Inlay vs. onlay humeral components in reverse total shoulder arthroplasty: a biorobotic shoulder simulator study.

BACKGROUND: Both inlay and onlay humeral implants are available for reverse total shoulder arthroplasty (rTSA), but biomechanical data comparing these components remain limited. This study investigated the effects of inlay and onlay rTSA humeral components on shoulder biomechanics using a biorobotic shoulder simulator. METHODS: Twenty fresh-frozen cadaveric shoulders were tested before and after rTSA with either an inlay or onlay humeral implant. Comparisons were performed between the most commonly implanted configurations for each implant (baseline) and with a modification to provide equivalent neck-shaft angles (NSAs) for the inlay and onlay configurations. Specimens underwent passive range-of-motion (ROM) assessment with the scapula held static, and scapular-plane abduction was performed, driven by previously collected human-subject scapulothoracic and glenohumeral kinematics. Passive ROM glenohumeral joint angles were compared using t tests, whereas muscle force and excursion data during scapular-plane elevation were evaluated with statistical parametric mapping and t tests. RESULTS: Maximum passive elevation was reduced for the inlay vs. onlay humeral components, although both implants caused reduced passive elevation vs. the native joint. Inlay rTSA also demonstrated reduced passive internal rotation at rest and increased external rotation at 90° of humerothoracic elevation vs. the native joint. All preoperative planning estimates of ROM differed from experiments. Rotator cuff forces were elevated with an onlay vs. inlay humeral implant, but simulated muscle excursions did not differ between systems. Compared with the native joint, rotator cuff forces were increased for both inlay and onlay implants and deltoid forces were reduced for inlay implants. Muscle excursions were dramatically altered by rTSA vs. the native joint. Comparisons of inlay and onlay humeral implants with equivalent NSAs were consistent with the baseline comparisons. CONCLUSIONS: Rotator cuff forces required to perform scapular-plane abduction increase following rTSA using both inlay and onlay implants. Rotator cuff forces are lower with inlay implants compared with onlay implants, although inlay implants also result in reduced passive-elevation ROM. Deltoid forces are lower with inlay implants in comparison to the native joint but not with onlay implants. The differences between inlay and onlay components are largely unaffected by NSA, indicating that these differences are inherent to the inlay and onlay designs. In those patients with an intact rotator cuff, decreased rotator cuff forces to perform abduction with an inlay humeral implant compared with an onlay implant may promote improved long-term outcomes owing to reduced deltoid muscle fatigue when using an inlay implant.

A stabilizing role of the glenoid labrum: the suction cup effect.

BACKGROUND: The glenoid labrum acts as a bumper, deepening glenoid concavity and amplifying the concavity-compression mechanism, and serves as the scapular attachment for glenohumeral ligaments. The role of the posterosuperior labrum in anteroinferior glenohumeral stability, and the role of the anterior labrum in posterior stability has been debated. The purpose of this study was to quantify the contribution of anteroinferior and posterosuperior labral tears to loss of glenohumeral stability in multiple directions. METHODS: Fourteen fresh-frozen cadaveric shoulders were tested on a custom stability ratio measurement apparatus. The peak force that was required to translate the humeral head in anterior, anteroinferior, posterior, and posteroinferior directions was measured under 5 conditions: intact labrum (n = 14), anteroinferior labral tear (n = 7), posterosuperior labral tear (n = 7), combined labral tear (n = 14), and no labrum (n = 14). The stability ratio was defined as the peak translational force divided by the compressive force. Within force-translation curves, we defined the suction cup effect as the force required to release the negative pressure created by an intact labrum. RESULTS: The suction cup effect was usually present with the intact labrum and always disappeared after removal of the labrum for anterior (100% vs. 0%) and posterior (86% vs. 0%) translations (P < .001). After creation of an anteroinferior labral tear, the stability ratio for posterior direction decreased (P < .001) and the suction cup effect disappeared (P < .001). After creation of a posterosuperior labral tear, stability ratios in the anterior and anteroinferior directions decreased (P ≤ .006) and the suction cup effect disappeared (P ≤ .015). The stability ratio for anterior and anteroinferior testing was more diminished by posterosuperior labral tears than anteroinferior labral tears, and the stability ratio for posterior testing was more diminished by anteroinferior labral tears than posterosuperior labral tears. CONCLUSION: Anteroinferior labral tears decreased posterior stability and posterosuperior labral tears decreased anterior and anteroinferior stability, largely because of loss of the suction cup effect.

