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IntroductionDecellularized uterine extracellular matrix has emerged as a pivotal focus in the realm of biomaterials, offering a promising source in uterine tissue regeneration, research on disease diagnosis and treatments, and ultimately uterine transplantation. In this study, we examined various protocols for decellularizing porcine uterine tissues, aimed to unravel the intricate dynamics of DNA removal, bioactive molecules preservation, and microstructural alterations.MethodsPorcine uterine tissues were treated with 6 different, yet rigorously selected and designed, protocols with sodium dodecyl sulfate (SDS), Triton® X-100, peracetic acid + ethanol, and DNase I. After decellularization, we examined DNA quantification, histological staining (H&E and DAPI), glycosaminoglycans (GAG) assay, scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (FT-IR), X-ray photoelectron spectroscopy (XPS), and Thermogravimetric Analysis (TGA).ResultsA comparative analysis among all 6 protocols was conducted with the results demonstrating that all protocols achieved decellularization; while 0.1% SDS + 1% Triton® X-100, coupled with agitation, demonstrated the highest efficiency in DNA removal. Also, it was found that DNase I played a key role in enhancing the efficiency of the decellularization process by underscoring its significance in digesting cellular contents and eliminating cell debris by 99.79% (19.63 ± 3.92 ng/mg dry weight).ConclusionsOur findings enhance the nuanced understanding of DNA removal, GAG preservation, microstructural alteration, and protein decomposition in decellularized uterine extracellular matrix, while highlighting the importance of decellularization protocols designed for intended applications. This study along with our findings represents meaningful progress for advancing the field of uterine transplantation and related tissue engineering/regenerative medicine.

Cardiac tissue engineering has been rapidly evolving with diverse applications, ranging from the repair of fibrotic tissue caused by “adverse remodeling,” to the replacement of specific segments of heart tissue, and ultimately to the creation of a whole heart. The repair or replacement of cardiac tissue often involves the development of tissue scaffolds or constructs and the subsequent assessment of their performance and functionality. For this, the design and/or selection of biomaterials, and cell types, scaffold fabrication, and in vitro characterizations are the first starting points, yet critical, to ensure success in subsequent implantation in vivo. This highlights the importance of scaffold fabrication and in vitro experiments/characterization with protocols for cardiac tissue engineering. Yet, a comprehensive and critical review of these has not been established and documented. As inspired, herein, the latest development and advances in scaffold fabrication and in vitro characterization for cardiac tissue engineering are critically reviewed, with focus on biomaterials, cell types, additive manufacturing techniques for scaffold fabrication, and common in vitro characterization techniques or methods. This article would be of benefit to the ones who are working on cardiac tissue engineering by providing insights into the scaffold fabrication and in vitro investigations.

Abstract Scaffolds play a key role in bone tissue engineering (BTE) as they provide a mechanically and biologically supportive template to treat bone defects. Yet, the ideal scaffold structures are far from certain, leaving a lot to be discovered in terms of the scaffold structure–performance relationships. In this study, we investigated the influence of pore size and internal structure on osteoblast performance in vitro. Three‐dimensional (3D) scaffolds were printed from polycaprolactone (PCL) reinforced with 30% (wt.) nano‐hydroxyapatite (nHAp), with two different internal structures (lattice and staggered) and four pore sizes (0.280, 0.380, 0.420, and 0.550 mm). Scaffolds were seeded with pre‐osteoblast cells (MC3T3‐E1). Metabolic activity of cells, osteoblast differentiation, and capability of osteoblasts to deposit mineralized matrix were examined in vitro. Staggered scaffolds better supported cellular performance. The pore size of 0.280 mm was more favorable to support cell proliferation while the pore size ≥0.420 mm was more effective to promote osteoblast differentiation and mineralization. Findings revealed that osteoblast activities were affected differently by the pore size. Our study further suggests that the structure with a gradient pore size would be better than a single size in terms of supporting cell proliferation, differentiation, and secretion of a mineralized matrix.

Abstract Background Bone tissue engineering, based on three-dimensional (3D) printing technology, has emerged as a promising approach to treat bone defects using scaffolds. The objective of this study was to investigate the influence of porosity and internal structure on the mechanical properties of scaffolds. Methods We fabricated composite scaffolds (which aimed to replicate trabecular bone) from polycaprolactone (PCL) reinforced with 30% (wt.) nano-hydroxyapatite (nHAp) by extrusion printing. Scaffolds with various porosities were designed and fabricated with and without an interlayer offset, termed as staggered and lattice structure, respectively. Mechanical compressive testing was performed to determine scaffold elastic modulus and yield strength. Linear regression was used to evaluate mechanical properties as a function of scaffold porosity. Results Different relationships between mechanical properties and porosities were noted for the staggered and lattice structures. For elastic moduli, the two relationships intersected (porosity = 55%) such that the lattice structure exhibited higher moduli with porosity values greater than the intersection point; vice versa for the staggered structure. The lattice structure exhibited higher yield strength at all porosities. Mechanical testing results also indicated elastic moduli and yield strength properties comparable to trabecular bone (elastic moduli: 14–165 MPa; yield strength: 0.9–10 MPa). Conclusions Taken together, this study demonstrates that scaffolds printed from PCL/30% (wt.) nHAp with lattice and staggered structure offer promise for treating trabecular bone defects. This study identified the effect of porosity and internal structure on scaffold mechanical properties and provided suggestions for developing scaffolds with mechanical properties for substituting trabecular bone.

Background: Heart failure (HF) is a complex and multifactorial syndrome caused by impaired heart function. The high morbidity and mortality of HF cause a heavy burden of illness worldwide. Non-thyroidal illness syndrome (NTIS) refers to aberrant serum thyroid parameters in patients without past thyroid disease. Observational studies have indicated that NTIS is associated with a higher risk of all-cause mortality in HF. This meta-analysis aimed to investigate the association between NTIS and HF prognosis. Methods: Medline, Embase, Web of Science, and the Cochrane database were searched for any studies reporting an association between NTIS and HF prognosis from inception to 1 July 2022. A meta-analysis was then performed. The quality of studies was assessed using the Newcastle–Ottawa Scale. The heterogeneity of the results was assessed with I2 and Cochran's Q statistics. Sensitivity analysis and publication bias analysis were also conducted. Results: A total of 626 studies were retrieved, and 18 studies were fina lly included in the meta-analysis. The results showed that NTIS in HF patients was significantly associated with an increased risk of all-cause mortality and major cardiovascular events (MACE), but not with in-hospital mortality. The stability of the data was validated by the sensitivity analysis. There was no indication of a publication bias in the pooled results for all-cause mortality and MACE. Conclusions: This meta-analysis showed that NTIS was associated with a worse outcome in HF patients. However, the association between NTIS and in-hospital mortality of HF patients requires further investigation.

