Evaluation of perioperative pachymetry of thin corneas during corneal crosslinking using hypo-osmolar riboflavin and hydroxypropyl methylcellulose

ABSTRACT Purpose: This study aimed to analyze variations in intraoperative corneal thickness during corneal cross-linking in patients with keratoconus and to investigate its possible correlation with presurgical maximal keratometry (Kmax) and pachymetry. Methods: This was a prospective case series. We used a method similar to the Dresden protocol, with the application of hydroxypropyl methylcellulose 0.1% hypo-osmolar riboflavin in corneas between 330 and 400 µm after epithelium removal. Corneal thickness was measured using portable calipers before and immediately after epithelium removal, and 30 and 60 min after the procedure. Results: The 30 patients in this study were followed up for one year. A statistically significant difference was observed in pachymetry values during the intraoperative period (p<0.0001) and an increase of 3.05 µm (95%C1: 0.56-5.54) for each diopter was seen after epithelium removal (p0.019). We found an average Kmax difference of —2.12 D between men and women (p0.013). One year after treatment, there was a statistically significant reduction in pachymetry (p<0.0001) and Kmax (p0.0170) values. Conclusions: A significant increase in pachymetry measurements was seen during the procedure, and most patients showed a regression in Kmax and pachymetry values one year after surgery.

Action of microbial transglutaminase (MTGase) on the processing properties of glutinous rice flour and the quality attributes of sweet dumplings and in vitro digestion.

The development and manufacture of high-quality starch are a new research focus in food science. Here, transglutaminase was used in the wet processing of glutinous rice flour to prepare customized sweet dumplings. Transglutaminase (0.2 %) lowered protein loss in wet processing and reduced the crystallinity and viscosity of glutinous rice flour. Moreover, it lowered the cracking and cooking loss of sweet dumplings after freeze-thaw cycles, and produced sweet dumplings with reduced hardness and viscosity, making them more suitable for people with swallowing difficulties. Additionally, in sweet dumplings with 0.2 % transglutaminase, the encapsulation of starch granules by the protein slowed down the digestion and reduced the final hydrolysis rate, which are beneficial for people with weight and glycemic control issues. In conclusion, this study contributes to the production of tasty, customized sweet dumplings.

Clustered ultra-small iron oxide nanoparticles as potential T1/T2dual-modal magnetic resonance imaging contrast agents and application to tumor model.

Many studies have been conducted on the use of ultra-small iron oxide nanoparticles (USIONs) (d < 3 nm) as potential positive magnetic resonance imaging (MRI)-contrast agents (CAs); however, there is dearth of research on clustered USIONs. In this study, nearly monodispersed clustered USIONs were synthesized using a simple two-step one-pot polyol method. First, USIONs (d = 2.7 nm) were synthesized, and clustered USIONs (d = 27.9 nm) were subsequently synthesized through multiple cross-linking of USIONs with poly(acrylic acid-co-maleic acid) (PAAMA) polymers with many -COOH groups. The clustered PAAMA-USIONs exhibited very weak ferromagnetism owing to the magnetic interaction between superparamagnetic USIONs; this was evidenced by their appreciable r1= 3.9 s‒1mM‒1and high r2/r1ratio of 14.6. Their ability to function as a dual-modal T1/T2MRI-CA in T1-weighted MRI was demonstrated when they simultaneously exhibited positive and negative contrasts in T1-weighted MRI of tumor model mice after intravenous injection. They displayed positive contrasts at the kidneys, bladder, heart, and aorta and negative contrasts at the liver and tumor. .

Singlet oxygen-mediated photochemical cross-linking of an engineered fluorescent flavoprotein iLOV.

