Drug exposure and risk factors of maculopathy in tamoxifen users.

Tamoxifen, a pivotal therapy for hormone receptor-positive breast cancer, is known for its efficacy in reducing breast cancer recurrence and mortality. However, concerns about potential ocular complications, particularly maculopathy, have emerged. This study aims to investigate the risk and associated factors of diverse macular conditions in tamoxifen users, considering drug exposure, demographics, and systemic diseases. A nationwide cohort of tamoxifen users, comprised of 14,267 tamoxifen users, was analyzed using the health insurance review and assessment database in South Korea. Demographic and clinical characteristics were examined, and the cumulative incidence of macular diseases was stratified by age and cumulative tamoxifen dosage. We conducted logistic regression analysis to identify potential risk factors among clinical variables such as age, sex, indications for tamoxifen use, and systemic diseases associated with various macular conditions. Additionally, Cox proportional hazard models were used to determine the baseline clinical characteristics predictive of these macular conditions, with subsequent calculation of hazard ratios. Cumulative incidences of overall macular diseases, other maculopathy excluding common macular diseases, and macular edema were 26.4, 11.4, and 6.5%, respectively. The incidence of various macular conditions increased with age and the cumulative tamoxifen dose. Age, cumulative dose group, and liver diseases demonstrated significant associations with overall macular diseases and maculopathy excluding common macular diseases in multivariate logistic regression analyses (all P < 0.05). Furthermore, age emerged as significant predictive factors of maculopathy in Cox proportional hazard models. Tamoxifen-induced maculopathy poses a concern for prescribing physicians and ophthalmologists, and this study provides valuable insights into its risk and risk factors. This study may contribute to evidence-based guidelines for tamoxifen maculopathy screening, emphasizing the importance of considering age, cumulative dose, and liver diseases for recommendation on screening timing and frequency.

Atypical Presentations of Hydroxychloroquine Retinopathy: A Case Series Study.

Background/Objective: Hydroxychloroquine retinopathy, traditionally characterized by parafoveal or pericentral outer retinal damage, is explored for atypical presentations in Asian patients. This challenges conventional beliefs regarding onset, retinopathy pattern, and associated visual field defects. Methods: Ninety-five patients diagnosed with hydroxychloroquine retinopathy at Hanyang University Hospital underwent screening from January 2010 to December 2023. Swept-source optical coherence tomography (SS-OCT), ultra-widefield fundus autofluorescence (UWF-FAF), and automated visual fields (VF) were employed for detailed structural and functional evaluations. Multifocal electroretinography was performed in selected cases requiring additional objective evidence of retinal toxicity. Results: Among 95 patients, 14 (14.7%) exhibited atypical presentations, including very early onset (n = 1), (far) peripheral-dominant damages (n = 4), perivascular involvement (n = 1), bitemporal hemianopsia due to nasal extensive lesions (n = 1), unilateral involvement (n = 2), and asymmetric involvement in retinopathy pattern or severity between the eyes (n = 7). These findings underscore the importance of utilizing expanded imaging techniques, such as ultra-widefield FAF imaging, to identify atypical presentations of retinal involvement. Conclusions: Screening physicians should consider these atypical presentations to ensure timely diagnosis and appropriate management in patients undergoing hydroxychloroquine treatment.

Screening practices and risk assessment for maculopathy in pentosan polysulfate users across different exposure levels.