Development of a continuum damage model to predict accumulation of sub-failure damage in tendons.

Many painful and physically debilitating conditions involve sub-failure mechanical damage to seemingly intact connective tissues such as tendons and ligaments. We found that the amount of denatured collagen in rat tail tendon (RTT) fascicles increased over experiments of cyclic loading to a constant load level (creep cyclic fatigue) with fluorescently tagged collagen hybridizing peptides (CHPs) that bind to denatured collagen. To better understand tendon sub-failure damage progression, computational modeling of tendon materials via finite element analysis in FEBio has been conducted. The objective of this project was to develop, implement, and test the ability of a new continuum damage mechanics (CDM) model in FEBio to represent the sub-failure damage behavior seen in our RTT fascicle creep cyclic fatigue experimental data. There appeared to be two distinct mechanisms responsible for the creep cyclic fatigue softening behavior of RTT fascicles over the number of cycles to failure: the preconditioning effect and overall collagen damage. In our finite element (FE) models, the RTT fascicle undamaged elastic constitutive material was composed of a matrix and fibers described by the Coupled Veronda-Westmann and exponential-linear materials. This undamaged elastic material was convolved with a modified CDM model adapted from Balzani et al., in 2012. The novelty of the Balzani damage model is the inclusion of two interrelated mechanisms described as continuous and discontinuous damage. The continuous damage formulation calculates damage accumulation during the loading and reloading of each new cycle, while the discontinuous damage approach accumulates damage from the maximum strain over the loading history to the current time. We modified the Balzani damage model formulations to represent exponential and sigmoidal increases in damage marked by the preconditioning effect and collagen damage in RTT fascicles as functions of continuous and discontinuous damage. The original Balzani damage model was first verified, then the modified CDM model was implemented into FEBio and used to reproduce the sample specific experimental creep cyclic fatigue stress-strain data as well as predict incremental cyclic fatigue. The resulting model will be useful for future experimental and computational studies of damage mechanics to understand tendon pathologies.

Proximal humeral coordinate systems can predict humerothoracic and glenohumeral kinematics of a full bone system.

BACKGROUND: Clinical imaging often excludes the distal humerus, confounding definition of common whole-bone coordinate systems. While proximal anatomy coordinate systems exist, no simple method transforms them to whole-bone systems. Their influence on humeral kinematics is unknown. RESEARCH QUESTION: How do humeral kinematics vary based on proximal and whole-bone coordinate systems, and can average rotation matrices accurately convert kinematics between them? METHODS: Three proximal coordinate systems were defined by the lesser and greater tuberosities (LT, GT), Crest of the greater tuberosity, and humeral shaft. Average rotation matrices derived from anatomic landmarks on cadaver humeri were generated between the proximal and whole-bone coordinate systems. Absolute angle of rotation was used to determine if anatomical variability within the cadaver population influenced the matrices. The matrices were applied to humerothoracic and glenohumeral motion (collected previously) and analyzed using the proximal coordinate systems, then expressed in the whole-bone system. RMSE was used to compare kinematics from the proximal and whole-bone systems. RESULTS: A single average rotation matrix between a given proximal and whole-bone coordinate system achieved consistent error, regardless of landmarks. Elevation and plane of elevation had <2° mean error when proximal coordinate systems were transformed to whole-bone kinematics. Axial rotation had a mean 7° error, primarily due to variable humeral head retroversion. Absolute angles of rotation did not statistically differ between subgroups. The average rotation matrices were independent of sex, side, and motion. SIGNIFICANCE: Proximal humerus coordinate systems can accurately predict whole-bone kinematics, with most error concentrated in axial rotation due to anatomic twist along the bone. These results enhance interpretability and reproducibility in expressing humerothoracic and glenohumeral motion data between laboratories by providing a simple means to convert data between common coordinate systems. This is necessitated by the lack of distal humerus anatomy present in most clinical imaging.

