Hydrogel-exosome system in tissue engineering: A promising therapeutic strategy.

Characterized by their pivotal roles in cell-to-cell communication, cell proliferation, and immune regulation during tissue repair, exosomes have emerged as a promising avenue for "cell-free therapy" in clinical applications. Hydrogels, possessing commendable biocompatibility, degradability, adjustability, and physical properties akin to biological tissues, have also found extensive utility in tissue engineering and regenerative repair. The synergistic combination of exosomes and hydrogels holds the potential not only to enhance the efficiency of exosomes but also to collaboratively advance the tissue repair process. This review has summarized the advancements made over the past decade in the research of hydrogel-exosome systems for regenerating various tissues including skin, bone, cartilage, nerves and tendons, with a focus on the methods for encapsulating and releasing exosomes within the hydrogels. It has also critically examined the gaps and limitations in current research, whilst proposed future directions and potential applications of this innovative approach.

Hydrogel-based immunoregulation of macrophages for tissue repair and regeneration.

The rational design of hydrogel materials to modulate the immune microenvironment has emerged as a pivotal approach in expediting tissue repair and regeneration. Within the immune microenvironment, an array of immune cells exists, with macrophages gaining prominence in the field of tissue repair and regeneration due to their roles in cytokine regulation to promote regeneration, maintain tissue homeostasis, and facilitate repair. Macrophages can be categorized into two types: classically activated M1 (pro-inflammatory) and alternatively activated M2 (anti-inflammatory and pro-repair). By regulating the physical and chemical properties of hydrogels, the phenotypic transformation and cell behavior of macrophages can be effectively controlled, thereby promoting tissue regeneration and repair. A full understanding of the interaction between hydrogels and macrophages can provide new ideas and methods for future tissue engineering and clinical treatment. Therefore, this paper reviews the effects of hydrogel components, hardness, pore size, and surface morphology on cell behaviors such as macrophage proliferation, migration, and phenotypic polarization, and explores the application of hydrogels based on macrophage immune regulation in skin, bone, cartilage, and nerve tissue repair. Finally, the challenges and future prospects of macrophage-based immunomodulatory hydrogels are discussed.

Extracellular Vesicles from Urine-Derived Stem Cell for Tissue Engineering and Regenerative Medicine.

The potential of urine-derived stem cells (USCs) for tissue engineering and regenerative medicine has attracted much attention during the last few decades. However, it has been suggested that the effects of the USCs may be endowed by their paracrine extracellular vesicles (EVs) rather than their differentiation. Compared with the USCs, the USC-EVs can cross the barriers more easily and safely, and their inclusions may mediate intercellular communication and promote the tissue repair. This article has summarized the current knowledge and applications about the USC-EVs in tissue engineering and regenerative medicine, and discussed the prospects and challenges for using them as an alternative to cell therapy. Impact statement Urine-derived stem cells (USCs) represent a newly discovered type of stem cells, and studies have proved that the beneficial effects of the USCs may be manifested through their paracrine extracellular vesicles (EVs) rather than through their own differentiation, which opens up new avenues for tissue engineering and regenerative medicine strategies. Therefore, this review aims to summarize the latest research progress and potential clinical applications of the USC-EVs, highlighting the promising potential of the USC-EVs as a therapeutic option in kidney regeneration, genital regeneration, nerve regeneration, bone and cartilage regeneration, and wound healing.

A Self-Assembly Pro-Coagulant Powder Capable of Rapid Gelling Transformation and Wet Adhesion for the Efficient Control of Non-Compressible Hemorrhage.

