Three-dimensional printed pure-titanium implantation for chest wall reconstruction involving the sternum and ribs: a novel approach.

Chest wall reconstruction is challenging due to the complex shape and large defect size. The three-dimensional printing technology enables the fabrication of customized implants, and 3D-printed pure-titanium could provide superior mechanical properties to conventional materials. The aim of this study was to evaluate long-term outcomes of patients undergoing chest wall reconstruction with a 3D-printed pure-titanium implant. Between August 2018 and May 2021, 5 patients underwent surgery due to sternal metastasis (n = 3), postoperative sternal wound infection (n = 1) and deformity (n = 1). The customized implant was designed and constructed based on the size and shape of the chest wall defect measured on computed tomography. All patients demonstrated uneventful recovery without complications during the hospital course. During the median follow-up of 20 months, 1 patient underwent revision surgery due to implant breakage, and 1 removed the implant due to trauma-related chest wall infection. One patient died from cancer progression, while 3 patients are alive without any implant-related complications. Chest wall reconstruction using a 3D-printed pure-titanium implant could be a novel alternative for patients with various conditions affecting the sternum and ribs.

Evaluation of the reliability and validity of the upright head roll test for lateral semicircular canal benign paroxysmal positional vertigo.

BACKGROUND: The upright head roll test (UHRT) is a recently introduced diagnostic maneuver for lateral semicircular canal benign paroxysmal positional vertigo (LSC-BPPV). OBJECTIVE: This study aimed to evaluate the reliability and validity of the UHRT. METHODS: Two separate studies were conducted. Study 1 analyzed 827 results of videonystagmography (VNG) to assess UHRT reliability, and Study 2 analyzed 130 LSC-BPPV cases to evaluate UHRT validity. RESULTS: The inter-test reliability between UHRT and the supine head roll test (SHRT) showed substantial agreement (Cohen's kappa = 0.753) in direction-changing positional nystagmus (DCPN) and almost perfect agreement (Cohen's kappa = 0.836) in distinguishing the direction of DCPN. The validity assessment of UHRT showed high accuracy in diagnosing LSC-BPPV (80.0%) and in differentiating the variant types (74.6%). UHRT was highly accurate in diagnosing the canalolithiasis type in LSC-BPPV patients (Cohen's kappa = 0.835); however, it showed only moderate accuracy in diagnosing the cupulolithiasis type (Cohen's kappa = 0.415). The intensity of nystagmus in UHRT was relatively weaker than that in SHRT (P < 0.05). CONCLUSION: UHRT is a reliable test for diagnosing LSC-BPPV and distinguishing subtypes. However, UHRT has a limitation in discriminating the affected side owing to a weaker intensity of nystagmus than SHRT.

Preoperative DLco and FEV1 are correlated with postoperative pulmonary complications in patients after esophagectomy.

Limited information is available regarding the association between preoperative lung function and postoperative pulmonary complications (PPCs) in patients with esophageal cancer who undergo esophagectomy. This is a retrospective cohort study. Patients were classified into low and high lung function groups by the cutoff of the lowest fifth quintile of forced expiratory volume in 1 s (FEV1) %predicted (%pred) and diffusing capacity of the carbon monoxide (DLco) %pred. The PPCs compromised of atelectasis requiring bronchoscopic intervention, pneumonia, and acute lung injury/acute respiratory distress syndrome. Modified multivariable-adjusted Poisson regression model using robust error variances and inverse probability treatment weighting (IPTW) were used to assess the relative risk (RR) for the PPCs. A joint effect model considered FEV1%pred and DLco %pred together for the estimation of RR for the PPCs. Of 810 patients with esophageal cancer who underwent esophagectomy, 159 (19.6%) developed PPCs. The adjusted RR for PPCs in the low FEV1 group relative to high FEV1 group was 1.48 (95% confidence interval [CI] = 1.09-2.00) and 1.98 (95% CI = 1.46-2.68) in the low DLco group relative to the high DLco group. A joint effect model showed adjusted RR of PPCs was highest in patients with low DLco and low FEV1 followed by low DLco and high FEV1, high DLco and low FEV1, and high DLco and high FEV1 (Reference). Results were consistent with the IPTW. Reduced preoperative lung function (FEV1 and DLco) is associated with post-esophagectomy PPCs. The risk was further strengthened when both values decreased together.

