Tissue Growth Research Articles

Sodium alginate hydrogels co-encapsulated with cell free fat extract-loaded core-shell nanofibers and menstrual blood stem cells derived exosomes for acceleration of articular cartilage regeneration

This study presents a novel scaffold system comprising sodium alginate hydrogels (SAh) co-encapsulated with cell-free fat extract (CEFFE)-loaded core-shell nanofibers (NFs) and menstrual blood stem cell-derived exosomes (EXOs). The scaffold integrates the regenerative potential of EXOs and CFFFE, offering a multifaceted strategy for promoting articular cartilage repair. Coaxially electrospun core-shell NFs exhibited successful encapsulation of CEFFE and seamless integration into the SAh matrix. Structural modifications induced by the incorporation of CEFFE-NFs enhanced hydrogel porosity, mechanical strength, and degradation kinetics, facilitating cell adhesion, proliferation, and tissue ingrowth. The release kinetics of growth factors from the composite scaffold demonstrated sustained and controlled release profiles, essential for optimal tissue regeneration. In vitro studies revealed high cell viability, enhanced chondrocyte proliferation, and migration in the presence of EXOs/CEFFE-NFs@SAh composite scaffolds. Additionally, in vivo experiments demonstrated significant cartilage regeneration, with the composite scaffold outperforming controls in promoting hyaline cartilage formation and defect bridging. Overall, this study underscores the potential of EXOs and CEFFE-NFs integrated into SAh matrices for enhancing chondrocyte viability, proliferation, migration, and ultimately, articular cartilage regeneration. Future research directions may focus on elucidating underlying mechanisms and conducting long-term in vivo studies to validate clinical applicability and scalability.

Extracellular matrix protein 1 binds to connective tissue growth factor against liver fibrosis and ductular reaction.

Extracellular matrix protein 1 (ECM1) can inhibit TGFβ activation, but its antifibrotic action remains largely unknown. This study aims to investigate ECM1 function and its physical interaction with the profibrotic connective tissue growth factor (CTGF) in fibrosis and ductular reaction (DR). Ecm1 knockouts or animals that ectopically expressed this gene were subjected to induction of liver fibrosis and DR by feeding 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) or α-naphthyl-isothiocyanate (ANIT). ECM1 and CTGF were also examined in the livers of patients with alcohol-associated liver disease (ALD) or ethanol-exposed animals that were fed the western diet for 4 months in the WDA model with liver pathology resembing ALD in patients. ECM1 bound to CTGF in yeast two-hybrid systems, cultured liver cells, and cholestatic livers damaged by DDC or α-naphthyl-isothiocyanate. This interaction blocked integrin αvβ6-mediated TGFβ activation, thereby reducing fibrotic responses in vitro. ECM1 downregulation was associated with biliary CTGF induction during human ALD progression. In experimental models, Ecm1 loss enhanced susceptibility to DDC-induced cholestasis with upregulation of Ctgf, αvβ6, alpha-smooth muscle actin, procollagen type I, serum transaminase, and total bilirubin levels in germline knockouts, whereas forced expression of this gene significantly attenuated DR and biliary fibrosis after the feeding of DDC or α-naphthyl-isothiocyanate containing diets. Moreover, ectopic Ecm1 inhibited not only alcohol-associated fibrosis but also TGFβ-mediated deregulation of hepatocyte nuclear factor 4α, preventing the production of the fetal p2 promoter-driven isoforms in the WDA model. We uncover a novel antifibrotic action by ECM1 that binds CTGF and inhibits integrin αvβ6-mediated TGFβ activation. Targeting its loss has therapeutic potential for the treatment of DR and liver fibrosis in chronic conditions, such as cholangiopathy and ALD.

