Biomechanical evaluation of Glenoid Component Stability after ATSA under phasic cyclic loading

Background Total shoulder arthroplasty (TSA) is considered a successful curative procedure for many stiff painful shoulder disorders. However, it may be associated with many complications. Glenoid loosening is thought to be the most common complication of anatomic total shoulder arthroplasty (ATSA); its underlying causes could be mechanical (abnormal loading), septic (infections) or aseptic (autoimmune reaction). This study discusses the mechanical glenoid component loosening after ATSA. II. Hypotheses (Hi, Hii & Hiii) (Hi) The recorded mean peak pressure values of the ATSA components are expected to vary greatly according to the motion type; (Hii) the recorded mean peak pressure values are expected to vary between the initial and final phases of each tested specimen; and (Hiii) the occurrence of glenoid component loosening and its degree of extension are expected to be related to the changes of the obtained mean peak pressure values. III. Objectives This study’s aim was to conduct a comprehensive experimental biomechanical evaluation of the stability of ATSA components under phasic cyclic loading, as follows: (i) testing of the degree of artificial glenoid component stability under repetitive phasic cyclic loading; (ii) testing of the relation between the criteria of the applied cyclic loading according to our testing plan and the occurrence of glenoid component loosening; (iii) measurement and assessment of the values, patterns and magnitudes of the contact pressure between the joint components under cyclic loading; (iv) comparison between the obtained mean peak contact pressure values under cyclic loading in the initial and final phases to detect any relations and/or differences; (v) correlation of the measured pressure values during testing with the QCT findings with respect to glenoid component loosening. IV. Materials A series of six fresh-frozen complete cadaveric shoulder joint specimens (bones and soft tissues) was used in this study. The specimens were implanted with ATSA components and tested successively by mounting them on the shoulder simulator. To measure the values mentioned above, we used a TekScan system with a group of two-headed pressure sensor foils, QCT, shoulder pointer and a digitalized 3Dimaging Zebris system with US, in addition to the routinely used surgical and lab instruments in such experiments. V. Methodology The specimens were scanned prior to experimentation to evaluate their articular surfaces morphology. Then the specimens were implanted with ATSA components and a pressure sensor was inserted within the joint cavity of each specimen and situated on the glenoid component surface. The six specimens were successively mounted on the shoulder simulator and each was tested through three phases of cyclic loading in the three directions of motion. The 1st and 3rd short phases took place for each specimen with insertion of a pressure sensor within the joint cavity, while the 2nd long phase took place without sensor insertion. After the completion of all experiments, the specimens were again scanned with QCT to evaluate the position of the implanted glenoids and any presence of radiolucency and/or loosening. VI. Findings (Observations & Examinations) Two specimens were severely unstable during testing, even with the application of lower loads, particularly during abduction/adduction motion cycles. Provisional and/or subsequent controlling physical examinations revealed either a malposition of the glenoid component or a suspected abnormal glenoid morphology. The other four specimens were completely stable during testing in all motion directions with the application of different loading forces and stabilizing weights. Four specimens were radiologically determined to have a massive glenoid component loosening after the completion of testing. VII. Results The recorded mean peak pressure values varied greatly between the testing phases, testing cycles and motion directions. The highest mean peak pressure values were recorded during AA testing episodes, followed by FE testing episodes. The lowest mean peak pressure values were recorded during IE testing episodes. However, high mean peak pressure values were also recorded during IE testing episodes, but with a low frequency. In seven testing episodes, the recorded mean peak pressure values were higher by 16.7 % in all directions of motion in the final testing phase than those recorded in the initial phase of all testing episodes (42 testing episodes). According to the computed t-test values between the initial and final phases per motion direction/per specimen, null hypothesis (Hypothesis (Hii)) was accepted in the whole AA & FE testing cycles with a percentage of 100%, while it was rejected in only one relation of IE testing cycles with a percentage of 5% and accepted in six relations of IE testing cycles with a percentage of 95%. In total, null hypothesis (Hypothesis (Hii)) was rejected in only one relation of the testing cycles, with a percentage of 5%, and accepted in twenty relations of the testing cycles with a percentage of 95%. According to the calculated t-test values between all initial and final phases for each specimen, null hypothesis (Hypothesis (Hii)) was rejected in two experiments with a percentage of 28.6% and accepted in five experiments with a percentage of 71.4%. Four specimens (three keeled and one pegged) were found to be loose, representing 66.7% of all specimens; one of them was unstable during the testing, representing 25% of the loose specimens and 16.7% of all specimens. VIII. Conclusion The recorded mean peak pressure values and load quantities of the tested shoulder joint varied greatly between motion phases, motion cycles and motion types. The resulting contact pressures across the shoulder joint during its action varied greatly according to the acting force, motion type, muscles status and pathologies within the joint and were directly proportional to the motion type, being higher during AA and FE motion cycles than during IE motion cycles. Also, they were directly proportional to the contact surface area and to the degree of compression between joint articulating surfaces during motion. The greatest degree of variability of SD and mean peak pressure values was seen during FE testing cycles. Shoulder joint instability after ATSA could result from component malposition and/or the articular surface morphological abnormalities. Both glenoid loosening and joint instability could incite the occurrence of the other and could worsen its course in a devastating vicious circle. We concluded that glenoid component loosening could be related to joint stability, loads and the mode of load application in relation to the application duration, and to some extent to the component type, which was apparently evident in our study. The first and third hypotheses were approved, while the second hypothesis was statistically rejected (according to the computed t-test values), which may require a further evaluation in future studies

