3D-Bioprinted Skin Tissues for Improving Wound Healing: Current Status and Perspective.

Advancements in tissue engineering enable the fabrication of complex and functional tissues or organs. In particular, bioprinting enables controlled and accurate deposition of cells, biomaterials, and growth factors to create complex 3D skin constructs specific to a particular individual. Despite these advancements, challenges such as vascularization, long-term stability, and regulatory considerations hinder the clinical translation of bioprinted skin constructs. This chapter focuses on such approaches using advanced biomaterials and bioprinting techniques to overcome the current barriers in wound-healing studies. Moreover, it addresses current obstacles in wound-healing studies, highlighting the need for continued research and innovation to overcome these barriers and facilitate the practical utilization of bioprinted skin constructs in clinical settings.

Leveraging Tissue Engineering for Skin Cancer Models.

Bioengineered in vitro three-dimensional (3D) skin model has emerged as a promising tool for recapitulating different types of skin cancer and performing pre-clinical tests. However, a full-thickness 3D model including the epidermis, dermis, and hypodermis layers is scarce despite its significance in human physiology and diverse biological processes. In this book chapter, an attempt has been made to summarize various skin cancer models, including utilized skin layers, materials, cell lines, specific treatments, and fabrication techniques for three types of skin cancer: melanoma, basal cell carcinoma (BCC), and squamous cell carcinoma (SCC). Subsequently, current limitations and future directions of skin cancer models are discussed. The knowledge of the current status of skin cancer models can provide various potential applications in cancer research and thus a more effective way for cancer treatment.

Investigation of Potential cGMP-Specific PDE V and Aminopeptidase N Inhibitors of Allium ampeloprasum L. and Its Bioactive Components: Kinetic and Molecular Docking Studies.

The primary objectives of this study were to assess the inhibitory effects of Allium ampeloprasum L. extract (AAE) and its derived organosulfur and polyphenolic compounds on the enzymatic activities of cGMP-specific PDE V (PDE5) and aminopeptidase N (APN). Additionally, the study aimed to investigate their potential as inhibitors against these two target enzymes through kinetic analyses and molecular docking studies. The in vitro enzyme assays demonstrated that both AAE and its derived compounds significantly decreased the activity of PDE5 and APN. Further analyses involving kinetics and molecular docking provided insights into the specific inhibitor types of AAE and its derived compounds along with the proposed molecular docking models illustrating the interactions between the ligands (the compounds) and the enzymes (PDE5 and APN). In particular, AAE-derived polyphenolic compounds showed relatively stable binding affinity (-7.2 to -8.3 kcal/mol) on PDE5 and APN. Our findings proved the potential as an inhibitor against PDE5 and APN of AAE and AAE-derived organosulfur and polyphenolic compounds as well as a functional material for erectile dysfunction improvement.

SARS-CoV-2 Infectivity and Antibody Titer Reduction for 6 Months After Second Dose of BNT162b2 mRNA Vaccine in Health Care Workers: A Prospective Cohort Study.

Several studies reported that severe acute respiratory syndrome coronavirus-2 antibody levels change over 6 months in participants receiving the vaccination. From the enrolled 272 health care workers (HCWs), blood samples were obtained at 2, 16, and 24 weeks after the second vaccination dose. In the 267 noninfected HCWs, the neutralizing antibodies decreased by 23.9%, and the anti-spike/receptor binding domain antibody decreased by 53.8% at 24 weeks. We observed no significant difference in antibody reduction between the sexes; however, in younger individuals, there was higher antibody formation and lower reduction rates of the neutralizing antibody. In 3 HCWs with breakthrough infections, the antibody levels were relatively low just before the coronavirus disease 2019 infection. In conclusion, as antibody titers decrease over time after the second vaccination dose and HCWs with low antibody titers tend to have a high probability of breakthrough infection, an additional dose should be considered after several months. Blood samples were obtained from health care workers at 2, 16, and 24 weeks after a second vaccination dose. Antibody titers decreased over time and the participants with low antibody titers tended to have a high probability of breakthrough infection.

Biochemical, structural and physical changes in aging human skin, and their relationship.

