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Biomedical subjects

L J Soslowsky

Publications and source records attributed to L J Soslowsky.

At least 19 recordsLinked to original sources

Development of tendon structure and function: regulation of collagen fibrillogenesis.

In the tendon, the development of mature mechanical properties is dependent on the assembly of a tendon-specific extracellular matrix. This matrix is synthesized by the tendon fibroblasts and composed of collagen fibrils organized as fibers, as well as fibril-associated collagenous and non-collagenous proteins. All of these components are integrated, during development and growth, to form a functional tissue. During tendon development, collagen fibrillogenesis and matrix assembly progress through multiple steps where each step is regulated independently, culminating in a structurally and functionally mature tissue. Collagen fibrillogenesis occurs in a series of extracellular compartments where fibril intermediates are assembled and mature fibrils grow through a process of post-depositional fusion of the intermediates. Linear and lateral fibril growth occurs after the immature fibril intermediates are incorporated into fibers. The processes are regulated by interactions of extracellular macromolecules with the fibrils. Interactions with quantitatively minor fibrillar collagens, fibril-associated collagens and proteoglycans influence different steps in fibrillogenesis and the extracellular microdomains provide a mechanism for the tendon fibroblasts to regulate these extracellular interactions.

Animals↗

Tendon to bone healing: differences in biomechanical, structural, and compositional properties due to a range of activity levels.

Little knowledge exists about the healing process of the tendon to bone insertion, and hence little can be done to improve tissue healing. The goal of this study is to describe the healing of the supraspinatus tendon to its bony insertion under a variety of loading conditions. Tendons were surgically detached and repaired in rats. Rat shoulders were then immobilized, allowed cage activity, or exercised. Shoulders that were immobilized demonstrated superior structural (significantly higher collagen orientation), compositional (expression of extracellular matrix genes similar to the uninjured insertion), and quasilinear viscoelastic properties (A = 0.30 +/- 0.10 MPa vs. 0.16 +/- 0.08 MPa, B = 17.4 +/- 2.9 vs. 15.1 +/- 0.9, and tau 2 = 344 +/- 161 s vs. 233 +/- 40 s) compared to those that were exercised, contrary to expectations. With this knowledge of the healing response, treatment modalities for rotator cuff tears can be developed.

Animals↗

The localized expression of extracellular matrix components in healing tendon insertion sites: an in situ hybridization study.

The localized expression of a number of extracellular matrix genes was evaluated over time in a novel rat rotator cuff injury model. The supraspinatus tendons of rats were severed at the bony insertion and repaired surgically. The healing response was evaluated at 1, 2, 4, and 8 weeks post-injury using histologic and in situ hybridization techniques. Expression patterns of collagens (I, II, III, IX, X, XII), proteoglycans (decorin, aggrecan, versican, biglycan, fibromodulin), and other extracellular matrix proteins (elastin, osteocalcin, alkaline phosphatase) were evaluated at the healing tendon to bone insertion site. Histologic results indicate a poor healing response to the injury, with only partial recreation of the insertion site by 8 weeks. In situ hybridization results indicate a specific pattern of genes expressed in each zone of the insertion site (i.e., tendon, fibrocartilage, mineralized cartilage, bone). Overall, expression of collagen types I and XII, aggrecan, and biglycan was increased, while expression of collagen type X and decorin was decreased. Expression of collagen type I, collagen type XII, and biglycan decreased over time, but remained above normal at 8 weeks. Results indicate that the rat supraspinatus tendon is ineffective in recreating the original insertion site, even at 8 weeks post-injury, in the absence of biological or biomechanical enhancements.

Animals↗

A noncontact, nondestructive method for quantifying intratissue deformations and strains.

The function of soft connective tissues is frequently characterized by quantifying tissue strain (e.g., during joint motion). Conventional techniques for quantifying tendon and ligament strain typically provide surface measures, using markers, stain lines or instrumentation that may influence the tissue. An alternative approach is to quantify intratendinous strain by applying texture correlation analysis to magnetic resonance (MR) images. This paper reports the accuracy and reproducibility of this approach by (1) assessing the reproducibility of MR images, (2) assessing texture correlation accuracy using simulated displacements, and (3) comparing texture correlation measures of displacement and strain from MR images to conventional techniques.

Cadaver↗

Proteoglycans and glycosaminoglycan fine structure in the mouse tail tendon fascicle.

