Alexander Scott

Professor

Research Classification

Research Interests

musculoskeletal
Musculoskeletal Lesions and Repair
orthopaedics
physical therapy
physiotherapy
sports medicine

Relevant Degree Programs

Affiliations to Research Centres, Institutes & Clusters

 
 

Research Methodology

biomechanics
mechanobiology
tendon cell culture
movement analysis
Histology
qPCR
systematic review

Recruitment

Master's students

Development and execution of clinical studies; tendinopathy

I support public scholarship, e.g. through the Public Scholars Initiative, and am available to supervise students and Postdocs interested in collaborating with external partners as part of their research.
I support experiential learning experiences, such as internships and work placements, for my graduate students and Postdocs.

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Graduate Student Supervision

Doctoral Student Supervision (Jan 2008 - May 2021)
Evaluation of the Role of ANGPTL4 in Tendon Vascularization (2016)

The mechanisms that regulate angiogenic activity in injured or mechanically loaded tendons are poorly understood. In this study we hypothesised that repetitive stretching of tendon cells alters the expression and release of angiogenic factors which may promote tendon vascularization. In order to examine the effects of repetitive stretching on the expression of angiogenic genes, primary human tendon cells were subjected to cyclic stretching. Cyclic stretching of two-dimensional primary tenocyte cell cultures increased the expression of VEGF, bFGF and Cox-2. But, by extending the time course, VEGF, bFGF and Cox-2 were progressively downregulated. Angiogenic profiling of tendon cells by qPCR array identified a number of other genes (ANGPTL4, FGF-1, TGFα, VEGF-C and SPHK1) that responded to tensile loading in a similar pattern. Further experiments revealed that cyclic stretching of human tendon fibroblasts stimulated the expression and release of ANGPTL4 protein via TGF-β and HIF-1α signalling. ANGPTL4 promoted the angiogenic activity of endothelial cells. Angiogenic activity was also increased following injury and following ANGPTL4 injection into mouse patellar tendons, whereas the patellar tendons of ANGPTL4 knock out mice displayed reduced angiogenesis following injury. In human rotator cuff tendons, there were both spatial and quantitative associations of ANGPTL4 with tendon endothelial cells. The experiments described in this thesis have shown that ANGPTL4 may assist in the regulation of vascularity in injured or mechanically loaded tendon. TGF-β and HIF-1α are two signalling pathways that modulate the expression of ANGPTL4 by tendon fibroblasts and which could, in future, be manipulated to influence tendon healing or adaptation.

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The potential role of MMP2 in the response of tendons to mechanical stimulation (2016)

Tendinopathy is a common problem in the population leaving people in pain, unable to work or be physically active. High levels of musculotendinous strain (resulting from heavy lifting or obesity) and repetitive movements are risk factors for tendinopathy. Because MMPs and TIMPs play a crucial role in the repair, remodeling, and degeneration of collagen fibers in tendon, the aim of this dissertation was to identify the potential roles of MMPs, TIMPs and collagens type I and III, using in-vitro and in-vivo models of overuse and repair. Having identified a potential role of MMP2 in these laboratory models, a clinical study was also conducted to evaluate the serum levels of MMPs and TIMPs in patients who had experienced Achilles tendon rupture. Cultured tendon cells, controlled by high frequency or high strain stimulation, simulating overuse, increased MMP2 mRNA expression. Collagen type I mRNA and protein levels were increased in cultured tendon cells by controlled mechanical stimulation with intermittent rest periods compared to continuous mechanical stimulation.In both the normal healthy rabbit and an overuse model of the rabbits’ Achilles tendon, regional differences in mRNA expression and histological structure were observed. After two weeks of repetitive tendon loading, collagen intensity, measured by second harmonic generation microscopy, was decreased in the flexor digitorum superficialis (FDS) tendon compared to the contralateral FDS tendon and healthy control FDS tendon, indicating damage or remodelling of the collagen in response to overuse. Structural changes were observed locally, combined with elevated tissue MMP2 protein levels suggesting a possible contribution of MMP2 to the development of early collagen degradation. MMP2 appears to play a role early in the response of tendon to repetitive loading. It is detectable in serum after 1 week of overuse, and high repetition number and high strain level are independent modulators of MMP2 expression in tenocytes. However, MMP2 levels in serum decline to baseline after 2 weeks in the animal model, and were downregulated compared to controls in patients with a more Achilles tendon rupture. Further research into the specific processes of tendon injury and repair played by MMP2 are warranted.