Magnesium (Mg)-based materials are a new generation of alloys with the exclusive ability to be biodegradable within the human/animal body. In addition to biodegradability, their inherent biocompatibility and similar-to-bone density make Mg-based alloys good candidates for fabricating surgical bioimplants for use in orthopedic and traumatology treatments. To this end, nowadays additive manufacturing (AM) along with three-dimensional (3D) printing represents a promising manufacturing technique as it allows for the integration of bioimplant design and manufacturing processes specific to given applications. Meanwhile, this technique also faces many new challenges associated with the properties of Mg-based alloys, including high chemical reactivity, potential for combustion, and low vaporization temperature. In this review article, various AM processes to fabricate biomedical implants from Mg-based alloys, along with their metallic microstructure, mechanical properties, biodegradability, biocompatibility, and antibacterial properties, as well as various post-AM treatments were critically reviewed. Also, the challenges and issues involved in AM processes from the perspectives of bioimplant design, properties, and applications were identified; the possibilities and potential scope of the Mg-based scaffolds/implants are discussed and highlighted.

Visualization of low-density tissue scaffolds made from hydrogels is important yet challenging in tissue engineering and regenerative medicine (TERM). For this, synchrotron radiation propagation-based imaging computed tomography (SR-PBI-CT) has great potential, but is limited due to the ring artifacts commonly observed in SR-PBI-CT images. To address this issue, this study focuses on the integration of SR-PBI-CT and helical acquisition mode (i.e. SR-PBI-HCT) to visualize hydrogel scaffolds. The influence of key imaging parameters on the image quality of hydrogel scaffolds was investigated, including the helical pitch (p), photon energy (E) and the number of acquisition projections per rotation/revolution (Np), and, on this basis, those parameters were optimized to improve image quality and to reduce noise level and artifacts. The results illustrate that SR-PBI-HCT imaging shows impressive advantages in avoiding ring artifacts with p = 1.5, E = 30 keV and Np = 500 for the visualization of hydrogel scaffolds in vitro. Furthermore, the results also demonstrate that hydrogel scaffolds can be visualized using SR-PBI-HCT with good contrast while at a low radiation dose, i.e. 342 mGy (voxel size of 26 µm, suitable for in vivo imaging). This paper presents a systematic study on hydrogel scaffold imaging using SR-PBI-HCT and the results reveal that SR-PBI-HCT is a powerful tool for visualizing and characterizing low-density scaffolds with a high image quality in vitro. This work represents a significant advance toward the non-invasive in vivo visualization and characterization of hydrogel scaffolds at a suitable radiation dose.

BackgroundObservational studies have reported the association between fatigue and coronary artery disease (CAD), but the causal association between fatigue and CAD is unclear.MethodWe conducted a bidirectional Mendelian randomization (MR) study using publicly available genome-wide association studies (GWAS) data. The inverse-variance weighted (IVW) method was used as the primary analysis. We performed three complementary methods, including weighted median, MR-Egger regression, and MR pleiotropy residual sum and outlier (MR-PRESSO) to evaluate the sensitivity and horizontal pleiotropy of the results.ResultSelf-reported fatigue had a causal effect on coronary artery atherosclerosis (CAA) (OR 1.047, 95%CI 1.033–1.062), myocardial infarction (MI) (OR 1.027 95%CI 1.014–1.039) and coronary heart disease (CHD) (OR 1.037, 95%CI 1.021–1.053). We did not find a significant reverse causality between self-reported fatigue and CAD. Given the heterogeneity revealed by MR-Egger regression, we employed the IVW random effect model. For the examination of fatigue on CHD and the reverse analysis of CAA, and MI on fatigue, the MR-PRESSO test found horizontal pleiotropy. No significant outliers were found.ConclusionThe MR analysis reveals a causal relationship between self-reported fatigue and CAD. The results should be interpreted with caution due to horizontal pleiotropy.

BackgroundSjögren’s syndrome (SS) is a chronic autoimmune disease characterized by exocrine and extra-glandular symptoms. The literature indicates that SS is an independent risk factor for atherosclerosis (AS); however, its pathophysiological mechanism remains undetermined. This investigation aimed to elucidate the crosstalk genes and pathways influencing the pathophysiology of SS and AS via bioinformatic analysis of microarray data.MethodsMicroarray datasets of SS (GSE40611) and AS (GSE28829) were retrieved from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were acquired using R software’s “limma” packages, and the functions of common DEGs were determined using Gene Ontology and Kyoto Encyclopedia analyses. The protein–protein interaction (PPI) was established using the STRING database. The hub genes were assessed via cytoHubba plug-in and validated by external validation datasets (GSE84844 for SS; GSE43292 for AS). Gene set enrichment analysis (GSEA) and immune infiltration of hub genes were also conducted.ResultsEight 8 hub genes were identified using the intersection of four topological algorithms in the PPI network. Four genes (CTSS, IRF8, CYBB, and PTPRC) were then verified as important cross-talk genes between AS and SS with an area under the curve (AUC) ≥0.7. Furthermore, the immune infiltration analysis revealed that lymphocytes and macrophages are essentially linked with the pathogenesis of AS and SS. Moreover, the shared genes were enriched in multiple metabolisms and autoimmune disease-related pathways, as evidenced by GSEA analyses.ConclusionThis is the first study to explore the common mechanism between SS and AS. Four key genes, including CTSS, CYBB, IRF8, and PTPRC, were associated with the pathogenesis of SS and AS. These hub genes and their correlation with immune cells could be a potential diagnostic and therapeutic target.

BackgroundAlthough observational studies have shown that patients who experienced transient ischemic attacks (TIAs) had a higher risk of coronary artery disease (CAD), the causal relationship is ambiguous.MethodsWe conducted a two-sample Mendelian randomization (MR) study to analyze the causal relationship between TIA and CAD using data from the FinnGen genome-wide association study. Analysis was performed using the inverse-variance weighted (IVW) method. The robustness of the results was evaluated using MR-Egger regression, the weighted median, MR pleiotropy residual sum, and outlier (MR-PRESSO) and multivariable MR analysis.ResultsResults from IVW random-effect model showed that TIA was associated with an increased risk of coronary artery atherosclerosis (OR 1.17, 95% CI 1.06–1.28, P = 0.002), ischemic heart disease (OR 1.15, 95% CI 1.04–1.27, P = 0.007), and myocardial infarction (OR1.15, 95% CI 1.02–1.29, P = 0.025). In addition, heterogeneity and horizontal pleiotropy were observed in the ischemic heart disease results, while the sensitivity analysis revealed no evidence of horizontal pleiotropy in other outcomes.ConclusionsThis MR study demonstrated a potential causal relationship between TIA and CAD. Further research should be conducted to investigate the mechanism underlying the association.

Synthesis of bioinks for bioprinting of respiratory tissue requires considerations related to immunogenicity, mechanical properties, printability, and cellular compatibility. Biomaterials can be tailored to provide the appropriate combination of these properties through the synergy of materials with individual pros and cons. Sodium alginate, a water-soluble polymer derived from seaweed, is a cheap yet printable biomaterial with good structural properties; however, it lacks physiological relevance and cell binding sites. Collagen, a common component in the extra cellular matrix of many tissues, is expensive and lacks printability; however, it is highly biocompatible and exhibits sites for cellular binding. This paper presents our study on the synthesis of bioinks from alginate and collagen for use in bioprinting respiratory tissue models. Bioinks were synthesized from 40 mg/mL (4%) alginate and 3 mg/mL (0.3%) collagen in varying ratios (1:0, 4:1, 3:1, 2:1, and 1:1); then examined in terms of rheological properties, printability, compressive, and tensile properties and cellular compatibility. The results illustrate that the ratio of alginate to collagen has a profound impact on bioink performance and that, among the examined ratios, the 3:1 ratio is the most appropriate for use in bioprinting respiratory tissue scaffolds.