Failure characteristics of all polyethylene cemented glenoid implants in total shoulder arthroplasty

Total shoulder arthroplasty (TSA) still suffers today from mid-term and long-term complications such as glenoid implant loosening, wear, humeral head subluxation/dislocation and implant fracture. Unlike the hip and knee joint replacements, the artificial shoulder joint has yet to offer a long-term satisfactory solution to shoulder replacement. With loosening being the number one reason for TSA revision, investigating methods of monitoring the glenoid implant loosening and investigate the effects of various design parameters on the loosening behaviour of the glenoid fixation is necessary to explore the problem. Several studies were carried out using in-vitro cyclic testing and FEA to; investigate failure progression and its correlation to quantitative measures in a 2D study (n = 60), investigating key glenoid design features in a 2D (n = 60) and 3D study (n = 20), investigating the validity of using bone substitute foam for studying glenoid fixation in a cadaveric study and investigating any correlation between failure and CT or in-vitro quantitative measures (n = 10). Visible failure was observed, for the first time, correlating to inferior rim displacement and vertical head displacement measures. CT failure was detected in 70% of specimens before visible failure was observed. Out of the design pairs tested; smooth-back/rough-back (range of roughnesses), peg/keel, curved-back/flat-back and conforming/non-conforming, roughening the back-surface to 3.4 μm or more improved fixation performance (p < 0.05). Roughening the back-surface changed the mode of failure from implant/cement failure inferiorly due to tensile/shear stresses, to cement/bone failure superiorly due to compressive/shear loading. Differences in the other design pairs were marked showing peg to perform better than keel, conforming over non-conforming and no difference in curved-back over flat-back, although these differences are marginal. Improvements in the standard testing method have also been suggested

Biomechanical evaluation of Glenoid Component Stability after ATSA under phasic cyclic loading

