Dissecting the Interplay Mechanism among Process Parameters toward the Biofabrication of High-Quality Shapes in Embedded Bioprinting.

Embedded bioprinting overcomes the barriers associated with the conventional extrusion-based bioprinting process as it enables the direct deposition of bioinks in 3D inside a support bath by providing in situ self-support for deposited bioinks during bioprinting to prevent their collapse and deformation. Embedded bioprinting improves the shape quality of bioprinted constructs made up of soft materials and low-viscosity bioinks, leading to a promising strategy for better anatomical mimicry of tissues or organs. Herein, the interplay mechanism among the printing process parameters toward improved shape quality is critically reviewed. The impact of material properties of the support bath and bioink, printing conditions, cross-linking mechanisms, and post-printing treatment methods, on the printing fidelity, stability, and resolution of the structures is meticulously dissected and thoroughly discussed. Further, the potential scope and applications of this technology in the fields of bioprinting and regenerative medicine are presented. Finally, outstanding challenges and opportunities of embedded bioprinting as well as its promise for fabricating functional solid organs in the future are discussed.

Evaluation of miRNA-146a, miRNA-34a, and pro-inflammatory cytokines as a potential early indicators for type 1 diabetes mellitus.

Background: Type I diabetes mellitus (T1DM) is one of the most common chronic autoimmune diseases worldwide. miRNAs are a class of small non-coding RNA molecules that have been linked to immune system functions, ß-cell metabolism, proliferation, and death, all of which contribute to pathogenesis of TIDM. Dysregulated miRNAs have been identified in Egyptian TIDM patients. Aim: Several miRNAs were profiled in Egyptian TIDM patients to determine whether they can be used as molecular biomarkers for T1DM. The relationship between the investigated miRNAs and pro-inflammatory cytokines (TNF-α and IL-6) has also been evaluated in the development of TIDM, in addition to the creation of a proposed model for TIDM prediction. Patients & methods: Case-control study included 177 Egyptian patients with confirmed type I diabetes mellitus and 177 healthy individuals. MiRNA-34 and miRNA-146 were detected in serum samples using real-time PCR, whereas TNF-α and IL-6 levels were assessed using ELIZA. Results: Patients with TIDM showed a significant decrease in the expression of miRNA-146, with a cut-off value ≤ 3.3, 48 % specificity, and 92.1 % sensitivity, whereas miRNA-34 had the highest sensitivity (95.5 %) and specificity (97.2 %) for differentiating diabetic patients from controls. Furthermore, other diagnostic proinflammatory markers showed lower sensitivity and specificity. Conclusion: Serum levels of miRNA-34a, miRNA-146, IL-6, and TNF-α provide new insights into T1DM pathogenesis and could be used for screening and diagnosis purposes. They can be also a potential therapeutic target, as well as allowing for more strategies to improve T1DM disease outcomes.

Investigating the impact of nanoemulsion of curcumin-loaded olive oil on growth performance, feed utilization, immunological responses, and redox status of Litopenaeus vannamei shrimp with emphasis on economic efficiency of supplementation.

The trail aimed to explore the effect of dietary supplementation of curcumin loaded olive oil nanoemulsion (CUR-OLNE) on growth performance, feed utilization, blood biochemical, redox status, and immune response of Litopenaeus vannamei shrimp, considering the economic efficiency of supplementation. A total of 280 healthy shrimps (3.42 ± 0.02 g) were randomly distributed into five equal groups and were fed diets containing 0 (CUR-OLNE0), 5(CUR-OLNE5), 10(CUR-OLNE10), 15(CUR-OLNE15) and 20 (CUR-OLNE20) mg CUR-OLNE/kg diet, respectively for 16 weeks. Among CUR-OLNE treated groups, CUR-OLNE20 showed the highest growth performance and feed utilization traits, including final body weight, specific growth rate, feed conversion ratio, and protein efficiency ratio. Notably, the photomicrographs provided further compelling evidence regarding the potential effect of CUR-OLNE supplementation on muscle structure and integrity. Compared to the control, the levels of blood protein significantly induced in CUR-OLNE15 and CUR-OLNE20 treated groups (p < 0.05). All CUR-OLNE -supplemented groups possessed lower activities of liver enzymes as well as the levels of urea and creatinine compared to the control (p < 0.05). The addition of 20 mg CUR-OLNE/kg diet decreased the concentrations of cortisol, glucose and triglycerides. The dietary treatment significantly improved the secretion of digestive enzymes, including amylase, lipase, and protease. The lowest levels of Malondialdehyde and the highest levels of total antioxidant capacity, super oxide dismutase, catalase, lysozyme and immunoglobulin M were detected in both of CUR-OLNE15, and CUR-OLNE20 treated groups compared to the control (p < 0.05). There were considerable significant effects of dietary supplementation of CUR-OLNE on economic efficiency. In conclusion, the application of nanocarriers for the delivery of dietary immune stimulants such as CUR-OLNE to Litopenaeus vannamei shrimp is a promising strategy for improving shrimp nutrition. The addition of 20 mg CUR-OLNE/kg to the diets of can be recommended as an affective intervention to improve growth performance, feed utilization, and health status of shrimp. Implementing this intervention can maximize the economic efficiency of shrimp farming while promoting sustainable practices in the industry.