In this population-based cohort study, we investigated screening practices for maculopathy and incidences of specific macular/retinal conditions in pentosan polysulfate (PPS) users and assessed the relationship between these outcomes and drug exposure levels. Using a health claims database that covers approximately 50 million Koreans, we identified 138,593 individuals who were prescribed PPS between 2010 and 2021. For the 133,762 PPS users who initiated therapy between 2012 and 2021, the cumulative PPS dose for each participant was evaluated, and based on their cumulative PPS dose, patients were categorized into the high-risk (≥ 500 g), low-risk (50-500 g), and minimal exposure (< 50 g) groups. We analyzed the performance and methods of these examination methods used between 2018 and 2021 and compared them among cumulative dose groups to determine whether high-risk users underwent maculopathy screening more frequently or appropriately. We assessed the cumulative incidence of overall macular degeneration and maculopathy excluding common macular diseases following PPS therapy initiation. Most PPS users (99.7%) received a cumulative PPS dose < 500 g and the high- and low-risk groups comprised 445 (0.3%) and 22,185 (16.6%) patients, respectively. During the study period, monitoring examinations were conducted in 52.6% and 49.4% of high- and low-risk patients, respectively, revealing no significant difference between the two groups (P = 0.156). No significant differences were observed in the annual percentages of patients receiving ophthalmic examinations between the high- and low-risk groups (all P > 0.05). The cumulative incidences of overall macular degeneration and maculopathy excluding common macular diseases in high-risk users were 19.3% and 9.0%, respectively, which were significantly different from those of low-risk users (both P < 0.001). Multivariate Cox regression analysis revealed significantly higher risks of maculopathy excluding common macular diseases in the low- (Hazard ratio [HR] of 1.55 [95% CI 1.13-2.12]) and high-risk groups (HR of 1.66 [95% CI 1.22-2.27]) compared to the minimal exposure group. Our findings suggest a need for increased emphasis on PPS maculopathy screening in high-risk patients, highlighting raising awareness regarding exposure-dependent risks and the establishment of screening guidelines.

COVID-19 Vaccine-Associated Uveitis in Patients With a History of Uveitis.

Importance: Understanding the potential risk of uveitis recurrence after COVID-19 vaccination in individuals with a history of uveitis is crucial for vaccination strategies and clinical monitoring. Objective: To investigate the risk of uveitis recurrence after COVID-19 vaccination in a cohort of individuals with a history of uveitis. Design, Setting, and Participants: This retrospective population-based cohort study included individuals diagnosed with uveitis between January 1, 2015, and February 25, 2021, in South Korea. After excluding individuals without COVID-19 vaccination or with SARS-CoV-2 infection, individuals with a history of uveitis who had received at least 1 dose of a messenger RNA (BNT162b2 [Pfizer-BioNTech] or mRNA-1273 [Moderna]) or adenovirus vector-based (ChAdOx1 [AstraZeneca] or Ad26.COV2.S [Janssen]) COVID-19 vaccine were included. Data were analyzed from February 26, 2021, to December 31, 2022. Exposure: Demographic and clinical data, along with vaccination details, were retrieved from the Korean National Health Insurance Service and Korea Disease Control and Prevention Agency databases. Main Outcomes and Measures: Outcomes of interest were incidence and risk of postvaccination uveitis in association with different COVID-19 vaccines and periods before and after COVID-19 vaccination. Uveitis was categorized by onset (early, within 30 days, or delayed) and type (anterior or nonanterior). Hazard ratios (HRs) with 95% CIs were calculated to evaluate the risk of uveitis following COVID-19 vaccination, stratified according to vaccine type and vaccination period. Results: Of 543 737 individuals with history of uveitis, 473 934 individuals (mean [SD] age, 58.9 [17.4] years; 243 127 [51.3] female) had documented COVID-19 vaccination and were included in analysis. The cumulative incidence of postvaccination uveitis was 8.6% at 3 months, 12.5% at 6 months, and 16.8% at 1 year, predominantly of the anterior type. Variations in the risk of postvaccination uveitis were observed across different vaccines and intervaccination periods. The risk of early postvaccination uveitis was increased for individuals receiving the BNT162b2 (HR, 1.68; 95% CI, 1.52-1.86), mRNA-1273 (HR, 1.51; 95% CI, 1.21-1.89), ChAdOx1 (HR, 1.60; 95% CI, 1.43-1.79), and Ad26.COV2.S (HR, 2.07; 95% CI, 1.40-3.07) vaccines. The risk of uveitis was higher particularly between the first and second vaccination doses (HR, 1.64; 95% CI, 1.55-1.73). Conclusions and Relevance: These findings suggest that there was an elevated risk of uveitis following COVID-19 vaccination, with the vaccine type and period mediating this risk. For individuals with a history of uveitis, clinicians should consider the potential risk of uveitis recurrence in vaccination strategies and clinical monitoring.

Nationwide Screening Practices for Tamoxifen Retinal Toxicity in South Korea: A Population-Based Cohort Study.