Fructose metabolism is unregulated in cancers and placentae

Fructose and lactate are present in high concentrations in uterine luminal fluid, fetal fluids and fetal blood of ungulates and cetaceans, but their roles have been ignored and they have been considered waste products of pregnancy. This review provides evidence for key roles of both fructose and lactate in support of key metabolic pathways required for growth and development of fetal-placental tissues, implantation and placentation. The uterus and placenta of ungulates convert glucose to fructose via the polyol pathway. Fructose is sequestered within the uterus and cannot be transported back into the maternal circulation. Fructose is phosphorylated by ketohexokinase to fructose-1-PO4 (F1P) by that is metabolized via the fructolysis pathway to yield dihydoxyacetone phosphate and glyceraldehyde-3-PO4 that are downstream of phosphofructokinase. Thus, there is no inhibition of the fructolysis pathway by low pH, citrate or ATP which allows F1P to continuously generate substrates for the pentose cycle, hexosamine biosynthesis pathway, one-carbon metabolism and tricarboxylic acid cycle, as well as lactate. Lactate sustains the activity of hypoxia-inducible factor alpha and its downstream targets such as vascular endothelial growth factor to increase utero-placental blood flow critical to growth and development of the fetal-placental tissues and a successful outcome of pregnancy. Pregnancy has been referred to as a controlled cancer and this review addresses similarities regarding metabolic aspects of tumors and the placenta.

Genistein inhibited endocytosis and fibrogenesis in keloid via CTGF signaling pathways

BackgroundThis study aimed to evaluate soy isoflavones' effect and potential use—specifically genistein—in treating human keloid fibroblast cells (KFs) and in a keloid tissue culture model.MethodsTo investigate the effects of genistein on keloid, a wound-healing assay was performed to detect cell migration. Flow cytometry was used to measure apoptosis. Western blotting and immunofluorescence staining were performed to detect the expression of target proteins. KF tissues were isolated, cultured, and divided into the control, silenced connective tissue growth factor (CTGF) proteins, and shNC (negative control) groups.ResultsGenistein suppressed cell proliferation and migration, triggering the cell cycle at the G2/M phase and increasing the expression of p53 dose-dependent in keloids. Genistein inhibited the expression of COL1A1, FN, and CTGF mRNA and protein. Knockdown CTGF reduced the migrated ability in KFs. Genistein also abated TGF-β1-induced keloid fibrosis through the endocytosis model. Separated and cultured the keloid patient’s tissues decreased the cell migration ability by genistein treatment and was time-dose dependent.ConclusionsThis study indicated that genistein-induced p53 undergoes cell cycle arrest via the CTGF pathway-inhibited keloid cultured cells, and genistein suppressed the primary keloid cell migration, suggesting that our research provides a new strategy for developing drugs for treating keloids.

Utilizing cluster analysis of biomarkers alongside echocardiographic deformation parameters to forecast the outcome of atrial fibrillation post-ablation

Abstract Background Atrial fibrillation (AF) management often involves catheter ablation, but its recurrence necessitates careful clinical management and potential adjustments in medication or further ablation procedures. This study aims to investigate the predictive value of biomarkers and echocardiographic parameters for early AF recurrence. Methods In the prospective study, we enrolled patients with symptomatic paroxysmal or persistent atrial fibrillation undergoing catheter ablation. Pulmonary vein isolation was performed in every index procedure, with additional ablation or substrate modification as per physician preference. Blood samples were collected from both the atrium and peripheral vein to assess levels of tumor endothelial marker 1 (TEM1), galectin 3, connective tissue growth factor (CTGF), transforming growth factor-beta (TGF-β), C-terminal propeptide of procollagen type I (PICP), and Smad3. Pre-procedural echocardiographic parameters, including the E/e’ ratio, peak atrial longitudinal strain (PALS), and peak atrial contractile strain (PACS), were recorded. Clustering models with sparse canonical association analysis (CCA) were employed to develop predictive models integrating biomarker and echocardiographic data for early atrial fibrillation recurrence. Results Out of 80 prospectively enrolled patients, 68 completed the study, with six cases of early atrial fibrillation recurrence observed. Following dimension reduction and clustering, we found that the combined use of biomarkers and echocardiography significantly predicted atrial fibrillation recurrence (HR: 9.44, p=0.05, 95% CI: 1.0-88.9). Notably, among these parameters, TEM1 biomarker sampled from the peripheral vein (p=0.02), left atrium dimension (p=0.07), and left ventricle dimension (p=0.02) exhibited the most significant predictive power. Conclusions Our study highlights the effectiveness of integrating biomarkers and echocardiography parameters in predicting early recurrence of atrial fibrillation post-ablation in patients undergoing catheter ablation.main_figure

Development of a minimally invasive technique to measure the interstitial fluid pressure for remote monitoring of heart failure

