Biomedical subjects

Louis J Soslowsky

Publications and source records attributed to Louis J Soslowsky.

At least 19 recordsLinked to original sources

PubMed2006

The inferior glenohumeral ligament: a correlative investigation.

The inferior glenohumeral ligament (IGHL) was investigated by correlating the biomechanical properties, biochemical composition, and histologic morphology of its 3 anatomic regions (superior band, anterior axillary pouch, and posterior axillary pouch) in 8 human cadaveric shoulders. The overall biochemical composition of the IGHL appeared similar to other ligaments, with average water content of 80.9 +/- 2.5%, collagen content of 80.0 +/- 9.2%, and crosslinks of 0.715 +/- 0.13 mol/mol collagen. The proteoglycan content was highest in the superior band (2.73 +/- 0.7 mg/g dry weight) and may, in part, explain its viscoelastic behavior. Histologic analysis demonstrated longitudinally organized fiber bundles that were more uniform in the mid-substance but more interwoven and less uniformly oriented near the insertion sites. The superior band had the most pronounced fiber bundle interweaving, while crimping was more evident in the anterior axillary pouch. Elastin was identified in each of the regions. Tensile testing demonstrated a trend toward higher ultimate tensile stress (16.9 +/- 7.9 MPa) and tensile modulus (130.3 +/- 47.9 MPa) in the superior band compared to the axillary pouch. The mean ultimate tensile strain of the IGHL was 16.8 +/- 4.6%. These complex IGHL properties may help to explain its unique functions in stabilizing the shoulder in different arm positions and at different rates of loading, including the failure patterns seen clinically, as in Bankart lesions (insertion site) versus capsular stretching (ligament substance).

Aged↗

PubMed2006

Decorin regulates assembly of collagen fibrils and acquisition of biomechanical properties during tendon development.

Tendon function involves the development of an organized hierarchy of collagen fibrils. Small leucine-rich proteoglycans have been implicated in the regulation of fibrillogenesis and decorin is the prototypic member of this family. Decorin-deficient mice demonstrate altered fibril structure and mechanical function in mature skin and tail tendons. However, the developmental role(s) of decorin needs to be elucidated. To define these role(s) during tendon development, tendons (flexor digitorum longus) were analyzed ultrastructurally from postnatal day 10 to 90. Decorin-deficient tendons developed abnormal, irregularly contoured fibrils. Finite mixture modeling estimated that the mature tendon was a three-subpopulation mixture of fibrils with characteristic diameter ranges. During development, in each subpopulation the mean diameter was consistently larger in mutant mice. Also, diameter distributions and the percentage of fibrils in each subpopulation were altered. Biomechanical analyses demonstrated that mature decorin-deficient tendons had significantly reduced strength and stiffness; however, there was no reduction in immature tendons. Expression of decorin and biglycan, a closely related family member, was analyzed during development. Decorin increased with development while biglycan decreased. Spatially, both had a comparable localization throughout the tendon. Biglycan expression increased substantially in decorin-deficient tendons suggesting a potential functional compensation. The accumulation of structural defects during fibril growth, a period associated with decorin expression and low biglycan expression, may be the cause of compromised mechanical function in the absence of decorin. Our findings indicate that decorin is a key regulatory molecule and that the temporal switch from biglycan to decorin is an important event in the coordinate regulation of fibrillogenesis and tendon development.

Animals↗

PubMed2006

The role of repair tension on tendon to bone healing in an animal model of chronic rotator cuff tears.

Rotator cuff tendon tears are one of the most common shoulder injuries. Although surgical repair is typically beneficial, re-tearing of the tendons frequently occurs. It is generally accepted that healing is worse for chronic tears than acute tears, but the reasons for this are unknown. One potential cause may be the large tensions that are sometimes required to repair chronically torn tendons back to bone (i.e., repair tension). Therefore, the objective of this study was to utilize an animal model of chronic rotator cuff repairs to investigate the role of increased repair tension on tendon to bone healing. We hypothesized that an increase in repair tension would be related to detrimental changes to the healing insertion site. To test this hypothesis, the supraspinatus tendon of rats was surgically detached and then repaired immediately or after a delay of 2, 4, or 16 weeks. The repair tension was measured using a tensiometer and the mechanical properties, collagen organization, and protein expression of the healing insertion site were evaluated 4 and/or 16 weeks following repair. We found that the repair tension increased with time following detachment, and was related to a decrease in the failure properties and viscoelastic peak stress and an increase in cross-sectional area and stiffness of the insertion site. Therefore, repair tension should be minimized in the clinical setting. Future studies will include additional animal model studies involving the relationship between tension and muscle properties and a clinical study investigating the role of repair tension on repair failure.

