The purposes of this study is to determine: (a) the relationship between the dependant variables, (b) the relationship between the Borg pain scale and the performance tests, (c) the difference in performance between involved and uninvolved extremities, and (d) the effects of the three different therapeutic exercise treatments on selected performance tests and pain free isometric strength testing. Fifty subjects with physician diagnosed anterior knee pain (AKP), completed initial performance testing and 14 subjects completed initial testing, therapy and six weeks later final performance testing. The 14 subjects were randomly assigned to one of three therapeutic exercise treatment groups. The performance tests included; pain free isometric strength tests (90, 60, 45, and 15 degrees knee flexion), stair test, timed hop, triple hop, crossover hop, Figure 8 and Borg pain scale rating for each performance test. The results indicated a significant correlation between performance tests and pain free isometric strength tests. There was no relationship indicated between the performance tests, Borg pain scale ratings. The contrast between the injured and uninjured extremities performance test values of the fifty subjects that completed the initial testing indicated no significant (p< 0.05) difference. The results of this study indicated that there was no significant difference between the therapeutic exercise treatment groups. In conclusion, the three anterior knee pain treatments had no effect on strength and performance. / School of Physical Education

The primary purpose of this study was to determine the ratio of activation between the VMO and VL while performing three selected knee exercises (drop squat, modified lateral squat, Muncie Method). Additionally, the data was analyzed to determine if a correlation existed between the muscle's activation rate per set and whether or not the rates are affected by Q-angle or gender. Twenty Ball State University subjects (10 male, 10 female) who were asymptomatic to Patellofemoral Syndrome (PFS), provided electroymyographic (EMG) data while performing the three selected exercises. A one-way ANOVA found no statistical significance (p=0.500) on any of the tested variables except the Drop Squat VL Root Mean Square (RMS). Significant correlations were found between: VL RMS to set number during drop squat, and VMO and VL RMS to set number during Muncie Method performance. Based on the results of this study, each of these exercises could be used to selectively strengthen the VMO in treatment of PFS. / School of Physical Education

Doctor of Philosophy / The aim of the work presented in this thesis was to examine the associations between the kinematics of the knee characterised by the tibiofemoral contact pattern, and degenerative change, in the context of anterior cruciate ligament (ACL) injury. While the natural history of degenerative change following knee injury is well understood, the role of kinematics in these changes is unclear. Kinematics of the knee has been described in a variety of ways, most commonly by describing motion according to the six degrees of freedom of the knee. The advantage of mapping the tibiofemoral contact pattern is that it describes events at the articular surface, important to degenerative change. It was hypothesised that the tibiofemoral contact pattern would be affected by injury to the knee. A model of ACL injury was chosen because the kinematics of the knee have been shown to be affected by ACL injury, and because the majority of chronic ACL-deficient knees develop osteoarthritis, the associations between kinematics and degenerative change could be explored. A technique of tibiofemoral contact pattern mapping was established using MRI, as a quantifiable measure of knee kinematics. The tibiofemoral contact pattern was recorded from 0º to 90º knee flexion while subjects performed a leg-press against a 150N load, using sagittal magnetic resonance imaging (MRI) scans. The technique was tested and found to be reliable, allowing a description of the tibiofemoral contact pattern in 12 healthy subjects. The tibiofemoral contact patterns of knee pathology were then examined in a series of studies of subjects at a variety of stages of chronicity of ligament injury and osteoarthritis. Twenty subjects with recent ACL injury, 23 subjects with chronic ACL deficiency of at least 10 years standing, and 14 subjects with established osteoarthritis of the knee were recruited. The 20 subjects with recent ACL injury were examined again at 12 weeks and 2 years following knee reconstruction. The tibiofemoral contact patterns were examined for each group of subjects and the associations between changes in the contact patterns and evidence of joint damage explored. Evidence of joint damage and severity of osteoarthritis were recorded from xrays, diagnostic MRI, operation reports and bone densitometry at the tibial and femoral condyles of the knee. Each of the three groups with knee pathology exhibited different characteristics in the tibiofemoral contact pattern, and these differences were associated with severity of joint damage and osteoarthritis. The recently ACL-injured knees demonstrated a tibiofemoral contact pattern that was posterior on the tibial plateau, particularly in the lateral compartment. Those with chronic ACL deficiency demonstrated differences in the contact pattern in the medial compartment, associated with severity of damage to the knee joint. Osteoarthritic knees showed reduced femoral roll back and longitudinal rotation that normally occur during knee flexion. Two years following knee reconstruction there was no difference between the contact pattern of the reconstructed and healthy contralateral knees. This technique of tibiofemoral contact pattern mapping is sensitive to the abnormal characteristics of kinematics in ligament injury and osteoarthritis. This is the first time the tibiofemoral contact characteristics of chronic ACL-deficient and osteoarthritis knees have been described and links examined between tibiofemoral contact patterns and degenerative change.