High-Throughput Bioprinting of Spheroids for Scalable Tissue Fabrication.

Tissue biofabrication that replicates an organ-specific architecture and function requires physiologically-relevant cell densities. Bioprinting using spheroids has the potential to create constructs with native cell densities, but its application is limited due to the lack of practical, scalable techniques. This study presents HITS-Bio (High-throughput Integrated Tissue Fabrication System for Bioprinting), a novel multiarray spheroid bioprinting technology enabling scalable tissue fabrication by rapidly positioning a number of spheroids simultaneously using a digitally-controlled nozzle array (DCNA) platform. HITS-Bio achieves an unprecedented speed, an order of magnitude faster compared to existing techniques while maintaining high cell viability (>90%). The platform's ability to pattern multiple spheroids simultaneously enhances fabrication rates proportionally to the size of DCNA used. The utility of HITS-Bio was exemplified in multiple applications, including intraoperative bioprinting with microRNA transfected spheroids for calvarial bone regeneration (∼30 mm 3 ) in a rat model achieving a near-complete defect closure (∼91% in 3 weeks and ∼96% in 6 weeks). Additionally, the successful fabrication of scalable cartilage constructs (1 cm 3 ) containing ∼600 chondrogenic spheroids highlights its high-throughput efficiency (under 40 min per construct) and potential for repairing volumetric tissue defects.

Bee venom enhances performance and immune function in thinlip mullet: A promising approach for sustainable aquaculture.

As an environmentally friendly alternative to antibiotics, bee venom holds promise for aquaculture due to its diverse health advantages, including immune-amplifying and anti-inflammatory features. This study investigated the effects of dietary bee venom (BV) on the growth and physiological performance of Thinlip mullet (Liza ramada) with an initial body weight of 40.04 ± 0.11 g for 60 days. Fish were distributed to five dietary treatments (0, 2, 4, 6, and 8 mg BV/kg diet) with three replicates. Growth traits, gut enzyme ability (lipase, protease, amylase), intestinal and liver histology, blood biochemistry, immune responses [lysozyme activity (LYZ), bactericidal activity (BA), nitroblue tetrazolium (NBT%)], and antioxidant status [superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), malondialdehyde (MDA)] were evaluated. BV supplementation significantly improved growth performance, digestive enzyme activity, histological integrity of organs, immune responses (LYZ, BA), and antioxidant status (SOD, CAT, GPx), while declining MDA levels. Optimal BV levels were identified between 4.2 and 5.8 mg/kg diet for different parameters. Overall, the findings suggest that BV supplementation can enhance growth and physiological performance in Thinlip mullet, highlighting its potential as a beneficial dietary supplement for fish health and aquaculture management.

Posttranscriptional Modification to Modulate Progenitor Differentiation on Heterotypic Spheroids.

