Coronary microevaginations characterize culprit plaques and their inflammatory microenvironment in a subtype of acute coronary syndrome with intact fibrous cap: results from the prospective translational OPTICO-ACS study.

AIMS: Coronary microevaginations (CMEs) represent an outward bulge of coronary plaques and have been introduced as a sign of adverse vascular remodelling following coronary device implantation. However, their role in atherosclerosis and plaque destabilization in the absence of coronary intervention is unknown. This study aimed to investigate CME as a novel feature of plaque vulnerability and to characterize its associated inflammatory cell-vessel-wall interactions. METHODS AND RESULTS: A total of 557 patients from the translational OPTICO-ACS study programme underwent optical coherence tomography imaging of the culprit vessel and simultaneous immunophenotyping of the culprit lesion (CL). Two hundred and fifty-eight CLs had a ruptured fibrous cap (RFC) and one hundred had intact fibrous cap (IFC) acute coronary syndrome (ACS) as an underlying pathophysiology. CMEs were significantly more frequent in CL when compared with non-CL (25 vs. 4%, P < 0.001) and were more frequently observed in lesions with IFC-ACS when compared with RFC-ACS (55.0 vs. 12.7%, P < 0.001). CMEs were particularly prevalent in IFC-ACS-causing CLs independent of a coronary bifurcation (IFC-ICB) when compared with IFC-ACS with an association to a coronary bifurcation (IFC-ACB, 65.4 vs. 43.7%, P = 0.030). CME emerged as the strongest independent predictor of IFC-ICB (relative risk 3.36, 95% confidence interval 1.67-6.76, P = 0.001) by multivariable regression analysis. IFC-ICB demonstrated an enrichment of monocytes in both culprit blood analysis (culprit ratio: 1.1 ± 0.2 vs. 0.9 ± 0.2, P = 0.048) and aspirated culprit thrombi (326 ± 162 vs. 96 ± 87 cells/mm2, P = 0.017), while IFC-ACB confirmed the accumulation of CD4+ T cells, as recently described. CONCLUSION: This study provides novel evidence for a pathophysiological involvement of CME in the development of IFC-ACS and provides first evidence for a distinct pathophysiological pathway for IFC-ICB, driven by CME-derived flow disturbances and inflammatory activation involving the innate immune system. TRIAL REGISTRATION: Registration of the study at clinicalTrials.gov (NCT03129503).

Novel application of in vivo microdialysis in a rat Achilles tendon acute injury model.

Tendon injury and healing involve intricate changes to tissue metabolism, biology, and inflammation. Current techniques often require animal euthanasia or tissue destruction, limiting assessment of dynamic changes in tendon, including treatment response, disease development, rupture risk, and healing progression. Microdialysis, a minimally invasive technique, offers potential for longitudinal assessment, yet it has not been applied to rat tendon models. Therefore, the objective of this study is to adapt a novel application of an in vivo assay, microdialysis, using acute injury as a model for extreme disruption of the tendon homeostasis. We hypothesize that microdialysis will be able to detect measurable differences in the healing responses of acute injury with high specificity and sensitivity. Overall results suggest that microdialysis is a promising in vivo technique for longitudinal assessment for this system with strong correlations between extracellular fluid (ECF) and dialysate concentrations and reasonable recovery rates considering the limitations of this model. Strong positive correlations were found between dialysate and extracellular fluid (ECF) concentration for each target molecule of interest including metabolites, inflammatory mediators, and collagen synthesis and degradation byproducts. These results suggest that microdialysis is capable of detecting changes in tendon healing following acute tendon injury with high specificity and sensitivity. In summary, this is the first study to apply microdialysis to a rat tendon model and assess its efficacy as a direct measurement of tendon metabolism, biology, and inflammation.NEW & NOTEWORTHY This study adapts a novel application of microdialysis to rat tendon models, offering a minimally invasive avenue for longitudinal tendon assessment. Successfully detecting changes in tendon healing after acute injury, it showcases strong correlations between extracellular fluid and dialysate concentrations. The results highlight the potential of microdialysis as a direct measure of tendon metabolism, biology, and inflammation, bypassing the need for animal euthanasia and tissue destruction.

Complement factor D as a predictor of Achilles tendon healing and long-term patient outcomes.

