Clinico-epidemiological characteristics of early- versus late-onset cytomegalovirus disease among renal transplant recipients: A two-decade experience.

BACKGROUND: Reactivation of cytomegalovirus (CMV) infection in transplant patients is high because of immunosuppression. We have evaluated the clinical and epidemiological characteristics of early versus late onset of CMV infection among renal transplant recipients. METHODS: A single center retrospective observational study was conducted among renal transplant recipients who underwent kidney transplant between January 2002 and December 2021. CMV disease was classified as early or late depending on its detection prior to or after 90 days post-transplantation. Herein, we reported the differences between early and late onset of CMV disease with respect to clinical symptoms, the use of immunosuppression and the impact on graft outcomes. RESULTS: Out of total 2164 renal transplant recipients, 156 patients (7.2%) were diagnosed with CMV disease. Among these 156 patients, 25 patients (16%) had early CMV while 131 patients (84%) had late CMV. Overall, the two groups did not differ with respect to the induction or maintenance of immunosuppressive agents. However, the proportion of CMV syndrome was greater among early (56.0%) than late (26.7%) CMV groups (p = 0.01). In contrast, tissue invasive disease was more frequent among late (73.3%) in comparison to early (44.0%) CMV groups (p = 0.01). Among clinical symptoms, diarrhea was more frequent in late (63.4%) vs. early (36%) CMV-affected patients (p = 0.01). Graft loss occurred in 4.0% of early CMV group vs. 25.2% of late CMV group (p = 0.03). Neither of the clinical groups differed with respect to occurrence of biopsy-proven allograft rejection post-infection. CONCLUSIONS: Early CMV disease presents more frequently as CMV syndrome while late CMV disease usually manifests itself as tissue invasive disease. Graft loss is more common in patients with late onset of CMV disease.

High Frequency of Recessive WFS1 Mutations Among Indian Children With Islet Antibody-negative Type 1 Diabetes.

BACKGROUND: While the frequency of islet antibody-negative (idiopathic) type 1 diabetes mellitus (T1DM) is reported to be increased in Indian children, its aetiology has not been studied. We investigated the role of monogenic diabetes in the causation of islet antibody-negative T1DM. METHODS: We conducted a multicenter, prospective, observational study of 169 Indian children (age 1-18 years) with recent-onset T1DM. All were tested for antibodies against GAD65, islet antigen-2, and zinc transporter 8 using validated ELISA. Thirty-four islet antibody-negative children underwent targeted next-generation sequencing for 31 genes implicated in monogenic diabetes using the Illumina platform. All mutations were confirmed by Sanger sequencing. RESULTS: Thirty-five (21%) children were negative for all islet antibodies. Twelve patients (7% of entire cohort, 34% of patients with islet antibody-negative T1DM) were detected to have pathogenic or likely pathogenic genetic variants. The most frequently affected locus was WFS1, with 9 patients (5% of entire cohort, 26% of islet antibody-negative). These included 7 children with homozygous and 1 patient each with a compound heterozygous and heterozygous mutation. Children with Wolfram syndrome 1 (WS) presented with severe insulin-requiring diabetes (including 3 patients with ketoacidosis), but other syndromic manifestations were not detected. In 3 patients, heterozygous mutations in HNF4A, ABCC8, and PTF1A loci were detected. CONCLUSION: Nearly one-quarter of Indian children with islet antibody-negative T1DM had recessive mutations in the WFS1 gene. These patients did not exhibit other features of WS at the time of diagnosis. Testing for monogenic diabetes, especially WS, should be considered in Indian children with antibody-negative T1DM.

Comparison of Human Papillomavirus Genotype Detection in Paired Urine and Self-Collected Cervical Swabs: A Pilot Study.

OBJECTIVES: With the objective of establishing a simple, cost-effective, and effective screening tool for the screening of Human Papilloma Virus infection, the study was undertaken. MATERIAL METHODS: This pilot study was conducted on 20 urine samples of women whose cervical swabs were tested positive while screening for Human papilloma virus in asymptomatic women. RESULTS: HPV genotypes were detected in 94% (16/17) patients in urine samples by real-time PCR while a 100% detection rate (15/15) was observed in the cervical swab samples. The results of the urine and cervical swab samples, tested by the TRUPCR ®HPV high-risk genotyping kit, are shown in Table 2. HPV genotype 68 was found in 82.3% urinary samples and 100% of self-collected vaginal swab samples. Out of 16 positive urine samples, 2 were positive for HPV genotype 16 and 5 were positive for HPV genotype 18, and in cervical swab testing out of 15 positive samples, 3 were positive for HPV genotype 16, and 5 were positive for HPV genotype 18. Diagnostic accuracy of urine was found to be 98.8% (95% CI 79.43% - 100.00%). CONCLUSION: This pilot study aims to assess the accuracy of urine samples in the screening of HPV infection among asymptomatic women and establish the distribution of prevalent HPV genotypes. This may further contribute to standardizing the urine and cervical swab testing methods for cervical cancer screening strategies.