Cell aggregates are widely used to study heterotypic cellular interactions during the development of vascularization in vitro. In this study, we examined heterotypic cellular spheroids made of adipose-derived stem cells and CD34+/CD31- endothelial progenitor cells induced by the transfection of miR-148b mimic for de novo induction of osteogenic differentiation and miR-210 mimic for de novo induction of endotheliogenesis, respectively. The effect of the microRNA (miRs) mimic treatment group and induction time on codifferentiation was assessed in spheroids formed of transfected cells over the course of a 4-week culture. Based on gene and protein markers of osteogenic and endotheliogenic differentiation, as well as mineralization assays, our results showed that miRs directed cell differentiation and that progenitor maturity influenced the development of heterotypic cellular regions in aggregates. Overall, the success of coculture to create a prevascularized bone model is dependent on a number of factors, particularly the induction time of differentiation before combining the multiple cell types in aggregates. The approach that has been proposed could be valuable in creating vascularized bone tissue by employing spheroids as the building blocks of more complex issues through the use of cutting-edge methods such as 3D bioprinting.

A Versatile Photocrosslinkable Silicone Composite for 3D Printing Applications.

Embedded printing has emerged as a valuable tool for fabricating complex structures and microfluidic devices. Currently, an ample of amount of research is going on to develop new materials to advance its capabilities and increase its potential applications. Here, we demonstrate a novel, transparent, printable, photocrosslinkable, and tuneable silicone composite that can be utilized as a support bath or an extrudable ink for embedded printing. Its properties can be tuned to achieve ideal rheological properties, such as optimal self-recovery and yield stress, for use in 3D printing. When used as a support bath, it facilitated the generation microfluidic devices with circular channels of diameter up to 30 µm. To demonstrate its utility, flow focusing microfluidic devices were fabricated for generation of Janus microrods, which can be easily modified for multitude of applications. When used as an extrudable ink, 3D printing of complex-shaped constructs were achieved with integrated electronics, which greatly extends its potential applications towards soft robotics. Further, its biocompatibility was tested with multiple cell types to validate its applicability for tissue engineering. Altogether, this material offers a myriad of potential applications (i.e., soft robotics, microfluidics, bioprinting) by providing a facile approach to develop complicated 3D structures and interconnected channels.

Clinical-Hematological Changes and Predictors of Severity in Acute Food Protein-Induced Enterocolitis Syndrome Reactions at Oral Food Challenge: A Multicenter Observational Study.

BACKGROUND: Oral food challenge (OFC) is the criterion standard for diagnosis of acute food protein-induced enterocolitis syndrome (FPIES). No diagnostic/prognostic biomarkers are available, and OFC assessment criteria are not validated. OBJECTIVE: To assess clinical-hematological changes and predictors of severity of FPIES reactions at OFC. METHODS: This was an observational multicenter prospective study. Children aged 0 to 18 years diagnosed with acute FPIES were recruited at follow-up OFC in 12 tertiary centers in Spain and Italy. OFC outcomes (as positive/negative/inconclusive and mild/moderate/severe) were assessed on the basis of published "2017 FPIES Consensus" criteria. Clinical characteristics were recorded, and full blood cell count was done at baseline, reaction onset, and 4 hours later. Regression analysis was performed to assess predictors of severe reactions at OFC. RESULTS: A total of 81 children had positive OFC (mild in 11% [9 of 81], moderate in 61% [49 of 81], and severe in 28% [23 of 81]). Increase in neutrophils and reduction in eosinophils, basophils, and lymphocytes were observed (P < .05). OFC was inconclusive in 19 cases despite objective signs or neutrophilia. Regression analysis showed that a 2-day OFC protocol where only 25% of an age-appropriate portion is given on day 1 (not sex, age, culprit food, cumulative dose, and previous reaction severity) was associated with reduced odds of severe reaction compared with giving multiple doses in a single day. CONCLUSIONS: Distinct hematological changes may help support FPIES diagnosis. Current OFC assessment criteria may not capture the broad spectrum of acute FPIES presentations. This 2-day protocol may be associated with a reduced risk of severe reactions. Future work should aim to develop safer OFC and non-OFC diagnostics for FPIES.

Ultrasound Neuromodulation of an Anti-Inflammatory Pathway at the Spleen Improves Experimental Pulmonary Hypertension.