Dense connective tissue healing, such as tendon, is protracted leading to highly variable and unsatisfactory patient outcomes. Biomarkers prognostic of long-term clinical outcomes is, however, unknown. The present study was designed to investigate the proteomic profile of healing, identify potential biomarkers, and assess their association with the patient's long-term outcomes after ATR. Quantitative mass spectrometry analysis demonstrated 1423 proteins in healing and contralateral healthy Achilles tendons of 28 ATR patients. Comparing healing at 2 weeks and healthy protein profiles, we identified 821 overlapping, 390 upregulated, and 17 downregulated proteins. Upregulated proteins are related mainly to extracellular matrix organization and metabolism, while downregulated pathways were associated with exocytosis in immune modulation and thrombosis formation. Further proteomic profiling in relation to validated patient outcomes revealed the downregulated pro-inflammatory complement factor D (CFD) as the most reliable predictive biomarker of successful tendon healing. Our finding showed a comprehensive proteomic landscape and bioinformatics on human connective tissue, indicating subtype-specific and shared biological processes and proteins in healing and healthy Achilles tendons, as well as in tendons related to good and poor patient outcomes. Inflammatory protein CFD and serpin family B member 1 were finally identified as potential predictive biomarkers of effective healing outcomes when combined the proteomic profiles with a validated clinical database. Following the future elucidation of the mechanisms associated with the identified biomarkers as predictors of good outcomes, our findings could lead to improved prognostic accuracy and development of targeted treatments, thus improving the long-term healing outcomes for all patients.

Gene expression profiling of primary fibrochondrocyte cultures in traumatic and degenerative meniscus lesions.

PURPOSE: This study aimed to investigate how fibroblastic and chondrocytic properties of human meniscal fibrochondrocytes are affected in culture conditions according to the type of meniscal pathology and localization, and to provide basic information for tissue-engineering studies. METHODS: Primary fibrochondrocyte cultures were prepared from meniscus samples of patients who had either traumatic tear or degeneration due to osteoarthritis. Cultures were compared in terms of mRNA expression levels of COL1A1, COL2A1, COMP1, HIF1A, HIF2A, and SOX9 and secreted total collagen and sulfated sGAG levels according to the type of meniscal pathology, anatomical localization, and the number of subcultures. RESULTS: mRNA expression levels of COL1A1, COMP1, HIF1A, HIF2A, and SOX9 were found to be increased in subsequent subcultures in all specimens. COL1A1 mRNA expression levels of both lateral and medial menisci of patients with traumatic tear were significantly higher than in patients with degenerative pathology, indicating a more fibroblastic character. P1 subculture of lateral and P3 or further subculture of medial meniscus showed more fibroblastic characteristics in patients with degenerative pathology. Furthermore, in patients with degenerative pathology, the subcultures of the lateral meniscus (especially on the inner part) presented more chondrocytic characteristics than did those of medial meniscus. CONCLUSIONS: The mRNA expression levels of the cultures showed significant differences according to the anatomical localization and pathology of the meniscus, indicating distinct chondrocytic and fibroblastic features. This fundamental knowledge would help researchers to choose more efficient cell sources for cell-seeding of a meniscus scaffold, and to generate a construct resembling the original meniscus tissue.

Elastin levels are higher in healing tendons than in intact tendons and influence tissue compliance.