Abstract Background Krüppel-like factor 7 (klf7), a transcription factor in the nervous system to regulate cell proliferation and differentiation, has been recently identified as a causal gene for autism spectrum disorder (ASD), but the mechanism behind remains unknown. Result To uncover this mechanism, in this study we characterized the involvement of klf7 in circadian rhythm by knocking down klf7 in N2A cells and examining the rhythmic expression of circadian genes, especially Clock gene. We constructed klf7−/− mice and then investigated into klf7 regulation on the expression of rhythm genes in vivo as well as the use of melatonin to rescue the autism behavior. Our results illustrated that circadian rhythm was disrupted in klf7 knockdown cells and that klf7−/− mice showed autism-like behavior. Also, we found that Clock gene was downregulated in the brain of these klf7−/− mice and that the downstream rhythm genes of Clock were disturbed. Melatonin, as a circadian regulation drug, could regulate the expression level and amplitude of rhythm genes in klf7 knockout cells and further rescue the autistic behavior of klf7−/− mice. Conclusion Klf7 deficiency causes ASD by disrupting circadian rhythm related genes to trigger rhythm oscillations. To treat ASD, maintaining circadian homeostasis is promising with the use of melatonin.

Tissue engineering aims to produce tissue/organ substitutes to improve upon current treatment approaches, thus providing a permanent solution to damaged tissues/organs. This project aimed to perform a market analysis for understanding and promoting the development and commercialization of tissue engineering in Canada. We searched companies that were established between October 2011 and July 2020 via publicly available information and for these companies, we collected and analyzed the corporate level information, including revenues, and number of employees and founder information. The companies assessed were mainly searched from four different industry segments, i.e., bioprinting, biomaterials, cells and biomaterials, and stem-cells related industry. Our results have demonstrated that there are twenty-five tissue-engineering companies registered in Canada. These companies generated an estimated revenue of USD $67 million in the year 2020, most generated by the tissue engineering and stem-cells related industries. Our results also show that Ontario has the largest number of headquarters of tissue engineering companies among the provinces or territories of Canada. It is expected that the number of new products undergoing clinical trials is increased, based on our results of current clinical trials. Altogether, tissue engineering in Canada has shown a huge growth in the past decade and is forecasted to be an emerging industry in Canada for the years to come.

Background: Engineering cardiac tissue that mimics the hierarchical structure of cardiac tissue remains challenging, raising the need for developing novel methods capable of creating structures with high complexity. Three-dimensional (3D)-printing techniques are among promising methods for engineering complex tissue constructs with high precision. By means of 3D printing, this study aims to develop cardiac constructs with a novel angular structure mimicking cardiac architecture from alginate (Alg) and gelatin (Gel) composite. The 3D-printing conditions were optimized and the structures were characterized in vitro, with human umbilical vein endothelial cells (HUVECs) and cardiomyocytes (H9c2 cells), for potential cardiac tissue engineering.Methods: We synthesized the composites of Alg and Gel with varying concentrations and examined their cytotoxicity with both H9c2 cells and HUVECs, as well as their printability for creating 3D structures of varying fibre orientations (angular design). The 3D-printed structures were characterized in terms of morphology by both scanning electron microscopy (SEM) and synchrotron radiation propagation-based imaging computed tomography (SR-PBI-CT), and elastic modulus, swelling percentage, and mass loss percentage as well. The cell viability studies were conducted via measuring the metabolic activity of the live cells with MTT assay and visualizing the cells with live/dead assay kit.Results: Among the examined composite groups of Alg and Gel, two combinations with ratios of 2 to 1 and 3 to 1 (termed as Alg2Gel1 and Alg3Gel1) showed the highest cell survival; they accordingly were used to fabricate two different structures: a novel angular and a conventional lattice structure. Scaffolds made of Alg3Gel1 showed higher elastic modulus, lower swelling percentage, less mass loss, and higher cell survival compared to that of Alg2Gel1. Although the viability of H9c2 cells and HUVECs on all scaffolds composed of Alg3Gel1 was above 99%, the group of the constructs with the angular design maintained significantly more viable cells compared to other investigated groups.Conclusion: The group of angular 3D-ptinted constructs has illustrated promising properties for cardiac tissue engineering by providing high cell viability for both endothelial and cardiac cells, high mechanical strength as well as appropriate swelling, and degradation properties during 21 days of incubation.Statement of Significance: 3D-printing is an emerging method to create complex constructs with high precision in a large scale. In this study, we have demonstrated that 3D-printing can be used to create compatible constructs from the composite of Alg and Gel with endothelial cells and cardiac cells. Also, we have demonstrated that these constructs are able to enhance the viability of cardiac and endothelial cells via creating a 3D structure mimicking the alignment and orientation of the fibers in the native heart.

Abstract Prevention and early intervention are the current focus of treatment for Alzheimer's disease (AD). An increase in reactive oxygen species (ROS) is a feature of the early stages of AD, thus suggesting that the removal of excess ROS can be a viable method of improving AD. Natural polyphenols are able to scavenge ROS and thus promising for treating AD. However, some issues need to be addressed. Among them, important are that most polyphenols are hydrophobic, have low bioavailability in the body, are easily degraded, and that single polyphenols have insufficient antioxidant capacity. In this study, we employed two polyphenols, resveratrol (RES) and oligomeric proanthocyanidin (OPC), and creatively grafted them with hyaluronic acid (HA) to form nanoparticles to address the aforementioned issues. Meanwhile, we strategically grafted the nanoparticles with the B6 peptide, enabling the nanoparticles to cross the blood–brain barrier (BBB) and enter the brain for AD treatment. Our results illustrate that B6‐RES‐OPC‐HA nanoparticles can significantly scavenge ROS, reduce brain inflammation, and improve learning and memory ability in AD mice. B6‐RES‐OPC‐HA nanoparticles have the potential to prevent and alleviate early AD.

The use of nanoparticle systems for the controlled release of growth factors is a promising approach to mimicking of the biochemical environment of native tissues in tissue engineering. However, sustaining growth factor release inside an appropriate therapeutic window is a challenge, particularly in bioprinted scaffolds. In this study, a chitosan-coated alginate-based nanoparticle system loaded with hepatocyte growth factor was developed and then incorporated into bioprinted scaffolds. The release kinetics were investigated with a focus on identifying the impact of the chitosan coating and culture conditions. Our results demonstrated that the chitosan coating decreased the release rate and lessened the initial burst release, while culturing in dynamic conditions had no significant impact compared to static conditions. The nanoparticles were then incorporated into bioinks at various concentrations, and scaffolds with a three-dimensional (3D) structure were bioprinted from the bioinks containing human pulmonary fibroblasts and bronchial epithelial cells to investigate the potential use of a controlled release system in respiratory tissue engineering. It was found that the bioink loaded with a concentration of 4 µg/mL of nanoparticles had better printability compared to other concentrations, while the mechanical stability of the scaffolds was maintained over a 14-day culture period. The examination of the incorporated cells demonstrated a high degree of viability and proliferation with visualization of the beginning of an epithelial barrier layer. Taken together, this study demonstrates that a chitosan-coated alginate-based nanoparticle system allows the sustained release of growth factors in bioprinted respiratory tissue scaffolds.