Animals↗

PubMed2006

Regenerative properties of fetal sheep tendon are not adversely affected by transplantation into an adult environment.

Tendon injuries account for a significant number of musculoskeletal afflictions each year. While new surgical techniques and rehabilitation protocols have led to improved clinical outcomes, postsurgical scarring remains the most problematic aspect of tendon repair. In contrast to this typical pattern of fibrosis, recent studies have shown that fetal tendon is capable of healing without scar. However, whether this regenerative healing pattern is intrinsic to the fetal tissue itself or the result of its environment is not known. Thus, the objective of this study is to examine the influence of an adult environment on healing in adult and fetal tendons. We hypothesized that injured fetal tendon tissue transplanted into an adult environment would retain a regenerative healing pattern after injury, demonstrating normal histological and mechanical properties. Our results support this hypothesis. Histological analyses revealed considerable alterations in adult tendon transplants after injury while fetal transplants showed no abnormalities. The injured adult tendons also demonstrated elevated levels of TGF-beta1, bFGF, and CD44 at the wound site, whereas the fetal specimens showed little or no such changes in response to injury. The data from our biomechanical studies further corroborate these observations, with significant decreases in the stiffness, modulus, and almost all viscoelastic properties in wounded versus unwounded adult tendons, and fetal specimens showing no differences in mechanical properties between the wounded and unwounded groups. Thus, the results of our investigation demonstrate that the adult environment is not an impediment to scarless repair and that this capability is intrinsic to the fetal tendon itself. Our study also begins to provide insight into the mechanisms controlling this regenerative response.

Age Factors↗

PubMed2006

Collagen dysregulation in the dermis of the Sagg/+ mouse: a loose skin model.

The Sagg/+ mouse is an ethylnitrosourea-derived mutant with a dermal phenotype similar to some of the subtypes of Ehlers-Danlos syndrome (EDS) and cutis laxa. The dermis of the Sagg/+ mouse has less dense and more disorganized collagen fibers compared to controls. The size of extracted Type I dermal collagen was the same as that observed in normal skin; however, more collagen could be extracted from Sagg/+ skin, which also showed decreased collagen content and decreased steady-state levels of alpha1(I), alpha2(I), alpha1(V), and alpha2(V) procollagen mRNAs. The biomechanical properties of Sagg/+ skin were significantly decreased relative to normal skin. However, there were no significant differences in the quantities of the major collagen cross-links, that is, dehydrohydroxylysinonorleucine and dehydrohistidinohydroxymerodesmosine between Sagg/+ and normal skin. Electron microscopic evaluation of Sagg/+ skin indicated that the mutation interferes with the proper formation of collagen fibrils and the data are consistent with a mutation in Type V collagen leading to haploinsufficiency with the formation of two sub-populations of collagen fibrils, one normal and one with irregular shape and a larger diameter. Further study of this novel mutation will allow the identification of new mechanisms involved in the regulation of normal and pathologic collagen gene expression.

Animals↗

PubMed2005

Tendon healing in interleukin-4 and interleukin-6 knockout mice.

Cytokines have been shown to play an important role in tendon and ligament healing by regulating cellular differentiation and activity. The majority of studies that have investigated the role of cytokines in tendon and ligament healing have added them to injured tissue and assessed their effect. Because the efficacy of exogenously applying cytokines is dependent upon many factors such as the correct dosage, timing, and frequency, conflicting results are often reported. To avoid these factors, this study used transgenic mice with knockouts of interleukin-4 (IL4 -/-) and interleukin-6 (IL6 -/-) to investigate their role in tendon healing. Because of the reported roles of both of these cytokines in inflammation and fibroplasia, it was hypothesized that the order of organizational, geometric, and mechanical properties would be (greatest to least) injured IL6 -/-, injured control, and injured IL4 -/- mice. In addition, it was hypothesized that specific cytokines would be upregulated in each knockout group, but not compensate for the lack of IL-4 or IL-6. Mechanical and organizational properties of injured tendons from IL6 -/- mice were inferior to that of control and IL4 -/- mice despite the upregulation of the pro-inflammatory cytokine TNF-alpha. Temporal levels of IL-10 and IL-13 in the IL4 -/- mice resulted in comparable and even superior properties when compared to CTL mice. This study shows that IL-6 could not be compensated for and plays an important role in tendon healing. This study also supports the use of this animal model to further investigate tendon healing.

Animals↗

PubMed2005

Tendon properties in interleukin-4 and interleukin-6 knockout mice.