The isolated mouse tail tendon fascicle, a functional and homogenous volume of tendon extracellular matrix, was utilized as an experimental system to examine the structure function relationships in tendon. Our previous work using this model system demonstrated relationships between mean collagen fibril diameter and fascicle mechanical properties in isolated tail tendon fascicles from three different groups of mice (3-week and 8-week control and 8-week Mov13 transgenic) K.A. Derwin, L.J. Soslowsky, J. Biomech. Eng. 121 (1999) 598-604. These groups of mice were chosen to obtain tendon tissues with varying collagen fibril structure and/or biochemistry, such that relationships with material properties could be investigated. To further investigate the molecular details of matrix composition and organization underlying tendon function, we report now on the preparation, characterization, and quantitation of fascicle PGs (proteoglycans) from these three groups. The chondroitin sulfate/dermatan sulfate (CS/DS)-substituted PGs, biglycan and decorin, which are the abundant proteoglycans of whole tendons, were also shown to be the predominant PGs in isolated fascicles. Furthermore, similar to the postnatal maturation changes in matrix composition previously reported for whole tendons, isolated fascicles from 8-week mice had lower CS/DS PG contents (both decorin and biglycan) and a higher collagen content than 3-week mice. In addition, CS/DS chains substituted on PGs from 8-week fascicles were shorter (based on a number average) and richer in disulfated disaccharide residues than chains from 3-week mice. Fascicles from 8-week Mov13 transgenic mice were found to contain similar amounts of total collagen and total CS/DS PG as age-matched controls, and CS/DS chain lengths and sulfation also appeared normal. However, both decorin and biglycan in Mov13 tissue migrated slightly faster on sodium dodecyl sulfate polyacrylamide gel electorphoresis (SDS-PAGE) than the corresponding species from 8-week control, and biglycan from the 8-week Mov 13 fascicles appeared to migrate as a more polydisperse band, suggesting the presence of a unique PG population in the transgenic tissue. These observations, together with our biomechanical data [Derwin and Soslowsky, 1999] suggest that compensatory pathways of extracellular matrix assembly and maturation may exist, and that tissue mechanical properties may not be simply determined by the contents of individual matrix components or collagen fibril size.

Animals↗

Chondrocyte differentiation is modulated by frequency and duration of cyclic compressive loading.

As part of a program of research aimed at determining the role of mechanical forces in connective tissue differentiation, we have developed a model for investigating the effects of dynamic compressive loading on chondrocyte differentiation in vitro. In the current study, we examined the influence of cyclic compressive loading of chick limb bud mesenchymal cells to a constant peak stress of 9.25 kPa during each of the first 3 days in culture. Cells embedded in agarose gel were subjected to uniaxial, cyclic compression at 0.03, 0.15, or 0.33 Hz for 2 h. In addition, load durations of 12, 54, or 120 min were evaluated while holding frequency constant at 0.33 Hz. For a 2 h duration, there was no response to loading at 0.03 Hz. A significant increase in chondrocyte differentiation was associated with loading at 0.15 Hz, and an even greater increase with loading at 0.33 Hz. Holding frequency constant at 0.33 Hz, a loading duration of 12 min elicited no response, whereas chondrocyte differentiation was enhanced by loading for either 54 or 120 min. Although not statistically significant from the 120 min response, average cartilage nodule density and glycosaminoglycan synthesis rate were highest in the 54 min duration group. This result suggests that cells may be sensitive to the level of cumulative (nonrecoverable) compressive strain, as well as to the dynamic strain history.

Animals↗

Total strain fields of the antero-inferior shoulder capsule under subluxation: a stereoradiogrammetric study.

The antero-inferior capsule (AIC) is the primary restraint to antero-inferior glenohumeral dislocation. This study utilizes a biomechanical model to determine the total strain field of the AIC in a subluxed shoulder. Strains were calculated from two capsule states: a nominal strain state set by inflation and a strained state set by subluxation. Marker coordinates on the AIC were reconstructed from stereoradiographs and strain fields calculated. Peak strain on the glenoid side of the AIC was significantly greater than the humeral side and strain fields were highly variable. This study reports an accurate method for measuring planar strains in a three-dimensional membrane.

Adult↗

Effect of compressive loading on chondrocyte differentiation in agarose cultures of chick limb-bud cells.