Discovery of a Novel Potent EGFR Inhibitor Against EGFR Activating Mutations and On-Target Resistance in NSCLC.

PURPOSE: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) serve as the standard first-line therapy for EGFR-mutated non-small cell lung cancer (NSCLC). Despite the sustained clinical benefits achieved through optimal EGFR-TKI treatments, including the third-generation EGFR-TKI osimertinib, resistance inevitably develops. Currently, there are no targeted therapeutic options available postprogression on osimertinib. Here, we assessed the preclinical efficacy of BI-4732, a novel fourth-generation EGFR-TKI, using patient-derived preclinical models reflecting various clinical scenarios. EXPERIMENTAL DESIGN: The antitumor activity of BI-4732 was evaluated using Ba/F3 cells and patient-derived cell/organoid/xenograft models with diverse EGFR mutations. Intracranial antitumor activity of BI-4732 was evaluated in a brain-metastasis mouse model. RESULTS: We demonstrated the remarkable antitumor efficacy of BI-4732 as a single agent in various patient-derived models with EGFR_C797S-mediated osimertinib resistance. Moreover, BI-4732 exhibited activity comparable to osimertinib in inhibiting EGFR-activating (E19del and L858R) and T790M mutations. In a combination treatment strategy with osimertinib, BI-4732 exhibited a synergistic effect at significantly lower concentrations than those used in monotherapy. Importantly, BI-4732 displayed potent antitumor activity in an intracranial model, with low efflux at the blood-brain barrier. CONCLUSIONS: Our findings highlight the potential of BI-4732, a selective EGFR-TKI with high blood-brain barrier penetration, targeting a broad range of EGFR mutations, including C797S, warranting clinical development.

Effects of autophagy-inhibiting chemicals on sialylation of Fc-fusion glycoprotein in recombinant CHO cells.

The occurrence of autophagy in recombinant Chinese hamster ovary (rCHO) cell culture has attracted attention due to its effects on therapeutic protein production. Given the significance of glycosylation in therapeutic proteins, this study examined the effects of autophagy-inhibiting chemicals on sialylation of Fc-fusion glycoproteins in rCHO cells. Three chemical autophagy inhibitors known to inhibit different stages were separately treated with two rCHO cell lines that produce the same Fc-fusion glycoprotein derived from DUKX-B11 and DG44. All autophagy inhibitors significantly decreased the sialylation of Fc-fusion glycoprotein in both cell lines. The decrease in sialylation of Fc-fusion glycoprotein is unlikely to be attributed to the release of intracellular enzymes, given the high cell viability and low activity of extracellular sialidases. Interestingly, the five intracellular nucleotide sugars remained abundant in cells treated with autophagy inhibitors. In the mRNA expression profiles of 27 N-glycosylation-related genes using the NanoString nCounter system, no significant differences in gene expression were noted. With the positive effect of supplementing nucleotide sugar precursors on sialylation, attempts were made to enhance the levels of intracellular nucleotide sugars by supplying these precursors. The addition of nucleotide sugar precursors to cultures treated with inhibitors successfully enhanced the sialylation of Fc-fusion glycoproteins compared to the control culture. This was particularly evident under mild stress conditions and not under relatively severe stress conditions, which were characterized by a high decrease in sialylation. These results suggest that inhibiting autophagy in rCHO cell culture decreases sialylation of Fc-fusion glycoprotein by constraining the availability of intracellular nucleotide sugars. KEY POINTS: •  The autophagy inhibition in rCHO cell culture leads to a significant reduction in the sialylation of Fc-fusion glycoprotein. •  The pool of five intracellular nucleotide sugars remained highly abundant in cells treated with autophagy inhibitors. •  Supplementation of nucleotide sugar precursors effectively restores decreased sialylation, particularly under mild stress conditions but not in relatively severe stress conditions.