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Master's Student Supervision (2010 - 2020)
Using the vert wearable device to monitor jumping loads in elite volleyball athletes (2020)

Sport is evolving into a more competitive industry, leaving athletes prone to injuries. Monitoring athletes using wearable technology provides a way to potentially manage training and competition loads with the goal of reducing injuries. One such technology is the VERT, a commercially available discrete wearable device that measures vertical displacement from the center of mass. While several studies have examined the accuracy of the VERT’s measures of jump height and jump count, landing impact has not yet been investigated. The objective of this research study was to explore the potential utility of the VERT as a load monitoring tool in elite volleyball players. This was done by (1) examining the accuracy of the VERT landing impact values in university volleyball players and (2) retrospectively analyzing a VERT data set collected over the course of a university volleyball season, documenting whether established relationships were observed between various load characteristics and knee pain. We hypothesized that the VERT landing impact values would fall within 10% of those derived from a research-grade accelerometer, the Shimmer. In the data set, we expected to see agreement with the literature in that acute:chronic workload ratio (ACR), average jump height, jump count and session rating of perceived exertion (sRPE) were positively associated with knee pain. We also expected knee pain to increase over the course of the season and for leftsides/middle blockers to report the highest pain. Methodology for the validation study included recruiting 14 players, having each perform 10 jumps while wearing both devices. For the retrospective analysis, we used linear mixed effect modelling. The results of the validation showed that VERT landing impacts were variable (limits of agreement of -84.13% and 52.37%) and had a propensity to be lower (mean bias of -15.88%) when compared to the Shimmer. In the retrospective analysis, average jump height (p=0.041) and date (p=0.032) were negatively associated with knee pain (however the associations were of small magnitude). In conclusion, the validity of the VERT device’s landing impact values are generally poor, with respect to Shimmer. The relationships in the data set were partially consistent with what previous literature has shown.

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Can achilles tendon xanthoma and achilles tendinopathy be distinguished using ultrasonography and MRI? An exploratory, comparative study (2019)

Familial hypercholesterolemia (FH) is a genetic condition characterized by the inability to properly metabolize low-density lipoprotein cholesterol (LDL-C). In addition to serious cardiovascular health complications, FH carriers often develop intratendinous cholesterol deposits, most notably located in the Achilles tendon, known as Achilles tendon xanthoma (ATX). Clinically, physical detection of ATX relies upon visual assessment and palpation. This practice is insensitive and is not capable of distinguishing FH from conditions with similar symptomology, such as Achilles tendinopathy (ATE). Advances in medical imaging, specifically Dixon method for magnetic resonance imaging (MRI) and ultrasound tissue characterization (UTC) for ultrasound (US), may be able to differentiate between ATX and ATE. The Dixon method allows for quantification of relative lipid and water contents within tissue and UTC allows for characterization of tendon structure through echo-type evaluation. We hypothesized that ATX will demonstrate greater relative lipid and water content than ATE or a healthy control population (C), and that ATX and ATE will demonstrate decreased tendon organization compared to C.To test the hypotheses, US and MRI scans of 59 tendons from 30 participants (n=10 ATX, n=10 ATE, n=10 C) were analyzed for relative lipid and water content, UTC echo-type I values, as well as Achilles tendon thickness (ATT). Relative lipid content was not greater in ATX compared to ATE and controls (ATX – ATE, p = 0.23; ATX – Control, p = 0.31; ATE – Control, p = 0.98). Relative water content was greater in ATX compared to controls (p = 0.04) but not compared to ATE (p = 0.16) and did not differ between ATE and control (p = 0.76). ATX tendons were significantly thicker than both ATE and control tendons (p = 0.04 and 0.002, respectively). UTC echo-type I values were significantly lower in ATX than ATE (p = 0.04) and nearly significantly lower in ATX than C (p=0.055), indicating decreased collagen organization in ATX.Results suggest that both US and MRI may serve as viable approaches to aid clinical detection of ATX as well as to differentiate ATX and ATE pathology.