Genetically-encoded photoactive proteins are integral tools in modern biochemical and molecular biological research. Within this tool box, truncated variants of the phototropin 2 light-oxygen-voltage (LOV) flavoprotein have been developed to photochemically generate singlet oxygen (1O2) in vitro and in vivo, yet the effect of 1O2 on these genetically encoded photosensitizers remains underexplored. In this study, we demonstrate that the "improved" LOV (iLOV) flavoprotein is capable of photochemical 1O2 generation. Once generated, 1O2 induces protein oligomerization via covalent cross-linking. The molecular targets of protein oligomerization by cross-linking are not endogenous tryptophans or tyrosines, but rather primarily histidines. Substitution of surface-exposed histidines for serine or glycine residues effectively eliminates protein cross-linking. When used in biochemical applications, such protein-protein cross-links may interfere with native biological responses to 1O2, which can be ameliorated by substitution of the surface exposed histidines of iLOV or other 1O2-generating flavoproteins.

3D Printing of Hierarchical Structures Made of Inorganic Silicon-Rich Glass Featuring Self-Forming Nanogratings.

Hierarchical structures are abundant in nature, such as in the superhydrophobic surfaces of lotus leaves and the structural coloration of butterfly wings. They consist of ordered features across multiple size scales, and their advantageous properties have attracted enormous interest in wide-ranging fields including energy storage, nanofluidics, and nanophotonics. Femtosecond lasers, which are capable of inducing various material modifications, have shown promise for manufacturing tailored hierarchical structures. However, existing methods, such as multiphoton lithography and three-dimensional (3D) printing using nanoparticle-filled inks, typically involve polymers and suffer from high process complexity. Here, we demonstrate the 3D printing of hierarchical structures in inorganic silicon-rich glass featuring self-forming nanogratings. This approach takes advantage of our finding that femtosecond laser pulses can induce simultaneous multiphoton cross-linking and self-formation of nanogratings in hydrogen silsesquioxane. The 3D printing process combines the 3D patterning capability of multiphoton lithography and the efficient generation of periodic structures by the self-formation of nanogratings. We 3D-printed micro-supercapacitors with large surface areas and a high areal capacitance of 1 mF/cm2 at an ultrahigh scan rate of 50 V/s, thereby demonstrating the utility of our 3D printing approach for device applications in emerging fields such as energy storage.

Progress in mass spectrometry approaches to profiling protein-protein interactions in the studies of the innate immune system.

Understanding protein-protein interactions (PPIs) is pivotal for deciphering the intricacies of biological processes. Dysregulation of PPIs underlies a spectrum of diseases, including cancer, neurodegenerative disorders, and autoimmune conditions, highlighting the imperative of investigating these interactions for therapeutic advancements. This review delves into the realm of mass spectrometry-based techniques for elucidating PPIs and their profound implications in biological research. Mass spectrometry in the PPI research field not only facilitates the evaluation of protein-protein interaction modulators but also discovers unclear molecular mechanisms and sheds light on both on- and off-target effects, thus aiding in drug development. Our discussion navigates through six pivotal techniques: affinity purification mass spectrometry (AP-MS), proximity labeling mass spectrometry (PL-MS), cross-linking mass spectrometry (XL-MS), size exclusion chromatography coupled with mass spectrometry (SEC-MS), limited proteolysis-coupled mass spectrometry (LiP-MS), and thermal proteome profiling (TPP).

A conserved peptide-binding pocket in HyNaC/ASIC ion channels.

The only known peptide-gated ion channels-FaNaCs/WaNaCs and HyNaCs-belong to different clades of the DEG/ENaC family. FaNaCs are activated by the short neuropeptide FMRFamide, and HyNaCs by Hydra RFamides, which are not evolutionarily related to FMRFamide. The FMRFamide-binding site in FaNaCs was recently identified in a cleft atop the large extracellular domain. However, this cleft is not conserved in HyNaCs. Here, we combined molecular modeling and site-directed mutagenesis and identified a putative binding pocket for Hydra-RFamides in the extracellular domain of the heterotrimeric HyNaC2/3/5. This pocket localizes to only one of the three subunit interfaces, indicating that this trimeric ion channel binds a single peptide ligand. We engineered an unnatural amino acid at the putative binding pocket entrance, which allowed covalent tethering of Hydra RFamide to the channel, thereby trapping the channel in an open conformation. The identified pocket localizes to the same region as the acidic pocket of acid-sensing ion channels (ASICs), which binds peptide ligands. The pocket in HyNaCs is less acidic, and both electrostatic and hydrophobic interactions contribute to peptide binding. Collectively, our results reveal a conserved ligand-binding pocket in HyNaCs and ASICs and indicate independent evolution of peptide-binding cavities in the two subgroups of peptide-gated ion channels.