BACKGROUND: Inflammation is pathogenically implicated in pulmonary arterial hypertension; however, it has not been adequately targeted therapeutically. We investigated whether neuromodulation of an anti-inflammatory neuroimmune pathway involving the splenic nerve using noninvasive, focused ultrasound stimulation of the spleen (sFUS) can improve experimental pulmonary hypertension. METHODS: Pulmonary hypertension was induced in rats either by Sugen 5416 (20 mg/kg SQ) injection, followed by 21 (or 35) days of hypoxia (sugen/hypoxia model), or by monocrotaline (60 mg/kg IP) injection (monocrotaline model). Animals were randomized to receive either 12-minute-long sessions of sFUS daily or sham stimulation for 14 days. Catheterizations, echocardiography, indices of autonomic function, lung and heart histology and immunohistochemistry, spleen flow cytometry, and lung single-cell RNA sequencing were performed after treatment to assess the effects of sFUS. RESULTS: Splenic denervation right before induction of pulmonary hypertension results in a more severe disease phenotype. In both sugen/hypoxia and monocrotaline models, sFUS treatment reduces right ventricular systolic pressure by 25% to 30% compared with sham treatment, without affecting systemic pressure, and improves right ventricular function and autonomic indices. sFUS reduces wall thickness, apoptosis, and proliferation in small pulmonary arterioles, suppresses CD3+ and CD68+ cell infiltration in lungs and right ventricular fibrosis and hypertrophy and lowers BNP (brain natriuretic peptide). Beneficial effects persist for weeks after sFUS discontinuation and are more robust with early and longer treatment. Splenic denervation abolishes sFUS therapeutic benefits. sFUS partially normalizes CD68+ and CD8+ T-cell counts in the spleen and downregulates several inflammatory genes and pathways in nonclassical and classical monocytes and macrophages in the lung. Differentially expressed genes in those cell types are significantly enriched for human pulmonary arterial hypertension-associated genes. CONCLUSIONS: sFUS causes dose-dependent, sustained improvement of hemodynamic, autonomic, laboratory, and pathological manifestations in 2 models of experimental pulmonary hypertension. Mechanistically, sFUS normalizes immune cell populations in the spleen and downregulates inflammatory genes and pathways in the lung, many of which are relevant in human disease.

Acaricidal Efficacy of Thirty-Five Egyptian Plants Against the Camel Tick, Hyalomma Dromedarii.

PURPOSE: Alternative and affordable tick control strategies are crucial to control and prevent tick bites and tick-borne diseases. METHODS: In this study, we evaluated the acaricidal efficacy of 35 aqueous plant extracts (17%) against the camel tick, Hyalomma dromedarii. RESULTS: The phytochemical profile indicated the presence of various secondary substances. Plants were classified into three groups according to their mortality percentage 15 days post-treatment with 17%. This highly effective group (91%-95%) comprised Ocimum basilicum, Mespilus germanica, and Viola alpine followed by Carum carvi, Cucurbita pepo (peel), and Peganum harmala. A moderately effective group (80%-90%) included Acacia nilotica, Apium graveolens, Capsicum annuum, Ceratonia siliqua, Cucurbita pepo (seeds), Equisetum arvense, Eruca sativa, Ginkgo biloba, Plantago psyllium, Phyllanthus emblica, Punica granatum, and Ziziphus spinachristi. The 20 remaining plants were assigned to the less effective group (< 80%). Viscum album (58.3%), which was the least effective reference plant. The high potency of six plant extracts as acaricides may be attributed to the high content of active principles, e.g., phenols, flavonoids, and tannins. CONCLUSION: All of these highly effective plants are recommended for use as an acaricide, in case of facing acaricidal resistance or limited options for tick control.

Vagus nerve stimulation modulates distinct acetylcholine receptors on B cells and limits the germinal center response.

Acetylcholine is produced in the spleen in response to vagus nerve activation; however, the effects on antibody production have been largely unexplored. Here, we use a chronic vagus nerve stimulation (VNS) mouse model to study the effect of VNS on T-dependent B cell responses. We observed lower titers of high-affinity IgG and fewer antigen-specific germinal center (GC) B cells. GC B cells from chronic VNS mice exhibited altered mRNA and protein expression suggesting increased apoptosis and impaired plasma cell differentiation. Follicular dendritic cell (FDC) cluster dispersal and altered gene expression suggested poor function. The absence of acetylcholine-producing CD4+ T cells diminished these alterations. In vitro studies revealed that α7 and α9 nicotinic acetylcholine receptors (nAChRs) directly regulated B cell production of TNF, a cytokine crucial to FDC clustering. α4 nAChR inhibited coligation of CD19 to the B cell receptor, presumably decreasing B cell survival. Thus, VNS-induced GC impairment can be attributed to distinct effects of nAChRs on B cells.