(1) Background/Objectives: To investigate the nationwide screening practices and trends in tamoxifen retinal toxicity (tamoxifen retinopathy) in South Korea using national health insurance claims data. (2) Methods: A total of 43,848 patients who started tamoxifen therapy between 2015 and 2020 and had no prior ophthalmic diseases or other conditions requiring screening for retinopathy were included. The annual numbers of tamoxifen users and new initiators of tamoxifen therapy were assessed. The screening examinations were separated into baseline (first ophthalmic examination after tamoxifen administration) and subsequent monitoring examinations. The timing and modalities for the baseline and subsequent monitoring examinations performed between 2015 and 2021 were assessed in tamoxifen users. (3) Results: The annual number of tamoxifen users increased over the study period from 54,056 in 2015 to 81,720 in 2021. The number of patients who underwent ophthalmic examination after tamoxifen administration was 8961 (20.4%). Baseline screening was performed in 6.5% of patients within 1 year of use, and subsequent monitoring was performed in 27.8% of patients who underwent baseline screening. Funduscopy or fundus photography was performed most commonly for baseline screening and subsequent monitoring (99.0% and 98.6%, respectively), while optical coherence tomography was performed only in 21.9% and 29.6% of baseline and monitoring examinations, respectively. The average number of monitoring examinations per year was 0.68 ± 0.45. Although the annual percentage of patients receiving a baseline examination within 1 year gradually increased over time, the percentage of those with subsequent monitoring performed within 1 year was similar over the study period. (4) Conclusions: Our finding, appropriate screening in a small proportion of patients receiving tamoxifen, suggests the need to promote awareness among healthcare professionals and develop a standardized approach for screening for tamoxifen retinopathy.

Comparison of Incidence or Recurrence of Anterior Uveitis in Patients with Ankylosing Spondylitis Treated with Tumor Necrosis Factor Inhibitors.

Background: Anterior uveitis (AU) is a significant concern in patients with ankylosing spondylitis (AS), and the choice of tumor necrosis factor inhibitors (TNFi) as a treatment modality raises questions regarding its effects on AU. We compared the effects of TNFi on AU in patients with AS. Methods: Patients diagnosed with AS and treated with at least one TNFi, including anti-TNFα antibodies (adalimumab and infliximab) or a soluble TNF receptor molecule (etanercept), between January 2010 and December 2022, were retrospectively reviewed. We compared the recurrence rate of AU in patients with a history of uveitis and the incidence of new-onset AU in those without a history of uveitis among the three TNFi groups. We also compared the effects of two different TNFi agents in patients who underwent TNFi switching. Results: Within two years of treatment initiation, there was no significant difference in AU recurrence among the three TNFi groups. However, the incidence of new-onset AU was significantly higher in the etanercept group than in the adalimumab group (26.4% vs. 6.3%; p = 0.024). After two years, the AU recurrence rate was significantly lower in the adalimumab group than in the other groups (p < 0.001). Among patients who underwent anti-TNFi switching, adalimumab treatment was associated with a significantly lower incidence of uveitis than etanercept (p = 0.023). Conclusion: In the short-term period following TNFi therapy, etanercept induced new-onset AU more frequently than adalimumab in patients with AS. Adalimumab recipients experienced fewer AU recurrences during the subsequent long-term period compared to other TNFi recipients.

Demographic and clinical characteristics associated with screening practices for hydroxychloroquine retinopathy.

In this nationwide population-based cohort study, we investigated the demographic and clinical characteristics associated with hydroxychloroquine retinopathy screening using the National Health Insurance Review and Assessment database in South Korea. This study included a total of 32,732 at-risk patients, identified based on having been prescribed hydroxychloroquine for at least 6 months, and 15,477 long-term (> 5 years) users between January 2010 and December 2020. Participants were categorized based on the performance of baseline examinations (within 1 year of hydroxychloroquine use) and monitoring examinations (after 5 years of hydroxychloroquine use). Demographic and clinical factors, including hospitals and medical specialties prescribing hydroxychloroquine, indications for hydroxychloroquine use, and prescription details, were compared between groups. Significant differences were found in sex, residence, departments and hospitals (primary vs. referral centers) where hydroxychloroquine was prescribed, diagnosis for hydroxychloroquine therapy, and mean daily dose between patients who did and did not undergo baseline or monitoring examinations (all P < 0.01). Patients who received hydroxychloroquine prescriptions from referral hospitals were more likely to undergo baseline and monitoring examinations compared to those from primary clinics (both P < 0.001). Additionally, patients who received hydroxychloroquine prescriptions from the rheumatology department and had systemic lupus erythematosus were more likely to undergo baseline and monitoring examinations compared to other patients (all P < 0.001). There were notable differences in the number of modalities used for retinopathy screening between primary and referral centers (P < 0.001). Our findings suggest that several clinical factors related to hydroxychloroquine prescription and screening centers are associated with retinopathy screening practices.