Abstract Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is a member of the coronavirus family that causes the novel coronavirus disease first diagnosed in 2019 (COVID‐19). Although many studies have been carried out in recent months to determine why the disease clinical presentations and outcomes can vary significantly from asymptomatic to severe or lethal, the underlying mechanisms are not fully understood. It is likely that unique individual characteristics can strongly influence the broad disease variability; thus, tailored diagnostic and therapeutic approaches are needed to improve clinical outcomes. The circadian clock is a critical regulatory mechanism orchestrating major physiological and pathological processes. It is generally accepted that more than half of the cell‐specific genes in any given organ are under circadian control. Although it is known that a specific role of the circadian clock is to coordinate the immune system's steady‐state function and response to infectious threats, the links between the circadian clock and SARS‐CoV‐2 infection are only now emerging. How inter‐individual variability of the circadian profile and its dysregulation may play a role in the differences noted in the COVID‐19‐related disease presentations, and outcome remains largely underinvestigated. This review summarizes the current evidence on the potential links between circadian clock dysregulation and SARS‐CoV‐2 infection susceptibility, disease presentation and progression, and clinical outcomes. Further research in this area may contribute towards novel circadian‐centred prognostic, diagnostic and therapeutic approaches for COVID‐19 in the era of precision health.

Three-dimensional (3D) extrusion-based bioprinting is widely used in tissue engineering and regenerative medicine to create cell-incorporated constructs or scaffolds based on the extrusion technique. One critical issue in 3D extrusion-based bioprinting is printability or the capability to form and maintain reproducible 3D scaffolds from bioink (a mixture of biomaterials and cells). Research shows that printability can be affected by many factors or parameters, including those associated with the bioink, printing process, and scaffold design, but these are far from certain. This review highlights recent developments in the printability assessment of extrusion-based bioprinting with a focus on the definition of printability, printability measurements and characterization, and printability-affecting factors. Key issues and challenges related to printability are also identified and discussed, along with approaches or strategies for improving printability in extrusion-based bioprinting.

Hydrogels show promise in cartilage tissue engineering (CTE) by supporting chondrocytes and maintaining their phenotype and extracellular matrix (ECM) production. Under prolonged mechanical forces, however, hydrogels can be structurally unstable, leading to cell and ECM loss. Furthermore, long periods of mechanical loading might alter the production of cartilage ECM molecules, including glycosaminoglycans (GAGs) and collagen type 2 (Col2), specifically with the negative effect of stimulating fibrocartilage, typified by collagen type 1 (Col1) secretion. Reinforcing hydrogels with 3D-printed Polycaprolactone (PCL) structures offer a solution to enhance the structural integrity and mechanical response of impregnated chondrocytes. This study aimed to assess the impact of compression duration and PCL reinforcement on the performance of chondrocytes impregnated with hydrogel. Results showed that shorter loading periods did not significantly affect cell numbers and ECM production in 3D-bioprinted hydrogels, but longer periods tended to reduce cell numbers and ECM compared to unloaded conditions. PCL reinforcement enhanced cell numbers under mechanical compression compared to unreinforced hydrogels. However, the reinforced constructs seemed to produce more fibrocartilage-like, Col1-positive ECM. These findings suggest that reinforced hydrogel constructs hold potential for in vivo cartilage regeneration and defect treatment by retaining higher cell numbers and ECM content. To further enhance hyaline cartilage ECM formation, future studies should focus on adjusting the mechanical properties of reinforced constructs and exploring mechanotransduction pathways.

Abstract Background It is known that a number of parameters can influence the post-printing properties of bone tissue scaffolds. Previous research has primarily focused on the effect of parameters associated with scaffold design (e.g., scaffold porosity) and specific scaffold printing processes (e.g., printing pressure). To our knowledge, no studies have investigated variations in post-printing properties attributed to the techniques used to synthesize the materials for printing (e.g., melt-blending, powder blending, liquid solvent, and solid solvent). Methods Four material preparation techniques were investigated to determine their influence on scaffold properties. Polycaprolactone/nano-hydroxyapatite 30% (wt.) materials were synthesized through melt-blending, powder blending, liquid solvent, and solid solvent techniques. The material printability and the properties of printed scaffolds, in terms of swelling/degradation, mechanical strength, morphology, and thermal properties, were examined and compared to one another using Kruskal-Wallis nonparametric statistical analysis. Results Material prepared through the liquid solvent technique was found to have limited printability, while melt-blended material demonstrated the highest degree of uniformity and lowest extent of swelling and degradation. Scaffolds prepared with powder-blended material demonstrated the highest Young’s modulus, yield strength, and modulus of resilience; however, they also demonstrated the highest degree of variability. The higher degree of inhomogeneity in the material was further supported by thermal gravimetric analysis. While scaffolds printed from melt-blended, powder-blended, and solid solvent materials demonstrated a high degree of micro-porosity, the liquid solvent material preparation technique resulted in minimal micro-porosity. Conclusions Study results indicate that specific techniques used to prepare materials influence the printing process and post-printing scaffold properties. Among the four techniques examined, melt-blended materials were found to be the most favorable, specifically when considering the combination of printability, consistent mechanical properties, and efficient preparation. Techniques determined to be favourable based on the properties investigated should undergo further studies related to biological properties and time-dependent properties beyond 21-days.

BackgroundThe 5-year outcomes and predictors of atrial fibrillation (AF) recurrence following cryoballoon (CB) ablation in Chinese population remain scarce. Our aim was to report 5-year outcomes and predictors of AF recurrence following a single CB ablation procedure in a Chinese population.MethodsFrom December 2013 to August 2016, we included 256 consecutive patients (mean age: 58 ± 10.9 years old; female: 41.0%) with paroxysmal or persistent AF successfully underwent first-generation CB ablation at Fuwai hospital in this prospective study. All patients were followed at least 5 years or when there was recurrent AF. Independent predictors of AF recurrence were determined by Cox proportional hazards regression analysis.ResultsThe 5-year success rate after pulmonary vein isolation (PVI) by a single procedure was 59.4%. The recurrence rate was the highest (14.5%) within the first year after the index procedure, and then stabilized. Patients with paroxysmal AF had a higher incidence of freedom from AF recurrence than patients with persistent AF (63.2% vs. 36.4%, log-rank P < 0.01). The overall incidence of complications related to CB ablation was 7.8%. Phrenic nerve injury (PNI) was the most common complication, with an incidence of 3.5%, and patients with PNI were recovered within the 1-year follow-up. Only persistent AF (HR 1.72, 95%CI 1.028–2.854, P < 0.05) was significantly and independently associated with an increased risk of AF recurrence after adjusting for other factors.ConclusionPulmonary vein isolation using CB ablation was safe and effective with an acceptable complication and 5-year success rate in a Chinese population with AF, and persistent AF was the independent predictor for 5-year AF recurrence after a single CB ablation procedure.