Abstract Background Heart failure (HF) induces fluid interstitial retention, leading to oedema and elevated interstitial fluid pressure (IFP).1-3 There is a clinical need for remotely assessing IFP and understanding its correlation with cardiopulmonary haemodynamics for early treatment optimization in HF. IFP can be measured from a preserved fluid pocket formed by a subcutaneous perforated capsule in animals.4 However, the structural understanding of tissue neovascularization within a perforated capsule and the temporal relationship between altered cardiopulmonary haemodynamics and IFP remains unknown. Purpose To determine the neovascularisation of the perforated capsule over time and demonstrate the relationship between haemodynamic metrics of congestion (CVP, PAP, and LVEDP) and IFP during HF development. Methods Ten 45-55kg swine were implanted with subcutaneous perforated capsules. Perforated capsule characterisation included MicroCT using MicroFil cast (Fig. 1A) and microscopy initially at 3 and 6 weeks. A perforated capsule containing a PTFE (polytetrafluoroethylene) membrane was subcutaneously implanted in animals and chronic stability was studied at 90 using MicroCT and microscopy. After 3 weeks of perforated capsule implantation, HF was induced under general anaesthesia with 12-16 mg/kg/hour of esmolol (i.v.) and 0.9% NaCl (10% body weight, i.v.) and fluid was removed to euvolemia via ultrafiltration (Fig 2A). Concurrent measurements of IFP from perforated capsules and haemodynamic metrics of congestion were made using interventional techniques. Results MicroCT and microscopy have demonstrated perforated capsule neovascularization containing a central fluid pocket at 3 weeks and loss at 6 weeks due to continued tissue growth (Fig 1B-E). The perforated capsule at 90 days demonstrated fluid pocket preservation due to the PTFE membrane on MicroCT and microscopy (Fig. 1F-G). During the development of HF and offloading, there is a strong correlation between IFP and haemodynamic metrics of congestion (Fig. 2B). Conclusion We have developed a minimally invasive technique for continuous IFP measurement demonstrating a relationship between IFP and cardiac filling pressure in HF. IFP assessment offers a direct measure of fluid status and an indirect measure of haemodynamics, facilitating early treatment optimisation.

The Potential of Aloe Vera in Solution and in Blended Nanofibers Containing Poly (3-Hydroxybutyrate-Co-3-Hydroxyvalerate) as Substrates for Neurite Outgrowth.

This pilot study investigated the potential of aloe vera (AV) to promote neurite outgrowth in organotypic dorsal root ganglia (DRG) explants (n = 230) from neonatal rats (n = 15). Using this invitro model of acute axotomy, we assessed neurite outgrowth exceeding 1.5 times the explant diameter (viable explants) and measured the longest neurite length. These parameters were evaluated under control conditions and in cultures supplemented with commercial AV and four aligned scaffolds: poly-L-lactate (PLLA), polydioxanone (PDS), poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV), and blended PHBV/AV. After 6 days of culture, explants were immunostained using neuron-specific marker Tuj1 and Schwann cell marker S100. Measurements were obtained with Image J software and analyzed using Jamovi 2.3. In control and AV dilution media, the study revealed radial tissue growth from the explant body with randomly oriented neurites, whereas in all scaffolds, bidirectional tissue growth occurred parallel to nanofibers. Binomial logistic regression analyses indicated that viable explants were more likely in the control group compared to PDS (p = 0.0042) and PHBV (p < 0.0001), with non-significant differences when compared to AV dilution, PLLA, and PHBV/AV. AV dilution showed a greater association with viable explants than PLLA (p = 0.0459), while non-significant difference was found between AV dilution and PHBV/AV. Additionally, the PHBV/AV scaffold predicted higher odds of viable explants than PLLA (p = 0.0479), PDS (p = 0.0001), and PHBV (p < 0.0001). Groups with similar probabilities of obtaining viable explants (control, AV dilution, and PHBV/AV) exhibited non-significant differences in their longest neurite lengths. In conclusion, control, AV dilution, and PHBV/AV yielded the highest probability of developing viable explants and the longest neurite lengths. This is the first study demonstrating the direct permissiveness of AV for axonal outgrowth. Furthermore, the blended PHBV/AV scaffold showed significant potential as a suitable scaffold for axonal regrowth and Schwann cell migration, ensuring controlled tissue formation for tissue engineering applications.

Soft Tissue Changes at the Pontic Sites of Cantilever Zirconia Ceramic Resin-Bonded Fixed Dental Protheses inthe Esthetic Zone: A Clinical Observational Study.