Cytomegalovirus reactivation with high viral load in a patient of coronavirus disease 2019 acute respiratory distress syndrome: a case report.

INTRODUCTION: Cytomegalovirus establishes life-long latency after primary infection in childhood. Cytomegalovirus reactivation has been well reported in immune-compromised patients; however, in the last few years it has been observed that cytomegalovirus reactivation also occurs in critically ill patients without exogenous immunosuppression, which increases length of intensive care unit stay and mortality rate. CASE REPORT: A 63-year-old Indian male, without any known comorbidity, developed severe coronavirus disease 2019 and was admitted to the intensive care unit. He received remdesivir, tocilizumab, steroids, anticoagulants, and empiric antibiotics over the next 3 weeks. However, his clinical condition did not improve much, and during the 9th week of illness his condition started deteriorating and routine bacterial cultures, fungal cultures, and cytomegalovirus real-time polymerase chain reaction on blood were negative. His clinical condition worsened rapidly, which led to the need for invasive mechanical ventilation. Tracheal aspirate bacterial and fungal culture showed no growth, but cytomegalovirus real-time polymerase chain reaction showed 21,86,000 copies/mL in tracheal aspirates. After 4 weeks of ganciclovir treatment, the patient improved clinically and was discharged. Currently he is doing well and able to do his routine activity without the need of oxygen. CONCLUSION: Timely management with ganciclovir is associated with favorable outcome in cytomegalovirus infection. Thus, it can be suggested that treatment should be initiated with ganciclovir if a patient with coronavirus disease 2019 has high cytomegalovirus load in tracheal aspirates, along with unexplained and prolonged clinical and/or radiological features.

Evaluation of Rapid Antigen Test as a Marker of SARS-CoV-2 Infectivity.

Background Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that emerged in late 2019 continues to spread globally. Reverse transcriptase polymerase chain reaction (RT-PCR), which is considered the gold standard for diagnosis, does not always indicate contagiousness. This study was planned to evaluate the performance of the rapid antigen test (RAT) with the duration of symptoms and the usefulness of these tests in determining the infectivity of patients by performing sub-genomic RT-PCR. Methodology This prospective, observational study was designed to compare the diagnostic value of the COVID-19 RAT (SD Biosensor, Korea) with COVID-19 RT-PCR (Thermo Fisher, USA) by serial testing of patients. To evaluate the infectivity of the virus, sub-genomic RT-PCR was performed on previous RAT and RT-PCR-positive samples. Results Of 200 patients, 102 were positive on both RT-PCR and RAT, with 87 patients serially followed and tested. The sensitivity and specificity of RAT were 92.73% and 93.33%, respectively, in symptomatic patients. The mean duration of RAT positivity was 9.1 days, and the mean duration of RT-PCR positivity was 12.6 days. Sub-genomic RT-PCR test was performed on samples that were reported to be positive by RAT, and 73/87 (83.9%) patients were found to be positive. RAT was positive in symptomatic patients whose duration of illness was less than 10 days or those with a cycle threshold value below 32. Conclusions Thus, RAT can be used as the marker of infectivity of SARS-CoV-2 in symptomatic patients, especially in healthcare workers.

Exaggerated levels of some specific TLRs, cytokines and chemokines in Japanese encephalitis infected BV2 and neuro 2A cell lines associated with worst outcome.