Elastic fibers containing elastin play an important role in tendon functionality, but the knowledge on presence and function of elastin during tendon healing is limited. The aim of this study was to investigate elastin content and distribution in intact and healing Achilles tendons and to understand how elastin influence the viscoelastic properties of tendons. The right Achilles tendon was completely transected in 81 Sprague-Dawley rats. Elastin content was quantified in intact and healing tendons (7, 14, and 28 days post-surgery) and elastin distribution was visualized by immunohistochemistry at 14 days post-surgery. Degradation of elastin by elastase incubation was used to study the role of elastin on viscoelastic properties. Mechanical testing was either performed as a cyclic test (20× 10 N) or as a creep test. We found significantly higher levels of elastin in healing tendons at all time-points compared to intact tendons (4% in healing tendons 28 days post-surgery vs 2% in intact tendons). The elastin was more widely distributed throughout the extracellular matrix in the healing tendons in contrast to the intact tendon where the distribution was not so pronounced. Elastase incubation reduced the elastin levels by approximately 30% and led to a 40%-50% reduction in creep. This reduction was seen in both intact and healing tendons. Our results show that healing tendons contain more elastin and is more compliable than intact tendons. The role of elastin in tendon healing and tissue compliance indicates a protective role of elastic fibers to prevent re-injuries during early tendon healing. PLAIN LANGUAGE SUMMARY: Tendons transfer high loads from muscles to bones during locomotion. They are primarily made by the protein collagen, a protein that provide strength to the tissues. Besides collagen, tendons also contain other building blocks such as, for example, elastic fibers. Elastic fibers contain elastin and elastin is important for the extensibility of the tendon. When a tendon is injured and ruptured the tissue heals through scar formation. This scar tissue is different from a normal intact tendon and it is important to understand how the tendons heal. Little is known about the presence and function of elastin during healing of tendon injuries. We have shown, in animal experiments, that healing tendons have higher amounts of elastin compared to intact tendons. The elastin is also spread throughout the tissue. When we reduced the levels of this protein, we discovered altered mechanical properties of the tendon. The healing tendon can normally extend quite a lot, but after elastin removal this extensibility was less obvious. The ability of the healing tissue to extend is probably important to protect the tendon from re-injuries during the first months after rupture. We therefore propose that the tendons heal with a large amount of elastin to prevent re-ruptures during early locomotion.

Joint Fluid Proteome after Anterior Cruciate Ligament Rupture Reflects an Acute Posttraumatic Inflammatory and Chondrodegenerative State.

OBJECTIVE: The purpose of this study was to evaluate changes in the synovial fluid proteome following acute anterior cruciate ligament (ACL) injury. DESIGN: This study represents a secondary analysis of synovial fluid samples collected from the placebo group of a previous randomized trial. Arthrocentesis was performed twice on 6 patients with an isolated acute ACL tear at a mean of 6 and 14 days postinjury. Synovial fluid was analyzed by a highly multiplexed assay of 1129 proteins (SOMAscan version 3, SomaLogic, Inc., Boulder, CO). Pathway analysis using DAVID was performed; genes included met 3 criteria: significant change between the 2 study time points using a paired t test, significant change between the 2 study time points using a Mann-Whitney nonparametric test, and significant Benjamini post hoc analysis. RESULTS: Fifteen analytes demonstrated significant increases between time points. Five of the 15 have been previously associated with the onset and/or severity of rheumatoid arthritis, including apoliopoprotein E and isoform E3, vascular cell adhesion protein 1, interleukin-34, and cell surface glycoprotein CD200 receptor 1. Chondrodegenerative enzymes and products of cartilage degeneration all increased over time following injury: MMP-1 (P = 0.08, standardized response mean [SRM] = 1.00), MMP-3 (P = 0.05, SRM = 0.90), ADAM12 (P = 0.03, SRM = 1.31), aggrecan (P = 0.08, SRM = 1.13), and CTX-II (P = 0.07, SRM = 0.56). Notable pathways that were differentially expressed following injury were the cytokine-cytokine receptor interaction and osteoclast differentiation pathways. CONCLUSIONS: The proteomic results and pathway analysis demonstrated a pattern of cartilage degeneration, not only consistent with previous findings but also changes consistent with an inflammatory arthritogenic process post-ACL injury.

Corneal Sensory Experience via Transient Receptor Potential Vanilloid 1 Accelerates the Maturation of Neonatal Tearing.

Tearing maturates rapidly after birth, and external environmental challenges play a key role in promoting lacrimal functional maturation. However, little is known about the facilitative factors underlying this developmental process or the potential of application of these factors to treat hypofunction of the lacrimal gland. In this study, eye opening and the subsequent ocular surface sensory experience, which is thought to be involved in postnatal maturation of lacrimal function, were investigated. Our results demonstrated that eye opening after birth is essential for the maturation of neonatal tearing. The maturation process of lacrimal function is dependent on the ocular surface sensory experience via transient receptor potential cation channel subfamily member 1 after birth. This study provides, for the first time, important evidence of the sensory experience of the ocular surface in relation to the maturation of functional tear secretion during the postnatal period.

