Philip Hansen

Fibril Morphology and Tendon Mechanical Properties in Patellar Tendinopathy Effects of Heavy Slow Resistance Training

Background Patellar tendinopathy is characterized by pathologic abnormalities. Heavy slow resistance training (HSR) is effective in the management of patellar tendinopathy, but the underlying functional mechanisms remain elusive. Purpose To investigate fibril morphology and mechanical properties in patellar tendinopathy and the effect of HSR on these properties. Study Design Cohort study; Level of evidence, 2. Methods Eight male patients with patellar tendinopathy completed 12 weeks of HSR. Nine healthy subjects served as controls. Assessments were conducted at baseline and at 12 weeks. Patients assessed symptoms/function and maximal tendon pain during activity. Tendon biopsy samples were analyzed for fibril density, volume fraction, and mean fibril area. Tendon mechanical properties were assessed using force and ultrasonography samplings. Results Patients improved in symptoms/function (P = .02) and maximal tendon pain during activity (P = .008). Stiffness and modulus of control and tendinopathy tendons were similar at baseline. Stiffness remained unaffected in control tendons (3487 ± 392 to 3157 ± 327 N/mm, P = .57) but declined in tendinopathic tendons at 12 weeks (3185 ± 187 to 2701 ± 201 N/mm, P = .04). At baseline, fibril volume fraction was equal, fibril density smaller (P = .03), and mean fibril area tended to be higher in tendinopathy versus controls (P = .07). Fibril morphology remained unchanged in controls but fibril density increased (70% ± 18%, P = .02) and fibril mean area decreased (—26% ± 21%, P = .04) in tendinopathic tendons after HSR. Conclusion Fibril morphology is abnormal in tendinopathy, but tendon mechanical properties are not. Clinical improvements after HSR were associated with changes in fibril morphology toward normal fibril density and mean fibril area. Heavy slow resistance training improved the clinical outcome of patellar tendinopathy, and these improvements were associated with normalization of fibril morphology, most likely due to a production of new fibrils.

Lower strength of the human posterior patellar tendon seems unrelated to mature collagen cross-linking and fibril morphology

The human patellar tendon is frequently affected by tendinopathy, but the etiology of the condition is not established, although differential loading of the anterior and posterior tendon may be associated with the condition. We hypothesized that changes in fibril morphology and collagen cross-linking would parallel differences in material strength between the anterior and posterior tendon. Tendon fascicles were obtained from elective ACL surgery patients and tested micromechanically. Transmission electron microscopy was used to assess fibril morphology, and collagen cross-linking was determined by HPLC and calorimetry. Anterior fascicles were markedly stronger (peak stress: 54.3 +/- 21.2 vs. 39.7 +/- 21.3 MPa; P < 0.05) and stiffer (624 +/- 232 vs. 362 +/- 170 MPa; P < 0.01) than posterior fascicles. Notably, mature pyridinium type cross-links were less abundant in anterior fascicles (hydroxylysylpyridinoline: 0.859 +/- 0.197 vs. 1.416 +/- 0.250 mol/mol, P = 0.001; lysylpyridinoline: 0.023 +/- 0.006 vs. 0.035 +/- 0.006 mol/mol, P < 0.01), whereas pentosidine and pyrrole concentrations showed no regional differences. Fibril diameters tended to be larger in anterior fascicles (7.819 +/- 2.168 vs. 4.897 +/- 1.434 nm(2); P = 0.10). Material properties did not appear closely related to cross-linking or fibril morphology. These findings suggest region-specific differences in mechanical, structural, and biochemical properties of the human patellar tendon.

Measuring mechanical properties of the vastus lateralis tendon-aponeurosis complex in vivo by ultrasound imaging.