From tap to table: An assessment of drinking water quality in Perak, Malaysia.

INTRODUCTION: A study on the quality of drinking water was conducted at Air Kuning Treatment Plant In Perak, Malaysia, based on a sanitary survey in 14 sampling points stations from the intake area to the auxiliary points. This was to ensure the continuous supply of clean and safe drinking water to the consumers for public health protection. The objective was to examine the physical, microbiological, and chemical parameters of the water, classification at each site based on National Drinking Water Standards (NDWQS) and to understand the spatial variation using environmetric technique; principal component analysis (PCA). MATERIALS AND METHODS: Water samples were subjected to in situ and laboratory water quality analyses and focused on pH, turbidity, chlorine, Escherichia coli, total coliform, total hardness, iron (Fe), aluminium (Al), zinc (Zn), magnesium (Mg) and sodium (Na). All procedures followed the American Public Health Association (APHA) testing procedures. RESULTS: Based on the results obtained, the values of each parameter were found to be within the safe limits set by the NDWQS except for total coliform and iron (Fe). PCA has indicated that turbidity, total coliform, E. coli, Na, and Al were the major factors that contributed to the drinking water contamination in river water intake. CONCLUSION: Overall, the water from all sampling point stations after undergoing water treatment process was found to be safe as drinking water. It is important to evaluate the drinking water quality of the treatment plant to ensure that consumers have access to safe and clean drinking water as well as community awareness on drinking water quality is essential to promote public health and environmental protection.

Respirable dust exposure impact on respiratory symptoms among cleaners in a Selangor Public University, Malaysia.

INTRODUCTION: Cleaners perform a vital role in environmental health by keeping the place clean, but they are also exposed to various hazards. Yet, there is a lack of effective and accessible occupational safety standard measures, thus making this to be difficult to monitor the long-term health effects of cleaners. This study aims to determine the respirable dust exposure on respiratory symptoms among cleaners in a public university in Selangor. MATERIALS AND METHODS: A cross-sectional study was carried out among 51 cleaners. The respondents' background information and respiratory symptoms were gathered using a series of standardised questionnaires validated by the American Thoracic Society (ATS-DLD-78-A). The 8- hour respirable dust exposure to cleaners was measured using an air sampling pump (Gillian & Sensodyne Gil Air 3). RESULTS: The mean of respirable dust was lower than permissible exposure limit with 0.63±0.57mg/m3. The respiratory symptoms among the cleaners showed no significant association between cough, phlegm, and breathing difficulties with working tenure. Meanwhile, wheezing and coughing with phlegm have an almost significant association with working tenure among cleaners with (Χ2=1.00, p=0.08) and (Χ2=1.00, p=0.07) respectively. Exposure to respirable dust has exhibited 6 times the prevalence of coughing with phlegm among cleaners (PR=6.28, 95% CI: 0.44, 89.38). CONCLUSION: The findings of this study demonstrated that the cleaners were significantly affected by the respirable dust. The cleaners' working environment has caused them to be exposed to respirable dust.

Effects of supplemental vitamin A on reproduction and antioxidative status of aged laying hens, and growth, blood indices and immunity of their offspring.

The purpose of this investigation was to evaluate the impacts of vitamin A (VA) supplementation in feed at levels of 0 (control), 2,000, 4,000, 6,000, and 8,000 IU VA/kg diet on the reproductive efficiency and antioxidative properties of aged Sinai laying hens at 52 wk of age (n = 300 females and 30 males) in 6 replicates (10 females + 1 male/replicate). As well as blood biochemical indicators, carcass characteristics, growth performance, immunity, and the antioxidative status of their chicks. Results showed that diets supplemented with 2,000 or 6,000 IU/kg of VA increased fertility rate and decreased early embryonic mortality (P < 0.05). Increasing VA from 4,000 to 6,000 IU/kg significantly boosted hatchability rates. All VA levels significantly enhanced glutathione peroxidase (GPx) and reduced malondialdehyde (MDA) and late embryonic mortality. In the shell gland, dietary supplementation of 6,000 or 8,000 IU/kg of VA enhanced actions of GPx actions, catalase (CAT), and superoxide dismutase (SOD). In hatched chicks, all VA levels boosted (P < 0.05) hemoglobin, red blood cell count, and serum concentration of total proteins and IgA while decreasing eosinophils percentage and aspartate aminotransferase activity (AST) concentration. Dietary VA supplementations from 4,000 to 8,000 IU/kg improved lymphocytes, serum total antioxidant capacity (TAC), SOD, and IgM, while decreasing heterophils, heterophils/lymphocytes ratio, and creatinine in hatched chicks. Serum triglyceride concentration was reduced by adding 6,000 or 8,000 IU/kg of VA, while globulin and high-density lipoprotein concentrations were heightened only by 8,000 IU/kg of VA. It could be concluded that the dietary supplementation of VA (6,000 IU/kg) improved reproductive efficiency and antioxidative status in the liver and the shell gland of aged laying hens and improved hemato-biochemicals parameters, antioxidative status, and immunity of their offspring.