Quantitative T2-Mapping and T2⁎-Mapping Evaluation of Changes in Cartilage Matrix after Acute Anterior Cruciate Ligament Rupture and the Correlation between the Results of Both Methods.

OBJECTIVES: To quantitatively assess changes in cartilage matrix after acute anterior cruciate ligament (ACL) rupture using T2- and T2⁎-mapping and analyze the correlation between the results of both methods. METHODS: Twenty-three patients and 23 healthy controls were enrolled and underwent quantitative MRI examination. The knee cartilage was segmented into six compartments, including lateral femur (LF), lateral tibia (LT), medial femur (MF), medial tibia (MT), trochlea (Tr), and patella (Pa). T2 and T2⁎ values were measured in full-thickness as well as superficial and deep layers of each cartilage compartment. Differences of T2 and T2⁎ values between patients and controls were compared using unpaired Student's t-test, and the correlation between their reciprocals was analyzed using Pearson's correlation coefficient. RESULTS: ACL-ruptured patients showed higher T2 and T2⁎ values in full-thickness and superficial layers of medial and lateral tibiofemoral joint. Meanwhile, patients exhibited higher T2⁎ values in deep layers of lateral tibiofemoral joint. The elevated percentages of T2 and T2⁎ value in superficial LT were most significant (20.738%, 17.525%). The reciprocal of T2⁎ value was correlated with that of T2 value (r = 0.886, P < 0.001). CONCLUSION: The early degeneration could occur in various knee cartilage compartments after acute ACL rupture, especially in the superficial layer of LT. T2⁎-mapping might be more sensitive in detecting deep layer of cartilage than T2-mapping.

Electrospun Heparin-Loaded Core-Shell Nanofiber Sutures for Achilles Tendon Regeneration In Vivo.

Achilles tendon reconstruction surgery is the primary clinical method for repairing acute Achilles tendon ruptures. However, the efficacy of the postoperative healing process and the recovery of physiological function are inadequate. This study examines the healing mechanism of ruptured rat Achilles tendons seamed with heparin-loaded core-shell fiber sutures fabricated via near-field electrospinning. High-heparin-concentration sutures (PPH3.0) perform better than the low-heparin-concentration sutures and commercial sutures (CSs). The PPH3.0 suture recruits fewer inflammatory cells and shows good histocompatibility in peritoneal implantation experiments. Staining of the Achilles tendon rupture repair zone demonstrates that a high heparin concentration in sutures reduces immune-inflammatory responses. Immunohistochemical analysis reveals that the transforming growth factor-ß staining scores of the PPH3.0 sutures are not significantly different from those of the corresponding control group but are significantly different from those of the CSs and non-heparin-loaded-suture groups. According to vascular endothelial growth factor (VEGF) analysis, the concentration of VEGF in the group treated with the PPH3.0 suture increases by 37.5% compared with that in its control group. No significant difference in tension strength is observed between the PPH3.0 group and healthy Achilles tendons. These findings illustrate that this novel method effectively treats Achilles tendon rupture and promotes healing and regeneration.

Predicting Catalyst Extrudate Breakage Based on the Modulus of Rupture.

The mechanical strength of extruded catalysts and their natural or forced breakage by either collision against a surface or by a compressive load in a fixed bed are important phenomena in catalyst technology. The mechanical strength of the catalyst is measured here by its bending strength or flexural strength. This technique is relatively new from the perspective of applying it to commercial catalysts of typical sizes used in the industry. Catalyst breakage by collision against a surface is measured after a fall of the extrudates through the ambient air in a vertical pipe. Quantifying the impact force is done theoretically by applying Newton's second law. Measurement of catalyst breakage due to stress in a fixed bed is done following the standard procedure of the bulk crush strength test. Novel here is the focus on measuring the reduction in the length to diameter ratio of the extrudates as a function of the stress.

Use of proteomic analysis to determine the protein constituents of synovial fluid samples from the stifle joints of dogs with and without osteoarthritis secondary to cranial cruciate ligament rupture.