Tendons exhibit greater resistance to tissue and molecular-level damage with increasing strain rate during cyclic fatigue.

Musculoskeletal soft connective tissues are commonly injured due to repetitive use, but the evolution of mechanical damage to the tissue structure during repeated loading is poorly understood. We investigated the strain-rate dependence of mechanical denaturation of collagen as a form of structural microdamage accumulation during creep fatigue loading of rat tail tendon fascicles. We cycled tendons at three strain rates to the same maximum stress relative to their rate-dependent tensile strength. Collagen denaturation at distinct points during the fatigue process was measured by fluorescence quantification of collagen hybridizing peptide binding. The amount of collagen denaturation was significantly correlated with fascicle creep strain, independent of the cyclic strain rate, supporting our hypothesis that tissue level creep is caused by collagen triple-helix unfolding. Samples that were loaded faster experienced more creep strain and denaturation as a function of the number of loading cycles relative to failure. Although this increased damage capacity at faster rates may serve as a protective measure during high-rate loading events, it may also predispose these tissues to subsequent injury and indicate a mechanism of overuse injury development. These results build on evidence that molecular-level collagen denaturation is the fundamental mechanism of structural damage to tendons during tensile loading. STATEMENT OF SIGNIFICANCE: This study is the first to investigate the accumulation of denatured collagen in tendons throughout fatigue loading when the maximum stress is scaled with the applied strain rate. The amount of denatured collagen was correlated with creep strain, independent of strain rate, but samples that were cycled faster withstood greater amounts of denaturation before failure. Differential accumulation of collagen damage between fast and slow repetitive loading has relevance toward understanding the prevalence of overuse musculoskeletal injuries following sudden changes in activity level. Since collagen is a ubiquitous biological structural component, the basic patterns and mechanisms of loading-induced collagen damage in connective tissues are relevant for understanding injury and disease in other tissues, including those from the cardiovascular and pulmonary systems.

Collagen denaturation is initiated upon tissue yield in both positional and energy-storing tendons.

Tendons are collagenous soft tissues that transmit loads between muscles and bones. Depending on their anatomical function, tendons are classified as positional or energy-storing with differing biomechanical and biochemical properties. We recently demonstrated that during monotonic stretch of positional tendons, permanent denatured collagen begins accumulating upon departing the linear region of the stress-strain curve. However, it is unknown if this observation is true during mechanical overload of other types of tendons. Therefore, the purpose of this study was to investigate the onset of collagen denaturation relative to applied strain, and whether it differs between the two tendon types. Rat tail tendon (RTT) fascicles and rat flexor digitorum longus (FDL) tendons represented positional and energy-storing tendons, respectively. The samples were stretched to incremental levels of strain, then stained with fluorescently labeled collagen hybridizing peptides (CHPs); the CHP fluorescence was measured to quantify denatured collagen. Denatured collagen in both positional and energy-storing tendons began to increase at the yield strain, upon leaving the linear region of the stress-strain curve as the sample started to permanently deform. Despite significant differences between the two tendon types, it appears that collagen denaturation is initiated at tissue yield during monotonic stretch, and the fundamental mechanism of failure is the same for the two types of tendons. At tissue failure, positional tendons had double the percentage of denatured collagen compared to energy-storing tendons, with no difference between 0% control groups. These results help to elucidate the etiology of subfailure injury and rupture in functionally distinct tendons.

Accumulation of collagen molecular unfolding is the mechanism of cyclic fatigue damage and failure in collagenous tissues.

