Remarkably, the biomechanical demands placed on a bat's shoulder are estimated to exceed those of a competitive swimmer’s by 45-fold, despite sharing similar coracoacromial arch anatomy with humans. We were inspired to study functional adaptations in the shoulders of bats that enable this overhead motion. We performed comparative anatomy studies of the shoulders of bats and mice, similarly-sized quadrupeds. By quantifying the constraints imposed by the bony anatomy, we identified adaptations of the shoulder, including the rotator cuff tendons, that allow bats to sustain overhead motion in a high stress, repeated loading environment, without injury. In the second part of the thesis, python teeth were used as inspiration to develop a repair device optimized to grasp the rotator cuff without tearing. Rotator cuff repair surgeries fail frequently, with 20-94% of the 600,000 repairs performed annually in the United States resulting in retearing of the rotator cuff. The most common cause of failure is sutures tearing through tendons at grasping points. To address this issue, we examined the specialized teeth of snakes of the Pythonoidea superfamily, which effectively grasp soft tissues without tearing. To apply this non-damaging and effective gripping approach to the surgical repair of tendons, we developed and optimized a python-tooth inspired array as an adjunct to current rotator cuff suture repair, and found that it nearly doubled repair strength. Integrated simulations, 3D printing, and ex vivo experiments revealed a relationship between tooth shape and grasping mechanics, and enabled optimization of a tooth array device to enhance rotator cuff repair to distribute stresses and increase tendon-bone contact. The efficacy of the approach was demonstrated via human cadaver tests, suggesting an alternative to traditional suturing paradigms that may reduce tendon re-tearing. Collectively, these studies contribute to a better understanding of the biomechanics of the GH joint and offer novel, bioinspired approaches for rotator cuff repair. The functional adaptations of bats provide insight into developing new approaches to treat GH joint instability, and a clinically relevant python-tooth inspired device can ultimately reduce the high rates of re-rupture currently observed in rotator cuff repair.

Current return-to-drive recommendations for patients following rotator cuff repair (RCR) surgery are not uniform due to a lack of empirical evidence relating driving safety and time-after-surgery. To address the limitations of previous work, Badger et al. (2022) evaluated, on public roads, the driving fitness of patients prior to RCR and at multiple post-operative timepoints. The goal of the Badger, et al. study was to make evidence-based return-to-drive recommendations in an environment with higher fidelity than that of a simulator and not subject to biases inherent to surveys. Badger et al., however, do not fully investigate the driving practices exhibited by subjects, overlooking the potential presence of compensatory driver behaviors. Further investigation of these behaviors through observation of direct driving techniques and practices over time can specifically answer how drivers may modify their behaviors to address a perceived state of impairment. Additionally, the degree of success in vehicle operation by comparing an ideal turn to the path taken by the driver allows for a level of quantification of the effectiveness of the compensatory techniques. Moreover, driver trajectories inferred from the vehicle Controller Area Network (CAN) metrics and from global positioning system (GPS) coordinates are contrasted with the ideal turn to assess minimum requirements for future sensors that are used to make these trajectory comparisons. This investigation leverages pre-existing data collected by the Virginia Tech Transportation Institute (VTTI) and Carilion Clinic as used in the analysis performed by Badger et al. (2022). RCR patients (n=27) executed the same prescribed driving maneuvers and drove the same route in a preoperative state and at 2-, 4-, 6-, and 12-weeks post operation. Behavioral data were annotated to extract key characteristics of interest and related them to relevant vehicle sensor readings. To construct vehicle paths, data was obtained from the on-board data acquisition system (DAS). Behavioral metrics considered the use of ipsilateral vehicle controls, performance of non-primary vehicle tasks, and steering techniques utilized to assess the impact of mobility restrictions due to sling use. Sling use was found to be a significant factor in use of the non-ipsilateral hand associated with the operative extremity (i.e., operative hand) on vehicle functions and, in particular, difficulty with the gear shifting control. Additionally, when considering the performance of non-primary vehicle tasks as assessed through a prescribed visor manipulation, sling use was