Cyril B. Frank

Current Concepts Review - The Science of Reconstruction of the Anterior Cruciate Ligament*

Very few subjects in contemporary orthopaedic surgery have evoked as much controversy, thought, and opinion as that of when and how to optimally reconstruct the anterior cruciate ligament of the knee. Fueled by an annual incidence of acute rupture of the anterior cruciate ligament that has been estimated to be one in 3000 in the American population—approximately 95,000 new injuries each year196—and combined with the fact that more than 50,000 knees that have such an injury are reconstructed annually in the United States alone149, it is not surprising that there has been a virtual explosion of literature on this topic. During the last twenty years, more than 2000 scientific articles on the anterior cruciate ligament have been published, including numerous excellent reviews47,149,151,255,282,294 and textbooks72,89,145. It is a challenging task to attempt to synthesize these sources and to try to resolve the conflicts that are inherent in such a massive body of information. Although many relevant issues will continue to be debated until better basic-science and clinical information becomes available, a number of scientifically supported concepts can be identified within the existing knowledge base. This knowledge can help orthopaedic surgeons to understand the reasons for previous and current successes and failures of reconstruction of the anterior cruciate ligament, and it can help them to plan the care of patients who have an injury of the ligament. In the present review, the current scientific understanding of reconstruction of the anterior cruciate ligament is discussed in a sequence based on the order in which clinical decisions are made. An overview of the normal function of the knee joint and the anterior cruciate ligament is followed by a discussion of decisions that must …

The Effect of Elastic Bandages on Human Knee Proprioception in the Uninjured Population

Elastic bandages are often used to treat musculoskel etal disorders, even though there is little scientific evi dence currently to support this generalized practice. We tested the hypothesis that elastic bandages improve proprioception of the bandaged joint during their use, and that this benefit was more than temporary. The un injured human knee was used as a model. Fifty-four volunteers (54 knees), aged 22 to 40 years, were asked to identify a prior set joint angle as their knee was pas sively extended. Each knee was tested without the elas tic bandage, immediately after bandage application, after 1 hour of bandage wear, and finally after removal of the bandage. Results showed that elastic bandages significantly improved knee joint proprioception in the uninjured knee during the entire interval of their use (mean decrease in inaccuracy of 1.0°, equivalent to 25% improvement, P < 0.05), and that this benefit was lost when the bandage was removed. The magnitude of the improvement, or the potential beneficial effect of the bandage, was inversely related to the participants in herent knee proprioceptive ability, which was demon strated in the test group before the initial application of the bandage.

Matrix Metalloproteinase and Tissue Inhibitor of Matrix Metalloproteinase mRNA Levels Are Specifically Altered in Torn Rotator Cuff Tendons

Background Rotator cuff tears are a cause of pain and disability in the shoulder. The molecular changes associated with rotator cuff tearing are unclear. A subset of matrix metalloproteinases and tissue inhibitors of metalloproteinase, which are involved in extracellular matrix remodeling and degradation, were evaluated. Hypothesis There would be an increase in the mRNA level of spcific matrix metalloproteinase and a decrease in the mRNA level of specific tissue inhibitors of metalloproteinase in rotator cuff tendon tissue obtained from patients with rotator cuff tears. Study Design Controlled laboratory study. Methods Tissue was obtained from 10 patients undergoing rotator cuff repair for full-thickness rotator cuff tears. Also, tissue was obtained from cadaveric specimens with no gross evidence of rotator cuff tearing. Reverse transcription polymerase chain reaction was performed for the collagenases (MMP-1, MMP-8, MMP-13), the stromelysins (MMP-3, MMP-10, MMP-11), and the tissue inhibitors of metalloproteinase (TIMP-1, TIMP-2, TIMP-3, TIMP-4). Western blotting was performed to confirm the mRNA changes demonstrated in collagenase-3 (MMP-13). Results There was a significant increase in collagenase-3 (MMP-13) mRNA levels, a decrease in stromelysin-1 (MMP-3) mRNA levels, and a decrease in tisue inhibitor of metalloproteinase-2, -3, and -4 mRNA levels. Western blotting demonstrated an increase in the active form of collagenase-3 (MMP-13) in rotator cuff tendon tears. Conclusions The mRNA levels of specific matrix metalloproteinases and tissue inhibitors of metalloproteinase are altered in torn rotator cuff tendons. Clinical Relevance With the known action of the matrix metalloproteinases and tissue inhibitors of metalloproteinase in extra-cellular matrix remodeling, these findings suggest that their roles in remodeling of rotator cuff tears should be further investigated.