Overuse injuries to dense collagenous tissues are common, but their etiology is poorly understood. The predominant hypothesis that micro-damage accumulation exceeds the rate of biological repair is missing a mechanistic explanation. Here, we used collagen hybridizing peptides to measure collagen molecular damage during tendon cyclic fatigue loading and computational simulations to identify potential explanations for our findings. Our results revealed that triple-helical collagen denaturation accumulates with increasing cycles of fatigue loading, and damage is correlated with creep strain independent of the cyclic strain rate. Finite-element simulations demonstrated that biphasic fluid flow is a possible fascicle-level mechanism to explain the rate dependence of the number of cycles and time to failure. Molecular dynamics simulations demonstrated that triple-helical unfolding is rate dependent, revealing rate-dependent mechanisms at multiple length scales in the tissue. The accumulation of collagen molecular denaturation during cyclic loading provides a long-sought "micro-damage" mechanism for the development of overuse injuries.

Microplate assay for denatured collagen using collagen hybridizing peptides.

The purpose of this study was to develop a microplate assay for quantifying denatured collagen by measuring the fluorescence of carboxyfluorescein bound collagen hybridizing peptides (F-CHP). We have shown that F-CHP binds selectively with denatured collagen, and that mechanical overload of tendon fascicles causes collagen denaturation. Proteinase K was used to homogenize tissue samples after F-CHP staining, allowing fluorescence measurement using a microplate reader. We compared our new assay to our previous image analysis method and the trypsin-hydroxyproline assay, which is the only other available method to directly quantify denatured collagen. Relative quantification of denatured collagen was performed in rat tail tendon fascicles subjected to incremental tensile overload, and normal and ostoeoarthritic guinea pig cartilage. In addition, the absolute amount of denatured collagen was determined in rat tail tendon by correlating F-CHP fluorescence with percent denatured collagen as determined by the trypsin-hydroxyproline assay. Rat tail tendon fascicles stretched to low strains (<7.5%) exhibited minimal denatured collagen, but values rapidly increased at medium strains (7.5-10.5%) and plateaued at high strains (≥12%). Osteoarthritic cartilage had higher F-CHP fluorescence than healthy cartilage. Both of these outcomes are consistent with previous studies. With the calibration curve, the microplate assay was able to absolutely quantify denatured collagen in mechanically damaged rat tail tendon fascicles as reliably as the trypsin-hydroxyproline assay. Further, we achieved these results more efficiently than current methods in a rapid, high-throughput manner, with multiple types of collagenous tissue while maintaining accuracy. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:431-438, 2019.

Load transfer, damage, and failure in ligaments and tendons.

The function of ligaments and tendons is to support and transmit loads applied to the musculoskeletal system. These tissues are often able to perform their function for many decades; however, connective tissue disease and injury can compromise ligament and tendon integrity. A range of protein and non-protein constituents, combined in a complex structural hierarchy from the collagen molecule to the tissue and covering nanometer to centimeter length scales, govern tissue function, and impart characteristic non-linear material behavior. This review summarizes the structure of ligaments and tendons, the roles of their constituent components for load transfer across the hierarchy of structure, and the current understanding of how damage occurs in these tissues. Disease and injury can alter the constituent make-up and structural organization of ligaments and tendons, affecting tissue function, while also providing insight to the role and interactions of individual constituents. The studies and techniques presented here have helped to understand the relationship between tissue constituents and the physical mechanisms (e.g., stretching, sliding) that govern material behavior at and between length scales. In recent years, new techniques have been developed to probe ever smaller length scales and may help to elucidate mechanisms of load transfer and damage and the molecular constituents involved in the in the earliest stages of ligament and tendon damage. A detailed understanding of load transfer and damage from the molecular to the tissue level may elucidate targets for the treatment of connective tissue diseases and inform practice to prevent and rehabilitate ligament and tendon injuries. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:3093-3104, 2018.

Fabrication of dense anisotropic collagen scaffolds using biaxial compression.