not a significant factor for the task duration or completion of the task in a fluid motion. Sling use was, however, significant with respect to operative hand position prior to the completion of the visor manipulation: the operative hand was often not on the steering wheel prior to the visor maneuver. In addition, the operative hand was never used to manipulate the visor when the sling was worn. One-handed steering was also more frequent with the presence of the sling. Further behavioral analysis assessed the presence of compensatory behavior exhibited by subjects during periods in which impairment was perceived. Perceived impairment was observed as a function of the different experimental timepoints. Findings indicated a significant decrease in the lateral vehicle jerk during post-operative weeks 6 and 12. Significant differences, however, were not observed in body position alteration to avoid contact with the interior vehicle cabin, in over-the-shoulder checks, and in forward leans during yield and merge maneuvers. Regarding trajectory analysis, sling use did not produce a significant difference in the error metrics between the actual and ideal paths. In completion of turning maneuvers, however, operative extremity was significant for left turns, with greater error against the ideal path observed from those in the left operative cohort compared to those in the right operative cohort. For the right turn, however, operative extremity was not found to be a significant factor. In addition, the GPS data accuracy proved insufficient to support comparison against the ideal path. Overall, findings from this study provide metrics beyond those used in Badger, et al. that can be used in answering when it is safe for rotator cuff repair patients to return-to-drive. With the limited differences observed as a function of study timepoint and sling use, it is recommended that patients are able to safely return-to-drive at two weeks post-operation. If anything, results suggest that overcompensation, as inferred from observation of safer driving behaviors than normal, is present during some experimental timepoints, particularly post-operative week 2. / Master of Science / Current recommendations based on when it is safe for rotator cuff repair patients to return-to-drive are not standard because of a lack of suitable evidence. Previous work and recommendations rely on surveys and simulators which do not create fully realistic conditions and are subject to biases. To address the limitations of previous work, Badger et. al (2022) studied actual rotator cuff repair patients on public roads prior and following operation at multiple timepoints. Badger et al., however, did not consider the potential adaptations in driver behavior due to mobility restrictions and the perception of inferiority due to injury. Additionally, the degree of success of the adaptive driving behaviors based on the error between the actual vehicle path taken and a defined ideal path have not been explored in conjunction with the injury. This investigation is based on the pre-existing data collected by the Virginia Tech Transportation Institute (VTTI) and Carilion Clinic as used in the analysis performed by Badger et al. (2022). RCR patients (n=27) executed identical driving maneuvers and drove the same route before operation and at 2-, 4-, 6-, and 12-weeks post operation. Behavioral observations were recorded and related to relevant vehicle sensor readings. To construct vehicle paths, data was taken from the on-board data acquisition system (DAS). Participants adopted different behaviors, such as using the right hand to use the turn signal when the left arm was in a sling and the left hand to operate the gear shifter when the right arm was on a sling, to assist in combating mobility restrictions. One-handed steering was also more prominent during periods of sling-use. Sling-use, however, did not produce a significant difference in error between the actual vehicle path taken and the ideal path available to the driver. For left-operated participants completing left turns, there was also greater error in comparison to the ideal path than for the group of right-operated patients. However, there was not a difference between left- and right-operated arm participant error in completion of a right turn. The GPS data did not provide a suitable approximation of vehicle trajectory. Overall, findings from this study help to answer when it is safe for rotator cuff repair patients to return-to-drive through evaluation of the effectiveness of compensatory behaviors adopted by participants. With no significant difference in turn execution based on sling use, results suggest that patients can safely return-to-drive at two weeks post-operation. In fact, results suggest that overcompensation towards safer behaviors is present during some experimental timepoints, particularly post-operative week 2.

No description available.