Background Total shoulder arthroplasty (TSA) is considered a successful curative procedure for many stiff painful shoulder disorders. However, it may be associated with many complications. Glenoid loosening is thought to be the most common complication of anatomic total shoulder arthroplasty (ATSA); its underlying causes could be mechanical (abnormal loading), septic (infections) or aseptic (autoimmune reaction). This study discusses the mechanical glenoid component loosening after ATSA. II. Hypotheses (Hi, Hii & Hiii) (Hi) The recorded mean peak pressure values of the ATSA components are expected to vary greatly according to the motion type; (Hii) the recorded mean peak pressure values are expected to vary between the initial and final phases of each tested specimen; and (Hiii) the occurrence of glenoid component loosening and its degree of extension are expected to be related to the changes of the obtained mean peak pressure values. III. Objectives This study’s aim was to conduct a comprehensive experimental biomechanical evaluation of the stability of ATSA components under phasic cyclic loading, as follows: (i) testing of the degree of artificial glenoid component stability under repetitive phasic cyclic loading; (ii) testing of the relation between the criteria of the applied cyclic loading according to our testing plan and the occurrence of glenoid component loosening; (iii) measurement and assessment of the values, patterns and magnitudes of the contact pressure between the joint components under cyclic loading; (iv) comparison between the obtained mean peak contact pressure values under cyclic loading in the initial and final phases to detect any relations and/or differences; (v) correlation of the measured pressure values during testing with the QCT findings with respect to glenoid component loosening. IV. Materials A series of six fresh-frozen complete cadaveric shoulder joint specimens (bones and soft tissues) was used in this study. The specimens were implanted with ATSA components and tested successively by mounting them on the shoulder simulator. To measure the values mentioned above, we used a TekScan system with a group of two-headed pressure sensor foils, QCT, shoulder pointer and a digitalized 3Dimaging Zebris system with US, in addition to the routinely used surgical and lab instruments in such experiments. V. Methodology The specimens were scanned prior to experimentation to evaluate their articular surfaces morphology. Then the specimens were implanted with ATSA components and a pressure sensor was inserted within the joint cavity of each specimen and situated on the glenoid component surface. The six specimens were successively mounted on the shoulder simulator and each was tested through three phases of cyclic loading in the three directions of motion. The 1st and 3rd short phases took place for each specimen with insertion of a pressure sensor within the joint cavity, while the 2nd long phase took place without sensor insertion. After the completion of all experiments, the specimens were again scanned with QCT to evaluate the position of the implanted glenoids and any presence of radiolucency and/or loosening. VI. Findings (Observations & Examinations) Two specimens were severely unstable during testing, even with the application of lower loads, particularly during abduction/adduction motion cycles. Provisional and/or subsequent controlling physical examinations revealed either a malposition of the glenoid component or a suspected abnormal glenoid morphology. The other four specimens were completely stable during testing in all motion directions with the application of different loading forces and stabilizing weights. Four specimens were radiologically determined to have a massive glenoid component loosening after the completion of testing. VII. Results The recorded mean peak pressure values varied greatly between the testing phases, testing cycles and motion directions. The highest mean peak pressure values were recorded during AA testing episodes, followed by FE testing episodes. The lowest mean peak pressure values were recorded during IE testing episodes. However, high mean peak pressure values were also recorded during IE testing episodes, but with a low frequency. In seven testing episodes, the recorded mean peak pressure values were higher by 16.7 % in all directions of motion in the final testing phase than those recorded in the initial phase of all testing episodes (42 testing episodes). According to the computed t-test values between the initial and final phases per motion direction/per specimen, null hypothesis (Hypothesis (Hii)) was accepted in the whole AA & FE testing cycles with a percentage of 100%, while it was rejected in only one relation of IE testing cycles with a percentage of 5% and accepted in six relations of IE testing cycles with a percentage of 95%. In total, null hypothesis (Hypothesis (Hii)) was rejected in only one relation of the testing cycles, with a percentage of 5%, and accepted in twenty relations of the testing cycles with a percentage of 95%. According to the calculated t-test values between all initial and final phases for each specimen, null hypothesis (Hypothesis (Hii)) was rejected in two experiments with a percentage of 28.6% and accepted in five experiments with a percentage of 71.4%. Four specimens (three keeled and one pegged) were found to be loose, representing 66.7% of all specimens; one of them was unstable during the testing, representing 25% of the loose specimens and 16.7% of all specimens. VIII. Conclusion The recorded mean peak pressure values and load quantities of the tested shoulder joint varied greatly between motion phases, motion cycles and motion types. The resulting contact pressures across the shoulder joint during its action varied greatly according to the acting force, motion type, muscles status and pathologies within the joint and were directly proportional to the motion type, being higher during AA and FE motion cycles than during IE motion cycles. Also, they were directly proportional to the contact surface area and to the degree of compression between joint articulating surfaces during motion. The greatest degree of variability of SD and mean peak pressure values was seen during FE testing cycles. Shoulder joint instability after ATSA could result from component malposition and/or the articular surface morphological abnormalities. Both glenoid loosening and joint instability could incite the occurrence of the other and could worsen its course in a devastating vicious circle. We concluded that glenoid component loosening could be related to joint stability, loads and the mode of load application in relation to the application duration, and to some extent to the component type, which was apparently evident in our study. The first and third hypotheses were approved, while the second hypothesis was statistically rejected (according to the computed t-test values), which may require a further evaluation in future studies