Treating large bone defects, known as critical-sized defects (CSDs), is challenging because they are not spontaneously healed by the patient’s body. Due to the limitations associated with conventional bone grafts, bone tissue engineering (BTE), based on three-dimensional (3D) bioprinted scaffolds, has emerged as a promising approach for bone reconstitution and treatment. Bioprinting technology allows for incorporation of living cells and/or growth factors into scaffolds aiming to mimic the structure and properties of the native bone. To date, a wide range of biomaterials (either natural or synthetic polymers), as well as various cells and growth factors, have been explored for use in scaffold bioprinting. However, a key challenge that remains is the fabrication of scaffolds that meet structure, mechanical, and osteoconductive requirements of native bone and support vascularization. In this review, we briefly present the latest developments and discoveries of CSD treatment by means of bioprinted scaffolds, with a focus on the biomaterials, cells, and growth factors for formulating bioinks and their bioprinting techniques. Promising state-of-the-art pathways or strategies recently developed for bioprinting bone scaffolds are highlighted, including the incorporation of bioactive ceramics to create composite scaffolds, the use of advanced bioprinting technologies (e.g., core/shell bioprinting) to form hybrid scaffolds or systems, as well as the rigorous design of scaffolds by taking into account of the influence of such parameters as scaffold pore geometry and porosity. We also review in-vitro assays and in-vivo models to track bone regeneration, followed by a discussion of current limitations associated with 3D bioprinting technologies for BTE. We conclude this review with emerging approaches in this field, including the development of gradient scaffolds, four-dimensional (4D) printing technology via smart materials, organoids, and cell aggregates/spheroids along with future avenues for related BTE.

Scar formation can lead to glaucoma filtration surgery (GFS) failure, wherein transforming growth factor (TGF)-β is the core regulator. To reducing scar formation, this paper presents our study on the design of hydrogels to deactivate TGF-β1. We hypothesized that excess TGF-β1 can be removed from aqueous humor through the addition of oxidized hyaluronic acid (O-HA) hydrogels that are seeded with decorin (O-HA ​+ ​D). Immunohistochemistry and enzyme-linked immunosorbent assay (ELISA) were performed to demonstrate the adsorption properties of O-HA ​+ ​D hydrogel, thus reducing the TGF-β1 concentration in aqueous humor. In the light that collagen contraction in human Tenon's capsule fibroblasts (HTFs) and the angiogenesis of human umbilical vein endothelial cells (HUVECs) can be activated by TGF-β1 and β2, we performed the quantitative analysis of polymerase chain reaction to determine the effect of O-HA ​+ ​D on the type I collagen, fibronectin, and angiogenesis. Our results illustrate that O-HA ​+ ​D can inhibit the increase of α-SMA expression in HTF induced by TGF-β1 and that O-HA ​+ ​D can inhibit the production of collagen I and fibronectin in HTF treated with TGF-β1. Furthermore, we performed in vivo studies by employing a rabbit model, where rabbits were treated with hydrogels post GFS. Our results demonstrate that, as compared with other groups, the rabbits treated with O-HA ​+ ​D had the greatest reduction in inflammatory cells with reduced level of collagen in wounds. Taken together, the present study paves the way toward the treatment of post-glaucoma fibrosis following surgery.

Chondrocytes that are impregnated within hydrogel constructs sense applied mechanical force and can respond by expressing collagens, which are deposited into the extracellular matrix (ECM). The intention of most cartilage tissue engineering is to form hyaline cartilage, but if mechanical stimulation pushes the ratio of collagen type I (Col1) to collagen type II (Col2) in the ECM too high, then fibrocartilage can form instead. With a focus on Col1 and Col2 expression, the first part of this article reviews the latest studies on hyaline cartilage regeneration within hydrogel constructs that are subjected to compression forces (one of the major types of the forces within joints) in vitro. Since the mechanical loading conditions involving compression and other forces in joints are difficult to reproduce in vitro, implantation of hydrogel constructs in vivo is also reviewed, again with a focus on Col1 and Col2 production within the newly formed cartilage. Furthermore, mechanotransduction pathways that may be related to the expression of Col1 and Col2 within chondrocytes are reviewed and examined. Also, two recently-emerged, novel approaches of load-shielding and synchrotron radiation (SR)–based imaging techniques are discussed and highlighted for future applications to the regeneration of hyaline cartilage. Going forward, all cartilage tissue engineering experiments should assess thoroughly whether fibrocartilage or hyaline cartilage is formed.

The multidisciplinary fields of tissue engineering and regenerative medicine have the potential to revolutionize the practise of medicine through the abilities to repair, regenerate, or replace tissues and organs with functional engineered constructs. To this end, tissue engineering combines scaffolding materials with cells and biologically active molecules into constructs with the appropriate structures and properties for tissue/organ regeneration, where scaffolding materials and biomolecules are the keys to mimic the native extracellular matrix (ECM). For this, one emerging way is to decellularize the native ECM into the materials suitable for, directly or in combination with other materials, creating functional constructs. Over the past decade, decellularized ECM (or dECM) has greatly facilitated the advance of tissue engineering and regenerative medicine, while being challenged in many ways. This article reviews the recent development of dECM for tissue engineering and regenerative medicine, with a focus on the preparation of dECM along with its influence on cell culture, the modification of dECM for use as a scaffolding material, and the novel techniques and emerging trends in processing dECM into functional constructs. We highlight the success of dECM and constructs in the in vitro, in vivo, and clinical applications and further identify the key issues and challenges involved, along with a discussion of future research directions.

To heighten the diagnostic efficiency, in this study, the algebraic reconstruction technology (ART)-based echocardiography (ECG) was used to analyze severe fever with thrombocytopenia syndrome bunyavirus (SFTSV) complicated by atrial fibrillation. From Jan. 2015 to Dec. 2019, 200 elderly patients with SFTSV infection and hypertrophic cardiomyopathy (HCM) admitted to our hospital were selected as the observation group, and 20 healthy volunteers were in the control group. Then 200 patients were randomly divided into two groups with 100 people in each group. One group received routine clinical observation after surgery, and the other group received artificial intelligence atrial fibrillation monitoring. ECG displayed the left ventricular ejection fraction (LVEF), left ventricular mass index (LVMI), left ventricular end diastolic volume index (EDVI), and end systolic volume index (ESVI) of patients. The accuracy and satisfaction of different methods in observation were recorded. The risk factors of postoperative atrial fibrillation in elderly patients with HCM were evaluated, and changes in their white blood cell levels were detected. The results showed that, there was a significant difference in ECG between normal people and patients after surgery. Also, differences were noted in accuracy and satisfaction of the two methods in observation group (P