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Measurement of tendon transverse stiffness in people with Achilles tendinopathy - a cross sectional study (2019)

The Achilles tendon is the largest and strongest tendon in the human body and is vital for locomotion. One of the most important indicators of tendon function is tendon stiffness. Tendinopathic Achilles tendon displays reduced stiffness compared to healthy tissue, meaning that it experiences more strain for a given load, putting the tendon at a higher risk of damage. Recently, in vivo measures of Achilles tendon stiffness have become more common, although they are limited to the research setting due to low reliability values. In order to address these limitations, we have begun validating a newly available technology, the MyotonPRO. This is a handheld, digital palpation device that sends out a small impulse into the tendon through a probe which houses an accelerometer. The measured deformation and acceleration determined by the device, are then used to derive the transverse stiffness of the tendon. The aim of this cross-sectional pilot study is to assess whether the transverse stiffness of tendinopathic Achilles tendon (the mid-portion tendinopathy group) is lower than those who are free from symptoms (the control group). We hypothesized that the injured tendons will be significantly less stiff than the tendons of the control group. To test this hypothesis, we used the MyotonPRO to measure the Achilles tendons of 25 individuals who either had midportion tendinopathy (n=10) or who were healthy controls (n=15), and compared their transverse stiffness values taken at the same average location on the tendon (3.7cm from the insertion). We found that there was a significantly lower transverse stiffness in tendinopathic subjects compared to controls (p=0.006). These findings suggest that the MyotonPRO can provide information about the tendon mechanical properties that may be useful in understanding how tendinopathy affects tendon function.This study opens the door to the continued investigation of a relatively inexpensive, accessible and easy-to-interpret device. We believe that this device could be used to monitor the healing in tendinopathy patients as well as predicting and preventing injuries and monitoring adaptive changes in tendons in response to exercise.

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The effects of familial hypercholesterolemia on achilles tendon biomechanics: a cross-sectional study (2019)

Familial hypercholesterolemia (FH), a common genetic metabolic disorder characterized by high cholesterol levels, is involved in the development of atherosclerosis and other preventable diseases. FH can also cause tendinous abnormalities, such as thickening and xanthoma (tendon lipid accumulation) in the Achilles and extensor tendons, which may impact and impede tendon biomechanics. There is evidence that high cholesterol may lead to tendon injury or pain, but tendon biomechanics has received little investigation in people with FH. The objective of this study was to investigate how FH can affect Achilles tendon biomechanics, in vivo. 16 FH participants were recruited locally from the British Columbia FH Registry database. 16 control participants were recruited from purposeful convenience sampling. All participants completed preferred pace walking trials, shod, on a fully instrumented treadmill to collect gait impact data. Achilles tendon (AT) biomechanical data was obtained according to previously published methodology; simultaneously, lower limb kinematics, and muscle-tendon junction displacement were measured by motion capture and b-mode ultrasound imaging, respectively. AT strain, stiffness and hysteresis were calculated using a custom built Matlab program. AT biomechanical outcomes were assessed for statistical differences using MANCOVA.16 FH participants (10 males, 6 females, 37±6 years, BMI of 28±4 kg/m²) and 16 control participants (10 males, 6 females, 36±7 years, BMI of 27±3 kg/m2) were recruited. FH participants displayed similar AT peak strain (FH: 5.07±0.9%, Controls: 4.95±0.9%; p=0.790), lower stiffness (FH: 87±20 N/mm, Controls: 111±18 N/mm; p=0.001), and higher hysteresis (FH: 56±17%, Controls: of 35±12%; p=0.007), when compared to controls. To the best of our knowledge, this is the first study that evaluates the impact of FH on AT biomechanics, in vivo. The results of the current study provide evidence that cholesterol accumulation can negatively affect AT biomechanics and potentially increase the chance of injury. The findings of this study will be of interest to clinicians, and people with FH and high cholesterol.