Guillain-Barré syndrome after COVID-19 vaccination: A systematic review and analysis of case reports.

INTRODUCTION: Cases of Guillain-Barré Syndrome (GBS) have been believed to be associated with the novel COVID-19 infection, and also with the following vaccines developed against the infection. Our work aims to investigate the incidence of GBS after COVID-19 vaccination, and describe its clinical characteristics and potential confounders. METHODS: An electronic search was conducted through four databases: PubMed, Scopus, medRxiv, and Google Scholar for all case reports and case series describing after COVID-19 vaccine administration. All published articles from inception until November 1st, 2022 were included. Differences between groups were assessed using Pearson chi-square test. Modified Erasmus GBS Outcome Score (mEGOS) for the ability to walk after GBS was calculated for all cases with sufficient clinical data, and Kaplan-Meier survival analysis was performed to study the effect of vaccine type on the relationship between vaccination time and complication of GBS. RESULTS: About 103 studies describing 175 cases of GBS following COVID-19 vaccination were included. The Acute Inflammatory Demyelinating Polyradiculoneuropathy subtype was the most reported subtype with 74 cases (42.29%). The affected age group averaged around 53.59 ±18.83 years, with AMSAN occurring in a rather older group (63.88 ±20.87 years, p=0.049). The AstraZeneca vaccine was associated with AIDP (n=38, 21.71%) more than other vaccines, p=0.02. The bilateral facial palsy subtype was mostly linked to adenoviral vector vaccinations, accounting for an average of 72% of the total BFP cases. Dysesthesias was the most reported sensory complication (60%, p=0.349). Most GBS patients survived (96%, p=0.036), however, most patients had low mEGOS scores (4 ±3.57, p<0.01). On average, patients developed GBS at 13.43 ±11.45 days from vaccination (p=0.73), and survival analysis for complication of GBS into mechanical ventilation or walking impairment yielded a severely increased probability of complication after 25 days (p<0.01). Intravenous immunoglobulins (p=0.03) along with rehabilitation (p=0.19) were the most commonly used treatment. CONCLUSION: This work investigates the incidence of Guillain-Barré Syndrome after COVID-19 vaccination. Most cases occurred after receiving the AstraZeneca or Pfizer vaccines, and despite low mortality rates, ambulation was compromised in most patients. A higher risk of GBS complication is associated with an onset later than 12-13 days, particularly with Pfizer, AstraZeneca, and Moderna vaccines. No specific predisposing or prognostic factor was identified, and the relation between the COVID-19 vaccines and GBS remain unclear.

Dynamical behavior of solitons of the (2+1)-dimensional Konopelchenko Dubrovsky system.

Utilizing nonlinear evolution equations (NEEs) is common practice to establish the fundamental assumptions underlying natural phenomena. This paper examines the weakly dispersed non-linear waves in mathematical physics represented by the Konopelchenko-Dubrovsky (KD) equations. The [Formula: see text]-expansion method is used to analyze the model under consideration. Using symbolic computations, the [Formula: see text]-expansion method is used to produce solitary waves and soliton solutions to the [Formula: see text]-dimensional KD model in terms of trigonometric, hyperbolic, and rational functions. Mathematica simulations are displayed using two, three, and density plots to demonstrate the obtained solitary wave solutions' behavior. These proposed solutions have not been documented in the existing literature.

A comprehensive review on 3D tissue models: Biofabrication technologies and preclinical applications.