It is well established that mechanical loading is important to homeostasis of cartilage tissue, and growing evidence suggests that it influences cartilage differentiation as well. Whereas the effect of mechanical forces on chondrocyte biosynthesis and gene expression has been vigorously investigated, the effect of the mechanical environment on chondrocyte differentiation has received little attention. The long-term objective of this research is to investigate the regulatory role of mechanical loading in cell differentiation. The goal of this study was to determine if mechanical compression could modulate chondrocyte differentiation in vitro. Stage 23/24 chick limb-bud cells, embedded in agarose gel, were subjected to either static (constant 4.5-kPa stress) or cyclic (9.0-kPa peak stress at 0.33 Hz) loading in unconfined compression during the initial phase of commitment to a phenotypic lineage. Compared with nonloaded controls, cyclic compressive loading roughly doubled the number of cartilage nodules and the amount of sulfate incorporation on day 8, whereas static compression had little effect on these two measures. Neither compression protocol significantly affected overall cell viability or the proliferation of cells within nodules. Since limb-bud mesenchymal cells were seeded directly into agarose, an assessment of cartilage nodules in the agarose reflects the proportion of the original cells that had given rise to chondrocytes. Thus, the results indicate that about twice as many mesenchymal cells were induced to enter the chondrogenic pathway by cyclic mechanical compression. The coincidence of the increase in sulfate incorporation and nodule density indicates that the primary effect of mechanical compression on mesenchymal cells was on cellular differentiation and not on their subsequent metabolism. Further studies are needed to identify the primary chondrogenic signal associated with cyclic compressive loading and to determine the mechanism by which it influences commitment to or progression through the chondrogenic lineage, or both.

Animals↗

Animal models of tendon and ligament injuries for tissue engineering applications.

Improved methods are needed for prevention and treatment of injuries to the musculoskeletal soft tissues. Tissue engineering techniques have led to more effective clinical protocols for treating these injuries. Improvement of tissue healing through the addition of biologic factors, and the development of biologically active tissue engineered replacements, are two promising areas of research. An essential component of progress in this field is the use of animal models of tendon and ligament injuries, which allows for rigorous testing of hypotheses related to disease pathogenesis and treatment. Because these animal models must be appropriate for the condition being studied, no single model exists that is appropriate for all investigations. It generally is necessary to differentiate between tendon and ligament tissues. Furthermore, ligaments should be divided into intraarticular and extraarticular models, whereas tendons should be divided into intrasynovial and extrasynovial models. Other important factors in the appropriate use of an animal model include size of the animal, anatomic features, and techniques available for tissue analysis. The tissues used should be large enough to allow for accurate and reproducible manipulations (injury creation, repair, reconstruction). In addition, it is preferable to use tissues that are amenable to quantitative analysis.

Animals↗

A quantitative investigation of structure-function relationships in a tendon fascicle model.

These studies sought to investigate quantitative relationships between the complex composite structure and mechanical properties of tendon. The isolated mouse tail tendon fascicle was chosen as an appropriate model for these so-called "structure-function" investigations. Specifically, collagen fibril diameters and mechanical properties were measured in fascicles from immature (3 week) control, adult (8 week) control, and adult (8 week) MovI3 transgenic mice. Results demonstrated a moderate correlation between mean fibril diameter and fascicle stiffness (r = 0.73, p = 0.001) and maximum load (r = 0.75, p < 0.001), whereas a weak correlation with fascicle modulus (r = 0.39, p = 0.11) and maximum stress (r = 0.48, p = 0.04). An analysis of pooled within-group correlations revealed no strong structure-function trends evidenced at the local or group level, indicating that correlations observed in the general structure-function analyses were due primarily to having three different experimental groups, rather than significant correlations of parameters within the groups.

Animals↗

Biomechanics of the rotator cuff.

Thorough understanding of rotator cuff mechanics is important for effective treatment and/or prevention of cuff injuries. This understanding is achieved through knowledge of normal cuff structure and mechanics. Only then, can the effects of injuries and pathologic processes on normal cuff function be carefuly assessed. Rotator cuff structures are viewed and analyzed on a number of different levels. This article presents current knowledge of rotator cuff mechanics through review of cuff structure and anatomy, corocoacromial arch structure and biomechanics, and biomechanical models.

Acromion↗

Posterior glenohumeral subluxation: active and passive stabilization in a biomechanical model.

