Search

Background: The objective of the COMET (COllection of MEtabolic Tissues) biobank project is to create a high-quality collection of insulin-sensitive tissues (liver, muscle, adipose tissues, and epiploic artery) and blood sample derivatives (plasma, serum, DNA and RNA), collected from 270 grade 2-3 obese patients undergoing bariatric surgery. Relevant data on patient such as clinical/biological characteristics and sample handling are also collected. For this, our aim was to establish a Quality Management System (QMS) to meet the reliability and quality requirements necessary for its scientific exploitation., Materials and Methods: The COMET QMS includes: (1) Quality Assurance to standardize all stages of the biobanking process, (2) Quality Controls on samples from the first patients included in order to validate the sample management process and ensure reproducible quality; and 3) "in process" Quality Controls to ensure the reliability of the storage procedures and the stability of the samples over time., Results: For serum and plasma, several corrective actions, such as temperature handling and centrifugation conditions, were made to the protocol and led to improvement of the volume and quality of samples. Regarding DNA, all samples evaluated achieved a satisfactory level of purity and integrity and most of them yielded the required DNA quantity. All frozen tissue samples had RNAs of good purity. RNA quality was confirmed by RIN, achieving values in most cases over 7 and efficient amplification of housekeeping genes by RT-qPCR, with no significant differences among samples from the same tissue type. In the "in process" Quality Controls, DNA, RNA, and histological integrity of tissues showed no differences among samples after different preservation times., Conclusion: Quality Control results have made it possible to validate the entire biobank process and confirm the utility of implementing QMS to guarantee the quality of a biospecimen collection., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Servais et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Purpose: To assess risk factors of rejection after penetrating keratoplasty (PKP)., Methods: This retrospective monocentric study assessed risk factors for rejection in patients who underwent PKP at Montpellier University Hospital between June 2005 and September 2018. Graft and donor data were obtained from our tissue bank in Montpellier. Clinical data of recipients were recorded from medical files. Survival was estimated by the Kaplan-Meir method. Potential risk factors of rejection were assessed by multivariate Cox proportional hazards analysis, estimating hazard ratios (HR) and 95% confidence intervals (CI)., Results: Among the 316 consecutive patients (59% male, mean SD] age 52 [17]), 360 eyes underwent PKP. Indications for PKP were bullous keratopathy (27%), infectious keratitis (20%), and keratoconus (15%). The median follow-up was 44 months (IQR 22-73). The overall graft survival and irreversible rejection rate at 5 years were 70% and 29%, respectively. Factors associated with risk of rejection were prior indication for graft rejection (SHR [CI 95%] = 7.8 [2.6-23.1]), trauma (SHR [CI 95%] = 3.6 [1.1-11.7]), and infectious keratitis (SHR [CI 95%] = 2.7 [1.2-11.1]), history of corneal neovascularization (SHR [CI 95%] = 2.1 [1.2-3.8]), hypertonia (SHR [CI 95%] = 2.8 [1.8-4.3]), and mixed sex matching (SHR [CI 95%] = 2.0 [1.01-4.0])., Conclusion: The significant risk factors of graft rejection after PKP found in this study agree with those from major international cohorts: prior indication for graft rejection, history of neovascularization and high intraocular pressure. Sex matching donor-recipient is a most recent parameter in the literature confirmed by the present analysis., Trial Registration: ClinicalTrials.gov Identifier: NCT04791696., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Aim: Diagnosis of nonalcoholic steatohepatitis (NASH) relies on liver biopsy. Noninvasive tools would be useful to target patients to refer for a biopsy. We aimed to determine the diagnostic value of the triglycerides and glucose (TyG) index, an insulin-resistance indicator, to predict NASH., Methods: Our study included grade II-III obese patients aged 18-65 years undergoing bariatric surgery and included in the COMET (COllection of MEtabolic Tissues) biobank (NCT02861781). Liver biopsies performed during bariatric surgery were collected from the biobank along with blood derivatives. Biopsies were analysed according to the steatosis, activity and fibrosis (SAF) scoring system to diagnose NASH, nonalcoholic fatty liver disease (NAFLD), and fibrosis. Logistic regression models were performed to identify factors predicting NASH, NAFLD, and fibrosis., Results: Of 238 analysed subjects (mean age 43±12 years, 33.6% men), 29% had type 2 diabetes. Steatosis was present in 67.2%, while NASH and advanced fibrosis (stage F3) were diagnosed in 18.1% and 2.9% respectively. TyG index was independently associated with NASH (odds ratio (OR): 4.7 [95% confidence interval: 2.3;9.5] P < 0.0001), NAFLD (OR: 2.0 [1.1;3.7] P = 0.03) and stages 2-3 fibrosis (OR: 4.0 [1.5;10.8] P = 0.007). NASH was also predicted by gamma-glutamyl transferase (GGT) with an area under the ROC curve: 0.79 [0.71;0.87 P = 0.04] for GGT and TyG index combined., Conclusion: In our cohort of severely obese patients, TyG index, when associated with GGT level, exhibited high diagnostic performance to predict NASH. Although validation in larger populations is needed, this result may be of considerable clinical value to predict need for liver biopsy., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests, (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

Constitution of biobank of human tissues requires careful handling and storage of biological material, to guarantee the quality of samples. Tissue preparation is also critical for further applications such as transcriptomic profiling. In this study, our aim was to evaluate the impact of different disruption techniques (FastPrep-24 instrument, GentleMACS dissociator, and syringe/needle) and homogenizing buffers (RLT versus QIAzol) on RNA purity and quality of metabolic tissues (adipose tissues, liver and skeletal muscle) present in the COMET Biobank. For all homogenization methods used and tissue types, the A260/280 ratios reached values ≥ 1.8, which are in the range of what is found in human tissues and cell lines, while the A260/230 ratios were however ≤ 1.8, with the lowest value obtained with GentleMACS Dissociator. In addition, GentleMACS Dissociator combined with QIAzol reagent gave the highest RIN value and 28S/18S ratio for all tissues tested, except for muscle. Performing RT-qPCR, Ct values for different housekeeping genes can be influenced by extraction methods and RNA quality of samples. In conclusion, we have demonstrated that different disruption techniques and homogenizing buffers impact the purity and some quality markers of RNA, and can also impact quantification of mRNAs by RT-qPCR in human metabolic tissues., (© 2021. The Author(s).)