Surgical repair of torn rotator cuff tendons have a high rate of failure and does not address the underlying pathophysiology. Tissue engineering strategies, employing the use of multipotent progenitor cells or growth factors, represent potential therapies to improve the outcome of rotator cuff surgery. The use of glycosaminoglycan-based biomaterials in these therapies may enhance the effectiveness of cell and growth factor delivery techniques. Furthermore, understanding the cellular and molecular mediators in tendon overuse can help elucidate the causes of tendon degeneration. Thus the overall goals of this dissertation were to 1) develop heparin-based biomaterials to enhance cell pre-culture and maintain growth factor bioactivity and 2) characterize the histological and enzymatic changes in a supraspinatus tendon overuse model. To investigate the use of heparin in enhancing dynamic signaling, mesenchymal stem cells (MSCs) were encapsulated in heparin-containing hydrogels and evaluated for differentiation markers when cocultured with a small population of differentiated cells. To probe the effect of sulfation of heparin on the interactions with protein, selectively desulfated heparin species were synthesized and evaluated for their ability to bind and protect proteins. Finally, to develop a tendon overuse model that can become a test bed for testing future targeted therapeutics, an animal model was evaluated for tissue damage and protease activity. Together these studies represent a multi-pronged approach to understanding how tendon tissues become degenerative and for developing technologies to improve the biological fixation of tendon to bone in order to reduce the need for revision surgeries.

Rotator cuff disease is multi-factored and has been attributed to both intrinsic and extrinsic factors. Extrinsic factors contribute to compression of the rotator cuff tendons. Intrinsic factors that contribute to rotator cuff tendon degradation with tensile/shear overload include alterations in biology, mechanical properties, morphology, and vascularity. Subacromial impingement is related to factors that encroach upon the subacromial space, while internal impingement affects the articular side of the tendons adjacent to glenoid. While the mechanisms of impingement are varied, further research is necessary to improve treatment and patient outcomes. Chapter 2 is a thorough review of literature on the mechanisms of rotator cuff disease. Alterations in scapular kinematics may influence subacromial space and either contribute to the etiology of subacromial impingement with rotator cuff tendon compression or serve as a compensation to alleviate compression. Furthermore alterations in scapular position may directly influence rotator cuff muscle strength. Chapter 3 compares the influence of the scapular assistance test on scapular upward rotation, posterior tilt, subacromial space, and shoulder strength between healthy individuals and subjects with subacromial impingement syndrome. Scapular upward rotation and posterior tilt induced with scapular assistance test appears to influence subacromial space, but not shoulder muscle strength; however, the influence of these scapular rotations do not differ between asymptomatic individuals and those with subacromial impingement. Furthermore scapular posterior tilt appears to have a greater influence on increasing subacromial space and should be emphasized in the treatment of individuals with subacromial impingement. In chapter 4, we examine the influence that obvious scapular dyskinesis and passive scapular correction with the scapular assistance test have on 3D scapular kinematics and subacromial space. Scapular dyskinesis did not alter scapular kinematics or acromiohumeral distance during active elevation in static positions, in the scapular plane, and without a load when compared to those without scapular dyskinesis. This suggests other contributing factors, such as pain, increased load, or fatigue is requisite to alterations in scapular kinematics or AHD. Passive correction with the scapular assistance test increased scapular upward rotation, posterior tilt, and subacromial space in individuals with and without dyskinesis. In patients with obvious dyskinesis, there was a greater increase in scapular upward rotation with passive scapular assistance. This increased scapular upward rotation had a negative relationship with change in the acromiohumeral distance. The scapular dyskinesis test increased acromiohumeral distance and therefore may be helpful identifying individuals where subacromial compression is producing symptoms, regardless of dyskinesis. The results of this research suggest scapular kinematics and subacromial space are altered with the passive maneuver of the scapular assistance test in all individuals, regardless of subacromial impingement syndrome or scapular dyskinesis. Scapular dyskinesis alone may not be detrimental to scapular position and subacromial space when evaluated in static positions of active arm elevation. Other potential factors may be required to alter scapular kinematics to reduce subacromial space including pain, dynamic movement, load or fatigue. Further study is necessary to determine the influence of the combination of these factors in individuals with scapular dyskinesis.