Data on the stability of soft tissues at pontic sites of resin-bonded fixed dental protheses (RBFDP) are lacking. The purpose of this study was to evaluate soft tissue changes at pontic sites of cantilever zirconia ceramic RBFDPs with and without surgical pretreatment after different follow-up periods in the esthetic zone. Impressions were taken after the insertion of the restorations and an intraoral scan was performed at follow-up examinations. Dental casts were digitalized and superimposed with the follow-up scan. Vertical and horizontal soft tissue changes were measured buccally and lingually at mucosal margin at the central cross-section of each pontic, and for horizontal change at 1 and 2 mm below. One-way ANOVA and Kruskal-Wallis test were performed to analyze the collected data. A total of 36 pontic sites with (n = 7) and without surgical pretreatment (n = 29) were evaluated at a follow-up period of either > 4, > 6, or > 10 years (n = 12). The follow-up period had no significant effect on the tissue change. Surgical pretreatment showed significantly higher tissue loss at 2 mm below the lingual mucosal margin than for sites without surgical pretreatment. Soft tissues at pontic sites remained stable with a tissue gain at the mucosal margin up to 10 years. Based on the findings of this study, cantilever resin-bonded fixed dental protheses provide excellent functional and esthetic outcomes with preservation of soft tissues in the edentulous area of single missing incisors and a gingival sulcus-like tissue growth at the mucosal margin forming an emergence profile at pontic sites similar to that of a natural tooth.

Optogenetics and Its Transformative Role in Tissue Engineering and Regenerative Medicine

ABSTRACTOptogenetics, a revolutionary technique leveraging light stimulation for precise cellular control, holds immense potential in regenerative medicine. Offering unparalleled spatial and temporal accuracy, the entrance of optogenetics into tissue engineering and regenerative medicine (TERM) empowers researchers to modify genes precisely and reversibly, control signal pathways and antibodies, as well as alter biomaterial properties. Optogenetics provides unprecedented control in the manipulation of physiological regeneration, replication of intricate developmental processes, and tissue engineering in a laboratory setting. Although further investigation is required for the safe and feasible injection of optogenetic systems into human bodies, the use of optogenetics has already led to a great amount of research on several tissues and systems. It has found diverse applications in TERM of skin and connective tissue, endothelium, bone, cartilage, and muscle; with researchers leveraging optogenetics for precise control over the in vitro or in vivo production of these tissues, the investigation of critical proteins and pathways, the creation of light‐controlled wound coverings and even as a tool for directional tissue growth in living subjects. Optogenetics emerges as a transformative force in shaping the future of medical science, demonstrating a pivotal role in advancing regenerative medicine and paving the way for innovative therapeutic strategies.

Estrogen enhances the proliferation, migration, and invasion of papillary thyroid carcinoma via the ERα/KRT19 signaling axis.

Estrogen is thought to be the reason for the higher prevalence of papillary thyroid carcinoma (PTC) in fertile women; however, more study is required to completely comprehend how estrogen affects PTC development at the cellular level. Therefore, we combined Oxford Nanopore Technologies (ONT) sequencing to explore molecular markers of PTC and to investigate the molecular mechanisms by which estrogen promotes PTC development. The expression levels of ESR1 (ERα) and KRT19 in normal thyroid tissues and cancer tissues as well as in different cancer stages, races, genders, age groups, histological subtypes and nodular metastasis status of the TCGA database were analyzed online by Ualcan; the relationship between ESR1, KRT19 and the survival of THCA patients was analyzed. A PTC xenograft tumor model was established. An ERα specific inhibitor (MPP) was administered and an EDU cell proliferation assay was used to verify the effect of estrogen on PTC proliferation. KRT19 was knocked down in KTC-1 cells, and the proliferation, migration, and invasion abilities of PTC cells were determined using CCK-8, immunofluorescence labeling, Western blot for EMT-related proteins, scratch assay, and Transwell assay. The role of ERα in relation to KRT19 was investigated by Western blot and immunofluorescence. The effects of ERα/KRT19 signaling axis on the proliferation, migration and invasion ability of PTC cells were evaluated using EDU cell proliferation assay and Transwell. Using ONT sequencing, 15 pairs of PTC tissue and paracancer tissue samples were collected. A PPI network was constructed to validate the differential expression of KRT19 in combination with biosignature analysis, and the protein interaction between KRT19 and ESR1 was verified using STRING. Ualcan showed that the expression of ESR1 and KRT19 was higher in THCA tissues than in normal thyroid tissues. E2 activation of ERα promoted the growth of PTC cells and tissues. si-KRT19 inhibited the proliferation, migration and invasion of PTC cells. KRT19 together with ERα formed the ERα/KRT19 signaling axis. E2 activation of the ERα/KRT19 signaling axis promoted the proliferation, migration, and invasion of PTC cells. ONT sequencing and STRING website verified that KRT19 is significantly differentially expressed in PTC and that ESR1 and KRT19 have protein interactions and are related to the estrogen signaling pathway. Using public databases, RNA sequencing, and bioinformatics, we discovered that E2 stimulates the ERα/KRT19 signaling axis to stimulate PTC proliferation, migration, and invasion.