Background: Standard operating rooms (SOR) are assumed to be the best place to prevent microbial contamination when performing tissue procurement. However, mobilizing an operating room is time and cost consuming if no organ retrieval is performed. In such case, non-operating dedicated rooms (NODR) are usually recommended by European guidelines for tissue harvesting. Performing the tissue retrieval in the Intensive care unit (ICU) when possible might be considered as it allows a faster and simpler procedure., Objective: Our primary objective was to study the relationship between the risk of microbial contamination and the location (ICU, SOR or NODR) of the tissue retrieval in heart-beating and non-heart-beating deceased donors., Materials and Method: We retrospectively reviewed all deceased donors' files of the local tissue banks of Montpellier and Marseille from January 2007 to December 2014. The primary endpoint was the microbial contamination of the grafts. We built a multivariate regression model and used a GEE (generalized estimating equations) allowing us to take into account the clustered structure of our data., Results: 2535 cases were analyzed involving 1027 donors. The retrieval took place for 1189 in a SOR, for 996 in a hospital mortuary (NODR) and for 350 in an ICU. 285 (11%) microbial contaminations were revealed. The multivariate analysis found that the location in a hospital mortuary was associated with a lower risk of contamination (OR 0.43, 95% CI [0.2-0.91], p = 0.03). A procurement performed in the ICU was not associated with a significant increased risk (OR 0.62, 95% CI [0.26-1.48], p = 0.4)., Conclusion: According to our results, performing tissue procurement in dedicated non-sterile rooms could decrease the rate of allograft tissue contamination. This study also suggests that in daily clinical practice, transferring patients from ICU to SOR for tissue procurement could be avoided as it does not lead to less microbial contamination., Competing Interests: The authors have declared that no competing interests exist.

In this study, a highly porous collagen-based biodegradable scaffold was developed as an alternative to synthetic, non-degradable corneal implants. The developed method involved lyophilization and subsequent stabilization through N-ethyl-N′-[3-dimethylaminopropyl] carbodiimide/N-hydroxy succinimide (EDC/NHS) cross-linking to yield longer lasting, porous scaffolds with a thickness similar to that of native cornea (500 μm). For collagen-based scaffolds, cross-linking is essential; however, it has direct effects on physical characteristics crucial for optimum cell behavior. Hence, the effect of cross-linking was studied by examining the influence of cross-linking on pore size distribution, bulk porosity and average pore size. After seeding the foam with human corneal keratocytes, cell proliferation, cell penetration into the scaffold and ECM production within the scaffold were studied. After a month of culture microscopical and immunohistochemical examinations showed that the foam structure did not undergo any significant loss of integrity, and the human corneal keratocytes populated the scaffold with cells migrating both longitudinally and laterally, and secreted some of the main constituents of the corneal ECM, namely collagen types I, V and VI. The foams had a layer of lower porosity (skin layer) both at the top and the bottom. Foams had an optimal porosity (93.6%), average pore size (67.7 μm), and chemistry for cell attachment and proliferation. They also had a sufficiently rapid degradation rate (73.6 ± 1.1% in 4 weeks) and could be produced at a thickness close to that of the natural corneal stroma. Cells were seeded at the top surface of the foams and their numbers there was higher than the rest, basically due to the presence of the skin layer. This is considered to be an advantage when epithelial cells need to be seeded for the construction of hemi or full thickness cornea. [ABSTRACT FROM AUTHOR]

Corneal stroma is a very complex structure, composed of 200 lamellae of oriented collagen fibers. This highly complex nature of cornea is known to be important for its transparency and mechanical integrity. Thus, an artificial cornea design has to take into account this complex structure. In this study, behavior of human corneal keratocytes on collagen films patterned with parallel channels was investigated. Keratocytes proliferated well on films and reached confluency after 7 days in the incubation medium. Nearly all of the cells responded to the patterns and were aligned in contrast to the cells on unpatterned surfaces. Collagen type I and keratan sulfate secreted by keratocytes on patterned films appeared to be aligned in the direction of the patterns. The films showed an intermediate degradation over the course of a month. On the whole, transparency of the films increased with degradation and decreased by the presence of the cells. The decrease was, however, low and transparency level was maintained on the patterned films while on the unpatterned films a sharp decrease in transparency was followed by an improvement. This was due to the more organized distribution of cells and the oriented secretion of extracellular matrix molecules on patterned collagen films. Thus, these results suggest that application of contact guidance in cornea tissue engineering may facilitate the remodeling process, hence decrease the rehabilitation period. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res, 2008 [ABSTRACT FROM AUTHOR]

For most xenobiotics, the rates of percutaneous absorption are limited by diffusion through the horny layer of skin. However, percutaneous absorption of chemicals may seriously increase when the skin is damaged. The aim of this work was to develop an in vitro representative model of mechanically damaged skins. The epidermal barrier was examined following exposure to a razor, a rotating brush, and a microneedle system in comparison to tape-stripping which acted as a reference. Excised full-thickness skins were mounted on a diffusion chamber in order to evaluate the effect of injuries and to mimic physiological conditions. The transepidermal water loss (TEWL) was greatly increased when the barrier function was compromised. Measurements were made for all the damaged biopsies and observed histologically by microscopy. On human and porcine skins, the tape-stripping application (0 to 40 times) showed a proportional increase in TEWL which highlights the destruction of the stratum corneum. Similar results were obtained for all cosmetic instruments. This is reflected in our study by the nonsignificant difference of the mean TEWL scores between 30 strips and mechanical damage. For a specific appreciation, damaged skins were then selected to qualitatively evaluate the absorption of a chlorogenic acid solution using fluorescence microscopy.

Collagen is the oldest and most abundant extracellular matrix protein and has many applications in biomedical, food, cosmetic, and other industries. Previous reviews have already introduced collagen's sources, structures, and biosynthesis. The biological and mechanical properties of collagen-based composite materials, their modification and application forms, and their interactions with host tissues are pinpointed. It is worth noting that self-assembly behavior is the main characteristic of collagen molecules. However, there is currently relatively little review on collagen-based composite materials based on self-assembly. Herein, we briefly reviewed the biosynthesis, extraction, structure, and properties of collagen, systematically presented an overview of the various factors and corresponding characterization techniques that affect the collagen self-assembly process, and summarize and discuss the preparation methods and application progress of collagen-based composite materials in different fields. By combining the self-assembly behavior of collagen with preparation methods of collagen-based composite materials, collagen-based composite materials with various functional reactions can be selectively prepared, and these experiences and outcomes can provide inspiration and practical techniques for the future development directions and challenges of collagen-based composite biomaterials in related applications fields. [ABSTRACT FROM AUTHOR]

We recently showed that the highly organized architecture of the corneal stroma could be reproduced using scaffolds consisting of orthogonally aligned multilayers of collagen fibrils prepared using a high magnetic field. Here we show that such scaffolds permit the reconstruction in vitro of human hemi-corneas (stroma + epithelium), using primary human keratocytes and limbal stem cell derived human keratinocytes. On the surface of these hemi-corneas, a well-differentiated epithelium was formed, as determined both histologically and ultrastructurally and by the expression of characteristic markers. Within the stroma, the keratocytes aligned with the directions of the fibrils in the scaffold and synthesized a new extracellular matrix with typical collagen markers and small, uniform diameter fibrils. Finally, in vivo experiments using a rabbit model showed that these orthogonally oriented multi-layer scaffolds could be used to repair the anterior region of the stroma, leading to re-epithelialization and recovery of both transparency and ultrastructural organization., (Copyright (c) 2010 Elsevier Ltd. All rights reserved.)