Protective effect of empagliflozin against palmitate-induced lipotoxicity through AMPK in H9c2 cells.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors have recently emerged as novel cardioprotective agents. However, their direct impact on cardiomyocyte injury is yet to be studied. In this work, we investigate the underlying molecular mechanisms of empagliflozin (EMPA), an SGLT2 inhibitor, in mitigating palmitate (PA)-induced cardiomyocyte injury in H9c2 cells. We found that EMPA significantly attenuated PA-induced impairments in insulin sensitivity, ER stress, inflammatory cytokine gene expression, and cellular apoptosis. Additionally, EMPA elevated AMP levels, activated the AMPK pathway, and increased carnitine palmitoyl transferase1 (CPT1) gene expression, which collectively enhanced fatty acid oxidation and reduced stress signals. This study reveals a novel mechanism of EMPA's protective effects against PA-induced cardiomyocyte injury, providing new therapeutic insights into EMPA as a cardioprotective agent.

Bioactive Bone Substitute in a Rabbit Ulna Model: Preclinical Study.

BACKGROUND: Current therapies to effectively treat long-bone defects and extensive bone tissue loss remains limited. In this study, we created a new bone substitute by integrating advanced technologies such as structure patterning, controlled release of a bone growth factor and conjugation system for clinically effective bone regeneration. This novel bioactive bone substitute was evaluated for its safety and efficacy using a rabbit ulna model. METHODS: A three dimensional bone patterned cylindrical structure with 1.5 cm in length and 5 mm in diameter was printed using poly(L-lactic acid)(PLLA) as a weight-bearing support and space-filling scaffold. And a bone morphogenetic protein 2 (BMP2) was employed to enhance bone regeneration, and coated to a 3D PLLA using alginate catechol and collagen to prolong the release kinetics. This novel bone substitute (BS)was evaluated for its physico-chemical and biological properties in vitro, and histological analysis and radiographical analysis such as X-ray, CT and micro-CT image analysis were performed to evaluate new bone formation in vivo. RESULTS: The BS possesses an ideal shape and mechanically suitable proeperties for clinical use, with an easy-to-grab and break-resistant design at both ends, 80 ± 10 MPa of compression strength, and BMP2 release for two months. Histological analysis demonstrated the biocompability of BS with minimal inflammation and immune response, and X-ray, CT and micro-CT demonstrated effective new bone formation in rabbit ulna defect model. CONCLUSION: The preclinical study of a novel bioactive bone substitute has shown its safe and effective properties in an animal model suggesting its clinical potential.

The Genome of the Korean Island-Originated Perilla citriodora 'Jeju17' Sheds Light on Its Environmental Adaptation and Fatty Acid and Lipid Production Pathways.

Perilla is a key component of Korean food. It contains several plant-specialized metabolites that provide medical benefits. In response to an increased interest in healthy supplement food from the public, people are focusing on the properties of Perilla. Nevertheless, unlike rice and soybeans, there are few studies based on molecular genetics on Perilla, so it is difficult to systematically study the molecular breed. The wild Perilla, Perilla citriodora 'Jeju17', was identified a decade ago on the Korean island of Jeju. Using short-reads, long-reads, and Hi-C, a chromosome-scale genome spanning 676 Mbp, with high contiguity, was assembled. Aligning the 'Jeju17' genome to the 'PC002' Chinese species revealed significant collinearity with respect to the total length. A total of 31,769 coding sequences were predicted, among which 3331 were 'Jeju17'-specific. Gene enrichment of the species-specific gene repertoire highlighted environment adaptation, fatty acid metabolism, and plant-specialized metabolite biosynthesis. Using a homology-based approach, genes involved in fatty acid and lipid triacylglycerol biosynthesis were identified. A total of 22 fatty acid desaturases were found and comprehensively characterized. Expression of the FAD genes in 'Jeju17' was examined at the seed level, and hormone signaling factors were identified. The results showed that the expression of FAD genes in 'Jeju17' at the seed level was high 25 days after flowering, and their responses of hormones and stress were mainly associated with hormone signal transduction and abiotic stress via cis-elements patterns. This study presents a chromosome-level genome assembly of P. citriodora 'Jeju17', the first wild Perilla to be sequenced from the Korean island of Jeju. The analyses provided can be useful in designing ALA-enhanced Perilla genotypes in the future.