We developed a new method to manufacture dense, aligned, and porous collagen scaffolds using biaxial plastic compression of type I collagen gels. Using a novel compression apparatus that constricts like an iris diaphragm, low density collagen gels were compressed to yield a permanently densified, highly aligned collagen material. Micro-porosity scaffolds were created using hydrophilic elastomer porogens that can be selectively removed following biaxial compression, with porosity modulated by using different porogen concentrations. The resulting scaffolds exhibit collagen densities that are similar to native connective tissues (∼10% collagen by weight), pronounced collagen alignment across multiple length scales, and an interconnected network of pores, making them highly relevant for use in tissue culture, the study of physiologically relevant cell-matrix interactions, and tissue engineering applications. The scaffolds exhibited highly anisotropic material behavior, with the modulus of the scaffolds in the fiber direction over 100 times greater than the modulus in the transverse direction. Adipose-derived mesenchymal stem cells were seeded onto the biaxially compressed scaffolds with minimal cell death over seven days of culture, along with cell proliferation and migration into the pore spaces. This fabrication method provides new capabilities to manufacture structurally and mechanically relevant cytocompatible scaffolds that will enable more physiologically relevant cell culture studies. Further improvement of manufacturing techniques has the potential to produce engineered scaffolds for direct replacement of dense connective tissues such as meniscus and annulus fibrosus. STATEMENT OF SIGNIFICANCE: In vitro studies of cell-matrix interactions and the engineering of replacement materials for collagenous connective tissues require biocompatible scaffolds that replicate the high collagen density (15-25%/wt), aligned fibrillar organization, and anisotropic mechanical properties of native tissues. However, methods for creating scaffolds with these characteristics are currently lacking. We developed a new apparatus and method to create high density, aligned, and porous collagen scaffolds using a biaxial compression with porogens technique. These scaffolds have a highly directional structure and mechanical properties, with the tensile strength and modulus up to 100 times greater in the direction of alignment. We also demonstrated that the scaffolds are a suitable material for cell culture, promoting cell adhesion, viability, and an aligned cell morphology comparable to the cell morphology observed in native aligned tissues.

Molecular level detection and localization of mechanical damage in collagen enabled by collagen hybridizing peptides.

Mechanical injury to connective tissue causes changes in collagen structure and material behaviour, but the role and mechanisms of molecular damage have not been established. In the case of mechanical subfailure damage, no apparent macroscale damage can be detected, yet this damage initiates and potentiates in pathological processes. Here, we utilize collagen hybridizing peptide (CHP), which binds unfolded collagen by triple helix formation, to detect molecular level subfailure damage to collagen in mechanically stretched rat tail tendon fascicle. Our results directly reveal that collagen triple helix unfolding occurs during tensile loading of collagenous tissues and thus is an important damage mechanism. Steered molecular dynamics simulations suggest that a likely mechanism for triple helix unfolding is intermolecular shearing of collagen α-chains. Our results elucidate a probable molecular failure mechanism associated with subfailure injuries, and demonstrate the potential of CHP targeting for diagnosis, treatment and monitoring of tissue disease and injury.

Quantification of continuous in vivo flexion-extension kinematics and intervertebral strains.

PURPOSE: Healthy subjects performed lumbar flexion and were assessed by video fluoroscopy to measure the in vivo kinematics of the lower lumbar motion segments. METHODS: Fifteen healthy subjects (8 male, 7 female, 28 ± 10 years) performed lumbar flexion and extension back to neutral while their vertebrae were imaged. The sagittal plane vertebral margins of L3-S1 were identified. Lumbar angle, segmental margin strains, axial displacements, anterior-posterior (A-P) translations, and segmental rotations over the course of flexion were measured. RESULTS: L4-L5 had the largest posterior margin Green strain (65%). Each segment displayed more axial displacement than A-P translation. Peak vertebral angulation occurred at approximately 75% of peak flexion during the extension phase. CONCLUSION: L4-L5 exhibited the largest anterior and posterior margin strains (29 and 65%, respectively). Strains in the disc during in vivo lumbar flexion are due to both angular rotation and linear translation.