OBJECTIVE To use proteomic analysis to determine the protein constituents of synovial fluid samples from the stifle joints of dogs with and without osteoarthritis secondary to cranial cruciate ligament rupture (CCLR). ANIMALS 12 dogs with clinically normal stifle joints (controls) and 16 dogs with osteoarthritis secondary to CCLR. PROCEDURES A synovial fluid sample was obtained from all dogs. Synovial fluid total protein concentration was determined by the Bradford assay. Proteins were separated by use of a 1-D SDS-PAGE to detect protein bands that differed between dogs with and without osteoarthritis. Those protein bands then underwent trypsin digestion and were analyzed by matrix-assisted laser desorption-ionization time-of-flight mass spectrometry, the results of which were compared with a curated protein sequence database for protein identification. One of the most frequently identified proteins, apoprotein (apo) A-I, was then quantified in all synovial fluid samples by use of a competitive-inhibition ELISA. Results were compared between dogs with and without osteoarthritis. RESULTS Median synovial fluid total protein and apo A-I concentrations for dogs with osteoarthritis were significantly greater than those for control dogs. The most abundant proteins identified in the synovial fluid were albumin and apo A-I. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that quantification of synovial fluid total protein and apo A-I concentrations might facilitate diagnosis of osteoarthritis secondary to CCLR in dogs. Further research and validation of synovial fluid apo A-I concentration as a biomarker for osteoarthritis in dogs are necessary before it can be recommended for clinical use.

Surgical reconstruction of ruptured anterior cruciate ligament prolongs trauma-induced increase of inflammatory cytokines in synovial fluid: an exploratory analysis in the KANON trial.

OBJECTIVE: Prospectively monitor how treatment of acutely ruptured anterior cruciate ligament (ACL) affects biomarkers of inflammation and proteolytic degradation over 5 years. DESIGN: We studied 119 subjects with acute ACL injury from the randomized controlled knee anterior cruciate ligament, non-surgical versus surgical treatment (KANON)-trial (Clinical trial ISRCTN 84752559) who had synovial fluid, serum and urine samples available from at least two out of six visits over 5 years after acute ACL rupture. All subjects followed a similar rehabilitation protocol where, according to randomization, 60 also had early ACL reconstruction and 59 had the option to undergo a delayed ACL reconstruction if needed. Interleukin (IL)-6, IL-8, IL-10, interferon-gamma (IFNγ), tumor necrosis factor (TNF), amino acids alanine, arginine, glycine, serine (ARGS)-aggrecan, C-terminal crosslinking telopeptide type II collagen (CTX-II) and N-terminal crosslinking telopeptide type I collagen (NTX-I) were quantified by enzyme-linked immunosorbent assays (ELISA). RESULTS: Subjects randomized to early ACL reconstruction had higher cytokine concentrations in index knee synovial fluid at 4 months (IL-6, IL-8, IL-10, TNF), 8 months (IL-6 and TNF) and at 5 years (IFNγ) compared to those randomized to optional delayed reconstruction. Those that underwent delayed ACL reconstruction within 5 years (30 subjects), had higher synovial fluid concentrations of IL-6 at 5 years compared to those treated with rehabilitation alone. No differences between groups were noted for ARGS-aggrecan in synovial fluid and serum or CTX-II and NTX-I in urine over 5 years, neither as randomized nor as treated. CONCLUSIONS: Surgical ACL reconstruction constitutes a second trauma to the acutely injured joint resulting in a prolonged elevation of already high synovial fluid levels of inflammatory cytokines.

Correlation between change in muscle excursion and collagen content after tendon rupture and delayed repair.

BACKGROUND: The objectives of the present study were to compare changes in muscle excursion, total collagen, and collagen subtypes after tenotomy over time and after delayed tendon repair. METHODS: Tenotomy on the extensor digitorum tendon of the right second toes of 48 New Zealand White rabbits was performed; toes on the left leg were used as controls. Passive muscle excursion, total collagen content, and type I, III, and IV collagen contents were measured at 1, 2, 4, and 6 weeks after tenotomy. Next, passive muscle excursion and total collagen content were measured at 8 weeks after delayed tendon repair at 1, 2, 4, and 6 weeks after a tenotomy. RESULTS: Passive muscle excursion decreased sequentially over time after tenotomy. Meanwhile, total collagen increased over time. These changes were significant after 4 weeks of injury. Type I collagen significantly increased, type III collagen significantly decreased, and type IV collagen had no significant change over time. Passive muscle excursion was negatively correlated with total collagen and type I collagen after tenotomy at each time point after tenotomy (p < 0.05). After tendon repair, increases in total collagen content after tenotomy were not reversed, despite early repairs at 1 and 2 weeks after tenotomy. CONCLUSIONS: Increases in type I collagen were found to be associated with decreased excursion after tendon rupture. The increase in collagen that was observed after tenotomy was not reversed by repair within 8 weeks.