Development of an SNP marker set for marker-assisted backcrossing using genotyping-by-sequencing in tetraploid perilla.

High-quality molecular markers are essential for marker-assisted selection to accelerate breeding progress. Compared with diploid species, recently diverged polyploid crop species tend to have highly similar homeologous subgenomes, which is expected to limit the development of broadly applicable locus-specific single-nucleotide polymorphism (SNP) assays. Furthermore, it is particularly challenging to make genome-wide marker sets for species that lack a reference genome. Here, we report the development of a genome-wide set of kompetitive allele specific PCR (KASP) markers for marker-assisted recurrent selection (MARS) in the tetraploid minor crop perilla. To find locus-specific SNP markers across the perilla genome, we used genotyping-by-sequencing (GBS) to construct linkage maps of two F2 populations. The two resulting high-resolution linkage maps comprised 2326 and 2454 SNP markers that spanned a total genetic distance of 2133 cM across 16 linkage groups and 2169 cM across 21 linkage groups, respectively. We then obtained a final genetic map consisting of 22 linkage groups with 1123 common markers from the two genetic maps. We selected 96 genome-wide markers for MARS and confirmed the accuracy of markers in the two F2 populations using a high-throughput Fluidigm system. We confirmed that 91.8% of the SNP genotyping results from the Fluidigm assay were the same as the results obtained through GBS. These results provide a foundation for marker-assisted backcrossing and the development of new varieties of perilla.

Fabrication of Tri-Directional Poly(2,5-benzimidazole) Membrane Using Direct Casting for Vanadium Redox Flow Battery.

In vanadium redox flow batteries (VRFBs), simultaneously achieving high proton conductivity, low vanadium-ion permeability, and outstanding chemical stability using electrolyte membranes is a significant challenge. In this study, we report the fabrication of a tri-directional poly(2,5-benzimidazole) (T-ABPBI) membrane using a direct casting method. The direct-cast T-ABPBI (D-T-ABPBI) membrane was fabricated by modifying the microstructure of the membrane while retaining the chemical structure of ABPBI, having outstanding chemical stability. The D-T-ABPBI membrane exhibited lower crystallinity and an expanded free volume compared to the general solvent-cast T-ABPBI (S-T-ABPBI) membrane, resulting in enhanced hydrophilic absorption capabilities. Compared to the S-T-ABPBI membrane, the enhanced hydrophilic absorption capability of the D-T-ABPBI membrane resulted in a decrease in the specific resistance (the area-specific resistance of S-T-ABPBI and D-T-ABPBI membrane is 1.75 and 0.98 Ωcm2, respectively). Additionally, the D-T-ABPBI membrane showed lower vanadium permeability (3.40 × 10-7 cm2 min-1) compared to that of Nafion 115 (5.20 × 10-7 cm2 min-1) due to the Donnan exclusion effect. Owing to the synergistic effects of these properties, the VRFB assembled with D-T-ABPBI membrane had higher or equivalent coulomb efficiencies (>97%) and energy efficiencies (70-91%) than Nafion 115 at various current densities (200-40 mA cm-2). Furthermore, the D-T-ABPBI membrane exhibited stable performance for over 300 cycles at 100 mA cm-2, suggesting its outstanding chemical stability against the highly oxidizing VO2+ ions during practical VRFB operation. These results indicate that the newly fabricated D-T-ABPBI membranes are promising candidates for VRFB application.