Understanding the pathogenesis of infertility in endometriosis - literature review

Introduction and objective Endometriosis is a complex systemic condition characterized by the growth of functional endometrial tissue outside the uterine cavity, affecting 10-15% of women of reproductive age. Up to 50% of these women face infertility challenges. Although there is a scientifically established connection between endometriosis and infertility, the underlying mechanisms remain not fully understood. Review methods The PubMed database was searched using phrases related to the topic of endometriosis-associated infertility. The search included original research articles, review papers, and guidelines, including the Polish guideline on managing women with endometriosis. Ultimately, 25 relevant sources presenting the latest knowledge were selected. Abbreviated description of the state of knowledge The pathogenesis of infertility associated with endometriosis is complex and involves multiple factors. The most frequently cited contributors in the scientific literature include pain and dyspareunia, mechanical factors, reduced ovarian reserve, oxidative stress, changes in embryo and oocyte quality, impaired ovulation, and compromised endometrial receptivity. Summary Endometriosis affects a growing number of women worldwide, with nearly half experiencing infertility. The complexity and involvement of multiple organ systems make it difficult to pinpoint a single cause, posing a challenge for clinicians. Addressing these diverse factors is essential for improving fertility management in women with endometriosis.

The long road of drug development for endometriosis – Pains, gains, and hopes

Endometriosis, defined by the growth of endometrial tissues outside of the uterine cavity, is a global health burden for ∼200 million women. Patients with endometriosis usually present with chronic pain and are often diagnosed with infertility. The pathogenesis of endometriosis is still an open question; however, tissue stemness and immunological and genetic factors have been extensively discussed in the establishment of endometriotic lesions. Current treatments for endometriosis can be categorized into pharmacological management of hormone levels and surgical removal of the lesions. Both approaches have limited efficacy, with recurrences often encountered; thus, there is no complete cure for the disease or its symptoms. We review the current knowledge of the etiology of endometriosis and summarize the advancement of pharmacological management of endometriosis. We also discuss our efforts in applying DNA-encoded chemistry technology (DEC-Tec) to identify bioactive molecules for the treatment of endometriosis, offering new avenues for developing non-hormonal treatment options for those patients who seek spontaneous pregnancies.

Empirical evidence and theoretical understanding of ecosystem carbon and nitrogen cycle interactions.

Interactions between carbon (C) and nitrogen (N) cycles in terrestrial ecosystems are simulated in advanced vegetation models, yet methodologies vary widely, leading to divergent simulations of past land C balance trends. This underscores the need to reassess our understanding of ecosystem processes, given recent theoretical advancements and empirical data. We review current knowledge, emphasising evidence from experiments and trait data compilations for vegetation responses to CO2 and N input, alongside theoretical and ecological principles for modelling. N fertilisation increases leaf N content but inconsistently enhances leaf-level photosynthetic capacity. Whole-plant responses include increased leaf area and biomass, with reduced root allocation and increased aboveground biomass. Elevated atmospheric CO2 also boosts leaf area and biomass but intensifies belowground allocation, depleting soil N and likely reducing N losses. Global leaf traits data confirm these findings, indicating that soil N availability influences leaf N content more than photosynthetic capacity. A demonstration model based on the functional balance hypothesis accurately predicts responses to N and CO2 fertilisation on tissue allocation, growth and biomass, offering a path to reduce uncertainty in global C cycle projections.

Activation of platelet-derived growth factor receptors regulate connective tissue growth factor protein levels via the AKT pathway in malignant mesothelioma cells.