Transferencias del extensor indicis proprius en casos de roturas del extensor pollicis longus / Extensor indicis proprius transferences in cases of extensor pollicis longus ruptures

Introducción y objetivos: La sutura directa en los casos de rotura del extensor pollicis longus (EPL) puede llevar asociado el fallo de la misma. Por ello, la transferencia tendinosa del extensor indicis proprius (EPI) es una buena alternativa. Nuestro objetivo es describir nuestra experiencia con esta técnica. Material y métodos: Estudio observacional descriptivo y retrospectivo sobre 29 casos. Variables: Edad, sexo, mano dominante, actividad laboral, tiempo quirúrgico. Análisis de resultados obtenidos en test de Geldmacher, SEEM y EVA. Resultados: Edad media de 48.04 ± 9.4 años. 72.4% varones, 27.6% mujeres. Brazo dominante en el 55.2%. 3.4% diabéticos y 6.9% con tratamiento corticoideo. Traumatismo directo en el 58.6%. Diagnóstico ecográfico en el 89.7%. Tiempo quirúrgico: 51.8 ± 12.5 minutos. Escala Geldmacher: 15.79 ± 5.8 puntos. Escala SEEM: 70.36 ± 20.4 puntos. Rotura de plastia en 13.8%. Altas por mejoría en 96.6%. Conclusiones: Las roturas de este tendón se asocian a fracturas de radio distal, tratamiento con corticoides, artritis reumatoide o tras osteosíntesis de fracturas de radio con placas volares. En nuestra experiencia, en los casos de rotura del EPL, consideramos que la trasposición del EPI es una alternativa eficaz, con un reducido número de complicaciones

Introduction and objectives: Direct suture in cases of rupture of extensor pollicis longus (EPL) tendon has been associated to suture tear. For this reason, tendon transfer of extensor indicis proprius (EPI) tendon is a good alternative. Our objective is describe our experience with this technique. Matherial and methods: Observational descriptive and retrospective study about 29 cases. Variables: Age, sex, dominant hand, laboral activity, time of surgery. We analize results with Geldmacher’ scale, SEEM and VAS scores. Results: Average age was 48.04 ± 9.4 years. 72.4% were males and 27.6% were females. Dominant arm was affected in 55.2% of cases. 3.4% were diabetics and 6.9% received corticoid treatment. Direct trauma appeared in 58.6% of cases. Sonographic diagnosis was in 89.7% of cases. Surgical time was of 51.8 ± 12.5 minutes. Geldmacher’ scale: 15.79 ± 5.8 points. SEEM score: 70.36 ± 20.4 points. Plastia rupture happened in 13.8% of patients. 96.6% of patients returned to their work. Conclusions: Ruptures of this tendon have been associated with distal radius fractures, corticoid treatment, rheumathoid arthritis or after osteosynthesis with volar plates in radius fractures. In our experience, in cases of rupture of EPL, we consider that transposition of EIP it is an effective alternative, with minimal number of complications

Modeling of Mechanical Stress Exerted by Cholesterol Crystallization on Atherosclerotic Plaques.

Plaque rupture is the critical cause of cardiovascular thrombosis, but the detailed mechanisms are not fully understood. Recent studies have found abundant cholesterol crystals in ruptured plaques, and it has been proposed that the rapid expansion of cholesterol crystals in a limited space during crystallization may contribute to plaque rupture. To evaluate the effect of cholesterol crystal growth on atherosclerotic plaques, we modeled the expansion of cholesterol crystals during the crystallization process in the necrotic core and estimated the stress on the thin cap with different arrangements of cholesterol crystals. We developed a two-dimensional finite element method model of atherosclerotic plaques containing expanding cholesterol crystals and investigated the effect of the magnitude and distribution of crystallization on the peak circumferential stress born by the cap. Using micro-optical coherence tomography (µOCT), we extracted the cross-sectional geometric information of cholesterol crystals in human atherosclerotic aorta tissue ex vivo and applied the information to the model. The results demonstrate that (1) the peak circumference stress is proportionally dependent on the cholesterol crystal growth; (2) cholesterol crystals at the cap shoulder impose the highest peak circumference stress; and (3) spatial distributions of cholesterol crystals have a significant impact on the peak circumference stress: evenly distributed cholesterol crystals exert less peak circumferential stress on the cap than concentrated crystals.