Cytokines are known to play an important role in normal tendon development, function, and maintenance through interactions with fibroblasts and extracellular matrix proteins. However, the role of interleukins on normal tendon activity remains poorly understood. Previous studies that have researched the role of specific cytokines by exogenously applying them have often reported conflicting results. Therefore, a knockout mouse model was used to investigate the role of interleukins 4 and 6 on normal tendon organizational and biomechanical properties. It was hypothesized that interleukin-6 knockout (IL6 -/-) mice will display more organized collagen orientation and greater cross-sectional area and mechanical properties when compared to that of control mice. In addition, interleukin-4 knockout (IL4 -/-) mice will display the most disorganized collagen orientation and lowest cross-sectional area and mechanical properties. As hypothesized, IL6 -/- mice show a trend towards lower angular deviation (more organized) (p<0.1) when compared to IL4 -/- mice. In addition, the IL6 -/- mice show a trend towards a higher percent relaxation (p<0.1) and a significantly higher modulus (p<0.01) when compared to CTL and IL4 -/- mice. Unexpectedly, the IL6 -/- mice exhibited no significant differences in collagen fiber distribution and maximum stress from the other groups and actually had a smaller cross-sectional area than CTL mice (p<0.1). This study supports transgenic mice as an animal model for investigating how cytokines affect normal tendon properties. In addition, this study demonstrates that interleukins may play an important role in tendon development, function, and maintenance.

Anatomy, Cross-Sectional↗

PubMed2005

Rat supraspinatus muscle atrophy after tendon detachment.

Rotator cuff tears are one of the most common tendon disorders found in the healthy population. Tendon tears not only affect the biomechanical properties of the tendon, but can also lead to debilitation of the muscles attached to the damaged tendons. The changes that occur in the muscle after tendon detachment are not well understood. A rat rotator cuff model was utilized to determine the time course of changes that occur in the supraspinatus muscle after tendon detachment. It was hypothesized that the lack of load on the supraspinatus muscle would cause a significant decrease in muscle mass and a conversion of muscle fiber properties toward those of fast fiber types. Tendons were detached at the insertion on the humerus without repair. Muscle mass, morphology and fiber properties were measured at one, two, four, eight, and 16 weeks after detachment. Tendon detachment resulted in a rapid loss of muscle mass, an increase in the proportion of fast muscle fibers, and an increase in the fibrotic content of the muscle bed, concomitant with the appearance of adhesions of the tendon to surrounding surfaces. At 16 weeks post-detachment, muscle mass and the fiber properties in the deep muscle layers returned to normal levels. However, the fiber shifts observed in the superficial layers persisted throughout the experiment. These results suggest that load returned to the muscle via adhesions to surrounding surfaces, which may be sufficient to reverse changes in muscle mass.

Animals↗

PubMed2005

Influence of decorin and biglycan on mechanical properties of multiple tendons in knockout mice.

Evaluations of tendon mechanical behavior based on biochemical and structural arrangement have implications for designing tendon specific treatment modalities or replacement strategies. In addition to the well studied type I collagen, other important constituents of tendon are the small proteoglycans (PGs). PGs have been shown to vary in concentration within differently loaded areas of tendon, implicating them in specific tendon function. This study measured the mechanical properties of multiple tendon tissues from normal mice and from mice with knock-outs of the PGs decorin or biglycan. Tail tendon fascicles, patellar tendons (PT), and flexor digitorum longus tendons (FDL), three tissues representing different in vivo loading environments, were characterized from the three groups of mice. It was hypothesized that the absence of decorin or biglycan would have individual effects on each type of tendon tissue. Surprisingly, no change in mechanical properties was observed for the tail tendon fascicles due to the PG knockouts. The loss of decorin affected the PT causing an increase in modulus and stress relaxation, but had little effect on the FDL. Conversely, the loss of biglycan did not significantly affect the PT, but caused a reduction in both the maximum stress and modulus of the FDL. These results give mechanical support to previous biochemical data that tendons likely are uniquely tailored to their specific location and function. Variances such as those presented here need to be further characterized and taken into account when designing therapies or replacements for any one particular tendon.

Animals↗

PubMed2004

Mechanical strength of repairs of the hip piriformis tendon.

Mechanical properties of repairs of the piriformis tendon to the proximal femur were examined in a cadaveric model. Four constructs were separately tested: a suture anchor in the proximal femur, the anchor to suture interface, the suture in tendon interface, and a bone bridge style repair. The weakest interface was the anchor in the bone in cases in which the bone quality was poor. In specimens with high bone quality, the weakest interface was the suture in the anchor. A positive correlation was seen between Singh score for each femur and failure load of the anchor-bone constructs. Therefore, repairing the short external rotators after procedures involving a posterior approach to the hip may be warranted in patients with good bone quality.