Rapid and effective control of non-compressible massive hemorrhage poses a great challenge in first-aid and clinical settings. Herein, a biopolymer-based powder is developed for the control of non-compressible hemorrhage. The powder is designed to facilitate rapid hemostasis by its excellent hydrophilicity, great specific surface area, and adaptability to the shape of wound, enabling it to rapidly absorb fluid from the wound. Specifically, the powder can undergo sequential cross-linking based on "click" chemistry and Schiff base reaction upon contact with the blood, leading to rapid self-gelling. It also exhibits robust tissue adhesion through covalent/non-covalent interactions with the tissues (adhesive strength: 89.57 ± 6.62 KPa, which is 3.75 times that of fibrin glue). Collectively, this material leverages the fortes of powder and hydrogel. Experiments with animal models for severe bleeding have shown that it can reduce the blood loss by 48.9%. Studies on the hemostatic mechanism also revealed that, apart from its physical sealing effect, the powder can enhance blood cell adhesion, capture fibrinogen, and synergistically induce the formation of fibrin networks. Taken together, this hemostatic powder has the advantages for convenient preparation, sprayable use, and reliable hemostatic effect, conferring it with a great potential for the control of non-compressible hemorrhage.

Promotion of uterine reconstruction by a tissue-engineered uterus with biomimetic structure and extracellular matrix microenvironment.

The recurrence rate for severe intrauterine adhesions is as high as 60%, and there is still lack of effective prevention and treatment. Inspired by the nature of uterus, we have developed a bilayer scaffold (ECM-SPS) with biomimetic heterogeneous features and extracellular matrix (ECM) microenvironment of the uterus. As proved by subtotal uterine reconstruction experiments, the mechanical and antiadhesion properties of the bilayer scaffold could meet the requirement for uterine repair. With the modification with tissue-specific cell-derived ECM, the ECM-SPS had the ECM microenvironment signatures of both the endometrium and myometrium and exhibited the property of inducing stem cell-directed differentiation. Furthermore, the ECM-SPS has recruited more endogenous stem cells to promote endometrial regeneration at the initial stage of repair, which was accompanied by more smooth muscle regeneration and a higher pregnancy rate. The reconstructed uterus could also sustain normal pregnancy and live birth. The ECM-SPS may thereby provide a potential treatment for women with severe intrauterine adhesions.

Antibacterial efficacy of epigallocatechin-3-gallate cross-linked small intestinal submucosa guided bone regeneration membrane.

The leading cause of guided bone regeneration (GBR) failure is infection. Herein, we developed a new GBR membrane with good mechanical and osteogenic properties by crosslinking the small intestinal submucosa (SIS) with epigallocatechin-3-gallate (EGCG). Meanwhile, EGCG is also a natural antibacterial agent. This study aimed to investigate the antibacterial efficacy of EGCG-crosslinked SIS (E-SIS) against Staphylococcus aureus and Escherichia coli through EGCG release, bacterial count, live/dead staining, scanning electron microscopy, growth curve, and biofilm formation tests. The results showed that E-SIS effectively inhibited bacteria's growth and adhesion, and its antibacterial activity against Staphylococcus aureus was stronger than that against Escherichia coli. 0.5% E-SIS had the most potent antibacterial activity. The antibacterial mechanism of E-SIS might be related to the release of EGCG and the surface properties of E-SIS. In conclusion, 0.5% E-SIS is a promising GBR membrane with good osteogenic and antibacterial properties.

A systematic review of digital health technologies for the care of older adults during COVID-19 pandemic.

Objective: During the Coronavirus Disease 2019 (COVID-19) pandemic, digital health technologies (DHTs) became increasingly important, especially for older adults. The objective of this systematic review was to synthesize evidence on the rapid implementation and use of DHTs among older adults during the COVID-19 pandemic. Methods: A structured, electronic search was conducted on 9 November 2021, and updated on 5 January 2023, among five databases to select DHT interventional studies conducted among older adults during the pandemic. The bias of studies was assessed using Version 2 of the Cochrane Risk-of-Bias Tool for randomized trials (RoB 2) and Risk of Bias in Non-randomized Studies of Interventions (ROBINS-I). Results: Among 20 articles included in the review, 14 (70%) focused on older adults with chronic diseases or symptoms, such as dementia or cognitive impairment, type 2 diabetes, and obesity. DHTs included traditional telehealth interventions via telephone, video, and social media, as well as emerging technologies such as Humanoid Robot and Laser acupuncture teletherapy. Using RoB 2 and ROBINS-I, four studies (20%) were evaluated as high or serious overall risk of bias. DHTs have shown to be effective, feasible, acceptable, and satisfactory for older adults during the COVID-19 pandemic compared to usual care. In addition, some studies also highlighted challenges with technology, hearing difficulties, and communication barriers within the vulnerable population. Conclusions: During the COVID-19 pandemic, DHTs had the potential to improve various health outcomes and showed benefits for older adults' access to health care services.