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A cross-sectional study to evaluate the effect of statins on Achilles tendon morphology using ultrasound tissue characterization (2017)

There has been growing interest in studying the possible effects of statins on tendons due to case studies and retrospective chart reviews that reported a potential relationship between statin use and tendon pathology, as well as laboratory studies demonstrating that statins directly influence tenocyte metabolism. However, a recent epidemiological study found no association between statin use and the risk of tendon rupture. Since statins are widely used cholesterol-lowering medications, it is important to understand the potential relationship between statin use and tendon health. With the use of Ultrasound Tissue Characterization (UTC), the aims of this pilot cross-sectional study were to see if there were signs of reduced collagen organization or increased cross-sectional area (CSA) of the Achilles tendon in individuals who had been taking statins for at least a year (the Statin group), compared to those who had never taken a statin (the Control group). We hypothesized that individuals in the Statin group would demonstrate a greater cross-sectional area and reduced collagen organization (determined by the percent of echo-type I) of their Achilles tendons compared to individuals in the Control group. To test this hypothesis, we analyzed the UTC scans of 66 individuals who were either taking Statins (n=33) or who had never taken statins (n=33, control group) and compared their resulting Achilles tendon CSA and echo-type I values. There were no significant differences in Achilles tendon CSA or proportion of echo-type I patterns between the two groups, implying that statins do not negatively impact the health of the Achilles tendon. In the entire cohort (n=66), there were significant effects of age (r = -0.31, p = 0.012) and BMI (r = -0.31, p = 0.012) on echo-type I values. These findings support previous work which demonstrated a lack of association betweenstatin use and tendon pathology, but demonstrate the negative effects of aging and elevated BMI on tendon health.

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Effect of isometric training with short or long rest periods on Achilles tendon morphology : an ultrasound tissue characterization study (2017)

Achilles tendon (AT) is the strongest tendon in the body. One of the major causes of AT pathology, chronic tendinopathy, is frequently due to excessive loading. Despite the risk of overuse injury, exercise training with appropriate mechanical loading parameters has been found to trigger an adaptation response in the AT. However, the influence of some loading parameters, such as the duration of rest periods between exercise repetitions, remains unknown. Therefore, the aim of this study was to examine the effect of 10s rest insertion during isometric resistance training (Long rest training; LRT) on the morphological properties of human AT, compared with same training intensity and volume but with 3s rest insertion (short rest training; SRT). I hypothesized that ATs exposed to LRT would demonstrate increased tendon collagen organization and tendon cross-sectional area (CSA) compared with baseline, but that SRT would not demonstrate any change in either variable.To test my hypothesis, we recruited healthy adults, and randomly allocated one leg to LRT and the other to SRT. The exercise protocol consisted of 5 sets of 10 isometric calf presses at 90% of maximum voluntary contraction, three times a week over a 12-weeks training period. Tendon collagen organization (proportion of type I echoes) and CSA were measured by ultrasound tissue characterization before and after the 12-weeks period. The primary outcome was the proportion of type I echoes.In contrast to our hypothesis, neither LRT nor SRT induced an improvement in collagen organization or tendon CSA. However, tendons exposed to SRT demonstrated a reduction in the proportion of type I echoes following exercise from 0.66 (95% CI= 0.60 to 0.70) to 0.55 (95% CI=0.49 to 0.60), (p
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The time course of the analgesic effect of acupuncture in the treatment of lateral epicondylalgia: a randomized controlled feasibility trial comparing standard acupuncture and electroacupuncture (2017)