Aged↗

PubMed2004

Supraspinatus tendon organizational and mechanical properties in a chronic rotator cuff tear animal model.

Rotator cuff tears of the shoulder are a common cause of pain and disability. The successful repair of rotator cuff tendon tears depends on the time from onset of injury to the time of surgical repair. However, the effect of time from injury to repair remains poorly understood. A rat model was used to investigate the supraspinatus tendon organizational and mechanical property changes that occur with time post-injury to understand the natural injury response in the absence of repair. It was hypothesized that increased time post-injury would result in increased detrimental changes to tendon organizational and mechanical properties. Tendons were detached at the insertion on the humerus without repair and the quantitative organizational and mechanical properties were analyzed at 1, 2, 4, 8, and 16 weeks post-detachment. Tendon detachment resulted in a dramatic decrease in mechanical properties initially followed by a progressive increase with time. The quantitative collagen fiber orientation results provided corroborating support to the mechanical property data. Based on similarities in histology and mechanical properties to rotator cuff tears in humans, the animal model presented here is promising for future investigations of the tendon's natural injury response in the absence of repair.

Animals↗

PubMed2004

The effect of overuse activity on Achilles tendon in an animal model: a biomechanical study.

Musculoskeletal soft tissue injuries from athletic activities are common in the rotator cuff tendons, lateral epicondyle of the elbow, the patella tendon, and the Achilles tendon. Despite the fact that the Achilles tendon is the largest and strongest tendon in the human body, it is frequently injured in the athletic setting. To study the etiology and pathogenesis of Achilles tendon injuries, our goal was to develop a model of Achilles tendon overuse by evaluating the Achilles tendons from animals subjected to the exercise protocol previously described as overuse for the supraspinatus tendon. We hypothesized that the same exercise protocol would produce injuries to the Achilles tendon as demonstrated by changes in the cross-sectional area and biomechanical properties. While a significant injury was induced into the supraspinatus tendon, we found no changes in the Achilles tendons of these exercised animals based on gross observation, geometric measurements, and mechanical testing analyses. Although surprising, there are many possible explanations for these findings including differences in potential injury mechanisms, functional capabilities of the differing tendons, and other factors.

Achilles Tendon↗

PubMed2004

Investigating tendon fascicle structure-function relationships in a transgenic-age mouse model using multiple regression models.

Proper replacement or repair of damaged tendons or ligaments requires functionally engineered tissue that mimics their native mechanical properties. While tendon structure-function relationships are generally assumed, there exists little quantitative evidence of the roles of distinct tendon components in tendon function. Previous work has used linear correlations to assess the independent, univariate effects of one structural or one biochemical variable on mechanics. The current study's objective was to simultaneously and rigorously evaluate the relative contributions of seven different structural and compositional variables in predicting tissue mechanical properties through the use of multiple regression statistical models. Structural, biochemical, and mechanical analysis were all performed on tail tendon fascicles from different groups of transgenic mice, which provide a reproducible, noninvasive, in vivo model of changes in tendon structure and composition. Interestingly, glycosaminoglycan (GAG) content was observed to be the strongest predictor of mechanical properties. GAG content was also well correlated with collagen content and mean collagen fibril diameter. Collagen fibril area fraction was a significant predictor only of material properties. Therefore, in a large multivariate model, GAG content was the largest predictor of mechanical properties, perhaps both through direct influence and indirectly through its correlation with collagen content and fibril structure.

Animals↗

PubMed2004

The tension required at repair to reappose the supraspinatus tendon to bone rapidly increases after injury.

Rotator cuff tears occur frequently and can cause significant pain and reduced shoulder function. A high percentage of patients are satisfied after surgical repair of rotator cuff tears, but a smaller percentage of patients with chronic tears continue to have pain and poor shoulder function. This may be partly attributable to an increase in the repair tension, the force required at repair to reappose the tendon to its original insertion site on the humerus. Increases in repair tension have been shown to occur for long-standing ruptures of the supraspinatus tendon, but the precise tension at various times after injury are unknown. Therefore, the objective of the current study was to determine the repair tension at various times after a rotator cuff tear. This was achieved by creating a full-thickness supraspinatus tendon tear in a rat model and measuring the mechanical characteristics of the musculotendinous unit at 0, 2, 4, 9, and 16 weeks after injury. The repair tension rapidly increased initially after injury followed by a progressive, but less dramatic, increase with additional time. These findings suggest that rotator cuff tears should be repaired early in the clinical setting. Future studies will investigate the effect of repair tension on tendon to bone healing after repair.