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.

Tendonopathy, resulting in the loss of mechanical strength of a tendon, is a serious health problem affecting many people. The common symptom of tendonopathy is pain – patients' daily activities, their participation in sport and exercise, and their ability to work are greatly compromised. Tendonopathy is considered to be a degenerative disorder caused by repetitive injury of the tendon. The most common tendon lesions are Achilles tendon rupture, lateral epicondylitis (tennis elbow) and rotator cuff tear. However, in spite of its clinical significance, our knowledge about tendonopathy is still very poor. This research was undertaken to investigate the pathology of tendonopathy. It is proposed that apoptosis, autophagic cell death and myofibroblasts play a role in the progression of tendonopathy in the rotator cuff; the aim of this study was therefore to determine if this was indeed the case. Tendon tissues were collected from 30 patients suffering from rotator cuff tears. A terminal deoxynucleotidyl transferase biotin-dUTP nick end labelling (TUNEL assay) was performed to detect apoptosis. Autophagic cell death of the tenocytes in the ruptured rotator cuff tendon was detected by immunohistochemical staining for ubiquitin. Myofibroblasts were identified immunohistochemically with anti-alpha-smooth muscle actin (anti--SMA) antibody. The distribution of apoptosis, autophagic cell death and myofibroblasts, as well as the total cell density, were assessed respectively and were correlated using a four-category (i.e. graded from 0-3) degeneration of collagen matrix. – 6 – The results showed that apoptosis, autophagic cell death and myofibroblasts were observed in all of the samples. The highest percentage of autophagic cell death was evidenced in the Grade 2 matrix, while the percentage of apoptosis increased significantly with the increase of matrix degeneration from Grade 0-3; a similar pattern was found for myofibroblasts. The total cell numbers varied among the matrix grades, with the maximum and minimum percentages occurring in Grades 1 and 3, respectively. It can be concluded that apoptosis, autophagic cell death and myofibroblasts might be closely related to the damage of the extracellular matrix (ECM) structure.

Orientador: Jose Inacio de Oliveira / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-08-06T19:26:31Z (GMT). No. of bitstreams: 1 Shiraishi_WilmaHideko_M.pdf: 1998354 bytes, checksum: 503ec8f6636f894c6c459636f7045b26 (MD5) Previous issue date: 2006 / Resumo: Neste estudo analisa-se o perfil epidemiológico dos pacientes com diagnóstico clinico de tendinite do supra-espinhal relacionada ao trabalho, atendidos no Ambulatório de Medicina do Trabalho do Hospital das Clínicas da UNICAMP, no período de janeiro de 2002 a dezembro de 2004 e verifica-se, dentre as lesões do manguito rotador, quais as tendinites mais freqüentes. Trata-se de um estudo descritivo, com dados coletados dos prontuários do Serviço de Arquivo Medico (SAME), utilizando-se o Software Epi-info 6 para o registro de dados. Foram analisados 246 prontuários de pacientes atendidos no Ambulatório com diagnóstico clínico de Distúrbios Osteomusculares Relacionados ao Trabalho (DORT). Desses, identificaram-se 112 pacientes com lesão do manguito rotador e, dentre estes, 106 eram especificamente tendinites do tendão do músculo supra-espinhal. Foram investigadas as variáveis relacionadas a sexo, idade, procedência, ocupação, lado do ombro comprometido, tipo de lesão, ramo de atividade econômica, situação de trabalho no primeiro atendimento, benefícios previdenciários, nexo com o trabalho e distribuição do diagnóstico clinico geral dos DORT neste período. Os resultados mostraram que, dentre as lesões do manguito rotador, a tendinite do tendão do músculo supra-espinhal obteve a maior freqüência, com 106 casos (94,6%); seguida do músculo subescapular com 4 (3,6%); músculo ínfra-espinhal com 2 (1,7%) e nenhuma referência do redondo menor. O grupo concentra-se na faixa etária de 22 a 71 anos de idade, com média de idade de 40 anos (dp= 8,75) sendo que, destes, 74 (69,8%) eram do sexo feminino. O lado do ombro mais comprometido foi o