The mechanical properties of the human vastus lateralis (VL) tendon‐aponeurosis complex were investigated in eight male subjects. Knee extensor force, knee joint angle, and corresponding longitudinal VL aponeurosis displacement were monitored synchronously during graded (10‐s) maximal isometric knee extension contractions. Displacement observed during isometric conditions may be regarded as an expression of deformation in the tissues distal to the measurement site. Furthermore, aponeurosis displacement was measured during passive knee extension (90–75°°), and used to correct displacement values obtained during active contraction for joint angular motion. The passive trial yielded a highly linear relationship between aponeurosis displacement and joint angular motion (r2 = 0.998 ± 0.002) with a mean correction factor of 0.41 ± 0.10 mm/degree. Maximal knee extensor force was 5834 ± 1341 N with a corresponding VL aponeurosis displacement of 12.7 ± 2.5 mm, while correcting for joint angular motion reduced maximal displacement ∼9% (to 11.6 ± 2.5 mm, P < 0.005) (data presented as means ± SD). Two separate graded contraction trials were performed, and no between‐trial differences were observed in either maximal force or maximal displacement. Between trial coefficient of determination and CV for maximal force and maximal displacement were r2 = 0.97, CV = 2.9% and r2 = 0.92, CV = 4.6%, respectively, indicating intra‐day reproducibility of measurements. These data demonstrate that when applying the newly established ultrasound‐based method of investigating quadriceps connective tissue mechanical properties, maximal isometric contraction is inevitably associated with some joint angular motion that significantly influences the calculations.

Mechanical properties of human patellar tendon at the hierarchical levels of tendon and fibril

Tendons are strong hierarchical structures, but how tensile forces are transmitted between different levels remains incompletely understood. Collagen fibrils are thought to be primary determinants of whole tendon properties, and therefore we hypothesized that the whole human patellar tendon and its distinct collagen fibrils would display similar mechanical properties. Human patellar tendons (n = 5) were mechanically tested in vivo by ultrasonography. Biopsies were obtained from each tendon, and individual collagen fibrils were dissected and tested mechanically by atomic force microscopy. The Youngs modulus was 2.0 ± 0.5 GPa, and the toe region reached 3.3 ± 1.9% strain in whole patellar tendons. Based on dry cross-sectional area, the Youngs modulus of isolated collagen fibrils was 2.8 ± 0.3 GPa, and the toe region reached 0.86 ± 0.08% strain. The measured fibril modulus was insufficient to account for the modulus of the tendon in vivo when fibril content in the tendon was accounted for. Thus, our original hypothesis was not supported, although the in vitro fibril modulus corresponded well with reported in vitro tendon values. This correspondence together with the fibril modulus not being greater than that of tendon supports that fibrillar rather than interfibrillar properties govern the subfailure tendon response, making the fibrillar level a meaningful target of intervention. The lower modulus found in vitro suggests a possible adverse effect of removing the tissue from its natural environment. In addition to the primary work comparing the two hierarchical levels, we also verified the existence of viscoelastic behavior in isolated human collagen fibrils.

Glutaraldehyde Cross-Linking of Tendon—Mechanical Effects at the Level of the Tendon Fascicle and Fibril

Conclusive insight into the microscopic principles that govern the strength of tendon and related connective tissues is lacking and the importance of collagen cross-linking has not been firmly established. The combined application of whole-tissue mechanical testing and atomic force spectroscopy allowed for a detailed characterization of the effect of cross-linking in rat-tail tendon. The cross-link inducing agent glutaraldehyde augmented the tensile strength of tendon fascicles. Stress at failure increased from ∼8 MPa to ∼39 MPa. The mechanical effects of glutaraldehyde at the tendon fibril level were examined by atomic force microscopy. Peak forces increased from ∼1379 to ∼2622 pN while an extended Hertz fit of force-indentation data showed a ∼24 fold increase in Youngs modulus on indentation. The effect of glutaraldehyde cross-linking on the tensile properties of a single collagen fibril was investigated by a novel methodology based on atomic force spectroscopy. The Youngs modulus of a secluded fibril increased from ∼407 MPa to ∼1.1 GPa with glutaraldehyde treatment. Collectively, the findings indicate that cross-linking at the level of the collagen fibril is of key importance for the mechanical strength of tendon tissue. However, when comparing the effects at the level of the tendon fascicle and fibril, respectively, further questions are prompted regarding the pathways of force through the tendon microstructure as fibril strength seems to surpass that of the tendon fascicle.