The Role of Scapular Dyskinesis in Rotator Cuff and Biceps Tendon Pathology

Shoulder tendon injuries including impingement, rotator cuff disease, and biceps tendon pathology are common clinical conditions and are a significant source of joint pain, instability, and dysfunction. These injuries may progress into partial tears then to complete tendon ruptures, which have limited healing capacity even when surgically repaired. These injuries are frequently seen in the presence of abnormal scapulothoracic joint kinematics (termed scapular dyskinesis). However, the cause and effect relationship between scapular dyskinesis and shoulder injury has not been directly defined. Additionally, while the incidence of shoulder injuries and recurrent failure of repairs is well-documented, the mechanisms behind them are not well-established, making optimal clinical management difficult. Therefore, the objectives of this study were to examine the effect of scapular dyskinesis on the initiation and progression of pathological changes in the rotator cuff and biceps tendon and to define the mechanical processes that lead to these changes. Unfortunately, clinical and cadaveric studies are unable to address the underlying causes of injury and cannot evaluate the injury process over time. Therefore, a rat model of scapular dyskinesis (created by denervating the trapezius and serratus anterior) was developed and used, both alone and in combination with overuse, to investigate the cause and effect relationships between changes in joint loading and alterations in tendon mechanical, histological, organizational, and biological properties. We hypothesized that scapular dyskinesis would result in altered joint loading conditions that would lead to degeneration of the rotator cuff and long head of the biceps. We found that scapular dyskinesis diminished joint function and passive joint mechanics and significantly reduced tendon properties. We also investigated the effect of overuse on tendon properties and found that overuse activity in the presence of scapular dyskinesis resulted in significantly more structural and biological adaptations than scapular dyskinesis alone. We also investigated the effect of scapular dyskinesis on supraspinatus tendon healing and found that scapular dyskinesis was detrimental to tendon properties. These results indicate that scapular dyskinesis is a causative mechanical mechanism of shoulder tendon injury. Identification of scapular dyskinesis as a mechanism of pathological changes will help inform and guide clinicians in developing optimal prevention and long-term rehabilitation strategies

Expansion microscopy of C. elegans.

Funder: John DoerrFunder: The Open Philanthropy ProjectFunder: Lisa YangWe recently developed expansion microscopy (ExM), which achieves nanoscale-precise imaging of specimens at ~70 nm resolution (with ~4.5x linear expansion) by isotropic swelling of chemically processed, hydrogel-embedded tissue. ExM of C. elegans is challenged by its cuticle, which is stiff and impermeable to antibodies. Here we present a strategy, expansion of C. elegans (ExCel), to expand fixed, intact C. elegans. ExCel enables simultaneous readout of fluorescent proteins, RNA, DNA location, and anatomical structures at resolutions of ~65-75 nm (3.3-3.8x linear expansion). We also developed epitope-preserving ExCel, which enables imaging of endogenous proteins stained by antibodies, and iterative ExCel, which enables imaging of fluorescent proteins after 20x linear expansion. We demonstrate the utility of the ExCel toolbox for mapping synaptic proteins, for identifying previously unreported proteins at cell junctions, and for gene expression analysis in multiple individual neurons of the same animal