direito em 52 casos (49,1%), o esquerdo em 28 (26,4%) e bilateral em 26 (24,5%). Dentre as principais ocupações, os operadores de máquina e os auxiliares de produção tiveram a maior prevalência (25,4%). Em seguida, auxiliar de cozinha (11,3%) e auxiliar de serviços gerais (6,6%). Do total, 44 (41,5%) pacientes pertenciam à indústria alimentícia e 25 (23,6%) à indústria metalúrgica. Dos pacientes com diagnóstico clínico de tendinite de supra-espinhal o nexo causal com o trabalho foi estabelecido em 100 pacientes (94,3%) / Abstract: Epidemiological profile of pacients with supraspinatus tendinitis related to work in an outpatient Clinic of A Medical School Hospital. This study analyzes the epidemiological profile of patients that consulted at the Occupational Health Outpatient Clinic of the UNICAMP General Hospital, in the period between January 2002 and December 2004, and had clinical diagnosis of work-related Supraspinatus Tendinitis. It also verifies the most frequent tendinitis among rotator cuff injuries. It is a descriptive study using data collected from patients' records in the Medical Record File Service (SAME) and Epi-info6 software was used for recording the data. A total of 246 records of outpatients seen at the Hospital Clinic with clinical diagnoses of Work Related Musculoskeletal Disorder (WRMD) were analyzed. In this group, 112 patients with Rotator Cuff Tendinitis were selected and among these there were 106, specifically, with Supraspinatus Tendinitis. Variables such as gender, age, origin, occupation, side of injured shoulder, type of injury, area of economic activity, work status at first appointment, workers compensation benefits, relation of injury to work, and the distribution of clinical diagnoses of WRMD during the period mentioned, were examined. The results showed that among rotator cuff injuries, supraspinatus tendinitis was the most frequent with 106 cases (94.6%); next came subscapular]s injuries with 4 cases (3.6%), infraspinatus with 2 (1.7%), and there was no reference to teres minor. The age of this group varies from 22 to 71 years old, mean age being 40 (sd=8,75). Among them, 74 (69.8%) patients were female. The side most frequently injured was the right shoulder in 52 cases (49.1%), the left in 28 (26.4%) and both in 26 (24.5%). Among the main occupations, machine operators and production helpers were the most prevalent, both with 25.4%. Next came cooks (11.3%) and all-task helpers (6.6%). A total of 44 (41.5%) patients pertained to the food industry and 25 (23.6%) to metallurgical industry. In the group of patients with clinical diagnosis of supraspinatus tendinitis the relation of injury to work was established in 100 patients (94.3%) / Mestrado / Saude Coletiva / Mestre em Saude Coletiva

Rotator cuff injuries cause pain, disability, and loss of shoulder function in over 17 million individuals in the United States that result in over 500,000 surgeries performed annually, though with alarming failure rates of 20-94% (Colvin et al., 2012; Galatz et al., 2004; Harryman et al., 1991; Jain et al., 2014; Mather et al., 2013; Oh et al., 2007; Vitale et al., 2007; Yamaguchi et al., 2006). These surgeries involve repair or reconstruction of the damaged rotator cuff tendon(s) along with enlargement of the subacromial space by debriding the overlying bone (acromion) and removing the subacromial bursa (Beard et al., 2018; Burkhart et al., 2016; Dines et al., 2006; Lo & Burkhart, 2003; Rossi & Ranalletta, 2020). The subacromial bursa is a synovial-like tissue that is situated between the acromion and the tendons of the rotator cuff. This tissue has been long understood to serve a primarily mechanical role by providing cushioning and protecting from friction-wear from the acromion on the underlying tendons. More recently, the identification of a robust vascular network within the bursa, a resident population of mesenchymal stem cells, and inflammatory responsiveness to rotator cuff pathology have supported the existence of a biological role of this tissue in addition to its mechanical one (Blevins et al., 1997; Gotoh et al., 1998, 2001; Põldoja et al., 2017; Rathbun & Macnab, 1970; Steinert et al., 2015; Yepes et al., 2007). These