Animals↗

PubMed2004

Strain-rate sensitive mechanical properties of tendon fascicles from mice with genetically engineered alterations in collagen and decorin.

Tendons have complex mechanical behaviors that are nonlinear and time dependent. It is widely held that these behaviors are provided by the tissue composition and structure. It is generally thought that type I collagen provides the primary elastic strength to tendon while proteoglycans, such as decorin, play a role in failure and viscoelastic properties. This study sought to quantify such structure-function relationships by comparing tendon mechanical properties between normal mice and mice genetically engineered for altered type I collagen content and absence of decorin. Uniaxial tensile ramp to failure experiments were performed on tail tendon fascicles at two strain rates, 0.5%/s and 50%/s. Mutations in type I collagen led to reduced failure load and stiffness with no changes in failure stress, modulus or strain rate sensitivity. Fascicles without decorin had similar elastic properties to normal fascicles, but reduced strain rate sensitivity. Fascicles from immature mice, with increased decorin content compared to adult fascicles, had inferior elastic properties but higher strain rate sensitivity. These results showed that tendon viscoelasticity is affected by decorin content but not by collagen alterations. This study provides quantitative evidence for structure-function relationships in tendon, including the role of proteoglycan in viscoelasticity.

Animals↗

PubMed2004

The effect of overshooting the target strain on estimating viscoelastic properties from stress relaxation experiments.

BACKGROUND: Tendon's mechanical behaviors have frequently been quantified using the quasi-linear viscoelastic (QLV) model. The QLV parameters are typically estimated by fitting the model to a single-step stress relaxation experiment. Unfortunately, overshoot of the target strain occurs to some degree in most experiments. This has never been formally investigated even though failing to measure, minimize, or compensate for overshoot may cause large errors in the estimation of parameters. Therefore, the objective of this study was to investigate the effect of overshoot on the estimation of QLV parameters. METHOD OF APPROACH: A simulated experiment was first performed to quantify the effect of different amounts of overshoot on the estimated QLV parameters. Experimental data from tendon was then used to determine if the errors associated with overshoot could be reduced when a direct fit is used (i.e., the actual strain history was used in the curve fit). RESULTS: We found that both the elastic and viscous QLV parameters were incorrectly estimated if overshoot was not properly accounted for in the fit. Furthermore, the errors associated with overshoot were partially reduced when overshoot was accounted for using a direct fit. CONCLUSIONS: A slow ramp rate is recommended to limit the amount of overshoot and a direct fit is recommended to limit the errors associated with overshoot, although other approaches such as adjusting the control system to limit overshoot could also be utilized.

Animals↗

PubMed2003

Etiologic and pathogenetic factors for rotator cuff tendinopathy.

Etiologic and pathogenetic factors for rotator cuff tendinopathy, although often compartmentalized to intrinsic or extrinsic causes, have multifactorial roots. The development of animal models for the study of rotator cuff disease has increased the fund of knowledge regarding this disease and has paved the way for future studies. Further multidisciplinary studies at molecular, biomechanical, and clinical levels should be undertaken to enhance the understanding of this common disorder. Ultimately, the goals of improved care, increased comprehension, and prevention of rotator cuff tendinopathy are attainable.

Animals↗

PubMed2003

Variation of biomechanical, structural, and compositional properties along the tendon to bone insertion site.

The tendon to bone insertion site is a complex transitional region that links two very different materials. The insertion site must transfer a complex loading environment effectively to prevent injury and provide proper joint function. In order to accomplish this load transfer effectively, the properties of the insertion site were hypothesized to vary along its length. The quasilinear viscoelastic (QLV) Model was used to determine biomechanical properties, polarized light analysis was used to quantitate collagen orientation (structure), and in situ hybridization was used to determine the expression of extracellular matrix genes (composition). All assays were performed at two insertion site locations: the tendon end of the insertion and the bony end of the insertion. Biomechanically, the apparent properties of peak strain, the coefficients (A and B) that describe the elastic component of the QLV model, and one of the coefficients (tau(1)) of the viscous component of the model were significantly higher, while another of the coefficients (C) of the viscous component was significantly lower at the tendon insertion compared to the bony insertion. The collagen was significantly more oriented at the tendon insertion compared to the bony insertion. Finally, collagen types II, IX, and X, and aggrecan were localized only to the bony insertion, while decorin and biglycan were localized only to the tendon insertion. Thus, the tendon to bony insertion site varies dramatically along its length in terms of its viscoelastic properties, collagen structure, and extracellular matrix composition.

Aggrecans↗