Tensile Force Transmission in Human Patellar Tendon Fascicles Is Not Mediated by Glycosaminoglycans

Correct mechanical function of tendons is essential to human physiology and therefore the mechanical properties of tendon have been a subject of research for many decades now. However, one of the most fundamental questions remains unanswered: How is load transmitted through the tendon? It has been suggested that the proteoglycan-associated glycosaminoglycans (GAGs) found on the surface of the collagen fibrils may be an important transmitter of load, but existing results are ambiguous and have not investigated human tendons. We have used a small-scale mechanical testing system to measure the mechanical properties of fascicles from human patellar tendon at two different deformation rates before and after removal of GAGs by treatment with chondroitinase ABC. Efficiency of enzyme treatment was quantified using dimethylmethylene blue assay. Removal of at least 79% of the GAGs did not significantly change the tendon modulus, relative energy dissipation, peak stress, or peak strain. The effect of deformation rate was not modulated by the treatment either, indicating no effect on viscosity. These results suggest that GAGs cannot be considered mediators of tensile force transmission in the human patellar tendon, and as such, force transmission must either take place through other matrix components or the fibrils must be mechanically continuous at least to the tested length of 7 mm.

A Case-Control Study of Hypertensive Women in a Post-Disaster Community: Wyoming Valley, Pennsylvania

Among 396 female flood victims participating in a five-year post-disaster survey, 31 cases were identified who developed hypertension during that time period. A case-control study of hypertension was carried out utilizing age and ponderal index as matching criteria. The purpose of the study was to assess risk factors for hypertension associated with the early recovery period. Pairwise matching yielded 29 case-control pairs for analysis. Such factors as property loss, financial difficulties, physical work, use of alcohol, and perceived distress--all associated with the recovery period--were significantly associated with hypertension. Two mental health dimensions--somatization and anxiety--and the respondents perceived effect of the flood on health assessed at the time of the survey also demonstrated significant positive correlations with hypertension.

Micromechanical Properties and Collagen Composition of Ruptured Human Achilles Tendon

Background: The Achilles tendon is one of the strongest tendons in the human body, and yet it frequently ruptures, which is a substantial clinical problem. However, the cause of ruptures remains elusive. Hypothesis: Ruptured human Achilles tendon displays inferior biomechanical properties and altered collagen composition compared with noninjured tendon. Study Design: Controlled laboratory study. Methods: Biopsy specimens were obtained at the rupture site and the noninjured part of the tendon (internal controls) in 17 patients with acute Achilles tendon rupture. Age- and weight-matched human cadaveric Achilles tendons (external controls) were also obtained. Tendon samples were tested micromechanically and biochemically. Results: The mean Young modulus was lower (P < .01) in ruptured (256.7 ± 100.8 MPa) and internal control tendon (262.4 ± 111.5 MPa) compared with external control tendon (512.9 ± 209.6 MPa; P < .01), whereas failure strength did not display similar differences (P = .06-.16). Collagen content, lysyl pyridinoline (LP), hydroxylysyl pyridinoline (HP), and pentosidine (PENT) did not display regional differences between ruptured and noninjured tendon. However, collagen content was less in ruptured (0.457 ± 0.093 mg/mg) and noninjured tendon (0.476 ± 0.072 mg/mg) compared with external control tendon (0.585 ± 0.044 mg/mg, P < .001). Pentosidine was similar in all tendon samples and was positively related to age in all samples (r2 = 0.44-0.72, P < .05). Collagen content was positively related to failure stress but only in ruptured samples (r2 = 0.36; P < .05). HP, LP, and PENT content were unrelated to failure stress and Young modulus in ruptured, noninjured, and cadaveric tendon. Conclusion: These data imply that there may be a mechanical weakening of the tendon and that a reduced collagen content may be related to the pathophysiological characteristics of Achilles tendon rupture. Clinical Relevance: Earlier studies have demonstrated that specific training regimens to treat tendon injury can improve tendon composition and mechanical properties. This study supports the notion that treatment measures should aim to increase tendon collagen content and improve micromechanical quality of the tendon matrix.