Purpose: To evaluate the in vivo toxicity and efficacy of previously developed poly-(lactide-co-glycolide)-vancomycin-based microparticles (V-MPLs) for eventual use for endophthalmitis prophylaxis during cataract surgery., Methods: The intraocular vancomycin concentration profile was evaluated after V-MPL injection into the anterior chamber of rabbit eyes. The toxicology of V-MPLs versus MPLs alone was tested by corneal cellular counting and retinal histology. The prophylactic efficacy of the V-MPLs was evaluated by bacterial counts after introducing contaminated intraocular lenses (IOLs) together with the V-MPLs into one anterior chamber of phakic rabbit eyes or without V-MPLs in control rabbit eyes., Results: Intraocular V-MPLs produced effective vancomycin concentrations over at least 6 hours. Corneal counts revealed no significant increase in dead cells. Retinal toxicity manifested as inflammation 3 hours after injection, reaching its maximum between 12 hours and 24 hours, decreasing by 48 hours, and completely disappearing at 72 hours. Inflammation was similar between V-MPLs and MPLs. Untreated eyes implanted with highly infected IOLs showed severe, reproducible endophthalmitis. No sign of infection was observed with infected IOLs and concomitant V-MPL treatment, supported by bacterial counts showing a significant decrease in colony-forming Staphylococcus epidermidis units in the anterior chamber and on the implant surfaces within 6 hours., Conclusions: The present study demonstrated the release and toxicologic properties of the authors' newly developed V-MPLs in vivo. In addition, the rabbit model shows that V-MPLs are effective in reducing the risk of experimental endophthalmitis.

Skin and cornea both feature an epithelium firmly anchored to its underlying connective compartment: dermis for skin and stroma for cornea. A breakthrough in tissue engineering occurred in 1975 when skin stem cells were successfully amplified in culture by Rheinwald and Green. Since 1981, they are used in the clinical arena as cultured epidermal autografts for the treatment of patients with extensive burns. A similar technique has been later adapted to the amplification of limbal-epithelial cells. The basal layer of the limbal epithelium is located in a transitional zone between the cornea and the conjunctiva and contains the stem cell population of the corneal epithelium called limbal-stem cells (LSC). These cells maintain the proper renewal of the corneal epithelium by generating transit-amplifying cells that migrate from the basal layer of the limbus towards the basal layer of the cornea. Tissue-engineering protocols enable the reconstruction of three-dimensional (3D) complex tissues comprising both an epithelium and its underlying connective tissue. Our in vitro reconstruction model is based on the combined use of cells and of a natural collagen-based biodegradable polymer to produce the connective-tissue compartment. This porous substrate acts as a scaffold for fibroblasts, thereby, producing a living dermal/stromal equivalent, which once epithelialized results into a reconstructed skin/hemicornea. This paper presents the reconstruction of surface epithelia for the treatment of pathological conditions of skin and cornea and the development of 3D tissue-engineered substitutes based on a collagen-GAG-chitosan matrix for the regeneration of skin and cornea.

Purpose: To develop an artificial cornea, the ability to coculture the different cell types present in the cornea is essential. Here the goal was to develop a full-thickness artificial cornea using an optimized collagen-chondroitin sulfate foam, with a thickness close to that of human cornea, by coculturing human corneal epithelial and stromal cells and transfected human endothelial cells., Methods: Corneal extracellular matrix was simulated by a porous collagen/glycosaminoglycan-based scaffold seeded with stromal keratocytes and then, successively, epithelial and endothelial cells. Scaffolds were characterized for bulk porosity and pore size distribution. The performance of the three-dimensional construct was studied by histology, immunofluorescence, and immunohistochemistry., Results: The scaffold had 85% porosity and an average pore size of 62.1 microm. Keratocytes populated the scaffold and produced a newly synthesized extracellular matrix as characterized by immunohistochemistry. Even though the keratocytes lost their CD34 phenotype marker, the absence of smooth muscle actin fibers showed that these cells had not differentiated into myofibroblasts. The epithelial cells formed a stratified epithelium and began basement membrane deposition. An endothelial cell monolayer beneath the foam was also apparent., Conclusions: These results demonstrate that collagen-chondroitin sulfate scaffolds are good substrates for artificial cornea construction with good resilience, long-term culture capability, and handling properties.

To reconstruct artificial stroma close to corneal stroma, it is necessary to use keratocytes with high proliferative potential that maintain the keratocyte phenotype as characterised by CD34. To select such cells, we tested the proliferative potential and characterised the keratocytes isolated from 4 different areas of the human cornea: superior perilimbal, inferior perilimbal, superior central and inferior central. Keratocytes isolated from these different areas had significantly different growth rates (p<0.05), as measured by population doublings: superior perilimbal (42.59+/-11.78) > inferior perilimbal (38.23+/-12.67) > superior central (35.69+/-8.07) > inferior central (25.35+/-7.63). Their clonogenic potential evolved in the same order. Moreover, CD34 labelling gave higher levels in the central areas in relation to the perilimbal areas. We found the best location for isolating keratocytes for stromal reconstruction. The superior perilimbal area had the greatest capacity for proliferation, as well as the best clonogenic potential and the average CD34 level (70%) remained high.