Safety reporting of Essure medical device: a qualitative and quantitative assessment on the FDA manufacturer and user facility device experience database in 2018.

Background: There have been numerous cases of adverse events since the introduction of Essure medical devices for sterilization in 2002. This study analyzed the safety event reports of the Essure reported in the Manufacturer and User Facility Device Experience (MAUDE). Methods: A retrospective analysis examined the MAUDE reports between Jan-1, 2018, and Oct-31, 2018 and focused on safety reports related to the Essure device. Safety reports were categorized and analyzed by their event type, device problem, patients' symptoms and the level of harm. Of this study cohort, 10% of samples were randomly selected for quantitative analyses. Thematic analysis was conducted for reports included death cases. Results: A total of 4,994 eligible reports were analyzed. There were ten reports associated with individuals' deaths, and the main themes of safety reports from qualitative analysis were pains, bleeding, surgery, migraine, and infection. Quantitative analysis of 500 randomly selected samples showed that 98% of adverse event reports were associated with different injuries such as surgery, pain, bleeding, hysterectomy, and menorrhagia. Additionally, more than 90% of reports were submitted by the manufacturer. Conclusion: These findings indicated several safety issues of Essure. More meaningful pre- and post-marketing surveillance and regulation are warranted in the medical device market to ensure safety and effectiveness, including investigating complaints, promptly sharing relevant information with regulators and users, and implementing corrective actions.

Multifunctional two-component in-situ hydrogel for esophageal submucosal dissection for mucosa uplift, postoperative wound closure and rapid healing.

Endoscopic submucosal dissection (ESD) for gastrointestinal tumors and premalignant lesions needs submucosal fluid cushion (SFC) for mucosal uplift before dissection, and wound care including wound closure and rapid healing postoperatively. Current SFC materials as well as materials and/or methods for post-ESD wound care have single treatment effect and hold corresponding drawbacks, such as easy dispersion, short duration, weak hemostasis and insufficient repair function. Thus, designing materials that can serve as both SFC materials and wound care is highly desired, and remains a challenge. Herein, we report a two-component in-situ hydrogel prepared from maleimide-based oxidized sodium alginate and sulfhydryl carboxymethyl-chitosan, which gelated mainly based on "click" chemistry and Schiff base reaction. The hydrogels showed short gelation time, outstanding tissue adhesion, favorable hemostatic properties, and good biocompatibility. A rat subcutaneous ultrasound model confirmed the ability of suitable mucosal uplift height and durable maintenance time of AM solution. The in vivo/in vitro rabbit liver hemorrhage model demonstrated the effects of hydrogel in rapid hemostasis and prevention of delayed bleeding. The canine esophageal ESD model corroborated that the in-situ hydrogel provided good mucosal uplift and wound closure effects, and significantly accelerated wound healing with accelerating re-epithelization and ECM remodeling post-ESD. The two-component in-situ hydrogels exhibited great potential in gastrointestinal tract ESD.

Associations Between Medicaid Expansion and Mental Health Among U.S. Racial and Ethnic Groups.