Crosslinking gelatin with robust inherent antibacterial natural polymer for wound healing.

Gelatin-based biomaterials are widely acknowledged as a promising choice for wound dressings, given their similarity to the extracellular matrix and biocompatibility. However, the challenge of cross-linking gelatin while preserving its biocompatibility and cost-effectiveness persists. This study aimed to enhance the properties of gelatin by incorporating the oxidized lignosulfonate (OLS) biopolymer as an inexpensive and biocompatible natural material. The polyphenolic structure of OLS acts as both a cross-linking agent and an antibacterial component. The OLS/gelatin films were prepared using a casting method with varying weight ratios (0.1, 0.2, 0.3, 0.4, and 0.5 w/w). FTIR analysis confirmed the formation of Schiff-base and hydrogen bonds between gelatin and OLS. The resulting films exhibited enhanced mechanical properties (Young's modulus ∼40 MPa), no cytotoxicity, and excellent cell adhesion and morphology. Antimicrobial tests showed significant activity against Escherichia coli and Staphylococcus aureus, with higher activity against S. aureus (17 mm inhibition zone and 99 % bactericidal rate). In vivo studies in a mouse model demonstrated that the gelatin/0.2OLS dressing significantly improved wound healing, including re-epithelialization, collagen formation, inflammation reduction, and blood vessel density, compared to untreated wounds. These findings suggest that the synthesized novel gelatin/OLS wound dressing has promising healing and antibacterial properties.

Static in-situ curing characteristics of CFRP based on near infrared laser.

STUDY ON STATIC IN-SITU CURING CHARACTERISTICS OF CFRP BASED ON NEAR INFRARED LASER: The quick curing method of carbon fibre reinforced plastics (CFRP) is one of the hotspots in current research. A static in-situ curing method for CFRP prepreg based on near-infrared laser was put forward in this study. The in-situ curing structural characteristics and the mechanism of CFRP were investigated through real-time surface temperature measurement, COMSOL temperature field simulation, 3D measurement of curing morphology and resin curing degree test. The thermal conductivity of the CFRP along the fiber direction is considerably higher than that along the perpendicular fiber direction. As a result, the temperature profile in the plane takes on an elliptical shape. During the transfer, the temperature field gradually decreases, resulting in an ellipsoidal 3D high-temperature distribution. The different shrinkage phenomena in the different curing regions between the layers lead to an irregular ellipsoidal solidification morphology of the unidirectional CFRP. The temperature in the center of the heat affected zone increases as a power exponential function with time. The area and depth of the heat-affected zone increases with the laser power, and the curing area is positively correlated with the degree of curing. As a result, curing temperature governing equations based on laser power and layer thickness have been proposed, while relationship equations based on laser power, curing depth and curing morphology have been developed. In addition, prediction equations based on curing morphology have been developed for curing degree, in order to achieve precise curing of CFRP.

Thermal stability and in vitro digestive behavior of Pickering emulsion stabilized by high-amylose starch nanocrystals.

In this study, high-amylose starch (HAS) was processed using sulfuric acid-ultrasonic cross-linking to produce high-amylose starch nanocrystals (HASNC). These nanocrystals were used to stabilize Pickering emulsions and assess their effectiveness in encapsulating ß-carotene. Normal starch nanocrystals (NSNC) were prepared similarly for comparison. The HASNC retained key HAS properties, such as heat and enzyme resistance, providing several advantages to HASNC-stabilized emulsions. First, after exposure to 100 °C heat and in vitro tests simulating the mouth and stomach, the HASNC-stabilized emulsions demonstrated significantly greater stability and higher ß-carotene retention compared to the NSNC-stabilized emulsions. This enhanced stability is attributed to the lower gelatinization degree and increased resistance to α-amylase hydrolysis of HASNC, which provides stronger steric stabilization of the oil droplets. Second, during in vitro small intestine tests, the greater enzyme resistance of HASNC allowed for the formation of a denser barrier around the oil droplets, effectively preventing lipase and bile salts from contacting the oil droplets. This led to a reduced rate and extent of lipid digestion and facilitated a sustained-release effect. Consequently, HASNC, as a starch-based emulsifier, show great potential as an effective delivery system for the sustained release of bioactive compounds.