Nationwide Usage of Pentosan Polysulfate and Practice Patterns of Pentosan Polysulfate Maculopathy Screening in South Korea.

OBJECTIVE: To investigate the nationwide use of pentosan polysulfate (PPS) and screening practices for PPS maculopathy (PPM), with a focus on the timing and modalities used. DESIGN: Population-based cohort study. PARTICIPANTS: For evaluation of nationwide usage, 133 762 individuals who received PPS prescriptions between 2012 and 2021 were included. To investigate practice patterns, 55 487 individuals (referred to as overall users) who initiated PPS therapy between 2018 and 2020 were identified using the Health Insurance Review and Assessment database. After excluding patients with ophthalmic diseases before PPS administration, 34 857 PPS users without prior ophthalmic diseases were identified. METHODS: Ophthalmic examinations performed after initiating PPS therapy were categorized as baseline and subsequent monitoring examinations. The timing and modalities employed for these examinations were analyzed. The annual trends in PPS utilization and maculopathy screening were evaluated by assessing the number of PPS users and determining the proportion of patients receiving retinal/macular examinations among these users. MAIN OUTCOME MEASURES: Performance of baseline and subsequent monitoring examinations and timing and modalities used for screening. RESULTS: The number of PPS users dramatically increased annually over the study period from 5494 in 2012 to 40 451 in 2021. However, the majority of PPS users did not undergo baseline or subsequent monitoring examinations for PPM. Only 27.2% and 12.4% of PPS users without prior ophthalmic disease underwent baseline and monitoring examinations, respectively. Funduscopy/fundus photography was the most commonly utilized, whereas OCT and fundus autofluorescence (FAF) were performed in only 45.2% and 5.3% of the PPS users without prior ophthalmic diseases for monitoring, respectively. The performance of the screening examinations differed significantly across the 3 different daily dose and duration groups (all P < 0.05). CONCLUSIONS: This study highlights the lack of performance of baseline and monitoring examinations for maculopathy in most patients taking PPS in South Korea. The limited use of OCT and FAF suggests potential insensitivity in detecting PPM. These findings emphasize the need for improvements in screening practices, including increased awareness and referrals to ophthalmologists, utilization of more sensitive modalities, and regular monitoring to enable early detection of PPM. FINANCIAL DISCLOSURE(S): The authors have no proprietary or commercial interest in any materials discussed in this article.

Aggregation-Induced Stimulated Emission of 100% Dye Microspheres.

Dyes with aggregation-induced emission (AIE) properties have gained interests due to their bright luminescence in solid-state aggregates. While fluorescence from AIE dyes have been widely exploited, relatively little is known about aggregation-induced stimulated emission. Here, we investigated stimulated emission of tetraphenylethene (TPE)-based organoboron AIE dyes, TPEQBN, in thin films and in microcavity lasers. Using femtosecond pump-probe spectroscopy, gain coefficients up to 230 cm-1 at 500 nm were measured. Using rate equations, we analyzed concentration- and pump-dependent gain dynamics as well as laser build up dynamics. During laser oscillation, radiative stimulated emission allows high instantaneous quantum yield greater than 90% to be achieved. We fabricated solid-state microspheres made of 100% AIE dyes via microfluidic emulsion and solvent evaporation method. Coupled with high gain and high refractive index of 1.76, microspheres as small as 2 µm in diameter showed lasing by nanosecond pumping with a threshold of ~10 pJ µm-2. Polymer coated, but not bare, microspheres were internalized by live cells and generated narrowband cavity mode emission from within the cytoplasm. Our work shows the potential of AIE dyes as laser materials.

Facile layer-by-layer fabrication of semiconductor microdisk laser particles.