OBJECTIVE: The authors examined associations between Medicaid expansion and self-reported mental health by race-ethnicity, focusing on lagged associations. METHODS: This retrospective, cross-sectional study used 2011-2019 data from the Behavioral Risk Factor Surveillance System. The sample included low-income, childless adults ages 25-64 years. Difference-in-differences (DID) analysis was used to estimate associations between Medicaid expansion and self-reported mental health. Lagged associations were examined by separating the postexpansion period into proximal (2014-2016) and distal (2017-2019) periods. RESULTS: In the overall sample (N=327,248), Medicaid expansion was associated with a reduction in the mean number of self-reported past-month poor mental health days (DID=-0.12, 95% CI=-0.21 to -0.03), after adjustment for covariates. The expansion was associated with significant reductions in past-month poor mental health days for the following groups: non-Hispanic White (DID=-0.18, 95% CI=-0.29 to -0.07), non-Hispanic Asian (DID=-1.15, 95% CI=-1.37 to -0.93), non-Hispanic other (DID=-0.62, 95% CI=-1.03 to -0.21), and Hispanic (DID=-0.48, 95% CI=-0.73 to -0.23). The non-Hispanic Black group had a significant increase in past-month poor mental health days (DID=0.27, 95% CI=0.06 to 0.49), and no significant change was noted for the American Indian or Alaska Native (AIAN) group. Improvements in mental health observed at the beginning of the policy implementation (proximal period) were not sustained over time for some racial-ethnic minority groups. CONCLUSIONS: Although Medicaid expansion improved mental health for the overall sample, some racial-ethnic disparities were detected. The negative and insignificant associations for the non-Hispanic Black and AIAN groups, respectively, highlight the need to better understand why the Medicaid expansion affected racial-ethnic groups differently.

Polyphenolic-modified cellulose acetate membrane for bone regeneration through immunomodulation.

To enhance the bioactivity of cellulosic derivatives has become an important strategy to promote their value for clinical applications. Herein, protocatechualdehyde (PCA), a polyphenolic molecule, was used to modify a cellulose acetate (CA) membrane by combining with metal ions to confer an immunomodulatory activity. The PCA-modified CA membrane has shown a significant radical scavenging activity, thereby suppressed the inflammatory response and created a favorable immune microenvironment for osteogenesis and mineralization. Moreover, addition of metal ions could further stimulate the osteogenic differentiation of stem cells and accelerate bone regeneration both in vitro and in vivo. This study may provide a strategy to promote the immunomodulatory activity of cellulose-based biomaterials for bone regeneration.

Application of metabolomics in urolithiasis: the discovery and usage of succinate.

Urinary stone is conceptualized as a chronic metabolic disorder punctuated by symptomatic stone events. It has been shown that the occurrence of calcium oxalate monohydrate (COM) during stone formation is regulated by crystal growth modifiers. Although crystallization inhibitors have been recognized as a therapeutic modality for decades, limited progress has been made in the discovery of effective modifiers to intervene with stone disease. In this study, we have used metabolomics technologies, a powerful approach to identify biomarkers by screening the urine components of the dynamic progression in a bladder stone model. By in-depth mining and analysis of metabolomics data, we have screened five differential metabolites. Through density functional theory studies and bulk crystallization, we found that three of them (salicyluric, gentisic acid and succinate) could effectively inhibit nucleation in vitro. We thereby assessed the impact of the inhibitors with an EG-induced rat model for kidney stones. Notably, succinate, a key player in the tricarboxylic acid cycle, could decrease kidney calcium deposition and injury in the model. Transcriptomic analysis further showed that the protective effect of succinate was mainly through anti-inflammation, inhibition of cell adhesion and osteogenic differentiation. These findings indicated that succinate may provide a new therapeutic option for urinary stones.

An Acquired Anterior Glottic Web Model by Heat Injury with a Laryngoscopic Approach in a Rabbit.