Effect of Transition Metal Dichalcogenide Based Confinement Layers on the Performance of Phase-Change Heterostructure Memory.

Phase-change random-access memory is a promising non-volatile memory technology. However repeated phase-change operations can cause durability issues owing to defects formed by long-distance atom diffusion. To mitigate these issues, phase-change heterostructure (PCH) devices with confinement material (CM) layers based on transition metal dichalcogenides (TMDs) such as TiTe2 have been proposed. This study implements PCH devices with additional TMDs, including NiTe2 and MoTe2 , alongside TiTe2 , and analyzes their characteristics by examining the differences in the CM layers. The results show that the NiTe2 -based PCH device demonstrates a RESET current of 1.4 mA, 38% lower than that of the TiTe2 -based device, enabling low-power operation. Furthermore, the MoTe2 -based PCH device exhibits a cycling endurance exceeding 107 cycles, a five-fold improvement in durability compare with the TiTe2 -based device. The performance differences observe in each PCH device can be attributed to the variation in the material properties, such as the cohesive energy and electrical conductivity, of the TMDs used as the CM layer. These results provide critical clues to improve the performance and reliability of conventional PCH memory devices.

The optimal interval of surveillance gastroscopy after endoscopic resection for gastric neoplasia: a multicenter cohort study.

BACKGROUND/AIMS: Due to the possible metachronous recurrence of gastric neoplasia, surveillance gastroscopy is mandatory after endoscopic resection for gastric neoplasia. However, there is no consensus on the surveillance gastroscopy interval. This study aimed to find an optimal interval of surveillance gastroscopy and to investigate the risk factors for metachronous gastric neoplasia. METHODS: Medical records were reviewed retrospectively in patients who underwent endoscopic resection for gastric neoplasia in 3 teaching hospitals from June 2012 to July 2022. Patients were divided into two groups; annual surveillance vs. biannual surveillance. The incidence of metachronous gastric neoplasia was identified, and the risk factors for metachronous gastric neoplasia were investigated. RESULTS: Among the 1,533 patients who underwent endoscopic resection for gastric neoplasia, 677 patients were enrolled in this study (annual surveillance 302, biannual surveillance 375). Metachronous gastric neoplasia was observed in 61 patients (annual surveillance 26/302, biannual surveillance 32/375, P = 0.989), and metachronous gastric adenocarcinoma was observed in 26 patients (annual surveillance 13/302, biannual surveillance 13/375, P = 0.582). All the lesions were removed by endoscopic resection successfully. In a multivariate analysis, severe atrophic gastritis on gastroscopy was an independent risk factor for metachronous gastric adenocarcinoma (odds ratio 3.8, 95% confidence interval 1.4‒10.1; P = 0.008). CONCLUSIONS: Meticulous observation to detect the metachronous gastric neoplasia is necessary for patients with severe atrophic gastritis during follow-up gastroscopy after endoscopic resection for gastric neoplasia. Annual surveillance gastroscopy might be enough after endoscopic resection for gastric neoplasia.

Structure-guided Mutagenesis Reveals the Catalytic Residue that Controls the Regiospecificity of C6-Indole Prenyltransferases.

Indole is a significant structural moiety and functionalization of the C-H bond in indole-containing molecules expands their chemical space, and modifies their properties and/or activities. Indole prenyltransferases (IPTs) catalyze the direct regiospecific installation of prenyl, C5 carbon units, on indole-derived compounds. IPTs have shown relaxed substrate flexibility enabling them to be used as tools for indole functionalization. However, the mechanism by which certain IPTs target a specific carbon position is not fully understood. Herein, we use structure-guided site-directed mutagenesis, in vitro enzymatic reactions, kinetics and structural-elucidation of analogs to verify the key catalytic residues that control the regiospecificity of all characterized regiospecific C6 IPTs. Our results also demonstrate that substitution of PriB_His312 to Tyr leads to the synthesis of analogs prenylated at different positions than C6. This work contributes to understanding of how certain IPTs can access a challenging position in indole-derived compounds.