Ultra-Low Alginate-Based Multifunctional Composite Binders for Enhanced Mechanical, Electrochemical, and Thermal Performance of Li-S Batteries.

The practical application of Li-S batteries, which hold great potential as energy storage devices, is impeded by various challenges, such as capacity degradation caused volume change, polysulfide shuttling, poor electrode kinetics, and safety concerns. Binder plays a crucial role in suppressing volume change of cathode side, thereby enhancing the electrochemical performance of Li-S batteries. In this research, a novel network binder (SA-Co-PEDOT) composed of sodium alginate is presented, Co2+ ions as cross-linking agent and PEDOT as an electronic conductor. The theoretical analysis and experimental testing confirm that the SA-Co-PEDOT binder with synergistic combination of catalytic center and electron transfer network effectively mitigates large volumetric changes during cycling while simultaneously enhancing electrode kinetics through controlling the deposition morphology of sulfur end product and its nucleation and dissolution. As a result, it achieves a capacity of 844 mAh g-1 after 150 cycles at 0.2 C. Moreover, the electrode with SA-Co-PEDOT binder subjected a bending test maintains a capacity of 395 mAh g-1 after 500 cycles at 0.5 C, exhibiting an impressively low decay rate of only 0.11%. Even with an ultra-low content of 2 wt.% SA-Co-PEDOT binder, the electrode still maintains a capacity of 999.7 mAh g-1 after 100 cycles at 0.5 C.

The plastidial protein acetyltransferase GNAT1 forms a complex with GNAT2, yet their interaction is dispensable for state transitions.

Protein N-acetylation is one of the most abundant co- and post-translational modifications in eukaryotes, extending its occurrence to chloroplasts within vascular plants. Recently, a novel plastidial enzyme family comprising eight acetyltransferases that exhibit dual lysine and N-terminus acetylation activities was unveiled in Arabidopsis. Among these, GNAT1, GNAT2, and GNAT3 reveal notable phylogenetic proximity, forming a subgroup termed NAA90. Our study focused on characterizing GNAT1, closely related to the state transition acetyltransferase GNAT2. In contrast to GNAT2, GNAT1 did not prove essential for state transitions and displayed no discernible phenotypic difference compared to the wild type under high light conditions, while gnat2 mutants were severely affected. However, gnat1 mutants exhibited a tighter packing of the thylakoid membranes akin to gnat2 mutants. In vitro studies with recombinant GNAT1 demonstrated robust N-terminus acetylation activity on synthetic substrate peptides. This activity was confirmed in vivo through N-terminal acetylome profiling in two independent gnat1 knockout lines. This attributed several acetylation sites on plastidial proteins to GNAT1, reflecting a subset of GNAT2's substrate spectrum. Moreover, co-immunoprecipitation coupled to mass spectrometry revealed a robust interaction between GNAT1 and GNAT2, as well as a significant association of GNAT2 with GNAT3 - the third acetyltransferase within the NAA90 subfamily. This study unveils the existence of at least two acetyltransferase complexes within chloroplasts, whereby complex formation might have a critical effect on the fine-tuning of the overall acetyltransferase activities. These findings introduce a novel layer of regulation in acetylation-dependent adjustments in plastidial metabolism.

Fabrication of Anatomically Equivalent Pectin-Based Multifilament Nerve Conduits.