Acquired anterior glottic webs (AGW) can lead to abnormally elevated phonatory pitch, dysphonia, and airway obstruction requiring urgent intervention. In this study, we construct a novel AGW rabbit model using heat injury by a laryngoscopic way. A primary study was conducted to identify the injury depth in rabbits' vocal folds (VFs) by graded heat energy, and the heat energy for the incurrence of epithelial layer, lamina propria, and muscular layer (ML) injury was 25, 30 and 35 W, respectively. Then, four different models were designed based on the depth and degree of the injury to determine the optimal procedure for AGW formation. Morphological features, vibratory capacity, and histopathologic features of the AGW were correspondingly evaluated. The procedure for conferring the heat injury to the depth of ML and the extent of anterior commissure and middle part of bilateral VFs showed the highest success rate of AGW formation (95%, 19/20). For its low cost, effectiveness, and stability for AGW formation, the heat injury rabbit model with a laryngoscopic approach may provide a new platform for testing novel anti-adhesion materials and bioengineered therapies. Impact Statement Tissue engineering based on biomaterials has been a very hot research field and may be introduced to prevent the acquired anterior glottic web (AGW) formation. However, lacking a widely recognized animal model for AGW has limited the trial of anti-adhesion materials in the larynx. In this study, we have developed a novel rabbit model for AGW formation by conferring a heat injury under a laryngoscope; this model is cheap, effective, and stable for the anti-adhesion materials and bioengineered therapies. Thus, this research would arouse crucial interest and be widely employed.

A self-fused hydrogel for the treatment of glottic insufficiency through outstanding durability, extracellular matrix-inducing bioactivity and function preservation.

Injection laryngoplasty with biomaterials is an effective technique to treat glottic insufficiency. However, the inadequate durability, deficient pro-secretion of extracellular matrix (ECM) and poor functional preservation of current biomaterials have yielded an unsatisfactory therapeutic effect. Herein, a self-fusing bioactive hydrogel comprising modified carboxymethyl chitosan and sodium alginate is developed through a dual-crosslinking mechanism (photo-triggered and dynamic covalent bonds). Owing to its characteristic networks, the synergistic effect of the hydrogel for vocal folds (VFs) vibration and phonation is adequately demonstrated. Notably, owing to its inherent bioactivity of polysaccharides, the hydrogel could significantly enhance the secretion of major components (type I/III collagen and elastin) in the lamina propria of the VFs both in vivo and in vitro. In a rabbit model for glottic insufficiency, the optimized hydrogel (C1A1) has demonstrated a durability far superior to that of the commercially made hyaluronic acid (HA) Gel. More importantly, owing to the ECM-inducing bioactivity, the physiological functions of the VFs treated with the C1A1 hydrogel also outperformed that of the HA Gel, and were similar to those of the normal VFs. Taken together, through a simple-yet-effective strategy, the novel hydrogel has demonstrated outstanding durability, ECM-inducing bioactivity and physiological function preservation, therefore has an appealing clinical value for treating glottic insufficiency.

Design of biopolymer-based hemostatic material: Starting from molecular structures and forms.

Uncontrolled bleeding remains as a leading cause of death in surgical, traumatic, and emergency situations. Management of the hemorrhage and development of hemostatic materials are paramount for patient survival. Owing to their inherent biocompatibility, biodegradability and bioactivity, biopolymers such as polysaccharides and polypeptides have been extensively researched and become a focus for the development of next-generation hemostatic materials. The construction of novel hemostatic materials requires in-depth understanding of the physiological hemostatic process, fundamental hemostatic mechanisms, and the effects of material chemistry/physics. Herein, we have recapitulated the common hemostatic strategies and development status of biopolymer-based hemostatic materials. Furthermore, the hemostatic mechanisms of various molecular structures (components and chemical modifications) are summarized from a microscopic perspective, and the design based on them are introduced. From a macroscopic perspective, the design of various forms of hemostatic materials, e.g., powder, sponge, hydrogel and gauze, is summarized and compared, which may provide an enlightenment for the optimization of hemostat design. It has also highlighted current challenges to the development of biopolymer-based hemostatic materials and proposed future directions in chemistry design, advanced form and clinical application.

Characteristics and Comparison of Adverse Events of Coronavirus Disease 2019 Vaccines Reported to the United States Vaccine Adverse Event Reporting System Between 14 December 2020 and 8 October 2021.