Doctor of Philosophy / The aim of the work presented in this thesis was to examine the associations between the kinematics of the knee characterised by the tibiofemoral contact pattern, and degenerative change, in the context of anterior cruciate ligament (ACL) injury. While the natural history of degenerative change following knee injury is well understood, the role of kinematics in these changes is unclear. Kinematics of the knee has been described in a variety of ways, most commonly by describing motion according to the six degrees of freedom of the knee. The advantage of mapping the tibiofemoral contact pattern is that it describes events at the articular surface, important to degenerative change. It was hypothesised that the tibiofemoral contact pattern would be affected by injury to the knee. A model of ACL injury was chosen because the kinematics of the knee have been shown to be affected by ACL injury, and because the majority of chronic ACL-deficient knees develop osteoarthritis, the associations between kinematics and degenerative change could be explored. A technique of tibiofemoral contact pattern mapping was established using MRI, as a quantifiable measure of knee kinematics. The tibiofemoral contact pattern was recorded from 0º to 90º knee flexion while subjects performed a leg-press against a 150N load, using sagittal magnetic resonance imaging (MRI) scans. The technique was tested and found to be reliable, allowing a description of the tibiofemoral contact pattern in 12 healthy subjects. The tibiofemoral contact patterns of knee pathology were then examined in a series of studies of subjects at a variety of stages of chronicity of ligament injury and osteoarthritis. Twenty subjects with recent ACL injury, 23 subjects with chronic ACL deficiency of at least 10 years standing, and 14 subjects with established osteoarthritis of the knee were recruited. The 20 subjects with recent ACL injury were examined again at 12 weeks and 2 years following knee reconstruction. The tibiofemoral contact patterns were examined for each group of subjects and the associations between changes in the contact patterns and evidence of joint damage explored. Evidence of joint damage and severity of osteoarthritis were recorded from xrays, diagnostic MRI, operation reports and bone densitometry at the tibial and femoral condyles of the knee. Each of the three groups with knee pathology exhibited different characteristics in the tibiofemoral contact pattern, and these differences were associated with severity of joint damage and osteoarthritis. The recently ACL-injured knees demonstrated a tibiofemoral contact pattern that was posterior on the tibial plateau, particularly in the lateral compartment. Those with chronic ACL deficiency demonstrated differences in the contact pattern in the medial compartment, associated with severity of damage to the knee joint. Osteoarthritic knees showed reduced femoral roll back and longitudinal rotation that normally occur during knee flexion. Two years following knee reconstruction there was no difference between the contact pattern of the reconstructed and healthy contralateral knees. This technique of tibiofemoral contact pattern mapping is sensitive to the abnormal characteristics of kinematics in ligament injury and osteoarthritis. This is the first time the tibiofemoral contact characteristics of chronic ACL-deficient and osteoarthritis knees have been described and links examined between tibiofemoral contact patterns and degenerative change.

A dissertation submitted in partial compliance with the requirements for the Masters Degree in Technology: Chiropractic, 2002. / The purpose of this study was to determine the effectiveness and relative effectiveness of a topical Capsaicin cream and knee joint mobilization in the treatment of Osteoarthritis (OA) of the knee. / M