Collagen fibril diameters in the healing adult rabbit medial collateral ligament

This study was carried out to test the hypothesis that improvements in ligament scar mechanical behavior during healing may be related, in part, to increases in collagen fibril diameters. Forty-eight adult female New Zealand White rabbits had standardized midsubstance gap injuries created in their right medial collateral ligaments (MCLs) and were allowed normal cage activity until sacrifice in groups of 12 at 3, 6, 14 or 40 weeks post-injury. Eight animals in each group had both MCLs tested biomechanically while 4 animals had transmission EM investigation of midsubstance collagen fibril diameters by a standardized protocol. Results of mechanical tests showed a three- to fourfold increase in scar strength and stiffness over the intervals of healing studied while there was no change in collagen mean fibril minimum diameters. These results demonstrate no correlation between material or structural properties of scar and collagen fibril diameters in this model of healing and suggest that other mechanisms for scar mechanical improvement under these conditions must be investigated.

Stress governs tissue phenotype at the femoral insertion of the rabbit MCL

The cells in the midsubstance portion of skeletal ligaments typically have elongated shapes, but where ligaments insert into bone the cells appear very rounded and the tissue phenotype is that of fibrocartilage. Between the midsubstance and the insertions there is a gradient in cell shape and tissue phenotype that has been hypothesized to reflect a gradient of mechanical stresses. To test this hypothesis, cell shapes (an index of tissue phenotype) were quantified in the central part of the femoral insertion of the rabbit medial collateral ligament by computer-assisted histomorphometry. Morphometric measurements were correlated with the mechanical stresses and strains in the central part of the insertion as predicted by finite element analysis. Throughout the ligament the direction of the predicted principal tensile stresses coincides with the direction of the collagen fibers which curve from the midsubstance to meet the femur at nearly right angles. Principal compressive stresses also occur within the ligament: the highest are localized near the bone; the lowest in the midsubstance. The areas with the roundest cells correspond to the areas with the highest principal compressive stresses in the model; the areas with the flattest cells correspond to the areas with the lowest compressive stresses in the model. A correlation between cell shape and mechanical stresses suggests that physiological loading of the MCL is important for the maintenance of tissue phenotype throughout this insertion. We theorize that the cells in ligament insertions adapt to the prevailing local mechanical environment.

Adaptive time-frequency analysis of knee joint vibroarthrographic signals for noninvasive screening of articular cartilage pathology

Vibroarthrographic (VAG) signals emitted by human knee joints are nonstationary and multicomponent in nature; time-frequency distributions (TFDs) provide powerful means to analyze such signals. The objective of this paper is to construct adaptive TFDs of VAG signals suitable for feature extraction. An adaptive TFD was constructed by minimum cross-entropy optimization of the TFD obtained by the matching pursuit decomposition algorithm. Parameters of VAG signals such as energy, energy spread. frequency, and frequency spread were extracted from their adaptive TFDs. The parameters carry information about the combined TF dynamics of the signals. The mean and standard deviation of the parameters were computed, and each VAG signal was represented by a set of just six features. Statistical pattern classification experiments based on logistic regression analysis of the parameters showed an overall normal/abnormal screening accuracy of 68.9% with 90 VAG signals (51 normals and 39 abnormals), and a higher accuracy of 77.5% with a database of 71 signals with 51 normals and 20 abnormals of a specific type of patellofemoral disorder. The proposed method of VAG signal analysis is independent of joint angle and clinical information, and shows good potential for noninvasive diagnosis and monitoring of patellofemoral disorders such as chondromalacia patella.