Effect of Lumbar Disc Degeneration and Low-Back Pain on the Lumbar Lordosis in Supine and Standing: A Cross-Sectional MRI Study.

Study Design. Cross-sectional study. Objective. To examine the influence of low-back pain (LBP) and lumbar disc degeneration (LDD) on the lumbar lordosis in weight-bearing positional magnetic resonance imaging (pMRI). Summary of Background Data. The lumbar lordosis increases with a change of position from supine to standing and is known as an essential contributor to dynamic changes. However, the lordosis may be affected by disc degeneration and pain. Methods. Patients with LBP >40 on a 0 to 100 mm Visual Analog Scale (VAS) both during activity and rest and a sex and age-decade matching control group without LBP were scanned in the supine and standing position in a 0.25-T open MRI unit. LDD was graded using Pfirrmanns grading-scale. Subsequently, the L2-to-S1 lumbar lordosis angle (LA) was measured. Results. Thirty-eight patients with an average VAS of 58 (±13.8) mm during rest and 75 (±5.0) mm during activities, and 38 healthy controls were included. MRI findings were common in both groups, whereas, the summation of the Pfirrmanns grades (LDD-score) was significantly higher in the patients [(MD 1.44; 95% confidence intervals (CI) 0.80 to 2.10; P < 0.001]. The patients were less lordotic than the controls in both the supine (MD −6.4°; 95% CI −11.4 to −1.3), and standing position (MD −5.6°; 95% CI −10.7 to −0.7); however, the changes between the positions (&Dgr;LA) were the same (MD 0.8°; 95% CI −1.8 to 3.3). Using generalized linear model the LDD-score was associated with age (P < 0.001) for both groups. The LDD-score and &Dgr;LA were negatively associated in the control group (P < 0.001), also after adjustments for gender and age (&bgr;-coefficient: −2.66; 95% CI −4.3 to −1.0; P = 0.002). Conclusion. Patients may be less lordotic in both the supine and standing position, whereas, change in the lordosis between the positions may be independent of pain. Decreasing lordosis change seems to be associated with age-related increasing disc degeneration in healthy individuals. Level of Evidence: 2

Conventional Supine MRI With a Lumbar Pillow-An Alternative to Weight-bearing MRI for Diagnosing Spinal Stenosis?: A Cross-sectional Study.

Study Design. Cross-sectional study. Objective. To investigate if adding a lumbar pillow in supine position during magnetic resonance imaging (MRI) is superior to standing positional MRI for diagnosing lumbar spinal stenosis (LSS). Summary of Background Data. The upright standing position and especially extension of the lumbar spine seem to worsening symptoms of LSS. However, it is unclear whether a forced lumbar extension by a pillow in the lower back during conventional supine MRI may improve the diagnostics of LSS compared with standing MRI. Methods. Patients suspected for LSS and referred to conventional MRI were included to an additional positional MRI scan (0.25T G-Scan) performed in: (1) conventional supine, (2) standing, (3) supine with a lumbar pillow in the lower back. LSS was evaluated for each position in consensus on a 0 to 3 semi-quantitative grading scale. Independently, L2-S1 lordosis angle, spinal cross-sectional diameter (SCSD), dural cross-sectional diameter (DCSD), and dural cross-sectional diameter (DCSA) were measured. The smallest dural diameter was defined as stenosis level and the largest control level for comparison. Results. Twenty-seven patients (60.6 years; ±9.4) were included. The lordosis angle increased significantly from supine to standing (3.2° CI: 1.2–5.2) and with the lumbar pillow (12.8° CI: 10.3–15.3). One-way analysis of variance (ANOVA) showed significant differences between positions (P < 0.001). When compared with the supine position, pairwise comparisons showed decreased SCSD, DCSD, DCSA, and increasing semi-quantitative grading, during both standing and supine with the lumbar pillow. A difference in the semi-quantitative grades was only found between standing and supine with a lumbar pillow, and the scan with a lumbar pillow was significantly more painful. Conclusion. Standing MRI and supine MRI with a lumbar pillow resulted in equal changes in the lumbar spine, although standing MRI may be more sensitive in the assessment of patients suspected for LSS. Level of Evidence: 2