Ligament tears are more prevalent than all other knee injury pathologies, and contribute significantly to musculoskeletal joint pain and disability reported worldwide. Despite current soft tissue reconstruction techniques, the injured ligament fails to regenerate due to dysregulated cell-extracellular matrix (ECM) interactions that culminate in scar formation. Hallmarks of scar formation, or fibrotic healing include disorganized ECM, pathological stiffness or tissue rigidity, and the accumulation and persistence of myofibroblasts. A primary driver of fibrosis, myofibroblasts are characterized by high contractility, excessive deposition of collagen type I, coupled with inflammatory and fibrotic signaling. Notably these cells are critical early on in the response to injury, by aiding in the contracture of the wound bed and depositing collagen to repair the injury site. However, myofibroblasts are not capable of fully regenerating the native ligamentous matrix, and resolution of the phenotype is necessary in order to cue surrounding cells, prevent chronic inflammation and aberrant tissue remodeling. Persistence of the myofibroblast phenotype thus leads to a ligament scar that is functionally weaker than the healthy tissue matrix, characterized by significantly different histological, biochemical, and biomechanical properties. The consequential instability of this scar disrupts load distribution within the knee joint and increases the risk of subsequent injury, osteochondral degeneration, and ultimately, the development of post-traumatic osteoarthritis. Therefore, there is a critical need for strategies that target the inflammatory and fibrotic myofibroblast phenotypes for soft tissue healing. It follows that the overarching goal of this thesis is to engineer an immunomodulatory matrix to regulate myofibroblast activation and downstream fibrogenic signaling. To this end, models of soft tissue fibrotic repair are explored in order to test the central hypothesis that cues from the repairing ECM play an important role in regulating myofibroblast activation and persistence. Specifically, this thesis will compare myofibroblast differentiation and signaling in three in vitro models of tissue repair: 1) 2D on tissue culture polystyrene (TCPS), and two 3D models namely 2) collagen hydrogel and 3) electrospun collagen fiber matrices. As expected, on the 2D model, a persistent myofibroblast phenotype could be generated over time with an optimized transforming growth factor beta 1 (TGF-β1) stimulation protocol. To create repair-relevant 3D matrix models, we engineered collagen hydrogels with controlled mechanical properties, as well as electrospun fiber platforms that isolate key matrix factors including, collagen content, stiffness, fiber diameter, and alignment. These models emulate the connective tissue repair process via recapitulating the increasing matrix stiffness and fiber assembly of the early (granulation tissue), proliferative, and remodeling stages of the repair. Myofibroblast differentiation potential, parallel inflammatory and fibrotic cytokine secretion, as well as matrix remodeling potential were observed to be dependent on matrix model parameters. Moreover, single-cell resolution RNA sequencing revealed heterogenous myofibroblast populations within the context of response to engineered collagenous substrates. Specifically, myofibroblast accumulation was observed on hydrogel substrates that recapitulate the pathologically stiff mechanics and disorganization of fibrotic scar tissue while architectural cues of engineered fiber substrates prevented myofibroblast differentiation in a diameter and alignment-dependent manner. Moreover, nanoscale fibers elicited the greatest anti-fibrotic and anti-inflammatory properties compared to microscale fibers and stiff collagen-based hydrogels. Throughout, this thesis also explores the contribution of NF-κB signaling to myofibroblast plasticity and persistence using engineered collagen-based platforms, highlighting the dynamic role of myofibroblasts as critical immunoregulating cells. The NF-κB signaling pathway is implicated in a broad array of fibrotic and chronic inflammatory conditions, and more recently has been associated with survival of persistent myofibroblast populations in soft-tissue fibrosis and tendon degeneration models. In this thesis, NF-κB activation was seen to be related to the persistent myofibroblast phenotype and increase over time in both 2D TCPS and 3D collagenous hydrogel matrices that mimic pathologically stiff scar tissue, while a temporally dependent activation pattern was observed in electrospun collagen fiber-based models. At the transcriptional level, NF-κB survival signaling was significantly enriched in myofibroblast populations supported by TCPS and stiff collagen-based hydrogels but downregulated on soft hydrogels and fibers with decreasing fiber diameter that prevented robust myofibroblast differentiation at single cell resolution. Building upon these new insights regarding matrix cues that drive myofibroblast activation, we designed an immunomodulatory matrix that mediates small molecule release targeting NF-κB inhibition. The immunomodulatory matrix achieved robust amelioration of the myofibroblast phenotype as well as reduced the secretion of key inflammatory and fibrotic cytokines by these cells. Moreover, a similar anti-fibrotic response was seen for human ligament fibroblasts treated with these matrices. Collectively, this thesis work presents a systematic evaluation of myofibroblast plasticity and persistence within the context of 2D (TCPS), 3D (collagen-based hydrogels), and finally 3D with defined microarchitectural cues (electrospun collagen-based fibers) that recapitulate the progressive stages of scar-mediated healing, and reveals NF-κB as a promising target for reducing myofibroblast persistence. Moreover, the immunomodulatory control of myofibroblast plasticity and persistence via matrix cues coupled with NF-κB inhibition informs future strategies for true ligament healing.