Purpose: To evaluate the influence of the 3-dimensional collagen-glycosaminogycan-chitosan (CGC 3D) scaffold, epithelialization, and the addition of tetracycline hydrochloride on the ultrastructural organization, measured by the diameter and spacing of newly synthesized collagen I fibrils., Methods: Little is known about the role of interactions between epithelial cells and fibroblasts in controlling the extracellular matrix of the cornea. We developed a hemicornea from a CGC 3D matrix cocultured with keratocytes and human epithelial cells. The keratocytes colonized this substrate, proliferated, and synthesized the extracellular matrix, reproducing a living stroma equivalent., Results: Without a 3D scaffold, the collagen fibrils produced had an average diameter that was 42.7 nm and sigma = 16.9 nm. In the CGC 3D scaffold, the fibrils had an average diameter of 33.4 nm, with little dispersion (sigma = 6.7 nm), suggesting a greater regulation. The epithelium permitted a significant reduction in fibril diameter and interfibrillar spacing. Tetracycline hydrochloride had no effect on spacing but did have a significant effect on fibril diameter. We found positive interactions between the epithelium and tetracycline hydrochloride on the regulation of collagen fibrils but not on spacing. The presence of epithelium led to the increased formation of collagens I and V in the subepithelial area of the newly formed matrix. Type VI collagen was localized around the keratocytes throughout the matrix., Conclusions: Epithelialization and the 3D scaffold had a great influence on the diameter of collagen I fibrils.

Collagen-based micropatterned films were seeded with human corneal keratocyte and epithelial cells to study their mechanical properties as tissue engineering substrates. The patterns were in the form of parallel channels with slanted walls. Influence of cell presence, type and growth on the mechanical properties of the films was investigated. Unseeded films showed gradual strength reduction from an initial value of 0.046 N/mm, possibly due to degradation, down to 0.032+/-0.012 N/mm in 2 weeks. Keratocyte growth was found to significantly improve the mechanical behavior of the films upon 1 week of incubation (0.067+/-0.017 N/mm) and the improvement continued gradually over the next 2 weeks. Films seeded with D407 retinal pigment epithelial cells, on the other hand, experienced a decrease (0.023+/-0.011 N/mm), followed by a slight increase in mechanical properties in the 21-day period. A steady increase in the number of keratocytes along the channels, cytoskeleton alignment and extracellular matrix (ECM) secretion restricted to the channels was observed. Increase in strength observed with keratocytes and, to a lesser extent, with the epithelial cells can be attributed to directional ECM synthesis and the orientation of the cells and their cytoskeleton which contribute to the strength in the direction of the channels. This study showed that cell, especially keratocyte, presence compensates for the degradation of collagen films and improve the overall mechanical properties of the engineered tissue.

The creation of 3D scaffolds that mimic the structure of physiological tissue required for normal cell function is a major bioengineering challenge. For corneal stroma reconstruction this necessitates the creation of a stroma-like scaffold consisting of a stack of orthogonally disposed sheets of aligned collagen fibrils. This study demonstrates that such a scaffold can be built up using magnetic alignment. By allowing neutralized acid-soluble type I collagen to gel in a horizontal magnetic field (7 T) and by combining a series of gelation-rotation-gelation cycles, a scaffold of orthogonal lamellae composed of aligned collagen fibrils has been formed. Although initially dilute, the gels can be concentrated without noticeable loss in orientation. The gels are translucent but their transparency can be greatly improved by the addition of proteoglycans to the gel-forming solution. Keratocytes align by contact guidance along the direction of collagen fibrils and respect the orthogonal design of the collagen template as they penetrate into the bulk of the 3D matrix. The scaffold is a significant step towards the creation of a corneal substitute with properties resembling those of native corneal stroma.

In this paper the mechanical properties of micropatterned polyester films prepared to serve as tissue engineering scaffolds of cornea were examined. Films were prepared by solvent casting of blends of poly(l-lactide-co-d,l-lactide) and poly(3-hydroxybutyric acid-co-3-hydroxyvaleric acid), on a micropatterned silicon template. They were seeded with keratocytes or retinal pigment epithelial cells and subjected to tensile testing to assess the contribution of cells and the deposited extra-cellular matrix (ECM) to the mechanical properties of the scaffold. In all the tests, the films used were wet and the cells were not fixed. Cell-free scaffolds showed a gradual deterioration in strength upon incubation in the cell culture medium at 37 degrees C; the deterioration rate was highest in the first week and decreased significantly over the second and third weeks. The ultimate strength of the cell-free scaffolds decreased from 0.99 to 0.42N/mm after 21 days of incubation. Cell seeded scaffolds showed a more complicated mechanical strength profile. Their response was found to depend both on the extent of surface coverage and on the cell type. The results were examined after dividing the data into two groups of lower and higher stiffness. For keratocyte seeded scaffolds, the strength of the high stiffness groups continued to increase as the incubation period increased while the lower stiffness groups did not show a distinct change. For the keratocyte seeded scaffolds, tensile strength increased from 0.65N/mm on Day 7 to 0.73N/mm on Day 21. On the other hand, the scaffolds seeded with retinal pigment epithelial cells showed a gradual deterioration over time in both the higher and lower stiffness groups. For epithelial cell seeded scaffolds this was 0.98N/mm on Day 7 and decreased to 0.77N/mm on Day 21 still an improvement over the unseeded scaffolds. This most probably was a result of a lower rate of ECM secretion in comparison to keratocytes and the newly secreted ECM could not compensate for the influence of scaffold degradation on the mechanical properties. It could, therefore, be concluded that cell seeding plays a positive role in strengthening a tissue engineered construct, and cell type has a significant influence on the extent of this improvement.

In this study, a highly porous collagen-based biodegradable scaffold was developed as an alternative to synthetic, non-degradable corneal implants. The developed method involved lyophilization and subsequent stabilization through N-ethyl-N'-[3-dimethylaminopropyl] carbodiimide/N-hydroxy succinimide (EDC/NHS) cross-linking to yield longer lasting, porous scaffolds with a thickness similar to that of native cornea (500 microm). For collagen-based scaffolds, cross-linking is essential; however, it has direct effects on physical characteristics crucial for optimum cell behavior. Hence, the effect of cross-linking was studied by examining the influence of cross-linking on pore size distribution, bulk porosity and average pore size. After seeding the foam with human corneal keratocytes, cell proliferation, cell penetration into the scaffold and ECM production within the scaffold were studied. After a month of culture microscopical and immunohistochemical examinations showed that the foam structure did not undergo any significant loss of integrity, and the human corneal keratocytes populated the scaffold with cells migrating both longitudinally and laterally, and secreted some of the main constituents of the corneal ECM, namely collagen types I, V and VI. The foams had a layer of lower porosity (skin layer) both at the top and the bottom. Foams had an optimal porosity (93.6%), average pore size (67.7 microm), and chemistry for cell attachment and proliferation. They also had a sufficiently rapid degradation rate (73.6+/-1.1% in 4 weeks) and could be produced at a thickness close to that of the natural corneal stroma. Cells were seeded at the top surface of the foams and their numbers there was higher than the rest, basically due to the presence of the skin layer. This is considered to be an advantage when epithelial cells need to be seeded for the construction of hemi or full thickness cornea.