Japanese encephalitis (JE) disease, a viral brain fever is caused by Japanese encephalitis virus (JEV). Despite the availability of effective vaccines against this deadly infection, JE is the leading cause of epidemic viral encephalitis in children in South-east Asia. There is no treatment available for the JE disease which might be due to incomplete understanding of the pathogenesis of JE virus. The JEV infections lead to permanent neurological deficits even in those who survive from the infection. Activated microglia may play a potentially detrimental role by eliciting the expression of pro-inflammatory cytokines such as interleukin (IL)-1ß, IL-6, and tumor necrosis factor-α (TNF-α) influencing the surrounding brain tissue. Microglial activation, proinflammatory cytokine release and leukocytes trafficking are associated following JEV infection in central nervous system (CNS). How the pattern recognition receptors sense the viral nucleic acid and how the microglial and neuronal cells behaves following JEV infection is still unelucidated. There is scarcity of data on the expression levels of toll like receptors (TLRs), cytokines and chemokines in JEV infection in invitro model. To explore the molecular mechanisms of JEV infection of microglial cells and neuronal cells, we studied the expression profile of TLRs, cytokines and chemokines in JEV infected microglial cell line BV2 and Neuronal cell line Neuro 2A. For the present study, we developed the mouse model of encephalitis by intracerebral (IC) injection of JE virus for virus propagation, disease progression and damage study. Our results demonstrate the exaggerated release of some specific TLRs, cytokines and chemokines in invitro cell culture of microglial and Neuro 2A cell line, which are associated with bad outcome in invivo study.

Bacterial coinfections in COVID: Prevalence, antibiotic sensitivity patterns and clinical outcomes from a tertiary institute of Northern India.

Purpose: Bacterial coinfections are a leading cause of morbidity and mortality during viral infections including corona virus disease (COVID-19). The COVID-19 pandemic has highlighted the need to comprehend the complex connection between bacterial and viral infections. During the current pandemic, systematic testing of the COVID-19 patients having bacterial coinfections is essential to choose the correct antibiotics for treatment and prevent the spread of antimicrobial resistance (AMR). This study was planned to study the prevalence, demographic parameters, comorbidities, antibiotic sensitivity patterns, and outcomes in hospitalized COVID-19 patients with bacterial coinfections. Material and Methods: The COVID-19 patients having bacterial coinfections were selected for the study and analyzed for the prevalence, antibiotic sensitivities, comorbidities, and clinical outcomes. The bacterial isolates were identified and the antibiotic susceptibility testing was performed according to the Clinical and Laboratory Standards Institute (CLSI) guidelines. Results: Of the total 1,019 COVID-19 patients screened, 5.2% (n = 53) demonstrated clinical signs of bacterial coinfection. Escherichia coli were the most common isolate followed by Pseudomonas aeruginosa and Klebsiella spp. among the gram-negative bacterial infections. Coagulase-negative Staphylococcus species (CONS) and Staphylococcus aureus were most common among the gram-positive bacterial infections. The antibiotic sensitivity profiling revealed that colistin (99%), imipenem (78%), and fosfomycin (95%) were the most effective drugs against the gram-negative isolates while vancomycin (100%), teicoplanin (99%), and doxycycline (71%) were most potent against the gram-positive isolates. The analysis of the clinical parameters and outcomes revealed that among the COVID-19 patients with bacterial coinfections, the mortality rate was higher (39%) than the control group (17%) (P-value < 0.001). Conclusion: This study reveals the significantly increased rates of bacterial coinfections among COVID-19 patients which may lead to an increase in mortality. This study will guide the physicians at the primary level on the rational and correct usage of antibiotics in such COVID cases. Hence, systematic testing of COVID-19 patients with bacterial coinfections is the need of the hour to decrease the mortality rate and limit the spread of AMR.

Electroconductive PEDOT nanoparticle integrated scaffolds for spinal cord tissue repair.