Background: Resistance exercise is effective in relieving pain and improving grip strength in patients with lateral epicondylalgia (LE). However, patients’ activity-related pain can hinder their active participation in an exercise program. Acupuncture, particularly electro-acupuncture (EA), may be an effective complementary modality for pain control in order to promote patients’ participation in an exercise program and further to enhance therapeutic effects. Objectives: 1) assess the feasibility of a study designed to compare the effect size of analgesia induced by EA vs. standard acupuncture (SA); 2) estimate the time course of the analgesic effect of EA and SA for patients with LE; and 3) investigate if the analgesic effect of either intervention is associated with a change in pain-free grip strength. Methods: A double-blind, parallel-group randomized controlled feasibility trial was conducted at a research centre located in Vancouver, Canada. Twenty-one participants with unilateral LE lasting more than 6 weeks duration were enrolled in the study. The participants were randomly allocated to receive a single treatment of either EA (10-30 Hz) or SA. The primary outcome measure was pain-free grip strength, and the secondary outcome measures included the severity of lateral elbow pain (numeric rating scale), and patients’ global rating of change. Outcomes were measured over a 72-hour period. Results: No significant differences in outcome measures were found between the two treatment groups at any time point. A pattern of gradual improvement of pain-free grip strength (approximately 12N /day) over the 72-hour monitoring period in both treatment groups was observed, and this improvement was statistically significant compared to baseline at the 72-hour time point (38 ± 13N). In contrast, there was a statistically significant reduction in patients’ perceived pain level immediately after either treatment, and this improvement was maintained throughout the 72-hour follow-up period (-0.99~-1.59 ± 0.35). After 24 hours, 5% of patients reported themselves as feeling ‘much better’, 55% ‘slightly better’, 15% ‘unchanged’, 10% ‘slightly worse’, 10% ‘moderately worse’ and 5% ‘much worse’. Conclusion: Acupuncture may complement the therapeutic effect of rehabilitation exercise program as it provides immediate pain relief for patients with chronic LE.Trial registration: ISRCTN14667535Funding: none

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Randomized Controlled Trial to Evaluate the Effects of Topical Diclofenac on the Pain Associated with Chronic Achilles Tendinopathy: A Pilot Study (2016)

Background: Exercise-based rehabilitation for chronic Achilles tendinopathy (CAT) has proven to be effective, but it can be a painful process. The purpose of this research is to see if a topically applied non-steroidal anti-inflammatory drug, diclofenac, will be able to relieve the pain associated with chronic tendinopathy. The effects of diclofenac on subjects’ pain and mechanical hyperalgesia will be evaluated at rest and during simple calf exercises. It is expected that diclofenac will reduce pain among subjects with Achilles tendinopathy. Methods:19 subjects (22 Achilles) with CAT were randomly assigned to a crossover treatment order (active gel containing 10% diclofenac, or placebo). The primary outcome measure was pain level during tendon loading (hopping) and at rest. The secondary outcome measures evaluated tendon loading characteristics, and mechanical hyperalgesia over the lesion, and over the bilateral trapezius muscles.Results:Pain was significantly reduced from baseline with the use of diclofenac during tendon loading (p=0.0003) and rest (p=0.0313). At baseline the average resting pain was 3.05 (+/-1.43), with the use of diclofenac the pain was 2.32 (+/- 1.52), and with the use of placebo the pain was 2.68 (+/- 2.03). At baseline the average hopping pain was 4.82 (+/-2.1), with the use of diclofenac the average hopping pain was 3.05 (+/-1.81), and with the use of placebo the average pain was 3.77 (+/-2.76). During the hopping test, subjects were able to generate significantly more force when experiencing less pain (p
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A histological observation of inflammatory cells in the rabbit Achilles tendon due to overuse injury (2014)