Skin is the largest organ of the human body, having the purpose of regulating temperature, protecting us from microbes or mechanical shocks, and allowing the sensations from touch. It is generally accepted that aging induces profound changes in the skin's biochemical, structural and physical properties, which can lead to impaired biological functions and/or diverse diseases. So far, the effects of aging on these skin properties have been well documented. However, very few studies have focused exclusively on the relationship among these critical properties in the aging process, which is this review's primary focus. Many in vivo, ex vivo, and in vitro techniques have been previously used to characterize these properties of the skin. This review aims to provide a comprehensive overview on the effects of aging on the changes in biochemical, structural, and physical properties, and explore the potential mechanisms of skin with the relation between these properties. First, we review different or contradictory results of aging-related changes in representative parameters of each property, including the interpretations of the findings. Next, we discuss the need for a standardized method to characterize aging-related changes in these properties, to improve the way of defining age-property relationship. Moreover, potential mechanisms based on the previous results are explored by linking the biochemical, structural, and physical properties. Finally, the need to study changes of various functional properties in the separate skin layers is addressed. This review can help understand the underlying mechanism of aging-related alterations, to improve the evaluation of the aging process and guide effective treatment strategies for aging-related diseases.

Strong SARS-CoV-2 Antibody Response After Booster Dose of BNT162b2 mRNA Vaccines in Uninfected Healthcare Workers.

Despite strict guidelines for coronavirus disease 2019 (COVID-19), South Korea is facing its fourth pandemic wave. In this study, by using an automated electrochemiluminescence immunoassay assay, we tracked anti-spike protein receptor-binding domain (anti-S-RBD) antibody titer from the second dose to 2 weeks after the booster dose vaccination. After the second dose, 234 participants had their anti-S-RBD antibody titers decrease over time. We also showed the booster dose (the third dose) increased antibody titer by average 14 (min-max, 2-255)-fold higher compared to the second dose among the 211-booster group participants, therefore, the booster dose could be recommended for low responders to the second dose. Our findings showed a distinct humoral response after booster doses of BNT162b2 mRNA vaccines and may provide further evidence of booster vaccination efficacy. These data will also be helpful in vaccination policy decisions that determine the need for the booster dose.

Cancer cells display increased migration and deformability in pace with metastatic progression.

In this study, we explored the relation between metastatic states vs the capacity of confined migration, amoeboid transition, and cellular stiffness. We compared across an isogenic panel of human breast cancer cells derived from MDA-MB-231 cells. It was observed that cells after lung metastasis have the fastest migration and lowest stiffness, with a significantly higher capacity to transition into an amoeboid mode. Our findings illustrate that metastasis is a selective process favoring motile and softer cells. Moreover, the observation that circulating tumor cells resemble the parental cell line, but not lung-metastatic cells, suggests that cells with higher deformability and motility are likely selected during extravasation and colonization.

Positivity of SARS-CoV-2 Antibodies among Korean Healthy Healthcare Workers 1 and 2 Weeks after Second Dose of Pfizer-BioNTech Vaccination.

The antibody titer of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was observed in 289 healthy healthcare workers who had completed the second dose of the Pfizer-BioNTech coronavirus disease 2019 (COVID-19) vaccine. Antibody tests were performed using both the automated electrochemiluminescence immunoassay (ECLIA) and the chromatographic lateral flow immunoassay (LFIA). All subjects had antibodies against the receptor binding domain of the spike protein of SARS-CoV-2 only one week after completing the vaccination, and the antibody titer became significantly higher after another week (P < 0.001). Since there was a large amount of antibody formation within two weeks after completion of vaccination, the less sensitive method, LFIA, also showed high sensitivity. There was no significant difference between whole blood and serum in detecting SARS-CoV-2 antibodies after vaccination. This is an early study of vaccinations among Koreans and is expected to contribute to the establishment of national guidelines on COVID-19 vaccination.

Comparison of bowel-cleansing efficacy of split-dose and same-day dose bowel preparation for afternoon colonoscopy in patients with gastrectomy: a prospective randomized study.