UNLABELLED: We examined the role of the glenohumeral and coracohumeral ligaments as well as the forces provided by the rotator cuff muscles, the long head of the biceps, the anterior and middle deltoids, and the pectoralis major in the stabilization of the glenohumeral joint in the posterior direction. Simulated muscle forces were mechanically applied to eight shoulder specimens. The humeroscapular position for testing simulated the 90-degree forward-flexion (humerothoracic) position used clinically for the so-called jerk test, which is the most clinically important position with regard to posterior instability of the shoulder. Experiments were performed with a variety of configurations of ligamentous and capsular cuts, humeral rotation, and levels of muscle force. Stability was investigated by measuring the force required to subluxate the humeral head a specified amount from its reduced position. Of the muscles and ligaments tested, the subscapularis muscle contributed the most to this subluxation force. The coracohumeral ligament was an effective contributor in neutral humeral rotation, and the inferior glenohumeral ligament was an effective contributor in internal humeral rotation. The long head of the biceps was found to reduce the subluxation force in certain positions. CLINICAL RELEVANCE: It is widely agreed that a complex interaction of passive and active stabilizing structures and forces is necessary for clinical stability of the shoulder. The present study identified the contributions of ligaments and muscles to posterior stability of the shoulder in the position of greatest clinical importance--posterior subluxation with the shoulder in forward flexion.

Aged↗

Anterior glenohumeral stabilization factors: progressive effects in a biomechanical model.

The aim of this study was to evaluate the anterior stabilizing factors of the glenohumeral joint over a range of translations. The stabilizers examined included the capsular ligaments, the coracohumeral ligament, the rotator cuff muscles, and the long head of the biceps. Simulated muscle forces were applied to eight shoulder specimens to produce 90 degrees of total elevation of the arm in the scapular plane. Stability, defined as the force required to reach a specified subluxation, then was evaluated under varying configurations of capsule cuts, humeral rotation, and muscular loads. The overall force-displacement relationship of the subluxation was found to increase exponentially in external rotation to 239 N at 10 mm of displacement and to level off in neutral rotation to 172 N at 10 mm of displacement. Among the muscles, the biceps was the most important stabilizer in neutral rotation, providing more than 30 N of stabilization; the subscapularis provided the greatest degree of stabilization in external rotation, increasing to approximately 20 N. The subscapularis and supraspinatus were the most consistently important stabilizers in both types of rotation. In external rotation, the superior, middle, and inferior glenohumeral ligaments were the most effective ligamentous stabilizers, and all provided progressively more stabilization as higher displacements were reached. The stability provided by some of the ligaments reached nearly 50 N at 10 mm of displacement.

Aged↗

Coracoacromial ligament: in situ load and viscoelastic properties in rotator cuff disease.

The coracoacromial ligament plays a role in rotator cuff disease. The changes in the in situ load and viscoelastic properties of the coracoacromial ligament in shoulders with rotator cuff tears were evaluated. Coracoacromial ligaments from 16 cadaveric shoulders (8 with rotator cuff tears, 8 without tears) were evaluated via biomechanical testing of bone ligament bone specimens. An in situ load existed in the coracoacromial ligaments of 19.6 +/- 15.4 N (rotator cuff tear) and 18.3 +/- 9.8 N (no rotator cuff tear). This difference was not statistically significant. Cyclic loading of the ligaments demonstrated a greater drop in peak stress in rotator cuff tear shoulders than in normal shoulders, whereas the stress relaxation response was not different. These changes in the coracoacromial ligament in shoulders with cuff tears may be attributable to ultrastructural changes within the ligament as a result of an altered loading environment. It remains unknown whether they occur as a result of a rotator cuff tear or if they contribute to the pathogenesis of cuff disease.

Aged↗

Contact areas in the thumb carpometacarpal joint.

The thumb carpometacarpal joint is a common site of osteoarthritis. It has been hypothesized that peaks of localized stress on the dorsoradial or volar-ulnar regions, or both, of the articular surfaces of the trapezium and metacarpal lead to erosion of cartilage and may be responsible for the progression of the disease. The objective of this study was to determine the contact areas in this joint under the functional position of lateral (key) pinch and in the extremes of range of motion of the joint. These contact areas were assessed relative to the observed sites of cartilage thinning. Eight hands from cadavers of women and five from cadavers of men were tested in vitro with the thumb under a 25 N load in the lateral pinch position, and under small muscle loads (0-5 N) with the thumb in flexion, extension, abduction, adduction, and neutral positions. Contact areas of articular surfaces of the thumb carpometacarpal joint were determined for these positions using a stereophotogrammetric technique. The lateral pinch position produced contact areas predominantly on the central, volar, and volar-ulnar regions of the trapezium and the metacarpal. In three specimens, contact areas were distinctly separated between the dorsoradial and volar-ulnar regions, and in one specimen, from a man, contact occurred exclusively on the dorsoradial region of the trapezium. Using stereophotogrammetry, maps of cartilage thickness also were determined for a subset of nine specimens. The volar-ulnar, ulnar, and dorsoradial regions of the trapezium were the most common sites of thin cartilage, and these may be sites of cartilage wear.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

A stereophotogrammetric method for determining in situ contact areas in diarthrodial joints, and a comparison with other methods.