Tissues and organs contain an extracellular matrix (ECM). In the case of blood vessels, endothelium cells are anchored to a specialized basement membrane (BM) embedded inside the interstitial matrix (IM). We introduce a multi-structural collagen-based scaffold with embedded microchannels that mimics in vivo structures within vessels. Our scaffold consists of two parts, each containing two collagen layers, i.e., a 3D porous collagen layer analogous to IM lined with a thin 2D collagen film resembling the BM. Enclosed microchannels were fabricated using contact microprinting. Microchannel test structures with different sizes ranging from 300 to 800 µm were examined for their fabrication reproducibility. The heights and perimeters of the fabricated microchannels were ~20% less than their corresponding values in the replication PDMS mold; however, microchannel widths were significantly closer to their replica dimensions. The stiffness, permeability, and pore size properties of the 2D and 3D collagen layers were measured. The permeability of the 2D collagen film was negligible, making it suitable for mimicking the BM of large blood vessels. A leakage test at various volumetric flow rates applied to the microchannels showed no discharge, thereby verifying the reliability of the proposed integrated 2D/3D collagen parts and the contact printing method used for bonding them in the scaffold. In the future, multi-cell culturing will be performed within the 3D porous collagen and against the 2D membrane inside the microchannel, hence preparing this scaffold for studying a variety of blood vessel–tissue interfaces. Also, thicker collagen scaffold tissues will be fabricated by stacking several layers of the proposed scaffold. [ABSTRACT FROM AUTHOR]

Background and Aim: The triglyceride glucose index (TyG) has been proposed as a promising indicator of both insulin resistance (IR) and non-alcoholic fatty liver disease (NAFLD). However, the efficacy of the TyG index in predicting NAFLD has not been adequately studied, particularly in obese individuals. Materials and Methods: We analyzed 190 morbidly obese individuals. The TyG index, anthropometric obesity indices, homeostatic model assessment (HOMA-IR), and biochemical parameters were compared. NAFLD was diagnosed by hepatic ultrasonography and classified into four grades (0, 1, 2, and 3). Individuals in grades 2 and 3 are considered to have severe steatosis, while those in grades 0 and 1 do not. Results: The area under the curve (AUC) values of the TyG index, body mass index, neck circumferences, waist-to-hip ratio, and HOMA-IR did not differ significantly in predicting severe steatosis (0.640, 0.742, 0.725, 0.620, and 0.624 respectively). However, the AUC values of waist circumference and alanine aminotransferase provided better predictions than the TyG index (0.782, 0.744, and 0.640 respectively). Conclusion: The TyG index is highly effective in predicting both the presence and severity of NAFLD. However, it did not outperform simple obesity indices in predicting NAFLD and its severity in obese patients. [ABSTRACT FROM AUTHOR]

Transplantology is a branch of medicine that is developing rapidly. Transplanted whole organs or segments of organs may be recovered from either living or deceased donors. New methods of preserving transplanted solid organs, including the kidney, liver, heart, lung, and pancreas, as well as tissues, such as the cornea and skin, are being developed. Preservation fluid, which is used to perfuse and store the donated organ or tissue, should reduce biological deterioration of organs and tissue, attenuate ischemia/reperfusion-induced cell/tissue injury, and protect against damage. Lowering the storage temperature of organs significantly reduces the risk of damage. Efforts are also made to shorten the time between collecting the organ or tissue from the donor and transplanting it in the recipient. However, during transplantation, the recipient may become infected, primarily with bacteria and fungi. Infections of organ recipients occur most often due to unhygienic organ collection, improper handling and transport, and inappropriate preservation conditions, especially contamination of preservation fluid. The literature on contamination of organ preservation fluid and infections in graft recipients is very diverse, both in terms of the isolated bacterial and fungal species and the number of incidents. A large percentage of contaminating microorganisms belong to the generally non-pathogenic skin microbiota, but there are also cases of multidrug-resistant bacteria. Besides, the transplanted organs themselves may pose a danger. They may contain latent microorganisms, mainly viruses and parasites, that could be activated in a patient who has been subjected to immunosuppression to reduce the risk of organ rejection. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to show that major losses can still occur on corneas judged suitable for grafting at the first count. In addition, we studied the frequency of these losses on 1992 corneas over a period of 4 years to evaluate the risk incurred., Methods: We evaluated the incidence of these major losses and the associated risk factors. An Ishigawa diagram was created with the Cornea Bank team and the ophthalmologists involved in organ retrieval. Endothelial losses caused by bacterial or fungicidal contamination were excluded from the study. For the 29 corneas that suffered major losses, we analyzed the donor files for donor age, clinical file, geographical origins of the corneas, the person who did the retrieval, the length of time the cornea was stored, the data resulting from examining the endothelium at the bank by optical microscope, and the method used for sterilizing the material used. Specific analyses in cases of major loss of endothelial content: anatomopathologic examination of the corneas and search for the herpes simplex virus (HSV; type 1 or 2) by polymerase chain reaction (PCR). We carried out a statistical analysis using a chi(2) test on the 1992 corneas studied to see if the presence of diabetes (type 1 or 2) in the donor led to reduction levels different from those of corneas originating from nondiabetic donors., Results: The incidence was evaluated at between 0.4% and 3% of corneas sampled, and the associated risk factor was between 0.8% and 6% of grafted corneas. The occurrence of major losses was independent of donor age and was independent of the person who did the retrieval. The occurrence of major losses was independent of geographical origin. We tested our media for endotoxin before use and found levels from 0.22 to 3.9 UI/mL. We verified the absence of a chronological relationship between the batches of media used in the bank and the number of major losses observed, showing that the pyrogenicity limit was independent of cytotoxicity limits. Data analysis showed no difference in reduction levels between diabetic and nondiabetic donors (P < 0.05). Results on the detection of HSV-1 by PCR on the storage media were all negative, and these results agree with the anatomopathologic examinations that showed no signs of viral infection., Conclusion: Total endothelial losses amounted to 1.4%/yr. Without the double endothelial counts, we would have had 29 primary graft rejections over that period. During storage, this loss has not been linked to a specific cause, but risk factors such as traumatic death, herpes infections, and badly controlled endotoxin levels should be considered when taking preventative actions. For the moment, a second endothelial count before grafting should be carried out, because all these problem grafts conformed to grafting criteria after the first count. The possibility of carrying out this second count is one of the recognized advantages of storage in organ culture.