Lam, Mak Ham. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2011. / Includes bibliographical references (leaves 110-131). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese.

[Truncated abstract] Hyaline articular cartilage is a highly specialised tissue consisting of chondrocytes embedded in a matrix of proteoglycan and collagens. Hyaline articular cartilage withstands high levels of mechanical stress and continuously renews its extracellular matrix. Despite this durability, mature articular cartilage is vulnerable to injury and disease processes that cause irreparable tissue damage. Native hyaline articular cartilage has poor regenerative capacity following injury, largely due to the tissue's lack of blood and lymphatic supply, as well as the inability of native chondrocytes to migrate through the dense extracellular matrix into the defect site. Articular cartilage injuries that fail to penetrate the subchondral bone plate evoke only a short-lived metabolic and enzymatic response, which fails to provide sufficient new cells or matrix to repair even minimal damage. Clinically, it has previously been accepted that treatment of such defects does not result in the restoration of normal hyaline articular cartilage, which is able to withstand the mechanical demands that are placed on the joint during every day activities of daily living. ... Historically, rehabilitation following ACI has not kept pace with the advances in cell culture and surgical technique. Subsequently, there exists a significant gap in knowledge regarding `best practice' in post operative rehabilitation following ACI. The importance of structured rehabilitation in ACI should not be underestimated when evaluating the clinical success of this chondral treatment. Patients should not be left to their own devices following ACI surgery, as the risk of damage to their implant (via delamination) is high if immediate postoperative movement is not controlled. Furthermore, the biological longevity and clinical success of the graft is dependent on a controlled and graduated return to ambulation and physical activity, and the biomechanical stimulation of the implanted chondrocytes.

Post-traumatic osteoarthritis (PTOA) of the knee is a complication resulting from direct injury to the joint, such as anterior cruciate ligament and meniscus tears, and accounts for approximately 12% of all OA cases. The economic and clinical impact of PTOA is also greater than idiopathic OA, as patients are younger and often more active, requiring treatments for symptomatic OA over a greater fraction of their lifetime. A common strategy to manage pain and inflammation associated with PTOA is the intraarticular administration of corticosteroids. However, these injections are limited due to the requirement of high-doses imposed by synovial joint clearance rates and their resulting systemic side effects. In addition, currently used broad-spectrum corticosteroids are palliative and not curative, stemming from incomplete knowledge of specific mechanisms that drive cartilage degeneration and other joint pathologies. Thus, most patients with PTOA eventually undergo surgical procedures such as osteochondral graft transplantation for focal defects and in more severe cases, total knee arthroplasty. As such, the studies presented in this dissertation (i) offer specific insights into mechanisms by which traumatic injury can drive joint degeneration and (ii) present novel strategies to modulate joint responses to pathological factors by leveraging sustained drug-delivery platforms. In Part I, mechanistic assessments of human cartilage and synovium responses to insults are conducted to identify novel pathways that may lead to impaired joint homeostasis. First, a direct consequence of traumatic injury, hemarthrosis, is explored as a potential contributor to the development of PTOA specifically through contributions by red blood cells. We demonstrate for the first time the differential roles of erythrocytes in their intact and lysed states through measures of oxidative stress and changes to metabolomic profiles in the context of ferroptosis. Furthermore, we demonstrate the therapeutic potential of Ferrostatin-1, a lipophilic radical scavenger in inhibiting pathological changes to cartilage and its crosstalk with the neighboring synovium in an in vitro model of hemophilic arthropathy. Second, a strategy to prevent an indirect consequence of traumatic injury, arthrofibrosis, is presented in an in vitro model of joint contraction. Fibrosis and the presence of hyperplastic synovium are implicated in the progression of OA through pathological shifts in tissue composition as well as secreted factors that promote cartilage degeneration and the maintenance of a pro-inflammatory joint environment. A type I transforming growth factor beta-1 receptor inhibitor, SB-431542, is encapsulated in polymeric microspheres for the prophylactic treatment of arthrofibrosis through sustained low-dose drug delivery to circumvent the challenges associated with resident joint clearance rates. Utilizing human-based in vitro models of cartilage and synovium pathology, we present novel mechanisms and therapeutic strategies to prevent pathological changes following traumatic joint injury that may contribute to the development of PTOA. In Part II, the sustained delivery platform introduced in Part I is extended to the treatment of PTOA. Osteochondral graft transplantation is currently the clinical gold standard for large focal cartilage lesions. However, allograft procedures are limited due to the lack of available donor tissues and autografts are associated with complications due to donor-site morbidity. In both cases, grafts are subject to failure, potentially in part due to the continual presence of pro-inflammatory factors following surgical procedure. In this section, we present cellular agarose hydrogels embedded with dexamethasone-releasing microspheres that are integrated with a titanium base as a functional tissue-engineered alternative to native osteochondral allografts. These allogenic tissue-engineered grafts were assessed in an in vivo preclinical canine model in their ability to maintain clinical function and to modulate the inflammatory response over the course of 12 months. We successfully demonstrated the feasibility of using engineered grafts by comparing clinical measures of range of motion, function, lameness, and pain, as well as modified cartilage graft scores, against native osteochondral allograft controls. In addition, improvements in the histopathological scoring of neighboring synovial and meniscal tissues indicate the therapeutic capacity of dexamethasone released from within the joint to modulate the inflammatory response up to one-year post-implantation. Taken together, the studies presented in this dissertation identify novel mechanisms behind pathological changes to the cartilage and synovium that may contribute to the development of PTOA following injury. Potential therapeutic targets, inhibitory compounds, and delivery strategies are also assessed using human-based in vitro models of disease and further validated in an in vivo canine model through a clinically relevant timeframe. Ultimately, we demonstrate for the first time, the use of dual-function tissue-engineered grafts in a weight-bearing region of the knee joint to circumvent limitations associated with the clinical gold standard for the treatment of large focal cartilage defects.