BACKGROUND: Hostile environment around the lesion site following spinal cord injury (SCI) prevents the re-establishment of neuronal tracks, thus significantly limiting the regenerative capability. Electroconductive scaffolds are emerging as a promising option for SCI repair, though currently available conductive polymers such as polymer poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS) present poor biofunctionality and biocompatibility, thus limiting their effective use in SCI tissue engineering (TE) treatment strategies. METHODS: PEDOT NPs were synthesized via chemical oxidation polymerization in miniemulsion. The conductive PEDOT NPs were incorporated with gelatin and hyaluronic acid (HA) to create gel:HA:PEDOT-NPs scaffolds. Morphological analysis of both PEDOT NPs and scaffolds was conducted via SEM. Further characterisation included dielectric constant and permittivity variances mapped against morphological changes after crosslinking, Young's modulus, FTIR, DLS, swelling studies, rheology, in-vitro, and in-vivo biocompatibility studies were also conducted. RESULTS: Incorporation of PEDOT NPs increased the conductivity of scaffolds to 8.3 × 10-4 ± 8.1 × 10-5 S/cm. The compressive modulus of the scaffold was tailored to match the native spinal cord at 1.2 ± 0.2 MPa, along with controlled porosity. Rheological studies of the hydrogel showed excellent 3D shear-thinning printing capabilities and shape fidelity post-printing. In-vitro studies showed the scaffolds are cytocompatible and an in-vivo assessment in a rat SCI lesion model shows glial fibrillary acidic protein (GFAP) upregulation not directly in contact with the lesion/implantation site, with diminished astrocyte reactivity. Decreased levels of macrophage and microglia reactivity at the implant site is also observed. This positively influences the re-establishment of signals and initiation of healing mechanisms. Observation of axon migration towards the scaffold can be attributed to immunomodulatory properties of HA in the scaffold caused by a controlled inflammatory response. HA limits astrocyte activation through its CD44 receptors and therefore limits scar formation. This allows for a superior axonal migration and growth towards the targeted implantation site through the provision of a stimulating microenvironment for regeneration. CONCLUSIONS: Based on these results, the incorporation of PEDOT NPs into Gel:HA biomaterial scaffolds enhances not only the conductive capabilities of the material, but also the provision of a healing environment around lesions in SCI. Hence, gel:HA:PEDOT-NPs scaffolds are a promising TE option for stimulating regeneration for SCI.

Identifying and Implementing Strategies to Reduce the Risk of Self-Contamination of Health Care Workers Caused by Doffing of Personal Protective Equipment During the COVID-19 Pandemic.

During the current coronavirus disease (COVID-19) pandemic, it is estimated that tens of thousands of health care workers have been infected. The doffing of personal protective equipment (PPE) has been identified an important place and procedure that might influence the self-contamination of health care workers. More recent evidence suggests that, in addition to existing infection control standards, there is an urgent need for the incorporation of various recent information and advancements pertaining to structure and process to reduce the self-contamination of health care workers during the doffing of PPE.

Assessing a chip based rapid RTPCR test for SARS CoV-2 detection (TrueNat assay): A diagnostic accuracy study.

COVID-19 testing is required before admission of a patient in the hospitals, invasive procedures, major and minor surgeries etc. Real Time Polymerase chain reaction is the gold standard test for the diagnosis, but requires well equipped biosafety laboratory along with trained manpower. In this study we have evaluated the diagnostic accuracy of novel TrueNat molecular assay for detecting SARS CoV-2. TrueNat is a chip-based real time PCR test and works on portable, light weight, battery powered equipment and can be used in remote areas with poor infrastructure. In this study 1807 patients samples were collected for both TrueNat and RTPCR COVID-19 testing during study period. Of these 174 (9.7%) and 174 (15%) were positive by RTPCR and TrueNat respectively and taking results of RTPCR as gold standard TrueNat test showed a sensitivity, specificity and diagnostic accuracy of 69.5, 90.9% and 89.2% respectively. It can be concluded that TrueNat is a simple, easy to use, good rapid molecular diagnostic test for diagnosis of COVID-19 especially in resource limited settings and will prove to be a game changer of molecular diagnostics in future.

Pandoraea apista Bacteremia in a COVID-Positive Man: A Rare Coinfection Case Report from North India.

Pandoraea apista is a novel gram-negative bacillus usually isolated from respiratory specimens of cystic fibrosis patients. Few cases of bacteremia have also been reported due to this rare pathogen. Emergence of multidrug-resistant isolates of this bacillus is of grave concern. Here, we report a very interesting and unusual case of Pandoraea apista bacteremia in a coronavirus disease (COVID)-positive elderly diabetic man suffering from pneumonia. Prompt isolation and antibiotic sensitivity testing guided the patient's treatment and yielded favorable outcome. The need of automated methods for identification and sensitivity testing limits the reporting of this rare but important pathogen in hospital settings. Detailed research work and studies are needed in this direction to better understand this pathogen and its clinical manifestations for better patient outcome.

Evaluation of seven commercial RT-PCR kits for COVID-19 testing in pooled clinical specimens.