Reuniting denuded nerve ends after a long segmental peripheral nerve defect is challenging due to delayed axonal regeneration and incomplete, nonspecific reinnervation, as conventional hollow nerve guides fail to ensure proper fascicular complementation and obstruct axonal guidance across the defects. This study focuses on fabricating multifilament conduits using a plant-derived anionic polysaccharide, pectin, where the abundant availability of carboxylate (COO-) functional groups in pectin facilitates instantaneous sol-gel transition upon interaction with divalent cations. Despite their advantages, pectin hydrogels encounter structural instability under physiological conditions. Hence, pectin is conjugated with light-sensitive methacrylate residues (49.8% methacrylation) to overcome these issues, enabling the fabrication of dual cross-linked multifilament nerve conduits through an ionic interaction-driven, template-free 3D wet writing process, followed by photo-cross-linking at 525 nm. The anatomical equivalence including peri-, epi-, and endoneurium structures of the customized multifilament conduits was confirmed through scanning electron micrographs and micro-CT analysis of rat and goat sciatic nerve tissues. Furthermore, the fabricated multifilament nerve conduits demonstrated cytocompatibility and promoted the expression of neuron-specific intermediate filament protein (NF-200) in PC12 cells and neurite outgrowth of 16.90 ± 1.82 µm on day 14. Micro-CT imaging of an anastomosed native goat sciatic nerve with an 8-filament conduit demonstrated precise fascicular complementation in an ex vivo interpositional goat model. This approach not only eliminates the need for a suture-intensive ligation process but also highlights the customizability of multifilament conduits to meet patient- and injury-specific needs.

Cross-Linking Agents in Three-Component Materials Dedicated to Biomedical Applications: A Review.

In biomaterials research, using one or two components to prepare materials is common. However, there is a growing interest in developing materials composed of three components, as these can offer enhanced physicochemical properties compared to those consisting of one or two components. The introduction of a third component can significantly improve the mechanical strength, biocompatibility, and functionality of the resulting materials. Cross-linking is often employed to further enhance these properties, with chemical cross-linking agents being the most widely used method. This article provides an overview of the chemical agents utilized in the cross-linking of three-component biomaterials. The literature review focused on cases where the material was composed of three components and a chemical substance was employed as the cross-linking agent. The most commonly used cross-linking agents identified in the literature include glyoxal, glutaraldehyde, dialdehyde starch, dialdehyde chitosan, and the EDC/NHS mixture. Additionally, the review briefly discusses materials cross-linked with the MES/EDC mixture, caffeic acid, tannic acid, and genipin. Through a critical analysis of current research, this work aims to guide the development of more effective and safer biopolymeric materials tailored for biomedical applications, highlighting potential areas for further investigation and optimization.

Prediction model for treatment outcomes 3 years after corneal cross-linking for keratoconus.

PURPOSE: This study aimed to identify preoperative factors that predict visual acuity and Kmax 3 years after corneal cross-linking (CXL) in patients with keratoconus (KC), and to develop a prediction model. METHODS: We enrolled 68 patients with KC and followed up on 100 eyes that received CXL for at least 3 years. Preoperative data, including age, UDVA, CDVA, cylinder, SE, and the parameters of tomography including Kmax were collected as predictors. The primary outcomes were changes in CDVA (Delta CDVA) and Kmax (Delta Kmax) postoperatively. Univariate and multivariate linear regression were used to identify the correlation between the primary outcomes and predictors and establish prediction models. RESULTS: Both CDVA and Kmax remained stable from baseline to 3 years after CXL: from 0.25 ± 0.18 to 0.22 ± 0.20 (P = 0.308) and from 58.70 ± 9.52 D to 57.02 ± 8.83 D (P = 0.187), respectively. Multivariate analysis showed that worse preoperative CDVA (ß coefficient - 0.668, P < 0.001) and lower preoperative Kmean (ß coefficient 0.018,P < 0.001) were associated with greater improvement in CDVA after CXL. A smaller preoperative eccentricity (ß coefficient 8.896, P = 0.01) and a higher preoperative Kmean (ß coefficient - 1.264, P < 0.001) predicted a more flattening of postoperative Kmax. The prediction model for CDVA (R2 = 0.43) and Kmax (R2 = 0.37) could accurately estimate treatment outcomes. CONCLUSIONS: CXL is highly effective in halting or preventing further progression of KC. The preoperative factors CDVA and Kmean were able to predict visual acuity changes 3 years after CXL. And preoperative eccentricity and Kmean could predict Kmax changes 3 years after CXL.