Effect of a Simple Collagen Type I Sponge for Achilles Tendon Repair in a Rat Model.

BACKGROUND: Several sophisticated approaches to tendon engineering have been investigated as ways to improve tendon healing with the early formation of repair tissue with possibly a high amount of type I collagen. Besides the new formation of collagen type I, there is evidence for the natural integration of surrounding collagen type I from healthy tendon parts into the healing defect. However, the simple application of a type I collagen sponge to the healing site to increase the amount of local collagen type I has not been investigated. HYPOTHESIS: Healing of the rat Achilles tendon can be accelerated by an additional supply of collagen type I, resulting in increased tear resistance. STUDY DESIGN: Controlled laboratory study. METHODS: The right Achilles tendons of 42 rats were transected. In half of the animals, a type I collagen sponge was placed into the gap. Animals were allowed to move freely in their cages to simulate early functional therapy. After 1, 2, and 4 weeks, tendon length, width, maximal load to failure, and stiffness were measured and the healing site studied histologically according to the Bonar score. Inflammation was evaluated by the appearance of macrophages and neutrophilic and eosinophilic granulocytes. RESULTS: Defects receiving collagen sponges showed improved healing, with significantly stronger (29.5 vs 5.0 N, respectively, at 1 week; P = .00003), shorter (11.6 vs 14.5 mm, respectively, at 4 weeks; P = .005), thicker (10.0 vs 1.8 mm(2), respectively, at 1 week; P = .00002), and less stiff (19.5 vs 30.5 N/mm, respectively, at 4 weeks; P = .02) tendons than control tendons. Overall, the biomechanical properties of the collagen-treated tendons appeared to be significantly closer to those of native, uninjured tendons compared with tendons in the control group. Histologically, no inflammatory reaction due to the collagen sponge was found. CONCLUSION: Tendon healing was accelerated by the type I collagen sponge. Moreover, the mechanical properties of collagen-treated tendons appeared to be significantly closer to those of normal, uninjured tendons compared with control tendons without collagen treatment. CLINICAL RELEVANCE: As a simple type I collagen sponge seems to increase the amount of local collagen type I, the careful use of such sponges might be an option for tendon augmentation during Achilles tendon surgery.

Ruptured human Achilles tendon has elevated metabolic activity up to 1 year after repair.

PURPOSE: Following Achilles tendon rupture, running is often allowed after 6 months. However, tendon healing is slow and the metabolic status of the tendon at this point is unknown. The purpose of this study was to investigate tendon metabolism (glucose uptake) and vascularization at 3, 6 and 12 months after Achilles tendon rupture as measured using PET and power Doppler ultrasonography (PDUS). METHODS: The study group comprised 23 patients with surgically repaired Achilles tendon rupture who were investigated at 3 months (n = 7), 6 months (n = 7) and 12 months (n = 9) after surgery. The triceps surae complex was loaded over 20 min of slow treadmill walking while a radioactive tracer ((18)F-FDG) was administered prior to PET. Vascularization was measured in terms of PDUS flow activity, and patient-reported outcomes were scored using the Achilles tendon rupture score (ATRS) and sports assessment (VISA-A) questionnaire. RESULTS: Relative glucose uptake ((18)F-FDG) was higher in repaired tendons than in intact tendons at all time-points (6, 3 and 1.6 times higher at 3, 6 and 12 months, respectively; P ≤ 0.001), and was also higher in the tendon core than in the periphery at 3 and 6 months (P ≤ 0.02), but lower at 12 months (P = 0.06). Relative glucose uptake was negatively related to ATRS at 6 months after repair (r = -0.89, P ≤ 0.01). PDUS flow activity was higher in repaired tendons than in intact tendons at 3 and 6 months (P < 0.05 for both), but had normalized by 12 months. CONCLUSION: These data demonstrate that the healing process as determined by metabolic activity and vascularization continues for 6 months after injury when large loads are typically allowed on the tendon. Indeed, metabolic activity remained elevated for more than 1 year after injury despite normalized vascularization. The robust negative correlation between tendon metabolism and patient-reported outcome suggests that a high metabolic activity 6 months after the injury may be related to a poor clinical healing outcome.