Purpose: The combination of a shortage of cornea grafts in France and a national average contamination rate of 9% to 10%, has led us to search for the origins of this contamination. The objective of our study was to reduce the number of unusable grafts resulting from contamination of corneas in organ culture., Methods: An external audit was carried out by an independent pharmacist on the removal conditions and treatment procedures for corneas. An environmental study was carried out, consisting of microbiological sampling of the corneas of donors who just died (<24 hours) as well as water and air samples in the premises used for removal. The Cornea Bank's procedures were submitted to a microbiological risk analysis using the "failure mode effects and criticity analysis" (FMECA) method., Results: The critical contamination periods were found to be before removal, during mortuary washing and during decontamination of the conjunctival cul-de-sac at the removal stage. The corrective measures taken have reduced contamination rates by half in 1 year., Conclusion: Highlighting the sources of contamination has led to the implementation of effective targeted and low-cost measures that have allowed us to reduce significantly the number of cornea graft losses as a result of bacterial and fungal contamination.

Unlabelled: Our objective was to formulate a medium for monolayer culture optimising both keratocyte growth and preservation of the keratocyte phenotype., Methods: An experimental matrix selected 14 media to test, using 7 components. Selection criteria were growth rates over 5 passages and expression of the CD34 marker., Results: Acetylcholine, insulin and vitamin C had no effect on growth and differentiation. The DMEM + Ham F12 1 : 1 based medium was selected for its initial effect on growth. At concentrations of 5 ng/ml, b-FGF improved the percentage of CD34+ cells without reducing growth rates. New-born calf serum (NCS) had a greater effect on growth than foetal calf serum (FCS). We showed three major interactions: between b-FGF and IGF-1, FCS and IGF-1 and NCS and b-FGF., Conclusion: We selected the following medium, which provides optimal growth and preservation of the CD34+ phenotype: DMEM/HAM-F12 + 10% NCS + 5 ng/ml b-FGF + antibiotics.

The clinical interest of using allogenic epidermal sheets (AES) has largely been shown [1,2,3]. As well as covering, they also stimulate healing, by simultaneously secreting numerous growth factors (GFs), although little is known on their mechanism of action. Our objectives were to: (a) devise a test for the efficacy of AES release, (b) select keratinocyte-secreting strains and optimal culture conditions. Three GFs were selected: IL-1alpha, IL-8 and VEGF. Three different keratinocyte strains were cultured for 3 and 6 days after confluence for 3 passages. Assays were performed after 3 h and 24 h+3 h after dispase treatment (AES conservation for 24 h then change of medium and sampling after 3 h). AES were found to secrete GFs in DMEM and the amounts were greater when cultured for 6 rather than 3 days after confluence. Each strain had different secretory patterns depending on passage and time in culture, this variability being explained by inter-individual heterogeneity.

Background: The relationship between the triglyceride–glucose (TyG) index and the risk of cardiovascular disease (CVD) in the U.S. population under 65 years of age with diabetes or prediabetes is unknown. The purpose of this study was to investigate the relationship between baseline TyG index and CVD risk in U.S. patients under 65 years of age with diabetes or prediabetes. Methods: We used data from the 2003–2018 National Health and Nutrition Examination Survey (NHANES). Multivariate regression analysis models were constructed to explore the relationship between baseline TyG index and CVD risk. Nonlinear correlations were explored using restricted cubic splines. Subgroup analysis and interaction tests were also conducted. Results: The study enrolled a total of 4340 participants with diabetes or pre-diabetes, with a mean TyG index of 9.02 ± 0.02. The overall average prevalence of CVD was 10.38%. Participants in the higher TyG quartiles showed high rates of CVD (Quartile 1: 7.35%; Quartile 2: 10.04%; Quartile 3: 10.71%; Quartile 4: 13.65%). For CVD, a possible association between the TyG index and the risk of CVD was observed. Our findings suggested a linear association between the TyG index and the risk of CVD. The results revealed a U-shaped relationship between the TyG index and both the risk of CVD (P nonlinear = 0.02583) and CHF (P nonlinear = 0.0208) in individuals with diabetes. Subgroup analysis and the interaction term indicated that there was no significant difference among different stratifications. Our study also revealed a positive association between the TyG index and comorbid MetS in the U.S. population under 65 years of age with prediabetes or diabetes. Conclusions: A higher TyG index was linked to an increased likelihood of CVD in the U.S. population aged ≤ 65 years with prediabetes and diabetes. Besides, TyG index assessment will contribute to more convenient and effective screening of high-risk individuals in patients with MetS. Future studies should explore whether interventions targeting the TyG index may improve clinical outcomes in these patients. [ABSTRACT FROM AUTHOR]

In the event of disease or injury, restoration of the native organization of cells and extracellular matrix is crucial for regaining tissue functionality. In the cornea, a highly organized collagenous tissue, keratocytes can align along the anisotropy of the physical microenvironment, providing a blueprint for guiding the organization of the collagenous matrix. Inspired by this physiological process, anisotropic contact guidance cues have been employed to steer the alignment of keratocytes as a first step to engineer in vitro cornea-like tissues. Despite promising results, two major hurdles must still be overcome to advance the field. First, there is an enormous design space to be explored in optimizing cellular contact guidance in three dimensions. Second, the role of contact guidance cues in directing the long-term deposition and organization of extracellular matrix proteins remains unknown. To address these challenges, here we combined two microengineering strategies—UV-based protein patterning (2D) and two-photon polymerization of topographies (2.5D)—to create a library of anisotropic contact guidance cues with systematically varying height (H, 0 µm ≤ H ≤ 20 µm) and width (W, 5 µm ≤ W ≤ 100 µm). With this unique approach, we found that, in the short term (24 h), the orientation and morphology of primary human fibroblastic keratocytes were critically determined not only by the pattern width, but also by the height of the contact guidance cues. Upon extended 7-day cultures, keratocytes were shown to produce a dense, fibrous collagen network along the direction of the contact guidance cues. Moreover, increasing the heights also increased the aligned fraction of deposited collagen and the contact guidance response of cells, all whilst the cells maintained the fibroblastic keratocyte phenotype. Our study thus reveals the importance of dimensionality of the physical microenvironment in steering both cellular organization and the formation of aligned, collagenous tissues. [ABSTRACT FROM AUTHOR]