DS86760016, a Leucyl-tRNA Synthetase Inhibitor, Is Active against Mycobacterium abscessus.

Benzoxaboroles are a new class of leucyl-tRNA synthetase inhibitors. Epetraborole, a benzoxaborole, is a clinical candidate developed for Gram-negative infections and has been confirmed to exhibit favorable activity against a well known pulmonary pathogen, Mycobacterium abscessus. However, according to ClinicalTrials.gov, in 2017, a clinical phase II study on the use of epetraborole to treat complicated urinary tract and intra-abdominal infections was terminated due to the rapid emergence of drug resistance during treatment. Nevertheless, epetraborole is in clinical development for nontuberculous mycobacteria (NTM) disease especially for Mycobacterium avium complex-related pulmonary disease (MAC-PD). DS86760016, an epetraborole analog, was further demonstrated to have an improved pharmacokinetic profile, lower plasma clearance, longer plasma half-life, and higher renal excretion than epetraborole in animal models. In this study, DS86760016 was found to be similarly active against M. abscessus in vitro, intracellularly, and in zebrafish infection models with a low mutation frequency. These results expand the diversity of druggable compounds as new benzoxaborole-based candidates for treating M. abscessus diseases.

Hydrocarbon-Based Composite Membrane Using LCP-Nonwoven Fabrics for Durable Proton Exchange Membrane Water Electrolysis.

A new hydrocarbon-based (HC) composite membrane was developed using liquid crystal polymer (LCP)-nonwoven fabrics for application in proton exchange membrane water electrolysis (PEMWE). A copolymer of sulfonated poly(arylene ether sulfone) with a sulfonation degree of 50 mol% (SPAES50) was utilized as an ionomer for the HC membranes and impregnated into the LCP-nonwoven fabrics without any surface treatment of the LCP. The physical interlocking structure between the SPAES50 and LCP-nonwoven fabrics was investigated, validating the outstanding mechanical properties and dimensional stability of the composite membrane in comparison to the pristine membrane. In addition, the through-plane proton conductivity of the composite membrane at 80 °C was only 15% lower than that of the pristine membrane because of the defect-free impregnation state, minimizing the decrease in the proton conductivity caused by the non-proton conductive LCP. During the electrochemical evaluation, the superior cell performance of the composite membrane was evident, with a current density of 5.41 A/cm2 at 1.9 V, compared to 4.65 A/cm2 for the pristine membrane, which can be attributed to the smaller membrane resistance of the composite membrane. From the results of the degradation rates, the prepared composite membrane also showed enhanced cell efficiency and durability during the PEMWE operations.

Efficacy of tegoprazan-based bismuth quadruple therapy compared with bismuth quadruple therapy for Helicobacter pylori infection: A randomized, double-blind, active-controlled study.