Injectable hydrogels, as carriers, offer great potential to incorporate cells or growth factors for dental tissue regeneration. Notably, the development of injectable hydrogels with appropriate structures and properties has been a challenging task, leaving much to be desired in terms of cytocompatibility, antibacterial and self-healing properties, as well as the ability to support dental stem cell functions. This paper presents our study on the development of a novel self-cross-linkable hydrogel composed of oxidized alginate and carboxymethyl chitosan and its characterization as a cell carrier for dental enamel regeneration in vitro. Oxidized alginate was synthesized with 60% theoretical oxidation degree using periodate oxidation and characterized by Fourier Transform Infrared spectroscopy, proton nuclear magnetic resonance spectroscopy, and Ultraviolet-visible absorption spectroscopy. Then, hydrogels were prepared at three varying weight ratios of oxidized alginate to carboxymethyl chitosan (4:1, 3:1, and 2:1) through Schiff base reactions, which was confirmed by Fourier Transform Infrared spectroscopy. The hydrogels were characterized in terms of gelation time, swelling ratio, structure, injectability, self-healing, antibacterial properties, and in vitro characterization for enamel regeneration. The results demonstrated that, among the three hydrogels examined, the one with the highest ratio of oxidized alginate (i.e., 4:1) had the fastest gelation time and the lowest swelling ability, and that all hydrogels were formed with highly porous structures and were able to be injected through a 20-gauge needle without clogging. The injected hydrogels could be rapidly reformed with the self-healing property. The hydrogels also showed antibacterial properties against two cariogenic bacteria: Streptococcus mutans and Streptococcus sobrinus. For in vitro enamel regeneration, a dental epithelial cell line, HAT-7, was examined, demonstrating a high cell viability in the hydrogels during injection. Furthermore, HAT-7 cells encapsulated in the hydrogels showed alkaline phosphatase production and mineral deposition, as well as maintaining their round morphology, after 14 days of in vitro culture. Taken together, this study has provided evidence that the oxidized alginate-carboxymethyl chitosan hydrogels could be used as an injectable cell carrier for dental enamel tissue engineering applications.

Extrusion bioprinting is an emerging technology to apply biomaterials precisely with living cells (referred to as bioink) layer by layer to create three-dimensional (3D) functional constructs for tissue engineering. Printability and cell viability are two critical issues in the extrusion bioprinting process; printability refers to the capacity to form and maintain reproducible 3D structure and cell viability characterizes the amount or percentage of survival cells during printing. Research reveals that both printability and cell viability can be affected by various parameters associated with the construct design, bioinks, and bioprinting process. This paper briefly reviews the literature with the aim to identify the affecting parameters and highlight the methods or strategies for rigorously determining or optimizing them for improved printability and cell viability. This paper presents the review and discussion mainly from experimental, computational, and machine learning (ML) views, given their promising in this field. It is envisioned that ML will be a powerful tool to advance bioprinting for tissue engineering.

Rapid progress in tissue engineering research in past decades has opened up vast possibilities to tackle the challenges of generating tissues or organs that mimic native structures. The success of tissue engineered constructs largely depends on the incorporation of a stable vascular network that eventually anastomoses with the host vasculature to support the various biological functions of embedded cells. In recent years, significant progress has been achieved with respect to extrusion, laser, micro-molding, and electrospinning-based techniques that allow the fabrication of any geometry in a layer-by-layer fashion. Moreover, decellularized matrix, self-assembled structures, and cell sheets have been explored to replace the biopolymers needed for scaffold fabrication. While the techniques have evolved to create specific tissues or organs with outstanding geometric precision, formation of interconnected, functional, and perfused vascular networks remains a challenge. This article briefly reviews recent progress in 3D fabrication approaches used to fabricate vascular networks with incorporated cells, angiogenic factors, proteins, and/or peptides. The influence of the fabricated network on blood vessel formation, and the various features, merits, and shortcomings of the various fabrication techniques are discussed and summarized. Keywords: 3D bioprinting, Tissue engineering, Vascularization, Extrusion, Laser-based printing, Co-axial printing

Virtual reality (VR) has the potential to be a powerful tool for the visualization of simulated blood flow in cerebral aneurysms. This paper presents our study aimed at developing the VR visualization of computational fluid dynamics (CFD) simulations of cerebral aneurysms treated with flow-diverting (FD) stents. First, a spherical sidewall aneurysm located at a simplified internal carotid artery was considered for investigating the impact of stent deployment and positioning on the corresponding spatially time-varying blood flow behavior. The three-dimensional unsteady blood flow over a cardiac cycle was simulated numerically using the finite volume method, and the distributions of hemodynamic parameters inside the aneurysm sac, and on its wall, were presented with and without stent cases. Two stent positions, with and without a gap between the artery wall and stent, were considered to show the influence of correct stent position on aneurysm treatment. Second, a straightforward workflow was developed to import, process, and visualize the CFD analysis data in a VR environment by using open-source software with a high resolution. The Unity3D engine was used for displaying the processed animations in a VR environment operated on a head-mounted display (HMD). The refining process of each frame of time-varying CFD data was automated. The animated flow elements rendered in the VR environment were velocity vectors, velocity contours, streamlines, particle traces, and point clouds. CFD results showed that proper stenting facilitates thrombosis and occlusion of the aneurysm by modification of the flow patterns, which leads to lower inflow jet velocities into the aneurysm, longer turnover time, lower aneurysm-averaged kinetic energy, and lower wall shear stress. Additionally, the results indicated that a gap between the stent and the parent artery may lead to undesirable hemodynamic alterations. The VR visualization illustrated that the recognition of the potential in danger regions of aneurysms and the evaluation of the performance of FD stents in aneurysm treatment can be conducted without the need for several slices through the parent artery and aneurysm, as is required for traditional postprocessing methods. Through VR visualization, the details of the simulation results become readily available by navigating in the 3D animated flow elements using a high-degree-of-freedom headset.

Three-dimensional (3D) bioprinting is an emerging fabrication technique to create 3D constructs with living cells. Notably, bioprinting bioinks are limited due to the mechanical weakness of natural biomaterials and the low bioactivity of synthetic peers. This paper presents the development of a natural bioink from chicken eggwhite and sodium alginate for bioprinting cell-laden patches to be used in endothelialized tissue engineering applications. Eggwhite was utilized for enhanced biological properties, while sodium alginate was used to improve bioink printability. The rheological properties of bioinks with varying amounts of sodium alginate were examined with the results illustrating that 2.0–3.0% (w/v) sodium alginate was suitable for printing patch constructs. The printed patches were then characterized mechanically and biologically, and the results showed that the printed patches exhibited elastic moduli close to that of natural heart tissue (20–27 kPa) and more than 94% of the vascular endothelial cells survived in the examination period of one week post 3D bioprinting. Our research also illustrated the printed patches appropriate water uptake ability (>1800%).

This article presents the data of using three phase-based X-ray imaging techniques to characterize biomaterial scaffold and soft tissues in situ, as reported in our study “Low-dose phase-based X-ray imaging techniques for in situ soft tissue engineering assessments” [1]. The examined parameters include the radiation dose, scan time, and image quality, which are all critical to longitudinal in situ live animal assessments. The data presented were obtained from three dimensional imaging of scaffolds in situ cartilage by means of synchrotron-based computed tomography-diffraction enhanced imaging (CT-DEI), analyzer based imaging (CT-ABI), and in-line phase contrast imaging (CT-PCI) at standard and low dose imaging modalities.