Background: This study assessed and compared the frequency and type of adverse events (AEs) of the Pfizer-BioNTech, Moderna, and Janssen coronavirus disease 2019 (COVID-19) vaccines reported in the Vaccine Adverse Event Reporting System (VAERS). Methods: A retrospective analysis examined VAERS reports between 14 December 2020 and 8 October 2021 and focused on AE reports related to COVID-19 vaccines and AE outcomes [e.g., emergency room (ER) visits after being vaccinated, hospitalization, prolongation of existing hospitalization, life-threatening events, disability, birth defect, and death]. Reporting odds ratios (RORs) and Breslow-Day statistics were used to compare AE reporting between COVID-19 and non-COVID vaccines and between individual COVID-19 vaccines. Results: A total of 604,157 AEs of COVID-19 vaccines were reported, including 43.51% for the Pfizer-BioNTech vaccine, 47.13% for the Moderna vaccine, and 9.12% for the Janssen COVID-19 vaccine. About 12.56% of patients visited ER after being vaccinated, 5.96% reported hospitalization, and 1.52% reported life-threatening events. Among the number of death cases (n = 7,674; mean age = 73), 2,025 patients (26.39%) had hypertension and 1,237 (16.12%) patients had cancer. RORs between COVID-19 vaccines and non-COVID vaccines identified increased ROR in ER visits, hospitalization, and life-threatening events. The results of the Breslow-Day statistics indicated heterogeneities between the disproportionality of reports across the four serious AE outcomes (i.e., ER visits, hospitalization, life-threatening events, and disability) between individual COVID-19 vaccines. Conclusion: Most current VAERS reports showed that the most commonly reported AEs of COVID-19 vaccines were mild. Cases with a mortality outcome tended to occur in older adults with underneath conditions. Close ongoing surveillance in the safety of COVID-19 vaccines is critical and will inform the use of individual COVID-19 vaccines. Given the known limitations associated with the passive spontaneous reporting system, such as VAERS, our findings need to be further assessed and verified through longitudinal, large healthcare data systems.

Multi-crosslinking hydrogels with robust bio-adhesion and pro-coagulant activity for first-aid hemostasis and infected wound healing.

Bio-adhesive polysaccharide-based hydrogels have attracted much attention in first-aid hemostasis and wound healing for excellent biocompatibility, antibacterial property and pro-healing bioactivity. Yet, the inadequate mechanical properties and bio-adhesion limit their applications. Herein, based on dynamic covalent bonds, photo-triggered covalent bonds and hydrogen bonds, multifunctional bio-adhesive hydrogels comprising modified carboxymethyl chitosan, modified sodium alginate and tannic acid are developed. Multi-crosslinking strategy endows hydrogels with improved strength and flexibility simultaneously. Owing to cohesion enhancement strategy and self-healing ability, considerable bio-adhesion is presented by the hydrogel with a maximal adhesion strength of 162.6 kPa, 12.3-fold that of commercial fibrin glue. Based on bio-adhesion and pro-coagulant activity (e.g., the stimulative aggregation and adhesion of erythrocytes and platelets), the hydrogel reveals superior hemostatic performance in rabbit liver injury model with blood loss of 0.32 g, only 54.2% of that in fibrin glue. The healing efficiency of hydrogel for infected wounds is markedly better than commercial EGF Gel and Ag+ Gel due to the enhanced antibacterial and antioxidant properties. Through the multi-crosslinking strategy, the hydrogels show enhanced mechanical properties, fabulous bio-adhesion, superior hemostatic performance and promoting healing ability, thereby have an appealing application value for the first-aid hemostasis and infected wound healing.

Shape-Recoverable Hyaluronic Acid-Waterborne Polyurethane Hybrid Cryogel Accelerates Hemostasis and Wound Healing.