Backgrounds: The widespread adoption of double eyelid tapes (DET) to achieve the desired double eyelid aesthetic has prompted investigations into their long-term effects. Given the delicate and complex anatomy of the eyelid, concerns have emerged about the impact of DETs on eyelid structure and the outcomes of subsequent surgical procedures., Methods: A cohort of 267 outpatients from our department was recruited between January 2022 and January 2024 to participate in a survey assessing the usage of double eyelid tape (DET). Eyelid laxity was subsequently tested in all outpatients using the Vertical Lid Pull and Parallel Lid Pull methods. Among all participants, 33 underwent double eyelid surgery, with 22 having a history of excessive DET usage and 11 with no DET usage. Post-operative outcomes, including operation duration, satisfaction levels, and complications were recorded. Additionally excised eyelid skin tissues during surgery underwent Masson's staining and EVG staining to analyze collagen and elastic fibers., Results: Among surveyed outpatients (mean age: 23.79 ± 3.71 years, 99.63% female, mean BMI: 21.56 ± 1.75 kg/m 2 ), 56.55% had oculopathy with ametropia being predominant (53.93%). Hooded eyelids were the most prevalent congenital condition (62.54%). Nearly half (49.44%) used Double Eyelid Tapes (DET) for 1-2 years, with 70.04% experiencing discomfort and 70.79% reporting permanent eyelid shape change. Lid pull measurements showed no significant difference in vertical pulls between DET users and non-users, but parallel pulls varied significantly (p<0.05). Complications like asymmetry, numbness, and hypertrophic scars were exclusive to DET users. Physician evaluations favored non-DET users significantly (p<0.05). Histological analysis revealed an interesting finding that individuals using DET have higher collagen levels and notable changes in skin structure when compared to non-users., Conclusions: Prolonged use of double eyelid tape (DET) may result in eyelid laxity, impacting ocular health and complicating blepharoplasty procedures., Level of Evidence Iv: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 ., (© 2024. Springer Science+Business Media, LLC, part of Springer Nature and International Society of Aesthetic Plastic Surgery.)

Background: The association between homeostatic model assessment (HOMA2-IR) and mortality in obese and non-obese populations has not been clearly explained. Methods: A total of 7,085 individuals aged ≥ 20 years from the 1999–2006 National Health and Nutrition Examination Survey were included in the study. Study endpoints were all-cause and cardiovascular mortality. Multivariate Cox proportional hazards regression models with restricted cubic spline analysis were used for analysis. Results: In the study populations, a total of 1666 all-cause deaths and 555 cardiovascular (CV) deaths were recorded during a mean follow-up of 195.53 months. Notably, a significant difference in obesity was observed in the association between HOMA2-IR and mortality. After adjustment for multiple variables, HOMA2-IR was positively associated with all-cause mortality in all participants, in those with normal BMI, and in those with obesity. Conversely, tertile 2 of HOMA2-IR was associated with a lower risk of all-cause mortality in participants with obesity compared with tertile 1 (adjusted hazard ratio, 0.68; 95% confidence interval, 0.52–0.89; P = 0.005). Results from restricted cubic spline analysis showed a J-shaped association between HOMA2-IR and all-cause and CV mortality. In addition, a nonlinear U-shaped correlation with all-cause (P for nonlinear < 0.001) and CV (P for nonlinear = 0.002) mortality was observed in the population with obesity, with inflection points of HOMA2-IR identified at 1.85 and 1.75. Below the inflection point of 1.85, a negative relationship between HOMA2-IR and all-cause mortality was observed. Conclusions: Elevated HOMA2-IR showed a notable correlation with increased risk of all-cause mortality. It was noteworthy that excessively reduced levels of insulin resistance showed a distinct association with increased mortality in individuals with obesity. [ABSTRACT FROM AUTHOR]

Background: Insulin resistance(IR) and inflammation have been regarded as common potential mechanisms in coronary heart disease (CHD) and nonalcoholic fatty liver disease (NAFLD). Triglyceride-glucose (TyG) index is a novel biomarker of insulin resistance, System immune-inflammation index(SII) and Systemic inflammation response index(SIRI) are novel biomarkers of inflammation, these biomarkers have not been studied in CHD with NAFLD patients. This study investigated the correlation between the TyG index, SII index, and SIRI index and CHD risk among NAFLD patients. Methods: This cross-sectional study included 407 patients with NAFLD in the Department of Cardiology, The Second Hospital of Shanxi Medical University. Of these, 250 patients with CHD were enrolled in the NAFLD+CHD group and 157 patients without CHD were enrolled as NAFLD control. To balance covariates between groups, 144 patients were selected from each group in a 1:1 ratio based on propensity score matching (PSM). Potential influences were screened using Lasso regression analysis. Univariate and multivariate logistic regression analyses and the Least Absolute Shrinkage and Selection Operator (LASSO) regression were used to assess independent risk and protective factors for CHD. Construction of nomogram using independent risk factors screened by machine learning. The receiver operating characteristic(ROC) curve was used to assess the ability of these independent risk factors to predict coronary heart disease. The relationship between the Gensini score and independent risk factors was reflected using the Sankey diagram. Results: The LASSO logistic regression analysis and Logistic regression analyses suggest that TyG index (OR, 2.193; 95% CI, 1.242-3.873; P = 0.007), SII index (OR, 1.002; 95% CI, 1.001-29 1.003; P <0.001), and SIRI index (OR, 1.483;95%CI, 1.058-2.079, P=0.022) are independent risk factors for CHD. At the same time, Neutrophils, TG, and LDL-C were also found to be independent risk factors in patients, HDL-C was a protective factor for CHD in patients with NAFLD. Further analysis using three machine learning algorithms found these independent risk factors to have good predictive value for disease diagnosis, SII index shows the highest predictive value. ROC curve analysis demonstrated that combining the SII index, SIRI index, and TyG index can improve the diagnostic ability of nonalcoholic liver cirrhosis patients with CHD.ROC curve analysis showed that the combined analysis of these independent risk factors improved the predictive value of CHD(AUC: 0.751; 95% CI: 0.704-0.798; P <0.001). Conclusion: TyG index, SII index, and SIRI index are all independent risk factors for CHD in patients with NAFLD and are strongly associated with prediction and the severity of CHD. [ABSTRACT FROM AUTHOR]

Toxicological assessment of chemicals is crucial for safeguarding human health and the environment. However, traditional animal experiments are associated with ethical, technical, and predictive limitations in assessing the toxicity of chemicals to the skin. With the recent development of bioengineering and tissue engineering, three-dimensional (3D) skin models have been commonly used as an alternative for toxicological studies. The skin consists of the subcutaneous, dermis, and epidermis. All these layers have crucial functions such as physical and biological protection and thermoregulation. The epidermis is the shallowest layer protecting against external substances and media. Because the skin is the first contact point for many substances, this organ is very significant for assessing local toxicity following skin exposure. According to the classification of the United Nations Global Harmonized System, skin irritation is a major potentially hazardous characteristic of chemicals, and this characteristic must be accurately assessed and classified for enhancing chemical safety management and preventing and reducing chemical accidents. This review discusses the research progress of 3D skin models and introduces their application in assessing chemical skin irritation., (© 2024 John Wiley & Sons Ltd.)