BACKGROUND: A split dose (SPD) of purgative is the recommended bowel-preparation method for colonoscopy, although for colonoscopy scheduled for the afternoon, a same-day dose (SDD) of purgative is recommended. However, it has not been determined whether SPD or SDD is better in patients with gastrectomy who are at high risk of suboptimal bowel cleansing. We compared the bowel-cleansing efficacy of SPD and SDD regimens in patients with gastrectomy who underwent colonoscopy in the afternoon. METHODS: This was a prospective, randomized, assessor-blinded study. For the SDD group, polyethylene glycol (PEG) was ingested on the day of colonoscopy starting at 7 AM. In the SPD group, 2 L PEG was ingested at 9 PM the day before colonoscopy, and the remaining 2 L from 10 AM on the day of colonoscopy. Colonoscopy was performed from 1:30 PM. Before colonoscopy, the participants completed questionnaires asking about bowel-movement kinetics, adverse events, tolerability, overall satisfaction, and willingness to reuse the protocol. The bowel-cleansing efficacy was assessed using the Boston Bowel Preparation Scale. RESULTS: A total of 193 subjects were included (SDD, 95; SPD, 98). The rate of successful bowel cleansing was comparable between the two groups (SDD, 92.6% vs. SPD, 95.9%; P = 0.37). The incidence of adverse events (nausea, vomiting, bloating, abdominal pain, and dizziness/headache) was also comparable between the two groups. However, sleep disturbance was higher in the SPD group (SDD, 10.5% vs. SPD, 25.5%; P = 0.01). Tolerability did not differ between the SDD and SPD groups (satisfaction, P = 0.11; willingness to reuse, P = 0.29). CONCLUSIONS: The bowel-cleansing efficacy, safety profile, and patient tolerability of SDD and SPD were comparable. Both SDD and SPD regimens are feasible bowel-preparation methods for patients with gastrectomy who undergo colonoscopy in the afternoon. TRIAL REGISTRATION: Clinical trial registration number: KCT0002699.

The Effects of Stiffness, Fluid Viscosity, and Geometry of Microenvironment in Homeostasis, Aging, and Diseases: A Brief Review.

Cells sense biophysical cues in the micro-environment and respond to the cues biochemically and biophysically. Proper responses from cells are critical to maintain the homeostasis in the body. Abnormal biophysical cues will cause pathological development in the cells; pathological or aging cells, on the other hand, can alter their micro-environment to become abnormal. In this minireview, we discuss four important biophysical cues of the micro-environment-stiffness, curvature, extracellular matrix (ECM) architecture and viscosity-in terms of their roles in health, aging, and diseases.

Understanding the patient population and test utilization for hepatitis B virus testing.

BACKGROUND: Hepatitis B virus (HBV) infection remains a global concern with different epidemiologies due to several factors including migration, vaccination policies, and new antiviral treatment regimens. It is important to understand the characteristics of a patient population, including the prevalence of diseases, and to assess test utilization to understand and evaluate the clinical performance of laboratory tests and to improve the quality of clinical laboratories. MATERIALS AND METHODS: In this study, we evaluated serologic and virologic laboratory tests including hepatitis B surface antigen, hepatitis B surface antibody, hepatitis B envelope antigen (HBeAg), hepatitis B envelope antibody, and HBV DNA in Korean adults who were exposed to HBV. RESULTS: During the 1-year study period, we obtained 22 750 specimens from 17 523 adult Korean patients (>18.0 years; 9894 males and 7629 females) with a median age of 50.1 years (interquartile range, 42.2-58.2 years). Among them, five serologic and virologic laboratory tests were performed for 1340 (5.9%) specimens from 1172 adult Korean patients (>18.0 years; 647 males and 525 females) with a median age of 46.8 years (range, 19.0-84.5 years). The prevalence of serologic and virologic tests indicating several clinical situations was evaluated. The correlation coefficient between HBV DNA and HBeAg was ρ = 0.85 (P < .0001). However, 51.9% (695/1340) of samples did not show agreement between the two test results. CONCLUSIONS: Analysis of the prevalence of patients categorized into five serologic and virologic laboratory results would be helpful to expand our knowledge about patient population characteristics and to improve test utilization.

Mixed Infection with Plasmodium falciparum and Plasmodium ovale in a Returned Traveller: the First Case in Korea.

Mixed-species malaria infections are often unrecognized or underestimated. We hereby report the first described case of mixed infection with Plasmodium falciparum and Plasmodium ovale malaria in a returned traveller in Korea. In August 2016, a 25-year-old returned traveller from Cameroon and Democratic Republic of Congo presented with fever. He was diagnosed as P. falciparum malaria and successfully treated with artesunate. And 5 weeks after the completion of treatment, he presented with fever and diagnosed as P. ovale infection. P. ovale infection is a rare cause of malaria and often shows delayed presentation due to its dormant liver stage as hypnozoites. At re-presentation, the immunochromatographic test and microscopic examinations of our patient did not reveal P. ovale, which was only detected via polymerase chain reaction (PCR) assay. This case highlights the importance of considering malaria infection even in persons who have previously received malaria treatment. It also shows the usefulness of PCR testing for diagnosing P. ovale infections, which often present with a low level of parasitaemia.