BACKGROUND: Bismuth-based quadruple therapy (BQT) is recommended as the first-line empirical therapy for Helicobacter pylori eradication as it is not associated with resistance. However, few studies have investigated the use of potassium-competitive acid blockers for BQT. AIM: To investigate the efficacy and safety profiles of tegoprazan-based BQT (TBMT) versus lansoprazole-based BQT (LBMT) for H. pylori eradication. METHODS: We included patients older than 18 with an H. pylori infection without a history of H. pylori eradication who visited four university-affiliated hospitals between March 2020 and December 2021. H. pylori infection was diagnosed using a rapid urease test or Giemsa staining. Patients were randomly assigned to the TBMT or LBMT group. RESULTS: 217 subjects were randomly allocated to receive either TBMT (n = 108) or LBMT (n = 109) therapy. Intention-to-treat (ITT) eradication rates of TBMT and LBMT were 80.0% and 77.4% (95% confidence interval [CI]: -8.4 to 13.7, p = 0.0124), respectively. Corresponding modified ITT rates were 90.3% and 84.5% (95% CI: -3.6 to 15.2, p = 0.0005), respectively. Per-protocol (PP) eradication rates of TBMT and LBMT were 90.2% and 82.4% (95% CI: -2.5 to 18.2, p = 0.0003), respectively. There was no significant difference in the rate of adverse events between the TBMT and LBMT groups (39.1% vs. 43.4%, p = 0.5211). TBMT showed higher eradication rates than that of LBMT in ITT, m-ITT, and PP analysis. CONCLUSION: TBMT showed a noninferior eradication rate and similar adverse events to LBMT as a first-line eradication regimen. Our results suggest that tegoprazan might be substituted for proton pump inhibitors in H. pylori eradication regimens.

Fabrication of 3D-Printed Implant for Two-Stage Ear Reconstruction Surgery and Its Clinical Application.

PURPOSE: Ear reconstruction is one of the most difficult areas in the field of reconstructive surgery. Due to limitations of the current practice, a novel method of auricular reconstruction is needed. Major advancements in three-dimensional (3D) printing technique have rendered the process of ear reconstruction more favorable. Herein, we present our experience in designing and clinically using 3D implants in both 1st and 2nd stage ear reconstruction surgery. MATERIALS AND METHODS: After obtaining 3D CT data from each patient, a 3D geometric ear model was created using mirroring and segmentation processes. The 3D-printed implant design resembles but does not exactly match the normal ear shape, and can be inserted in harmony with the currently used surgical technique. The 2nd stage implant was designed to minimize dead space and support the posterior ear helix. The 3D implants were finally fabricated with a 3D printing system and used in ear reconstruction surgery in our institute. RESULTS: The 3D implants were manufactured for application to the currently used two-stage technique while maintaining the shape of the patient's normal ear. The implants were successfully used for ear reconstruction surgery in microtia patients. A few months later, the 2nd stage implant was used in the 2nd stage operation. CONCLUSION: The authors were able to design, fabricate, and apply patient-specific 3D-printed ear implants for 1st and 2nd stage ear reconstruction surgeries. This design, combined with 3D bioprinting technique, may be a future alternative for ear reconstruction.

Mesoscale Simulation Based on the Dynamic Mean-Field Density Functional Method on Block-Copolymeric Ionomers for Polymer Electrolyte Membranes.

Block copolymers generally have peculiar morphological characteristics, such as strong phase separation. They have been actively applied to polymer electrolyte membranes for proton exchange membrane fuel cells (PEMFCs) to obtain well-defined hydrophilic regions and water channels as a proton pathway. Although molecular simulation tools are advantageous to investigate the mechanism of water channel formation based on the chemical structure and property relationships, classical molecular dynamics simulation has limitations regarding the model size and time scale, and these issues need to be addressed. In this study, we investigated the morphology of sulfonated block copolymers synthesized for PEM applications using a mesoscale simulation based on the dynamic mean-field density functional method, widely applied to investigate macroscopic systems such as polymer blends, micelles, and multi-block/grafting copolymers. Despite the similar solubility parameters of the monomers in our block-copolymer models, very different morphologies in our 3D mesoscale models were obtained. The model with sulfonated monomers, in which the number of sulfonic acid groups is twice that of the other model, showed better phase separation and water channel formation, despite the short length of its hydrophilic block. In conclusion, this unexpected behavior indicates that the role of water molecules is important in making PEM mesoscale models well-equilibrated in the mesoscale simulation, which results in the strong phase separation between hydrophilic and hydrophobic regions and the ensuing well-defined water channel. PEM synthesis supports the conclusion that using the sulfonated monomers with a high sulfonation degree (32.5 mS/cm) will be more effective than using the long hydrophilic block with a low sulfonation degree (25.2 mS/cm).