Nitrogen mustard induces dynamic nuclear protein spectrum change and DNA-protein crosslinking, with p97 mediating repair.

Nitrogen mustard (NM) is a chemotherapeutic agent capable of alkylating nucleophilic proteins and DNA, causing severe cell damage. However, no reports have been on the dynamic changes in proteomics induced by NM. In this study, we established a model of acute exposure to NM for 1 h and a continuous cultured model for 24 h after NM removal (repair stage) using 16HBE cells. The nuclear protein spectrum and nuclear proteins crosslinked with DNA were analyzed, and the function of p97 during NM damage was examined. An hour of NM exposure resulted in severe changes in the nuclear protein spectrum and protein into the cell nucleus, which is mainly involved in nuclear acid-related issues. After 24 h, the return to normal process of the types and amounts of differentially expressed proteins was inhibited by si-p97. The main processes involved in si-p97 intervention were nucleocytoplasmic transport, processing in the endoplasmic reticulum, metabolic abnormalities, and DNA-response; however. An hour of exposure to NM increased DNA-protein crosslinking (DPC), total-H2AX, and p-H2AX. In contrast, si-p97 only further increased or maintained their levels at 24 h yet not at 1 h. The effect of the proteasome inhibitor, MG132, was similar to that of si-p97. The siRNA of DVC1, a partner of p97, also increased the DPC content. Both si-p97 and si-DVC1 increased the cytoplasmic levels of the proteasome (PSMD2). These results suggest acute NM exposure induces severe nuclear protein spectral changes, rapid protein influx into the nucleus, DPC formation, and DNA double-strand breaks. Furthermore, our data indicated that p97 is involved in normal protein spectrum maintenance and DPC removal after NM withdrawal, requiring the participation of DVC1 and the proteasome.

Dual effect of pH and X-ray irradiation on properties of gelatin/trans-cinnamaldehyde-based composite films for sustainable packaging.

Gelatin (Gel) based water-insoluble films with antimicrobial properties were developed by the green method using trans-cinnamaldehyde (TCA) and low-energy X-ray irradiation as dual crosslinkers. The Gel/TCA composite films (GTCF) were prepared at different pH (4, 6, 8, and 10) and crosslinked by incorporating 5 % (w/w, based on Gel) TCA and X-ray irradiation (350 kV and 11.4 mA) with doses of 0, 5, 10 and 15 kGy. The presence of TCA in GTCF forms dense, flexible, and strong films when exposed to X-ray irradiation. The GTCF at pH 6, incorporated with 5 wt% TCA and irradiated with 10 kGy X-ray, displayed the highest degree of crosslinking (DOC) (93.4 ± 3.4 %), tensile strength, excellent UV-barrier (> 99.9 %), antimicrobial (inhibitory capacity of >50 %), and water vapor permeability (4.1 ± 0.6 g.mm/m2.day. kPa), and low solubility in water (0.5 ± 0.3 %), and oxygen permeability. The GTCF, crosslinked with X-ray irradiation, has multifunctional properties and strong potential in the sustainable packaging industry to augment the shelf life of food and reduce food waste. To the best of our information, this is the first and novel report investigating the effects of pH on the properties of GTCF crosslinked with X-ray.

Design of improved acellular fish skin as a promising scaffold for tissue regeneration applications.