An Economic, Modular, and Portable Skin Viscoelasticity Measurement Device for In Situ Longitudinal Studies.

A indentation-based device to measure tissue mechanical property was designed and built using over-the-counter and 3D-printed parts. The device costs less than 100 USD and is capable of measuring samples of various geometry because of its modular design. The device is light-weight, thus portable, for measurements that can be performed at different sites. It was demonstrated that the measurement results obtained using our device are comparable to previous observations. The elastic shear modulus of the human skin was in the range of 2 kPa to 8 kPa, and skin tissues in old mice were stiffer than young mice. Mechanical properties of the skin tissues belonging to the same test subject varied depending on the location of the measurement. In conclusion, because our device is economic, modular, portable, and robust, it is suitable to serve as a standard measurement platform for studying tissue mechanics.

Consecutive analysis of mutation spectrum in the dystrophin gene of 507 Korean boys with Duchenne/Becker muscular dystrophy in a single center.

INTRODUCTION: Duchenne and Becker muscular dystrophies (DMD and BMD) are allelic X-linked recessive muscle diseases caused by mutations in the large and complex dystrophin gene. METHODS: We analyzed the dystrophin gene in 507 Korean DMD/BMD patients by multiple ligation-dependent probe amplification and direct sequencing. RESULTS: Overall, 117 different deletions, 48 duplications, and 90 pathogenic sequence variations, including 30 novel variations, were identified. Deletions and duplications accounted for 65.4% and 13.3% of Korean dystrophinopathy, respectively, suggesting that the incidence of large rearrangements in dystrophin is similar among different ethnic groups. We also detected sequence variations in >100 probands. The small variations were dispersed across the whole gene, and 12.3% were nonsense mutations. CONCLUSIONS: Precise genetic characterization in patients with DMD/BMD is timely and important for implementing nationwide registration systems and future molecular therapeutic trials in Korea and globally. Muscle Nerve 55: 727-734, 2017.

Performance of two commercially available BCR-ABL1 quantification assays that use an international reporting scale.

BACKGROUND: Quantifying the BCR-ABL1 rearrangement is important for monitoring chronic myelogenous leukemia (CML). To standardize BCR-ABL1 quantification, the World Health Organization (WHO) established the first international genetic reference panel. Here, we compared the BCR-ABL1 levels determined using international scale (IS)-based commercially available assays. METHODS: BCR-ABL1 transcripts were quantified using two IS-based assays. 10-1, 10-2, 10-3, 10-4, 10-5 and 10-6 dilutions of the b3a2 positive RNA were used for evaluating linearity, precision, and limit of detection. Correlation of the assay was evaluated by using DNA obtained from CML patients carrying the BCR-ABL1 b3a2 and b2a2 types. RESULTS: Both Ipsogen and Asuragen assays showed fine linearity with reasonable %CV. LOD of each assay was calculated as 0.003% for Ipsogen, and 0.005% for Asuragen. By comparing the results that were lower than 10% by either one of the assay, Ipsogen and Asuragen results showed an overall good linear correlation with a tendency for the Ipsogen assay to show slightly higher levels than the Asuragen assay for b3a2 transcript. For b2a2, the tendency was opposite, with Asuragen showing higher values than the Ipsogen. CONCLUSIONS: Two commercially available IS-based BCR-ABL1 assays showed an overall good quantitative correlation. It should be taken into consideration that each assay tended to produce higher values than the other, depending on the BCR-ABL1 subtypes, suggesting that a separate conversion factor for each subtype can be more helpful when BCR-ABL1 transcript levels are converted into IS.

Endoscopic submucosal dissection versus surgical resection for early gastric cancer: a retrospective multicenter study on immediate and long-term outcome over 5 years.

BACKGROUND: Endoscopic submucosal dissection (ESD) is an alternative to surgical resection for treating early gastric cancer (EGC). However, there have been limited reports on the long-term outcome of ESD compared to that of surgical resection. The aim of this study was to evaluate the immediate and long-term clinical and oncologic outcomes of ESD compared to surgical resection. METHOD: We retrospectively reviewed data of patients in five centers who were treated with ESD or surgical resection for EGC within expanded criteria for ESD from 2006 to 2008. RESULT: ESD group had significantly shorter procedure times, shorter fasting period, and shorter hospital stay than the surgical resection group. Immediate complications in the surgical resection group were more common compared to those in the ESD group. Five-year cancer recurrence rate of the ESD group was 12.3 % and significantly higher than 2.1 % of the surgical resection group (P = 0.001). Five-year disease-free survival rate of the surgical resection group was 97 %, which was significantly higher than 85 % of the ESD group (P = 0.001). Metachronous lesions were equally found every year during the follow-up period in the ESD group. Five-year overall survival rates were 100 % for both groups. CONCLUSION: ESD might be an acceptable and effective treatment for EGC considering overall survival rates with fewer early complication rates and shorter duration of hospital stay compared to surgical resection. However, intensive and persistent endoscopic surveillance should be performed after ESD for early detection of metachronous lesions.