Wound dressings that promote quick hemostasis and are highly efficient in healing wounds are urgently needed to meet the increase in clinical demands worldwide. Herein, a dihydrazide-modified waterborne biodegradable polyurethane emulsion (PU-ADH) and oxidized hyaluronic acid (OHA) were autonomously cross-linked to form a hybrid hyaluronic acid-polyurethane (HA-PU) cryogel by hydrazone bonding at -20 °C. Through its specific macroporous structure (which is approximately 220 µm) constructed by aggregated PU-ADH particles and long-chain OHA, a dried cryogel can have a dramatically compressed volume (1/7 of its original volume) with stable fixation, and it can swell rapidly by absorbing water or blood to approximately 22 and 16 times its dried weight, respectively, in a few minutes. This instantaneous shape-recovering ability favors fast hemostasis in minimally invasive surgery. Moreover, this cryogel is superior to gauze, has excellent biocompatibility, and quickly coagulates blood (in approximately 2 min) by activating the endogenous coagulation system. Comparably, an injectable HA-PU hydrogel with the same components as the HA-PU cryogel was prepared at room temperature, and it exhibited good self-healing properties. An in vivo evaluation of a rat liver hemostasis model and rat skin defect model revealed that the cryogel in fast hemostasis has great potential and superior wound-healing abilities, decreases immune inflammation, and promotes the regeneration of angiogenesis and hair follicles. Consequently, this work proposes a versatile method for constructing biodegradable hybrid cryogels via autonomous cross-linking between synthesized polymer emulsions and natural polymers. The hybrid cryogels demonstrated great potential for applications as high-performance wound dressings.

Stem cell-based therapy for ameliorating intrauterine adhesion and endometrium injury.

Intrauterine adhesion refers to endometrial repair disorders which are usually caused by uterine injury and may lead to a series of complications such as abnormal menstrual bleeding, recurrent abortion and secondary infertility. At present, therapeutic approaches to intrauterine adhesion are limited due to the lack of effective methods to promote regeneration following severe endometrial injury. Therefore, to develop new methods to prevent endometrial injury and intrauterine adhesion has become an urgent need. For severely damaged endometrium, the loss of stem cells in the endometrium may affect its regeneration. This article aimed to discuss the characteristics of various stem cells and their applications for uterine tissue regeneration.

Interactions of hydrogen with the iron and iron carbide interfaces: a ReaxFF molecular dynamics study.

Hydrogen embrittlement (HE) is a well-known material phenomenon that causes significant loss in the mechanical strength of structural iron and often leads to catastrophic failures. In order to provide a detailed atomistic description of HE we have used a reactive bond order potential to adequately describe the diffusion of hydrogen as well as its chemical interaction with other hydrogen atoms, defects, and the host metal. The currently published ReaxFF force field for Fe/C/H systems was originally developed to describe Fischer-Tropsch (FT) catalysis [C. Zou, A. C. T. van Duin and D. C. Sorescu, Top. Catal., 2012, 55, 391-401], and especially had been trained for surface formation energies, binding energies of small hydrocarbon radicals on different surfaces of iron and the barrier heights of surface reactions. We merged this force field with the latest ReaxFF carbon parameters [S. Goverapet Srinivasan, A. C. T. van Duin and P. Ganesh, J. Phys. Chem. A, 2015, 119, 1089-5639] and used the same training data set to refit the Fe/C interaction parameters. The present work is focused on evaluating the applicability of this reactive force field to describe material characteristics and study the role of defects and impurities in the bulk and at the precipitator interfaces. We study the interactions of hydrogen with pure and defective α-iron (ferrite), Fe3C (cementite), and ferrite-cementite interfaces with a vacancy cluster. We also investigate the growth of nanovoids in α-iron using a grand canonical Monte Carlo (GCMC) scheme. The calculated hydrogen diffusion coefficients for both ferrite and cementite phases predict a decrease in the work of separation with increasing hydrogen concentration at the ferrite-cementite interface, suggesting a hydrogen-induced decohesion behavior. Hydrogen accumulation at the interface was observed during molecular dynamics (MD) simulations, which is consistent with experimental findings. These results demonstrate the ability of the ReaxFF potential to elucidate various aspects of hydrogen embrittlement in α-iron and hydrogen interactions at a more complex metal/metal carbide interface.