Background: The triglyceride-glucose (TyG) index is a predictor of cardiovascular diseases; however, to what extent the TyG index is associated with cardiovascular diseases through renal function is unclear. This study aimed to evaluate the complex association of the TyG index and renal function with cardiovascular diseases using a cohort design. Methods: This study included participants from the China Health and Retirement Longitudinal Study (CHARLS) free of cardiovascular diseases at baseline. We performed adjusted regression analyses and mediation analyses using Cox models. The TyG index was calculated as Ln [fasting triglyceride (mg/dL) × fasting glucose (mg/dL)/2]. Renal function was defined by the estimated glomerular filtration rate (eGFR). Results: A total of 6 496 participants were included in this study. The mean age of the participants was 59.6 ± 9.5 years, and 2996 (46.1%) were females. During a maximum follow-up of 7.0 years, 1 996 (30.7%) people developed cardiovascular diseases, including 1 541 (23.7%) cases of heart diseases and 651 (10.0%) cases of stroke. Both the TyG index and eGFR level were significantly associated with cardiovascular diseases. Compared with people with a lower TyG index (median level) and eGFR ≥ 60 ml/minute/1.73 m2, those with a higher TyG index and decreased eGFR had the highest risk of cardiovascular diseases (HR, 1.870; 95% CI 1.131–3.069). Decreased eGFR significantly mediated 29.6% of the associations between the TyG index and cardiovascular diseases. Conclusions: The combination of a higher TyG index and lower eGFR level was associated with the highest risk of cardiovascular diseases. Renal function could mediate the association between the TyG index and cardiovascular risk. [ABSTRACT FROM AUTHOR]

Background: Mesenchymal stem cells (MSCs) have shown promising potential in allograft survival. However, few reports have focused on comparing the immunosuppressive capacity of MSCs from different sources and administered via different routes in inhibiting transplant rejection. Moreover, virtually nothing is known about the role of MSCs in the regulation of graft neovascularization and lymphangiogenesis. In this study, we compared the efficacy of human adipose MSCs (hAD-MSCs) and human umbilical cord MSCs (hUC-MSCs) in vitro and in corneal transplantation models to explore the underlying molecular mechanisms and provide a powerful strategy for future clinical applications. Methods: hAD-MSCs and hUC-MSCs were generated, and their self-renewal and multi-differentiation abilities were evaluated. The inhibitory effect of human MSCs (hMSCs) was examined by T-cell proliferation assays with or without transwell in vitro. Two MSCs from different sources were separately adoptively transferred in mice corneal transplantation (5 × 105 or 1 × 106/mouse) via topical subconjunctival or intravenous (IV) routes. Allograft survival was evaluated every other day, and angiogenesis and lymphomagenesis were quantitatively analyzed by immunofluorescence staining. The RNA expression profiles of hMSCs were revealed by RNA sequencing (RNA-seq) and verified by quantitative real-time PCR (qRT‒PCR), western blotting or ELISA. The function of the differentially expressed gene FAS was verified by a T-cell apoptosis assay. Results: hAD-MSCs induced stronger immunosuppression in vitro than hUC-MSCs. The inhibitory effect of hUC-MSCs but not hAD-MSCs was mediated by cell–cell contact-dependent mechanisms. Systemic administration of a lower dose of hAD-MSCs showed better performance in prolonging corneal allograft survival than hUC-MSCs, while subconjunctival administration of hMSCs was safer and further prolonged corneal allograft survival. Both types of hMSCs could inhibit corneal neovascularization, while hAD-MSCs showed greater superiority in suppressing graft lymphangiogenesis. RNA-seq analysis and confirmation experiments revealed the superior performance of hAD-MSCs in allografts based on the lower expression of vascular endothelial growth factor C (VEGF-C) and higher expression of FAS. Conclusions: The remarkable inhibitory effects on angiogenesis/lymphangiogenesis and immunological transplantation effects support the development of hAD-MSCs as a cell therapy against corneal transplant rejection. Topical administration of hMSCs was a safer and more effective route for application than systemic administration. [ABSTRACT FROM AUTHOR]

Background: Insulin resistance (IR) negatively affects several risk factors of chronic kidney disease (CKD). This cross-sectional study investigated whether the triglyceride-glucose (TyG) index, which reflects IR, was independently associated with CKD in a geriatric population, regardless of obesity and sex. Methods: The analysis included 7,326 individuals (2,864 males and 4,462 females) aged ≥60 years. Non-obesity or obesity was evaluated using a body mass index cutoff of 25 kg/m². The TyG index was calculated as ln [triglyceride concentration (mg/dL)×fasting plasma glucose concentration (mg/dL)]/2. All participants were categorized into three groups according to TyG tertiles. Moderate-to-severe CKD (MSCKD) was defined as an estimated glomerular filtration rate (eGFR) of <45.0 mL/min/1.73 m². Results: In males and females with or without obesity, a trend test showed a decreasing tendency in the eGFR from the lowest to highest TyG tertiles. Males without obesity and females with obesity in the middle and highest tertiles of the TyG index were 2.342 and 2.393, and were 2.313 and 3.516 times more likely to have MSCKD, respectively. Those with or without obesity in the highest tertile of the TyG index were 1.736 and 2.374 times more likely to have MSCKD, respectively. Conclusion: Geriatric populations with an increased TyG index have a high risk of MSCKD regardless of obesity and sex. Our findings suggest that increased IR is associated with CKD in the geriatric population independent of obesity and sex. [ABSTRACT FROM AUTHOR]

Bioengineered corneal substitutes offer a solution to the shortage of donor corneal tissue worldwide. As one of the major structural components of the cornea, collagen has shown great potential for tissue‐engineered cornea substitutes. Herein, free‐standing collagen membranes fabricated using electro‐compaction were assessed in corneal bioengineering application by comparing them with nonelectro‐compacted collagen (NECC). The well‐organized and biomimetic fibril structure resulted in a significant improvement in mechanical properties. A 10‐fold increase in tensile and compressive modulus was recorded when compared with NECC membranes. In addition to comparable transparency in the visible light range, the glucose permeability of the electro‐compacted collagen (ECC) membrane is higher than that of the native human cornea. Human corneal epithelial cells adhere and proliferate well on the ECC membrane, with a large cell contact area observed. The as‐described ECC has appropriate structural, topographic, mechanical, optical, glucose permeable, and cell support properties to provide a platform for a bioengineered cornea; including the outer corneal epithelium and potentially deeper corneal tissues. [ABSTRACT FROM AUTHOR]