Semiconductor-based laser particles (LPs) with exceptionally narrowband spectral emission have been used in biological systems for cell tagging purposes. Fabrication of these LPs typically requires highly specialized lithography and etching equipment, and is typically done in a cleanroom environment, hindering the broad adoption of this exciting new technology. Here, using only easily accessible laboratory equipment, we demonstrate a simple layer-by-layer fabrication strategy that overcomes this obstacle. We start from an indium phosphide (InP) substrate with multiple epitaxial indium gallium arsenide phosphide (InGaAsP) layers which are sequentially processed to yield LPs of various compositions and spectral properties. The LPs isolated from each layer are characterized, exhibiting excellent optical properties with lasing emission full width at half maximum as narrow as < 0.3 nm and typical thresholds of approximately 6 pJ upon excitation using a 3 ns pulse duration 1064 nm pump laser. The high quality of these particles renders them suitable for large-scale biological experiments including those requiring spectral multiplexing.

The Apoptotic and Anti-Warburg Effects of Brassinin in PC-3 Cells via Reactive Oxygen Species Production and the Inhibition of the c-Myc, SIRT1, and ß-Catenin Signaling Axis.

Though Brassinin is known to have antiangiogenic, anti-inflammatory, and antitumor effects in colon, prostate, breast, lung, and liver cancers, the underlying antitumor mechanism of Brassinin is not fully understood so far. Hence, in the current study, the apoptotic mechanism of Brassinin was explored in prostate cancer. Herein, Brassinin significantly increased the cytotoxicity and reduced the expressions of pro-Poly ADP-ribose polymerase (PARP), pro-caspase 3, and B-cell lymphoma 2 (Bcl-2) in PC-3 cells compared to DU145 and LNCaP cells. Consistently, Brassinin reduced the number of colonies and increased the sub-G1 population and terminal deoxynucleotidyl transferase (TdT) dUTP Nick-End Labeling (TUNEL)-positive cells in the PC-3 cells. Of note, Brassinin suppressed the expressions of pyruvate kinase-M2 (PKM2), glucose transporter 1 (GLUT1), hexokinase 2 (HK2), and lactate dehydrogenase (LDH) as glycolytic proteins in the PC-3 cells. Furthermore, Brassinin significantly reduced the expressions of SIRT1, c-Myc, and ß-catenin in the PC-3 cells and also disrupted the binding of SIRT1 with ß-catenin, along with a protein-protein interaction (PPI) score of 0.879 and spearman's correlation coefficient of 0.47 being observed between SIRT1 and ß-catenin. Of note, Brassinin significantly increased the reactive oxygen species (ROS) generation in the PC-3 cells. Conversely, ROS scavenger NAC reversed the ability of Brassinin to attenuate pro-PARP, pro-Caspase3, SIRT1, and ß-catenin in the PC-3 cells. Taken together, these findings support evidence that Brassinin induces apoptosis via the ROS-mediated inhibition of SIRT1, c-Myc, ß-catenin, and glycolysis proteins as a potent anticancer candidate.

Selective Extracellular Matrix Guided Mesenchymal Stem Cell Self-Aggregate Engineering for Replication of Meniscal Zonal Tissue Gradient in a Porcine Meniscectomy Model.

Degenerative meniscus tears (DMTs) are prevalent findings in osteoarthritic knees, yet current treatment is mostly limited to arthroscopic partial meniscectomy rather than regeneration, which further exacerbates arthritic changes. Translational research regarding meniscus regeneration is hindered by the complex, composite nature of the meniscus which exhibit a gradient from inner cartilage-like tissue to outer fibrous tissue, as well as engineering hurdles often requiring growth factors and cross-linking agents. Here, a meniscus zonal tissue gradient is proposed using zone-specific decellularized meniscus extracellular matrix (DMECM) and autologous synovial mesenchymal stem cells (SMSC) via self-aggregation without the use of growth factors or cross-linking agents. Combination with zone-specific DMECM during self-aggregation of MSCs forms zone-specific meniscus tissue that reflects the respective DMECM harvest site. The implantation of these constructs leads to the regeneration of meniscus tissue resembling the native meniscus, demonstrating inner cartilaginous and outer fibrous characteristics as well as recovery of native meniscal microarchitecture in a porcine partial meniscectomy model at 6 months. In all, the findings offer a potential regenerative therapy for DMTs that may improve current partial meniscectomy-based patient care.

All-natural-molecule, bioluminescent photodynamic therapy results in complete tumor regression and prevents metastasis.