The Migration and Wear of Reverse Total Shoulder Arthroplasty

Reverse total shoulder arthroplasty (RTSA) inverts the ball and socket geometry of the shoulder. Though projected to become the most common shoulder replacement in the next decade, RTSA suffers from a high complication and revision rate, with implant loosening requiring revision. As the number of indications and demand from younger patients for RTSA continues to grow, there is the need to identify implant fixation techniques that promote longevity. Radiostereometric analysis (RSA) is the current standard for measuring implant migration, which, if continuous in the first year postoperatively is highly predictive of later loosening and failure. RSA has also been used to measure polyethylene wear, known to contribute to implant loosening through periprosthetic bone resorption. The objectives of this thesis were to compare early implant migration between different RTSA fixation techniques, and to assess the in vivo polyethylene wear rate of RTSA at mid-to-long-term follow-up. To accomplish these objectives, the use of RSA for RTSA was first validated using a phantom setup. Subsequently, patients were prospectively randomized to compare cemented to press-fit humeral stems, and bone graft to porous metal-augmented glenosphere baseplates. Imaging was acquired postoperatively through one year. Separately, patients with an implant term-of-service greater than five years were recruited and imaged at a single timepoint. All migration analyses were performed in model-based RSA, with the addition of an in-house software for wear analysis. Significantly greater migration was observed with press-fit compared to cemented stems six months and one year postoperatively, though both groups demonstrated stability from six months onward. There were no differences at any time point between glenosphere lateralization groups. Polyethylene wear was measurable and multidirectional, with values comparable to simulation studies. The primary contribution of this work is the first-ever clinical RSA for RTSA study, the results of which provide the best possible evidence on the predicted longevity of cemented vs. press-fit humeral fixation, and bony vs. porous metal glenosphere lateralization. The secondary contribution is the first evaluation of in vivo RTSA polyethylene wear; the results from both studies influencing clinical care and the design of next-generation shoulder implants

The role of stromal-immune cell interactions in the pathogenesis of tendinopathy

Background: Overuse injuries of the tendon—encompassed by the term ‘tendinopathy’—represent a largely underestimated group of musculoskeletal disorders associated with chronic inflammation and dysregulated tissue repair. Tendinopathies account for 30-50% of all sporting injuries and a high proportion of rheumatological and orthopaedic referrals from primary care physicians. Despite historical disagreement between ‘inflammation’ vs ‘degeneration’ hypotheses it is now widely accepted that inflammatory mechanisms elicited by persistent mechanical injury at a microscopic level disturb the intricate homeostatic balance that exists between stromal and immune cell compartments within the tendon during the initial stages of disease. The molecular mechanisms that regulate inflammatory pathways in tendinopathy are largely unknown therefore this thesis sought to characterize mechanisms involved in activation of the innate immune system and subsequent development of persistent inflammation and aberrant matrix repair. Key results: Gene expression analysis of tendon tissue identified the presence of myeloid associated alarmins S100A8 and S100A9 in early tendinopathy. Treatment of primary human tenocytes with exogenous S100A8 & A9 enhanced cytokine and chemokine release; however, no alterations in genes associated with matrix remodelling were observed indicating these alarmins act to exaggerate the inflammatory response in the early stages of disease. Extensive phenotyping of tendon stromal cells by flow cytometry identified the presence of novel subsets of tenocytes that are expanded under chronic inflammatory conditions. Furthermore, enhanced expression of markers associated with stromal cell activation was observed ex vivo in late tendinopathic tissue and in vitro in response to inflammatory stimuli. I next identified a contact dependent mechanism through which stromal cells influence immune cell phenotype and differentiation in a direct tenocyte-monocyte co-culture model. Finally, expression of stromal activation markers podoplanin and VCAM1 in tenocytes was silenced by siRNA mediated knockdown; however, no discernible alterations in tenocyte behaviour or changes in monocyte phenotype (induced by monocyte-tenocyte co-culture) were observed indicating alternate mechanisms are responsible for these interactions. Conclusions: This study has identified novel stromal-immune cell crosstalk in tendinopathy and highlighted the significance of these interactions in the development of non-resolving chronic inflammation

Nonresonant surface enhanced Raman optical activity

Nanoshells (NS) and nanoparticles (NP) are tunable plasmonic particles that can be precisely engineered for specific applications including surface enhanced spectroscopies. A new, general method for the synthesis of core-shell and solid nanoparticles has been developed and is presented. Based on the CO reduction of Au3+, this new process yields the highest quality gold nanoshells synthesized to date. The constraints on precursor lifetime have been relaxed and post-synthesis purification has been eliminated. Nonresonant surface enhanced Raman optical activity (SEROA) has been investigated using biomolecular analytes deposited on Au nanoshell or nanoparticle substrates. The first, and currently the only, near-infrared (780 nm) excited scattered circular polarization Raman optical activity spectrometer (NIROAS) has been constructed. Surface enhanced Raman optical activity spectroscopy has been validated by the collection of symmetrical, surface enhanced, signed circular polarization intensity difference spectra from several test molecules including, (S)- and (R)-tryptophan, and (SS)- and (RR)-phenylalanine-cysteine