The incidence of malignant mesothelioma (MM), a disease linked to refractory asbestos exposure, continues to increase globally, and remains largely resistant to various treatments. Our previous studies have identified a strong correlation between connective tissue growth factor (CTGF) protein expression and MM malignancy, underscoring the importance of understanding CTGF regulation in MM cells. In this study, we demonstrate for the first time that stimulation with platelet-derived growth factor receptor (PDGFR) ligand, PDGF-BB, increases CTGF protein expression levels without affecting CTGF mRNA levels. Inhibition of PDGFR resulted in a reduction of CTGF protein expression, indicating that PDGFR activation is essential in regulating CTGF protein expression in MM cells. PDGF-BB also activated the protein kinase B (AKT) pathway, and inhibition of AKT phosphorylation abolished the PDGFR-induced CTGF protein expression, suggesting that PDGFR acts upstream of CTGF via the AKT pathway. This reinforces the role of CTGF protein as a key regulator of MM malignancy. Additionally, PDGFR activation led to the phosphorylation of mTOR and 4E-BP1, critical regulators of protein synthesis downstream of AKT, suggesting that PDGFR controls CTGF protein expression through the regulation of CTGF mRNA translation.

Leveraging Xenobiotic-Responsive Cancer Stemness in Cell Line-Based Tumoroids for Evaluating Chemoresistance: A Proof-of-Concept Study on Environmental Susceptibility

Emerging evidence suggests that cancer stemness plays a crucial role in tumor progression, metastasis, and chemoresistance. Upon exposure to internal or external stress, ribosomes stand sentinel and facilitate diverse biological processes, including oncological responses. In the present study, ribosome-inactivating stress (RIS) was evaluated for its modulation of cancer cell stemness as a pivotal factor of tumor cell reprogramming. Based on the concept of stress-responsive cancer cell stemness, we addressed human intestinal cancer cell line-based off-the-shelf spheroid cultures. Intestinal cancer cell line-based spheroids exhibited heightened levels of CD44+CD133+ cancer stemness, which was improved by chemical-induced RIS. Further evaluations revealed the potential of these stress-imprinted spheroids as a platform for chemoresistance screening. Compared to adherent cells, stemness-improved spheroid cultures displayed reduced apoptosis in response to 5-fluorouracil (5-FU), a frontline chemotherapeutic agent against colorectal cancer. Moreover, serial subcultures with repeated RIS exposure maintained and even enhanced cancer stemness and chemoresistance patterns. In particular, isolated CD44+CD133+ cancer stem cells exhibited higher chemoresistance compared to unsorted cells. To elucidate the mechanisms underlying RIS-induced stemness, RNA-seq analysis identified Wnt signaling pathways and stemness-associated signals as notable features in spheroids exposed to RIS. Loss-of-function studies targeting connective tissue growth factor (CTGF), a negative regulator of Wnt signaling, revealed that CTGF-deficient spheroids exhibited improved cancer stemness and resistance to 5-FU, with RIS further enhancing these effects. In conclusion, this proof-of-concept study demonstrates the feasibility of leveraging stress-responsive cancer stemness for the development of spheroid-based platforms for chemoresistance evaluation and elucidation of pathophysiological processes of colorectal tumorigenesis under environmental stress.

Continuous Viscoelasticity Measurement of Cell Spheroids via Microfluidic Electrical Aspiration.

Measurement of viscoelastic characteristics of cells cultured in three-dimensional (3D) is critical to study many biological processes including tissue and organ growth. In this article, we present a unique electrical aspiration method to measure the viscoelastic properties of cell spheroids. A microfluidic sensor was created to demonstrate this method. Unlike the traditional optical aspiration method, the aspiration of the cell spheroids is monitored via monitoring the dynamic electrical resistance change of a symmetrical microfluidic aspiration channel. We first used the microfluidic device to measure the viscoelastic properties of two types of biological tissues derived from calfskin and porcine left ventricular myocardium. The equilibrium elastic modulus and creep time constants were measured to be 148.1 ± 24.1 kPa and 76.7 ± 3.5 s and 64.5 ± 7.7 kPa and 31.4 ± 2.7 s respectively, which matched well with reported data. The test validated the principle of the electrical aspiration method. Next, we applied the method for measuring cell spheroids made of human mesenchymal stem cells at different culture stages. The equilibrium elastic modulus and apparent viscosity decreased with increasing culture time. Compared to optical aspiration methods, this microfluidic electrical aspiration method has no reliance on transparent materials and image processing, which thus allows simple setup, fast data acquisition and analysis. The use of a symmetric aspiration channel and the linear half-space model enable measurements of a large number of viscoelastic properties via a single measurement with higher accuracy. This method will enable high throughput, continuous viscoelastic measurement of cell spheroids as well as other 3D cell culture models in flow conditions without the need for any optical measurements.