Self-luminescent photodynamic therapy (PDT) has gained attention owing to its potential to enable effective phototherapy without the bottleneck of shallow light penetration into tissues. However, the biosafety concerns and low cytotoxic effect of self-luminescent reagents in vivo have been problems. Here, we demonstrate efficacious bioluminescence (BL)-PDT by using bioluminescence resonance energy transfer (BRET) conjugates of a clinically approved photosensitizer, Chlorin e6, and a luciferase, Renilla reniformis; both derived from biocompatible, natural molecules. With over 80% biophoton utilization efficiency and membrane-fusion liposome-assisted intracellular delivery, these conjugates produce effective, targeted cancer cell killing. Specifically, in an orthotopic mouse model of 4T1 triple-negative breast cancer, BL-PDT showed strong therapeutic effects on large primary tumors and a neoadjuvant outcome in invasive tumors. Furthermore, BL-PDT resulted in complete tumor remission and prevention of metastasis for early-stage tumors. Our results demonstrate the promise of molecularly-activated, clinically viable, depth-unlimited phototherapy.

Precise photoelectrochemical tuning of semiconductor microdisk lasers.

Micro- and nano-disk lasers have emerged as promising optical sources and probes for on-chip and free-space applications. However, the randomness in disk diameter introduced by standard nanofabrication makes it challenging to obtain deterministic wavelengths. To address this, we developed a photoelectrochemical (PEC) etching-based technique that enables us to precisely tune the lasing wavelength with sub-nanometer accuracy. We examined the PEC mechanism and compound semiconductor etching rate in diluted sulfuric acid solution. Using this technique, we produced microlasers on a chip and isolated particles with distinct lasing wavelengths. Our results demonstrate that this scalable technique can be used to produce groups of lasers with precise emission wavelengths for various nanophotonic and biomedical applications.

Apoptotic and DNA Damage Effect of 1,2,3,4,6-Penta-O-galloyl-beta-D-glucose in Cisplatin-Resistant Non-Small Lung Cancer Cells via Phosphorylation of H2AX, CHK2 and p53.

Herein, the apoptotic mechanism of 1,2,3,4,6-penta-O-galloyl-ß-D-glucopyranose (PGG) was examined in cisplatin-resistant lung cancer cells. PGG significantly reduced viability; increased sub-G1 accumulation and the number of terminal deoxynucleotidyl transferase (TdT) dUTP Nick-End Labeling (TUNEL)-positive cells; induced the cleavage of poly (ADP-ribose) polymerase (PARP), caspases (8,9,3,7), B-cell lymphoma protein 2 (Bcl-2)-associated X (Bax) and phosphatase and tensin homolog deleted on chromosome 10 (PTEN); and attenuated the expression of p-AKT, X-linked inhibitor of apoptosis protein (XIAP), Bcl-2, Bcl-xL and survivin in A549/cisplatin-resistant (CR) and H460/CR cells. Notably, PGG activated p53, p-checkpoint kinase 2 (CHK2) and p-H2A histone family member X (p-H2AX), with increased levels of DNA damage (DSBs) evaluated by highly expressed pH2AX and DNA fragmentation registered on comet assay, while p53 knockdown reduced the ability of PGG to reduce viability and cleave caspase 3 and PARP in A549/CR and H460/CR cells. Additionally, PGG treatment suppressed the growth of H460/CR cells in Balb/c athymic nude mice with increased caspase 3 expression compared with the cisplatin group. Overall, PGG induces apoptosis in cisplatin-resistant lung cancer cells via the upregulation of DNA damage proteins such as γ-H2AX, pCHK2 and p53.

Circumferential Rim Augmentation Suture Around the Perimeniscal Capsule Decreases Meniscal Extrusion and Progression of Osteoarthritis in Rabbit Meniscus Root Tear Model.