Compensatory hypertrophy of the teres minor muscle after large rotator cuff tear model in adult male rat.

BACKGROUND: Rotator cuff tear (RCT) is a common musculoskeletal disorder in the elderly. The large RCT is often irreparable due to the retraction and degeneration of the rotator cuff muscle. The integrity of the teres minor (TM) muscle is thought to affect postoperative functional recovery in some surgical treatments. Hypertrophy of the TM is found in some patients with large RCTs; however, the process underlying this hypertrophy is still unclear. The objective of this study was to determine if compensatory hypertrophy of the TM muscle occurs in a large RCT rat model. METHODS: Twelve Wistar rats underwent transection of the suprascapular nerve and the supraspinatus and infraspinatus tendons in the left shoulder. The rats were euthanized 4 weeks after the surgery, and the cuff muscles were collected and weighed. The cross-sectional area and the involvement of Akt/mammalian target of rapamycin (mTOR) signaling were examined in the remaining TM muscle. RESULTS: The weight and cross-sectional area of the TM muscle was higher in the operated-on side than in the control side. The phosphorylated Akt/Akt protein ratio was not significantly different between these sides. The phosphorylated-mTOR/mTOR protein ratio was significantly higher on the operated-on side. CONCLUSION: Transection of the suprascapular nerve and the supraspinatus and infraspinatus tendons activates mTOR signaling in the TM muscle, which results in muscle hypertrophy. The Akt-signaling pathway may not be involved in this process. Nevertheless, activation of mTOR signaling in the TM muscle after RCT may be an effective therapeutic target of a large RCT.

Greater Mechanical Loading During Walking Is Associated With Less Collagen Turnover in Individuals With Anterior Cruciate Ligament Reconstruction.

BACKGROUND: Individuals who have sustained an anterior cruciate ligament (ACL) injury and undergo ACL reconstruction (ACLR) are at higher risk of developing knee osteoarthritis. It is hypothesized that altered knee loading may influence the underlying joint metabolism and hasten development of posttraumatic knee osteoarthritis. PURPOSE: To explore the associations between serum biomarkers of cartilage metabolism and peak vertical ground-reaction force (vGRF) and vGRF loading rate in the injured and uninjured limbs of individuals with ACLR. STUDY DESIGN: Descriptive laboratory study. METHODS: Patients with a history of a primary unilateral ACLR who had returned to unrestricted physical activity (N = 19) participated in the study. Resting blood was collected from each participant before completing 5 walking gait trials at a self-selected comfortable speed. Peak vGRF was extracted for both limbs during the first 50% of the stance phase of gait, and the linear vGRF loading rate was determined between heel strike and peak vGRF. Sera were assessed for collagen breakdown (collagen type II cleavage product [C2C]) and synthesis (collagen type II C-propeptide [CPII]), as well as aggrecan concentrations, via commercially available specific enzyme-linked immunosorbent assays. Pearson product-moment correlations (r) and Spearman rank-order correlations (ρ) were used to evaluate associations between loading characteristics and biomarkers of cartilage metabolism. RESULTS: Lower C2C:CPII ratios were associated with higher peak vGRF in the injured limb (ρ = -0.59, uncorrected P = .007). There were no significant associations between peak vGRF or linear vGRF loading rate and CPII, C2C, or aggrecan serum concentrations. CONCLUSION: Lower C2C:CPII ratios were associated with higher peak vGRF in the ACLR limb during gait, suggesting that higher peak loading in the ACLR limb is related to lower type II collagen breakdown relative to type II collagen synthesis. CLINICAL RELEVANCE: These data suggest that type II collagen synthesis may be higher relative to the amount of type II collagen breakdown in the ACLR limb with higher lower extremity loading. Future study should determine if metabolic compensations to increase collagen synthesis may affect the risk of developing osteoarthritis after ACLR.

Rotura de cuerpo cavernoso peneano / Traumatic rupture of corpus cavenosum

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