Delta-shaped anastomosis, a good substitute for conventional Billroth I technique with comparable long-term functional outcome in totally laparoscopic distal gastrectomy.

BACKGROUND: Delta-shaped anastomosis (DA) is a new Billroth I reconstruction technique using only a laparoscopic linear stapler under a totally laparoscopic approach. The present study compared the outcomes of DA with those of laparoscopic conventional Billroth I anastomosis (cBIA). METHODS: A total of 138 and 100 patients with gastric cancer who underwent laparoscopic distal gastrectomy with DA and cBIA, respectively, were selected. Clinicopathological data and short- and long-term outcomes were compared between the two groups. RESULTS: The mean operating time in the DA group was similar to that in the cBIA group. Short-term outcomes, such as bowel function recovery, morbidity, and mortality, did not differ between the DA and cBIA groups. There were no significant differences in the 5-year disease-free and overall survival rates between the two groups. All nutritional indices (body weight change, albumin level, transferrin level, and total lymphocyte count) were similar between the two groups with the exception of a few points in the early follow-up period. Endoscopic evaluation using the Residual food, Gastritis, Bile reflux classification revealed relatively better gastritis findings in the DA group despite worse bile reflux for 5 postoperative years. The food amount was significantly larger in the DA group for 2 postoperative years. CONCLUSIONS: The outcomes of DA were comparable to those of cBIA. DA is a recommendable reconstruction method, especially in totally laparoscopic distal gastrectomy.

A Simple Method of Liver Retraction for Various Types of Laparoscopic Upper Gastrointestinal Surgeries: The Prolene Hanging-Up Method.

This study describes a safe and the simple method for liver retraction during various types of laparoscopic upper gastrointestinal surgeries. The technique was performed using only a 75 cm 2-0 prolene suture, which was passed through the abdominal wall with a straight needle at the two points of the epigastrium and at the pars condensa of the gastrohepatic ligament without any protective material or knotting. Seventy-six patients who underwent various types of laparoscopic upper gastrointestinal surgeries from August, 2012 to March, 2013 at Incheon St. Mary's Hospital were included in the study. The mean time for the liver retraction was 2.7 ± 0.6 min. Among the 76 cases, complication of this method was one case of the puncture site bleeding on the abdominal wall. The mean levels of alanine aminotransferase and aspartate aminotransferase on the day of the surgery were 54.9 ± 26.3 U/L and 45.2 ± 23.1 U/L, respectively, and these had decreased to 22.4 ± 13.2 U/L and 21.8 ± 14.0 U/L, respectively, on the fourth postoperative day. The prolene hanging-up method is very simple and safe, and it can be used in various types of laparoscopic upper gastrointestinal surgeries.

Microstructural parameter-based modeling for transport properties of collagen matrices.

Recent advances in modulating collagen building blocks enable the design and control of the microstructure and functional properties of collagen matrices for tissue engineering and regenerative medicine. However, this is typically achieved by iterative experimentations and that process can be substantially shortened by computational predictions. Computational efforts to correlate the microstructure of fibrous and/or nonfibrous scaffolds to their functionality such as mechanical or transport properties have been reported, but the predictability is still significantly limited due to the intrinsic complexity of fibrous/nonfibrous networks. In this study, a new computational method is developed to predict two transport properties, permeability and diffusivity, based on a microstructural parameter, the specific number of interfibril branching points (or branching points). This method consists of the reconstruction of a three-dimensional (3D) fibrous matrix structure based on branching points and the computation of fluid velocity and solute displacement to predict permeability and diffusivity. The computational results are compared with experimental measurements of collagen gels. The computed permeability was slightly lower than the measured experimental values, but diffusivity agreed well. The results are further discussed by comparing them with empirical correlations in the literature for the implication for predictive engineering of collagen matrices for tissue engineering applications.