The limitations of traditional two-dimensional (2D) cultures and animal testing, when it comes to precisely foreseeing the toxicity and clinical effectiveness of potential drug candidates, have resulted in a notable increase in the rate of failure during the process of drug discovery and development. Three-dimensional (3D) in-vitro models have arisen as substitute platforms with the capacity to accurately depict in-vivo conditions and increasing the predictivity of clinical effects and toxicity of drug candidates. It has been found that 3D models can accurately represent complex tissue structure of human body and can be used for a wide range of disease modeling purposes. Recently, substantial progress in biomedicine, materials and engineering have been made to fabricate various 3D in-vitro models, which have been exhibited better disease progression predictivity and drug effects than convention models, suggesting a promising direction in pharmaceutics. This comprehensive review highlights the recent developments in 3D in-vitro tissue models for preclinical applications including drug screening and disease modeling targeting multiple organs and tissues, like liver, bone, gastrointestinal tract, kidney, heart, brain, and cartilage. We discuss current strategies for fabricating 3D models for specific organs with their strengths and pitfalls. We expand future considerations for establishing a physiologically-relevant microenvironment for growing 3D models and also provide readers with a perspective on intellectual property, industry, and regulatory landscape.

Influence of nano-formulations of clove bud (Syzygium aromaticum) extract on freezing ability, antioxidant capacity, caspase-3 activity, acrosome reaction and fertility of frozen rabbit semen.

The current study aimed to investigate the impact of nano-formulations of clove bud ethanolic extract (CBENF) in the extender on sperm characteristics, antioxidant capacity, oxidative biomarkers, enzymatic activity, apoptosis and fertility of post-thawed rabbit semen. Twelve mature male rabbits semen samples were pooled and cryopreserved in a Tris-egg yolk-based extender containing varying concentrations of CBENF (0, 25, 50, 75 and 100 µg/mL). After the equilibration and freezing-thawing process, CBENF (100 µg /mL) significantly enhanced progressive motility, viability and membrane integrity. Conversely, sperm abnormality was significantly reduced by CBENF supplementation. Total antioxidant capacity was increased in the post-thawed sperm medium, while nitric oxide and malondialdehyde were decreased in all CBENF concentrations. The lactic dehydrogenase and caspase-3 activities were decreased, whereas the number of live spermatozoa with an intact acrosome was increased in all CBENF concentrations. Conception rate and litter size per doe were higher in doe rabbits inseminated with semen supplemented with 100 µg CBENF/mL than un-supplemented group (76% vs. 52% and 8.4 vs. 7.7/doe), with no statistical differences. These findings suggest that supplementing rabbit extenders with 100 µg of CBENF/mL could be an effective strategy for enhancing freeze-thawing rabbit sperm attributes and fertility.

Intraoperative bioprinting of human adipose-derived stem cells and extra-cellular matrix induces hair follicle-like downgrowths and adipose tissue formation during full-thickness craniomaxillofacial skin reconstruction.

Craniomaxillofacial (CMF) reconstruction is a challenging clinical dilemma. It often necessitates skin replacement in the form of autologous graft or flap surgery, which differ from one another based on hypodermal/dermal content. Unfortunately, both approaches are plagued by scarring, poor cosmesis, inadequate restoration of native anatomy and hair, alopecia, donor site morbidity, and potential for failure. Therefore, new reconstructive approaches are warranted, and tissue engineered skin represents an exciting alternative. In this study, we demonstrated the reconstruction of CMF full-thickness skin defects using intraoperative bioprinting (IOB), which enabled the repair of defects via direct bioprinting of multiple layers of skin on immunodeficient rats in a surgical setting. Using a newly formulated patient-sourced allogenic bioink consisting of both human adipose-derived extracellular matrix (adECM) and stem cells (ADSCs), skin loss was reconstructed by precise deposition of the hypodermal and dermal components under three different sets of animal studies. adECM, even at a very low concentration such as 2 % or less, has shown to be bioprintable via droplet-based bioprinting and exhibited de novo adipogenic capabilities both in vitro and in vivo. Our findings demonstrate that the combinatorial delivery of adECM and ADSCs facilitated the reconstruction of three full-thickness skin defects, accomplishing near-complete wound closure within two weeks. More importantly, both hypodermal adipogenesis and downgrowth of hair follicle-like structures were achieved in this two-week time frame. Our approach illustrates the translational potential of using human-derived materials and IOB technologies for full-thickness skin loss.