Decellularized marine tissues have been regarded as a desirable biomaterial because of their biological risk reduction, less religious constraints, and resemblance to mammalian tissues. The properties of these matrices can be improved by adding cross-linkers. In this study, after decellularization of the of Tilapia and Grass carp fish skin, a comparative study was conducted between them. Due to the higher abundance of collagen and glycosaminoglycans (GAGs) in Tilapia skin, it was selected for further study. In the next step, the cross-linking process was performed with three concentrations of 1-Ethyl-3-(3-dimethylaminopropyl) carbodiimide/ N-Hydroxysuccinimide (EDC/NHS) and tannic acid cross-linkers. The MTT results showed that the cross-linked samples with low concentrations of EDC/NHS had higher biocompatibility compared to the cross-linked sample with high concentration of EDC/NHS, as well as all samples cross-linked with tannic acid. Mechanical and physical studies conducted on the skin of Tilapia fish showed that the 15 mM/7.5 mM concentration of EDC/NHS increased the mechanical and temperature strength and decreased the degradability and it did not influence cell attachment. In general, it was shown that different fish skins differ in terms of collagen and GAGs, and the optimal concentration of EDC cross-linker improves the mechanical and physical properties of the matrix derived from fish skin.

Permeation characteristics and cross-linking efficacy of iontophoresis-assisted riboflavin delivery for accelerated riboflavin-ultraviolet A scleral collagen cross-linking in porcine eyes.

The purpose of this study is to investigate whether the iontophoresis-assisted riboflavin delivery to posterior sclera with less delivery time, can achieve the same riboflavin permeation efficiency as the passive soaking way, and its effect on the mechanical properties of posterior sclera for accelerated scleral collagen cross-linking (A-SXL). In this study, 0.1% riboflavin solution was applied into the posterior sclera of porcine eyes either by the iontophoresis-assisted or passive soaking method, with delivery time of 5, 7.5, 10, 12.5, 15, 17.5, and 20 min, respectively. The fluorescence intensity and the distribution of riboflavin concentration in the 10 µm frozen sections of the sclera were evaluated by fluorescence inverted microscope. The posterior sclera with riboflavin treatment through either the iontophoresis-assisted or the passive soaking method for different durations ranging from 5 to 20 min was treated with ultraviolet A (UVA) irradiation at an intensity of 10 mW/cm2 for 9 min. The elastic modulus was determined at the physiological strain level using the uniaxial tensile test after ASXL. The results showed that the fluorescence intensity of riboflavin increased by prolonging the delivery time in both the iontophoresis and passive soaking groups, and the permeation depth of riboflavin remained constant over 15 min. The fluorescence intensity in the iontophoresis group was significantly higher than in the passive soaking group at 12.5 min and 15 min, respectively. The elastic modulus at 12.5 min in the iontophoresis group was significantly higher than in the passive soaking group at the same delivery time and showed no significant difference compared to the passive soaking group at 20 min. In conclusion, it indicated that iontophoresis-assisted delivery could not only shorten the surgery time but also achieve similar mechanical performance to the passive soaking method in ASXL.

Pharmaceutical chitosan hydrogels: A review on its design and applications.

Chitosan (CS) has become a focal point of extensive research in the pharmaceutical industry due to its remarkable biodegradability, biocompatibility and sustainability. Chitosan hydrogels (CS HGs) are characterized by their viscoelasticity, flexibility and softness. The polar surfaces exhibit properties that mitigate interfacial tension between the hydrogel and body fluids. The inherent compatibility of CS HGs with body tissues and fluids positions them as outstanding polymers for delivering therapeutic proteins, peptides, DNA, siRNA, and vaccines. Designed to release drugs through mechanisms such as swelling-based diffusion, bioerosion, and responsiveness to stimuli, CS HGs offer a versatile platform for drug delivery. CS HGs play pivotal roles in serving purposes such as prolonging the duration of preprogrammed drug delivery, enabling stimuli-responsive smart delivery to target sites, protecting encapsulated drugs within the mesh network from adverse environments, and facilitating mucoadhesion and penetration through cell membranes. This review comprehensively outlines various novel preparation methods of CS HGs, delving into the parameters influencing drug delivery system design, providing a rationale for CS HG utilization in drug delivery, and presenting diverse applications across the pharmaceutical landscape. In synthesizing these facets, the review seeks to contribute to a nuanced understanding of the multifaceted role that CS HGs play in advancing drug delivery methodologies.