Flow diverting stents are deployed to reduce the blood flow into the aneurysm, which would thereby induce thrombosis in the aneurysm sac; the stents prevent its rupture. The present study aimed to examine and quantify the impacts of different flow stents on idealized configurations of the cerebral artery. In our study, we considered a spherical sidewall aneurysm located on curved and tortuous idealized artery vessels and three stents with different porosities (70, 80 and 90%) for deployment. Using computational fluid dynamics, the local hemodynamics in the presence and absence of the stents were simulated, respectively, under the assumption that the blood flow was unsteady and non-Newtonian. The hemodynamic parameters, such as the intra-aneurysmal flow, velocity field and wall shear stress and its related indices, were examined and compared among the 12 cases simulated. The results illustrated that with the stent deployment, the intra-aneurysmal flow and the wall shear stress and its related indices were considerably modified depending on both stent and aneurysm/artery geometries, and that the intra-aneurysmal relative residence time increased rapidly with decreasing stent porosity in all the vessel configurations. These results also inform the rationale for selecting stents for treating aneurysms of different configurations.

Biodegradable Mg alloys have appeared as the most appealing metals for biomedical applications, particularly as temporary bone implants. However, issues regarding high corrosion rate and biocompatibility restrict their application. Hence, in the present work, nanostructured clinoenstatite (CLT, MgSiO3)/tantalum nitride (TaN) was deposited on the Mg-Ca-Zn alloy via electrophoretic deposition (EPD) along with physical vapor deposition (PVD) to improve the corrosion and biological characteristics of the Mg-Ca-Zn alloy. The TaN intermediate layer with bubble like morphology possessed a compact and homogenous structure with a thickness of about 950 nm while the thick CLT over-layer (~15 μm) displayed a less compact structure containing nano-porosities as well as nanoparticles with spherical morphology. The electrochemical tests demonstrated that the as prepared CLT/TaN film is able to substantially increase the anticorrosion property of Mg-Ca-Zn bare alloy. Cytocompatibility outcomes indicated that formation of CLT and TaN on the Mg bare alloy surface enhanced cell viability, proliferation and growth, implying excellent biocompatibility. Taken together, the CLT/TaN coating exhibits appropriate characteristic including anticorrosion property and biocompatibility in order to employ in biomedical files.

Osteoarthritis is a painful degenerative joint disease that could be better managed if tissue engineers can develop methods to create long-term engineered articular cartilage tissue substitutes. Many of the tissue engineered cartilage constructs currently available lack the chemical stimuli and cell-friendly environment that promote the matrix accumulation and cell proliferation needed for use in joint cartilage repair. The goal of this research was to test the efficacy of using a fibrin-alginate hydrogel containing hyaluronic acid (HA) and/or chondroitin sulphate (CS) supplements for chondrocyte culture. Neonatal porcine chondrocytes cultured in fibrin-alginate hydrogels retained their phenotype better than chondrocytes cultured in monolayer, as evidenced by analysis of their relative expression of type II versus type I collagen mRNA transcripts. HA or CS supplementation of the hydrogels increased matrix glycosaminoglycan (GAG) production during the first week of culture. However, the effects of these supplements on matrix accumulation were not additive and were no longer observed after two weeks of culture. Supplementation of the hydrogels with CS or a combination of both CS and HA increased the chondrocyte cell population after two weeks of culture. Statistical analysis indicated that the HA and CS treatment effects on chondrocyte numbers may be additive. This research suggests that supplementation with CS and/or HA has positive effects on cartilage matrix production and chondrocyte proliferation in three-dimensional (3D) fibrin-alginate hydrogels.

Extrusion-based bioprinting of hydrogel scaffolds is challenging due to printing-related issues, such as the lack of capability to precisely print or deposit hydrogels onto three-dimensional (3D) scaffolds as designed. Printability is an index to measure the difference between the designed and fabricated scaffold in the printing process, which, however, is still under-explored. While studies have been reported on printing hydrogel scaffolds from one or more hydrogels, there is limited knowledge on the printability of hydrogels and their printing processes. This paper presented our study on the printability of 3D printed hydrogel scaffolds, with a focus on identifying the influence of hydrogel composition and printing parameters/conditions on printability. Using the hydrogels synthesized from pure alginate or alginate with gelatin and methyl-cellulose, we examined their flow behavior and mechanical properties, as well as their influence on printability. To characterize the printability, we examined the pore size, strand diameter, and other dimensions of the printed scaffolds. We then evaluated the printability in terms of pore/strand/angular/printability and irregularity. Our results revealed that the printability could be affected by a number of factors and among them, the most important were those related to the hydrogel composition and printing parameters. This study also presented a framework to evaluate alginate hydrogel printability in a systematic manner, which can be adopted and used in the studies of other hydrogels for bioprinting.

The controlled release or delivery of proteins encapsulated in micro/nanospheres is an emerging strategy in regenerative medicine. For this, micro/nanospheres made from alginate have drawn considerable attention for the use as a protein delivery device because of their mild fabrication process, inert nature, non-toxicity and biocompatibility. Though promising, one key issue associated with using alginate micro/nanospheres is the burst release of encapsulated protein at the beginning of the release, which may be responsible for exerting toxic side effects and poor efficiency of the delivery device. To address this issue, this study aimed to investigate the effect of process parameters of fabricating protein-loaded alginate nanospheres on the initial burst release. The alginate nanospheres were prepared via a combination of water-in-oil emulsification and the external gelation method and loaded with bovine serum albumin (BSA) as a model protein. The examined process parameters included alginate concentration, ionic cross-linking time and drying time. Once fabricated, the nanospheres were then subjected to the examination of BSA release, as well as the characterization of their morphology, size, and encapsulation efficiency. Our results revealed that by properly adjusting the process parameters, the initial burst release can be reduced by 13%. Taken together, our study demonstrates that regulating process parameters of fabricating alginate nanospheres is a possible means to reduce the initial burst release.

Oral squamous cell carcinoma (OSCC), which encompasses the oral cavity-derived malignancies, is a devastating disease causing substantial morbidity and mortality in both men and women. It is the most common subtype of the head and neck squamous cell carcinoma (HNSCC), which is ranked the sixth most common malignancy worldwide. Despite promising advancements in the conventional therapeutic approaches currently available for patients with oral cancer, many drawbacks are still to be addressed; surgical resection leads to permanent disfigurement, altered sense of self and debilitating physiological consequences, while chemo- and radio-therapies result in significant toxicities, all affecting patient wellbeing and quality of life. Thus, the development of novel therapeutic approaches or modifications of current strategies is paramount to improve individual health outcomes and survival, while early tumour detection remains a priority and significant challenge. In recent years, drug delivery systems and chronotherapy have been developed as alternative methods aiming to enhance the benefits of the current anticancer therapies, while minimizing their undesirable toxic effects on the healthy non-cancerous cells. Targeted drug delivery systems have the potential to increase drug bioavailability and bio-distribution at the site of the primary tumour. This review confers current knowledge on the diverse drug delivery methods, potential carriers (e.g., polymeric, inorganic, and combinational nanoparticles; nanolipids; hydrogels; exosomes) and anticancer targeted approaches for oral squamous cell carcinoma treatment, with an emphasis on their clinical relevance in the era of precision medicine, circadian chronobiology and patient-centred health care.