BACKGROUND: We recently analyzed the joint capsule adjacent to the medial meniscus and found that the perimeniscal joint capsule has collagen fiber orientation similar to that of circumferential meniscal fibers, potentially playing a role in preventing extrusion. PURPOSE: To analyze the meniscal extrusion prevention potential of the circumferential rim augmentation suture around the perimeniscal capsule in a rabbit root tear model and analyze the biomechanical function in a porcine cadaveric knee. STUDY DESIGN: Controlled laboratory study. METHODS: Rabbit medial meniscus root tear models were divided into 3 experimental groups: root tear, root tear and suture repair, and root tear and circumferential rim augmentation suture. As for the circumferential rim augmentation suture procedure, a suture was placed to circumscribe the outer rim of the medial meniscus and passed through bone tunnels located at the tibial insertion of each root. After 4 and 8 weeks, meniscal extrusion was analyzed by micro-computed tomography, gross morphology, and histologic analysis of the medial femoral cartilage. For biomechanical analysis, porcine knees were divided into groups similar to rabbit experiments. Tibiofemoral contact parameters were assessed using a pressure mapping sensor system after applying a load of 200 N on the knee joint. RESULTS: The root tear and circumferential rim augmentation suture group showed less meniscal extrusion, less gap within the tear site, and less cartilage degeneration compared with other groups after 4 and 8 weeks of surgery in the rabbit root tear model. Biomechanical analysis showed the root tear and circumferential rim augmentation suture group had larger contact area and lower peak contact pressure compared with root tear and root tear and suture repair groups. CONCLUSION: The circumferential rim augmentation suture reduced the degree of meniscal extrusion while restoring meniscal function, potentially preventing progression of arthritis in a rabbit root tear model and porcine knee biomechanical analysis. CLINICAL RELEVANCE: The circumferential rim augmentation suture may be a novel augmentation option during root tear treatment.

Droplet microfluidic generation of a million optical microparticle barcodes.

Micron-scale barcode particles enable labelling of small objects. Here, we demonstrate high-throughput barcode fabrication inside a microfluidic chip that can embed multiple, dye-doped high quality-factor whispering gallery mode cavities inside aqueous droplets at kilohertz rates. These droplets are then cured to form polyacrylamide hydrogel beads as small as 30 µm in diameter. Optical resonance spectra of the embedded cavities provide the hydrogels with unique barcodes with their diversity combinatorically scaled with the number of embedded cavities. Using 3 cavities per hydrogel, we obtain approximately one million uniquely identifiable, optically readable barcode microparticles.

Fabrication of decellularized meniscus extracellular matrix according to inner cartilaginous, middle transitional, and outer fibrous zones result in zone-specific protein expression useful for precise replication of meniscus zones.

Meniscus is a fibrocartilage composite tissue with three different microstructual zones, inner fibrocartilage, middle transitional, and outer fibrous zone. We hypothesized that decellularized meniscus extracellular matrix (DMECM) would have different characteristics according to zone of origin. We aimed to compare zone-specific DMECM in terms of biochemical characteristics and cellular interactions associated with tissue engineering. Micronized DMECM was fabricated from porcine meniscus divided into three microstructural zones. Characterization of DMECM was done by biochemical and proteomic analysis. Inner DMECM showed the highest glycosaminoglycan content, while middle DMECM showed the highest collagen content among groups. Proteomic analysis showed significant differences among DMECM groups. Inner DMECM showed better adhesion and migration potential to meniscus cells compared to other groups. DMECM resulted in expression of zone-specific differentiation markers when co-cultured with synovial mesenchymal stem cells (SMSCs). SMSCs combined with inner DMECM showed the highest glycosaminoglycan in vivo. Outer DMECM constructs, on the other hand, showed more fibrous tissue features, while middle DMECM constructs showed both inner and outer zone characteristics. In conclusion, DMECM showed different characteristics according to microstructural zones, and such material may be useful for zone-specific tissue engineering of meniscus.

Compact Quantum-Dot Microbeads with Sub-Nanometer Emission Linewidth.

Fluorescent microbeads are widely used for applications in life sciences and medical diagnosis. The spectral contrast and sharpness of photoluminescence are critical in the utilities of microbeads for imaging and multiplexing. Here, we demonstrate microbeads capable of generating single-peak laser emission with a sub-nanometer linewidth. The microbeads are made of quantum dots that are tightly packed and crosslinked via ligand exchange for high optical gain and refractive index as well as material stability. Bright single-mode lasing with no photobleaching is achieved with particle diameters as small as 1.5 µm in the air. Sub-nm lasing emission is maintained even inside high-index surroundings, such as organic solvents and biological tissues. Feasibility of intracellular tagging and multi-color imaging in vivo is demonstrated.