Mechanical Trapping of the Cell Nucleus Into Microgroove Concavity But Not On Convexity Induces Cell Tissue Growth and Vascular Smooth Muscle Differentiation

Mechanical Trapping of the Cell Nucleus Into Microgroove Concavity But Not On Convexity Induces Cell Tissue Growth and Vascular Smooth Muscle Differentiation

Antitumor effect of the Newcastle disease virus strain NDV/Altai/pigeon/777/2010 on a model of solid Lewis carcinoma

Aim. To evaluate the efficacy of intratumoral administrations of the Newcastle disease virus strain NDV/Altai/pigeon/777/2010, to compare progression of the tumor nodes after virotherapy and to analyse pathomorphological changes in the tumor tissue in vitro and in vivo. Single intratumoral injections of the mesogenic strain of Newcastle disease virus NDV/Altai/pigeon/777/2010, isolated from a rock dove in Siberia, were done into outbred mice of the C57Bl/6 line into solid nodes of Lewis lung carcinoma that were grafted subcutaneously. Then the dynamics of tumor growth and pathomorphological changes in the tumor tissue were assessed and analyzed.It was shown that single intratumoral injections into immunocompetent C57Bl/6 mice with the mesogenic strain of Newcastle disease virus NDV/Altai/pigeon/777/2010 led to an increase in peculiar pathomorphological changes in the tumor tissue of subcutaneously grafted Lewis lung carcinoma and to a decrease in tumor growth compared to the control group of mice in vivo. A direct cytotoxic effect of the NDV strain on the Vero E6 cell line in vitro was noted.The results of this study indicate that the NDV strain NDV/Altai/pigeon/777/2010 has antitumor properties. This may enable clinical trials to prove its effectiveness as an antitumor drug.

Mechanical and Corrosion Behaviour in Simulated Body Fluid of As-Fabricated 3D Porous L-PBF 316L Stainless Steel Structures for Biomedical Implants.

Laser powder bed fusion (L-PBF) is one of the most promising additive manufacturing technologies for creating customised 316L Stainless Steel (SS) implants with biomimetic characteristics, controlled porosity, and optimal structural and functional properties. However, the behaviour of as-fabricated 3D 316L SS structures without any surface finishing in environments that simulate body fluids remains largely unknown. To address this knowledge gap, the present study investigates the surface characteristics, the internal porosity, the corrosion in simulated body fluid (SBF), and the mechanical properties of as-fabricated 316L SS structures manufactured by L-PBF with rhombitruncated cuboctahedron (RTCO) unit cells with two distinct relative densities (10 and 35%). The microstructural analysis confirmed that the RTCO structure has a pure austenitic phase with a roughness of ~20 µm and a fine cellular morphology. The micro-CT revealed the presence of keyholes and a lack of fusion pores in both RTCO structures. Despite the difference in the internal porosity, the mechanical properties of both structures remain within the range of bone tissue and in line with the Gibson and Ashby model. Additionally, the as-fabricated RTCO structures demonstrated passive corrosion behaviour in the SBF solution. Thus, as-fabricated porous structures are promising biomaterials for implants due to their suitable surface roughness, mechanical properties, and corrosion resistance, facilitating bone tissue growth.

Lethal Complication of Postairway Stenting to Trachea and Left Main Bronchus: A Case Series with Discussion of the Diagnosis and Management

Abstract The insertion of a metallic airway stent is a valuable method for the treatment of benign and malignant airway stenosis and tracheoesophageal fistula. Although stenting for airway stenosis has become widely popular with favorable outcomes, several complications can arise after stenting, such as migration, tendency for stent fracture, and ingrowth of tumor or granulation tissue into the stent. Very few of these reports have described the complications of poststenting pneumothorax. We report the cases of three patients diagnosed with squamous cell carcinoma of the esophagus, complicated by tracheoesophageal fistula, and treated with a tracheal stent or bronchial stent, who developed poststenting pneumothorax.