Determination of contact areas in diarthrodial joints is necessary for understanding the state of stress within the articular cartilage layers and the supporting bony structures. The present study describes the use of a stereophotogrammetry (SPG) system [Huiskes et al., J. Biomechanics 18, 559-570 (1985) and Ateshian et al., J. Biomechanics 24, 761-776 (1991)] for determining contact areas in diarthrodial joints, using a surface proximity concept similar to the one used by Scherrer et al. [ASME J. biomech. Engng 101, 271-278 (1979)]. This method consists of evaluating the proximity of the articular surfaces to determine joint contact areas using precise geometric models of the joint surfaces obtained from the SPG system, and precise kinematic data, also obtained from SPG. In this study, the SPG method for determining contact areas is compared to other commonly used methods such as dye staining, silicone rubber casting and Fuji film contact measurement techniques which have been often used and reported by other investigators. The bovine glenohumeral joint and the bovine lateral tibiofemoral articulation (without the meniscus) were used to represent congruent and incongruent joints, respectively. While all the methods yielded consistent contact patterns for the incongruent tibiofemoral articulations, the results for the congruent bovine glenohumeral joints showed that the SPG and Fuji film methods were in better agreement than those obtained from the dye staining and silicone rubber casting methods. The advantages of the new SPG method are that it can be used for intact joints, and used repeatedly and quickly thus making contact-area movement analyses possible [Soslowsky et al., J. orthop. Res. 10, 524-534 (1992)]. The results of this comparison study show that the SPG technique is a reliable and versatile method for determining contact areas in diarthrodial joints.

Animals↗

A new optical system for the determination of deformations and strains: calibration characteristics and experimental results.

Many types of optical strain measurement systems have been used for the determination of deformations and strains in soft biological tissues. The purpose of this investigation is to report a new optical strain measurement system developed in our laboratory which offers distinct advantages over systems developed in the past. Our optical strain system has demonstrated excellent performance in calibration and experimental tests. Calibration tests illustrate the system's accuracy to 0.05% strain at 3.52% strain and 0.18% strain at 11.74% strain. Further, this system can measure strains to within 2% measurement error for strains in a 0-11.74% range when 100 microns increments of motion are used for calibration. The resolution of our system appears to be at least as good as the linear micrometer (2 microns) used as a calibrating standard. Errors in strain measurement due to whole specimen rotation or translation are quantified. Rotations about an in-plane axis perpendicular to the direction of strain and translations in/out of the plane of focus result in the largest sources of error. Finally, in an in vitro biomechanical study of the rabbit Achilles tendon, experimental failure strains are 4.3 +/- 0.9% using this system.

Achilles Tendon↗

Geometric and mechanical properties of the coracoacromial ligament and their relationship to rotator cuff disease.

One of the most common causes of pain and disability in the upper limb is inflammation of the rotator cuff tendons. When no significant bony abnormality exists in the surrounding structures, the coracoacromial ligament has been implicated as a possible cause of impingement on the cuff tendons. Geometric and mechanical properties of 20 coracoacromial ligaments, 10 from shoulders with rotator cuff tears and 10 from normal shoulders, were accurately determined. In comparing rotator cuff tear and normal specimens, statistically significant changes in geometric properties were measured in the lateral band, but not in the medial band, of the ligament. The lateral band, which is the region most likely to impinge on the rotator cuff, was shorter and had a larger cross-sectional area in specimens with rotator cuff tears. Although there were no statistical differences in structural properties of the ligament between normal and rotator cuff tear groups, significant changes were evident in material properties. Previously reported histologic differences in the ligament in shoulders with rotator cuff tears are supported by the decreased material properties measured in the current study. Whether the differences in the coracoacromial ligament cause impingement or are due to impingement is still unknown at this time.

Acromioclavicular Joint↗