The presence or absence of inflammatory cells in chronic Achilles tendinopathy has been a controversial subject in previous studies. Macrophages, T lymphocytes, and neutrophils have previously been detected in injured human Achilles tendons, whereas other authors have reported that there is no evidence for their occurrence. This controversy may stem from the fact that human Achilles tendon overuse injuries usually develop gradually over time, and the time course of inflammation in response to overuse has been difficult to establish in clinical populations. The aim of my study was to examine the presence of inflammatory cells in the Achilles tendon of rabbits that were subjected to repetitive mechanical loading of defined durations. Twenty-Four New Zealand male rabbits were subjected to repetitive mechanical loading of the Achilles tendon and grouped into four groups in this study, according to the exercise time period for each group: 0, 1, 3, and 6 weeks. Achilles tendons were harvested at the end of each time period. Achilles tendons sections were stained with Hematoxylin and Eosin to examine the histological changes. Both Neutrophils and T-lymphocytes were detected by Immunohistochemistry. Macrophages were detected using the Prussian blue staining. A very small number of inflammatory cells were detected in some tissue sections in the control group. Tissue sections from exercised groups 1, 3, and 6 weeks respectively, showed some qualitative changes in tendon morphology. Collagen bundles were disorganized, and hyalinized patches and spaces between collagen fibers were observed. Tenocyte nuclei were rounder and basophilic, and there was an increase in their numbers with loss of parallel alignment. Macrophages, T-lymphocytes, and neutrophils were detected in tendon sections, specifically in the paratenon. Statistically both lymphocytes and macrophages were significantly higher than control at 6 weeks. While the number of macrophages in the control was lower than the 6 weeks group, there was no significant difference between 1 week and 3 weeks. However, no lymphocytes were found at week 3. Neutrophils in all groups showed no significant difference. The evidence of inflammation was not evenly distributed, as some tissue sections from the same groups showed no evidence of inflammatory cells.

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The link between hypercholesterolemia and tendon pathology (2013)

Tendinopathy is a major cause of morbidity in athletic populations and in the work force, traditionally thought to occur as a consequence of an imbalance between damage (resulting from mechanical loading) and repair. However, one third of the cases for midportion Achilles tendinopathy occur in sedentary individuals, and recent data suggests an association between hypercholesterolemia and the occurrence of tendon rupture or tendinopathy. The aim of this study was to examine the link between elevated lipids and tendon pathology. We used an apolipoprotein E-knockout model (ApoE-KO), in which apolipoprotein E deficiency leads to development of atherosclerosis. We hypothesized that tendons from ApoE-KO mice fed a high fat diet, in comparison to those fed a regular chow diet and the wild type (non-atherosclerotic mice), will demonstrate increased lipid deposition, increased cross-sectional area, and increased expression levels of collagen genes (Col1a1 and Col3a1), a growth factor gene (TGF-β), and an indicator of mast cell presence (Cpa3). To test these hypotheses, ApoE-KO and control mice were fed a regular or high fat diet and sacrificed at different time points: 0, 15, and 30 weeks. The morphological properties were examined on H&E stained Achilles tendon sections while the lipid content was analyzed with Oil Red O staining. Tendon thickening was measured by ultrasonography of patellar tendon cross-sectional area. qPCR analysis was carried out on tail tendons at 30 week time point to analyze gene expression of Cpa3, TGF-β, Col1a1, and Col3a1. ApoE-KO mice developed xanthomatous lesions, and showed less weight gain than control mice. ApoE-KO mice showed no appreciable changes in tendon histomorphology. Compared to control mice, ApoE-KO mice had lower tendon lipid content but demonstrated an increase in tendon cross-sectional area. Col1a1 gene expression levels were decreased in ApoE-KO mice. Cpa3, TGF-β, and Col3a1 showed no differences between strains; however, Cpa3 expression was decreased in mice that were fed the high fat diet. ApoE-KO mice demonstrated significant tendon alterations, demonstrating thicker tendons with decreased collagen expression. Future work is required to determine the mechanism involved and the potential impact on tendon function.

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