There are more than 350 real-time polymerase chain reaction (RT-PCR) coronavirus disease-2019 (COVID-19) testing kits commercially available but these kits have not been evaluated for pooled sample testing. Thus, this study was planned to compare and evaluate seven commercially available kits for pooled samples testing. Diagnostic accuracy of (1) TRUPCR SARS-CoV-2 Kit (Black Bio), (2) TaqPath RT-PCR COVID-19 Kit (Thermo Fisher Scientific), (3) Allplex 2019-nCOV Assay (Seegene), (4) Patho detect COVID-19 PCR kit (My Lab), (5) LabGun COVID-19 RT-PCR Kit (Lab Genomics, Korea), (6) Fosun COVID-19 RT-PCR detection kit (Fosun Ltd.), (7) Real-time Fluorescent RT-PCR kit for SARS CoV-2 (BGI) was evaluated on precharacterised 40 positive and 10 negative COVID-19 sample pools. All seven kits detected all sample pools with low Ct values (<30); while testing weak positive pooled samples with high Ct value (>30); the TRUPCR Kit, TaqPath Kit, Allplex Assay, and BGI RT-PCR kit showed 100% sensitivity, specificity, and accuracy. However, the Fosun kit, LabGun Kit, and Patho detect kit could detect only 90%, 85%, and 75% of weakly positive samples, respectively. We conclude that all seven commercially available RT-PCR kits included in this study can be used for routine molecular diagnosis of COVID-19. However, regarding performing pooled sample testing, it might be advisable to use those kits that performed best regarding positive identification in samples' pool, that is TRUPCR SARS-CoV-2 Kit, TaqPath RT-PCR COVID-19 Kit, Allplex 2019-nCOV Assay, and BGI Real-time RT-PCR kit for detecting SARS CoV-2.

The Spectrum of Gastrointestinal Symptoms in Patients With Coronavirus Disease-19: Predictors, Relationship With Disease Severity, and Outcome.

INTRODUCTION: We prospectively studied the frequency, spectrum, and predictors of gastrointestinal (GI) symptoms among patients with coronavirus disease-19 (COVID-19) and the relationship between GI symptoms and the severity and outcome. METHODS: Consecutive patients with COVID-19, diagnosed in a university hospital referral laboratory in northern India, were evaluated for clinical manifestations including GI symptoms, their predictors, and the relationship between the presence of these symptoms, disease severity, and outcome on univariate and multivariate analyses. RESULTS: Of 16,317 subjects tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA in their oropharyngeal and nasopharyngeal swabs during April-May 2020, 252 (1.5%) were positive. Of them, 208 (82.5%) were asymptomatic; of the 44 symptomatic patients, 18 (40.9%) had non-GI symptoms, 15 (34.1%) had a combination of GI and non-GI symptoms, and 11 (25.0%) had GI symptoms only. Thirty-three had mild-to-moderate disease, 8 severe, and 5 critical. Five patients (1.98%) died. On multivariate analysis, the factors associated with the presence of GI symptoms included the absence of contact history and presence of non-GI symptoms and comorbid illnesses. Patients with GI synptoms more often had severe, critical illness and fatal outcome than those without GI symptoms. DISCUSSION: Eighty-two percent of patients with COVID-19 were asymptomatic, and 10.3% had GI symptoms; severe and fatal disease occurred only in 5% and 2%, respectively. The presence of GI symptoms was associated with a severe illness and fatal outcome on multivariate analysis. Independent predictors of GI symptoms included the absence of contact history, presence of non-GI symptoms, and comorbid illnesses.(Equation is included in full-text article.).

Molecular epidemiology & therapeutic options of carbapenem-resistant Gram-negative bacteria.

Background & objectives: The growing incidence and the wide diversity of carbapenemase-producing bacterial strains is a major concern as only a few antimicrobial agents are active on carbapenem-resistant bacteria. This study was designed to study molecular epidemiology of carbapenem-resistant Gram-negative bacterial (GNB) isolates from the community and hospital settings. Methods: In this study, non-duplicate GNB were isolated from clinical specimens, and phenotypic test such as modified Hodge test, metallo ß-lactamase E-strip test, etc. were performed on carbapenem-resistant bacteria. Multiplex PCR was performed to identify the presence of blaIMP, blaVIM, blaKPC, blaOXA48, blaOXA23, blaSPM, blaGIM, blaSIM and blaNDM. Minimum inhibitory concentration (MIC) of colistin, fosfomycin, minocycline, chloramphenicol and tigecycline was also determined. Results: Of the 3414 GNB studied, carbapenem resistance was 9.20 per cent and maximum resistance (11.2%) was present at tertiary care centre, followed by secondary care (4%) and primary centre (2.1%). Among the carbapenem-resistant bacteria, overall, the most common isolate was Pseudomonas aeruginosa (24%). On multiplex PCR 90.3 per cent carbapenem-resistant isolates were positive for carbapenemase gene. The blaNDM(63%) was the most prevalent gene followed by blaVIM(18.4%). MIC results showed that 88 per cent carbapenem-resistant Enterobacteriaceae were sensitive to fosfomycin, whereas 78 per cent of P. aeruginosa and 85 per cent Acinetobacter spp. were sensitive to colistin. Interpretation & conclusions: Carbapenem resistance in GNB isolates from the community and hospital settings was found to be on the rise and should be closely monitored. In the absence of new antibiotics in pipeline and limited therapeutic options, prudent use of antibiotics and strict infection control practices should be followed in hospital to limit the emergence and spread of multidrug-resistant bacteria.