observations make surgical excision of the bursa problematic, given our current lack of understanding of the implications of removing the bursa on the biological response to tendon injury. Therefore, the goals of this dissertation were three-fold: (1) to determine the role of the subacromial bursa in the rotator cuff tendon response to injury and healing, (2) to interrogate patterns of cellular crosstalk between the subacromial bursa and the rotator cuff following injury, and (3) to demonstrate therapeutic potential of targeting the subacromial bursa for modulating inflammation and improving tendon healing.Motivated by clinically observed phenotypic changes in the subacromial bursa with rotator cuff pathology, the profiles of human bursa and rotator cuff tendon tissues were assessed using histology, proteomics, and transcriptomics. This data set, analyzed in the context of patient demographics and diagnoses, revealed distinct bursa proteomes according to tissue phenotype (i.e., fibrous, vascular, or fatty), patient age, and presence of a tear in the underlying rotator cuff. These results suggested the presence of crosstalk between the rotator cuff and the bursa that had not been previously appreciated. Employing multiple methods of validation, including histology, microcomputed tomography, gene expression, and flow cytometry, the rat bursa was established as an appropriate animal model of the human bursa. Therefore, we used the rat model to investigate the role of the bursa in tendon injury response and healing; tendon injuries were created surgically with or without a subsequent repair to study healing and responses to injury, respectively. The role of the bursa in the response to injury was assessed using gene expression, transcriptomics, and histology. The bursa promoted inflammatory gene expression in the injured supraspinatus but resolved inflammatory gene expression in the intact infraspinatus. The role of the bursa in tendon healing was assessed using gene expression, histology, microcomputed tomography, and tensile mechanical testing of the cuff tendons. Consistent with responses during the inflammatory phase of healing, the bursa promoted expression of genes related to aberrant, scar-mediated healing in the supraspinatus, whereas it promoted tenogenic and tendon extracellular matrix gene expression in the intact infraspinatus. Mechanical testing demonstrated that the bursa protected the infraspinatus from the inflammatory environment caused by the supraspinatus injury but had a limited functional effect on the healing supraspinatus. Microcomputed tomography also indicated bursa-dependence in cortical and trabecular bone remodeling following tendon injury. Cross-talk between the bursa and the tendon was then studied in a novel tissue explant co-culture platform using gene expression and nitric oxide release as outcome measures. These experiments revealed that the activated bursa engaged in immunomodulation of tendon fibroblast responses to inflammatory stimulus. The in vitro platform also established the glucocorticoid dexamethasone as a viable therapeutic candidate for bursa-targeted treatment based on its capacity to regulate the bursa’s response to an inflammatory stimulus and enhance the bursa’s immunomodulatory potential. Therefore, in the final component of this thesis, dexamethasone was delivered via PLGA microspheres in vivo to the bursa to modulate the post-injury inflammatory response in the supraspinatus and the infraspinatus tendons. Results supported the therapeutic potential of this treatment approach to improve rotator cuff healing outcomes. This body of work demonstrated a robust involvement of the bursa in rotator cuff responses to injury, with distinct roles in the underlying injured and intact tendons. This work also established, for the first time, the immunomodulatory capacity of the activated bursa and provided strong evidence against the clinical practice of bursectomy. Finally, use of sustained-release dexamethasone to dampen the inflammatory responses to rotator cuff injury offers a new direction for harnessing the inherent properties of the subacromial bursa therapeutically for improved rotator cuff tendon healing.