Dissertation submitted in partial compliance with the requirements for a Master's Degree in Technology: Chiropractic, Durban University of Technology, 2010. / Motion palpation is used to assess the functional status of a joint and is defined as “The manual palpation of bony structures and soft tissues, through pressure applied in various directions of joint motion to ascertain areas of joint hypomobility and hypermobility.” Motion palpation is a collection of manual examination procedures, used to identify the site and characteristics of altered joint motion and which has been an important part of chiropractic since its inception. One of the most important goals for any clinical instrument is for it to have good reliability and reproducibility, this is because the clinical value of a test must be demonstrated before the results are considered valid. The extent to which a repeated test will produce the same result when evaluating an unchanged characteristic is its reliability. Reliability is evaluated by multiple blinded measurements performed on a sample of subjects. Inter-examiner reliability evaluates the consistency of different examiners and is determined through repeated assessment by two or more raters. Objective The aim of this study was to determine the inter-examiner reliability of motion palpation of knee joints with patellofemoral pain syndrome and asymptomatic knee joints, and to compare the inter-examiner reliability of motion palpation between the two groups. Method This quantitative, inter-examiner, clinical reliability study, included 30 patients each with one knee with patellofemoral pain syndrome and one asymptomatic knee. Each patient had both of their knees motion palpated by three independent examiners blinded to which was the symptomatic knee. The examiners were senior student interns at the DUT Chiropractic Clinic. The motion palpation findings were recorded and statistically analyzed through the SPSS statistical package. Fleiss Kappa statistic was used to give a Kappa score for each direction of motion palpation and these scores evaluated the inter-examiner reliability of motion palpation in the symptomatic and the asymptomatic knee. A comparison of the inter-examiner reliability of motion palpation between the two groups was performed using a paired Wilcoxin signed ranks test. Results The Kappa scores for motion palpation ranged from -0.2081 to 0.1802 for the symptomatic knee joint and -0.2836 to 0.0339 for the asymptomatic knee. This shows poor agreement in both cases. There was no significant difference in Kappa values (p= 0.609) for the two groups for the Wilcoxin signed ranks test and the number of positive and negative ranks were similar. This indicates that the reliability of motion palpation in both groups was similar. Conclusion It was concluded that inter-examiner reliability of motion palpation of the knee joint was poor in knees with patellofemoral pain syndrome and in knees that were asymptomatic. Motion palpation was found to be equally reliable in both groups, indicating that motion palpation of a symptomatic joint does not improve its reliability. This research suggests that motion palpation should be used together with other diagnostic tests to identify patellofemoral pain syndrome as it is not a reliable tool when used in isolation.