Elongation and Forces of Ankle Ligaments in a Physiological Range of Motion

The purposes of this study were: (1) to measure the distances between the insertion sites of selected ankle ligament fibers, (2) to measure the force-elongation characteristics of isolated bone-ligament-bone preparations, and (3) to relate the force measurements to angular positions of the ankle. The findings can be used to discuss clinically the correlation between possible ligament injuries and associated foot movement. Three fresh cadaveric ankles were dissected to expose the anterior talofibular ligament, the calcaneofibular ligament, and the superficial deltoid ligament. The ankles were first mounted on a fixture, and insertion to insertion distances of the ligament fibers were measured for selected positions of the ankle/subtalar joint. Bone-ligament-bone preparations were then removed, returned to their anatomical length and uniaxial force-extension testing was performed. The forces in each ligament were recorded for distances corresponding to those measured in situ for various ankle positions. These results allowed: (1) estimation of the forces in these three ligaments in various ankle positions, (2) identification of positions where ligaments were carrying no force, and (3) identification of positions where they carry large forces. The clinical analysis reveals that the anterior talofibular ligament is sensitive to excessive plantarflexion or dorsiflexion, the calcaneofibular ligament is sensitive to excessive inversion or eversion as well as dorsiflexion or plantarflexion, and that the deltoid ligament appears to be sensitive to plantarflexion, external rotation, and eversion. The fact that all three ligaments tested demonstrated different ranges of tension supports the view that there are optimal positions for testing ankle ligament integrity.

POSTMORTEM STABILITY OF TOTAL RNA ISOLATED FROM RABBIT LIGAMENT, TENDON AND CARTILAGE

The stability of RNA, particularly mRNA, in tissues is under complex regulation. Most studies to date have focused on very cellular tissues and not connective tissues such as ligaments, tendons and cartilage. As the availability of such tissues for transplantation or research purposes is frequently delayed following death, it is important to determine whether RNA stability in such tissues is influenced by time postmortem. To approach this question, skeletally mature NZW rabbits were used to investigate RNA integrity over time in dense, hypocellular connective tissues and in several hypercellular organ tissues such as brain, kidney, liver and lung. Samples were analyzed at varying intervals postmortem with respect to rRNA integrity by agarose gel electrophoresis and ethidium bromide staining and mRNA integrity by Northern blot analysis and RT-PCR. No degradation of rRNA or loss in integrity of mRNA for genes of low and high copy number was observed up to 96 h postmortem. These findings confirm that it is likely appropriate to use properly stored postmortem dense connective tissues for molecular biological investigations.

Altered levels of extracellular matrix molecule mRNA in healing rabbit ligaments

RT-PCR methods were used to amplify, semi-quantify, clone and sequence cDNA fragments specific for rabbit extracellular matrix molecules biglycan, collagen I, collagen III, decorin, lumican, versican, fibromodulin, and also glyceraldehyde-3-phosphate dehydrogenase (G3PDH), using RNA isolated from rabbit ligaments. Sequence analysis of two independent clones of PCR products was used to verify the identity of the cDNA. Semi-quantitative RT-PCR was used to study mRNA levels for these matrix molecules in normal and healing rabbit ligament at three, six, and fourteen weeks post-injury. The yield of RNA from the ligament scar was increased at three and six weeks post-injury, but it had returned to near normal levels by fourteen weeks. On a microgram RNA basis, it was demonstrated that biglycan, collagen I, collagen III and lumican mRNA levels are significantly elevated, versican mRNA levels significantly depressed, and decorin and fibromodulin mRNA levels showed no significant change in response to tissue injury in the ligament during the course of healing. These findings suggest that differential regulation of mRNA levels for these extracellular matrix molecules occurs during ligament healing.

Gender and Neurogenic Variables in Tendon Biology and Repetitive Motion Disorders

The incidence of repetitive motion disorders is increasing. Numerous studies have indicated that the incidence in females exceeds that in males. Some of the evidence regarding gender related factors in tendon biology is discussed and new data related to the regulation of gene expression in an animal model of tendon overuse, the determination of sex hormone receptors in tendons, and the influence of pregnancy associated factors on gene expression in four different tendons is provided. Furthermore, because neurogenic mechanisms may contribute to inflammatory conditions, new evidence is provided that supports the concept that neurotransmitters can influence expression of genes that could participate in such inflammation. By increasing our understanding of the regulation of tendon cellular and molecular biology, new approaches to preventing disease development and treatment of existing disease may evolve.