The Meniscus in Normal and Osteoarthritic Tissues: Facing the Structure Property Challenges and Current Treatment Trends.

The treatment of meniscus injuries has recently been facing a paradigm shift toward the field of tissue engineering, with the aim of regenerating damaged and diseased menisci as opposed to current treatment techniques. This review focuses on the structure and mechanics associated with the meniscus. The meniscus is defined in terms of its biological structure and composition. Biomechanics of the meniscus are discussed in detail, as an understanding of the mechanics is fundamental for the development of new meniscal treatment strategies. Key meniscal characteristics such as biological function, damage (tears), and disease are critically analyzed. The latest technologies behind meniscal repair and regeneration are assessed.

Can rapid dengue diagnostic kits be trusted? A comparative study of commercially available rapid kits for serodiagnosis of dengue fever.

BACKGROUND: Dengue virus infection is an important emerging disease of the tropical and subtropical regions and is mainly diagnosed by serological detection of NS1 antigen and IgM antidengue antibodies. Since enzyme-linked immunosorbent assay (ELISA) facilities are not easily available at most diagnostic centers, so most of them use various commercially available rapid diagnostic tests (RDTs) kits. AIMS AND OBJECTIVES: This study was designed to access the diagnostic accuracy of four commercially available and widely used RDTs for serodiagnosis of dengue virus infection in Indian laboratories. SUBJECTS AND METHODS: The study was conducted at Department of Microbiology, G.S.V.M Medical College, Kanpur, India, to estimate the sensitivity and specificity of following RDTs: (1) Dengue Cassette (Panbio, Australia), (2) Bioline Dengue Duo (SD Diagnostics, Korea), (3) Dengue Day 1 test (J Mitra and Co., India), and (4) Dengucheck Duo (Tulip Diagnostics, India) on 72 confirmed dengue serum samples that were positive by dengue reverse transcription-polymerase chain reaction, dengue NS1, and IgM ELISA along with 80 serum samples from nondengue febrile illness patients. RESULTS: The majority of the RDTs demonstrated low sensitivity but good specificity for detecting NS1 antigen. Detection of antidengue IgM antibodies by RDTs demonstrated low sensitivity ranging from 27.8% to 77.7%. However, specificity was generally higher (50%-86.2%) and more consistent across the assays. CONCLUSION: The study results differed markedly from the RDTs manufacturers' claimed performance characteristics. Therefore, the RDT results should be interpreted cautiously and ELISA should be performed as far as possible for serodiagnosis of dengue virus infection.

Regional dependency of bovine meniscus biomechanics on the internal structure and glycosaminoglycan content.

Menisci play a major role in the mechanical function of the knee. They are subjected to large compressive forces and as a result and due to its avascular structure, menisci are prone to irreparable damage. Meniscectomy was once a common procedure for damaged menisci, however alternative approaches involving meniscus regeneration to restore function are of current interest. In order to enable these regenerative strategies, it is of utmost importance to initially establish he structure/property/function relationships of native menisci. Therefore, this study explores the influence of major constituents of the meniscal extracellular matrix; namely the glycosaminoglycan (GAG), and the collagen fibre orientation on the mechanical properties of the bovine meniscus. GAG distribution and mechanical properties are mapped with respect to depth and regional variance within the meniscus. Results show that the inner zone of the meniscus has a significantly larger quantity of GAG compared to the peripheral zone. The tibial and femoral layers contain a higher quantity of GAG than the mid-section and collagen fibre alignment differed depending on region. Overall, it was established that the viscoelastic properties of the meniscus are determined by the co-dependent relationship between the solid and fluid fractions of the meniscus and this varied depending on region. The hydrophilic nature of the GAG molecules play an important role in maintaining the solid/fluid balance while collagen fibre orientation restricts fluid flow within tissue, combined these processes act to support the meniscus under compressive loads.