Nanofibrous-based pH sensors have shown promise in a wide range of industrial and medical applications due to their fast response time and good mechanical properties. In the present study, we fabricated pH-sensitive sensors of nanofibrous membranes by electrospinning polyurethane (PU)/poly 2-acrylamido-2-methylpropanesulfonic acid (PAMPS)/graphene oxide (GO) with indicator dyes. The morphology of the electrospun nanofibers was examined using scanning electron microscopy (SEM). The effect of hydrophilic polymer ratio and concentration of GO on the sensing response time was investigated. The sensitivity of the membranes was studied over a wide pH range (1−8) in solution tests, with color change measured by calculating total color difference using UV-vis spectroscopy. The membranes were also subjected to vapor tests at three different pH values (1, 4, 8). SEM results show the successful fabrication of bimodal fiber diameter distributions of PU (mean fiber diameter 519 nm) and PAMPS (mean fiber diameter 78 nm). Sensing response time decreased dramatically with increasing concentrations of PAMPS and GO. The hybrid hydrophobic/hydrophilic/GO nanofibrous membranes are capable of instantly responding to changes in solution pH as well as detecting pH changes in chemical vapor solution in as little as 7 s.

Flow-diverting stents (FDSs) show considerable promise for the treatment of cerebral aneurysms by diverting blood flow away from the aneurysmal sacs, however, post-treatment complications such as failure of occlusion and subarachnoid haemorrhaging remain and vary with the FDS used. Based on computational fluid dynamics (CFD), this study aimed to investigate the performance of a new biodegradable stent as compared to two metallic commercially available FDSs. CFD models were developed for an idealized cerebral artery with a sidewall aneurysmal sac treated by deploying the aforementioned stents of different porosities (90, 80, and 70 % ) respectively. By using these models, the simulation and analysis were performed, with a focus on comparing the local hemodynamics or the blood flow in the stented arteries as compared to the one without the stent deployment. For the comparison, we computed and compared the flow velocity, wall shear stress (WSS) and pressure distributions, as well as the WSS related indices, all of which are of important parameters for studying the occlusion and potential rupture of the aneurysm. Our results illustrate that the WSS decreases within the aneurysmal sac on the treated arteries, which is more significant for the stents with lower porosity or finer mesh. Our results also show that the maximum WSS near the aneurysmal neck increases regardless of the stents used. In addition, the WSS related indices including the time-average WSS, oscillatory shear index and relative residence time show different distributions, depending on the FDSs. Together, we found that the finer mesh stents provide more flow reduction and smaller region characterized by high oscillatory shear index, while the new stent has a higher relative residence time.

Due to their fast response, high accuracy and non-friction force, piezo-actuators have been widely employed in multiple degree-of-freedom (DOF) stages for various nano-positioning applications. The use of flexible hinges in these piezo-actuator-driven stages allows the elimination of the influence of friction and backlash clearance, as observed in other configurations; meanwhile it also causes more complicated stage performance in terms of dynamics and the cross-coupling effect between different axes. Based on the system identification technique, this paper presents the development of a model for the 3-DOF piezo-actuator-driven stages with unknown configuration, with its parameters estimated from the Hankel matrix by means of the maximum a posteriori (MAP) online estimation. Experiments were carried out on a commercially-available piezo-actuator-driven stage to verify the effectiveness of the developed model, as compared to other methods. The results show that the developed model is able to predict the stage performance with improved accuracy, while the model parameters can be well updated online by using the MAP estimation. These capabilities allow investigation of the complicated stage performance and also provide a starting point from which the mode-based control scheme can be established for improved performance.

Damage to articular cartilage can eventually lead to osteoarthritis (OA), a debilitating, degenerative joint disease that affects millions of people around the world. The limited natural healing ability of cartilage and the limitations of currently available therapies make treatment of cartilage defects a challenging clinical issue. Hopes have been raised for the repair of articular cartilage with the help of supportive structures, called scaffolds, created through tissue engineering (TE). Over the past two decades, different designs and fabrication techniques have been investigated for developing TE scaffolds suitable for the construction of transplantable artificial cartilage tissue substitutes. Advances in fabrication technologies now enable the strategic design of scaffolds with complex, biomimetic structures and properties. In particular, scaffolds with hybrid and/or biomimetic zonal designs have recently been developed for cartilage tissue engineering applications. This paper reviews critical aspects of the design of engineered scaffolds for articular cartilage repair as well as the available advanced fabrication techniques. In addition, recent studies on the design of hybrid and zonal scaffolds for use in cartilage tissue repair are highlighted.

Three-dimensional (3D) bioplotting has been widely used to print hydrogel scaffolds for tissue engineering applications. One issue involved in 3D bioplotting is to achieve the scaffold structure with the desired mechanical properties. To overcome this issue, various numerical methods have been developed to predict the mechanical properties of scaffolds, but limited by the imperfect representation of one key feature of scaffolds fabricated by 3D bioplotting, i.e., the penetration or fusion of strands in one layer into the previous layer. This paper presents our study on the development of a novel numerical model to predict the elastic modulus (one important index of mechanical properties) of 3D bioplotted scaffolds considering the aforementioned strand penetration. For this, the finite element method was used for the model development, while medium-viscosity alginate was selected for scaffold fabrication by the 3D bioplotting technique. The elastic modulus of the bioplotted scaffolds was characterized using mechanical testing and results were compared with those predicted from the developed model, demonstrating a strong congruity between them. Once validated, the developed model was also used to investigate the effect of other geometrical features on the mechanical behavior of bioplotted scaffolds. Our results show that the penetration, pore size, and number of printed layers have significant effects on the elastic modulus of bioplotted scaffolds; and also suggest that the developed model can be used as a powerful tool to modulate the mechanical behavior of bioplotted scaffolds.

Three-dimensional (3D) printing is an emerging technology for the fabrication of scaffolds to repair/replace damaged tissue/organs in tissue engineering. This paper presents our study on 3D printed alginate scaffolds treated with phosphate buffered saline (PBS) and polyethyleneimine (PEI) coating and their impacts on the surface morphology and cellular response of the printed scaffolds. In our study, sterile alginate was prepared by means of the freeze-drying method and then, used to prepare the hydrogel for 3D printing into calcium chloride, forming 3D scaffolds. Scaffolds were treated with PBS for a time period of two days and seven days, respectively, and PEI coating; then they were seeded with Schwann cells (RSC96) for the examination of cellular response (proliferation and differentiation). In addition, swelling and stiffness (Young’s modulus) of the treated scaffolds was evaluated, while their surface morphology was assessed using scanning electron microscopy (SEM). SEM images revealed significant changes in scaffold surface morphology due to degradation caused by the PBS treatment over time. Our cell proliferation assessment over seven days showed that a two-day PBS treatment could be more effective than seven-day PBS treatment for improving cell attachment and elongation. While PEI coating of alginate scaffolds seemed to contribute to cell growth, Schwann cells stayed round on the surface of alginate over the period of cell culture. In conclusion, PBS-treatment may offer the potential to induce surface physical cues due to degradation of alginate, which could improve cell attachment post cell-seeding of 3D-printed alginate scaffolds.

Myocardial infarction (MI), caused by the occlusion of the left ventricular coronary artery, leads to the loss of cardiomyocytes and, potentially, heart failure. Cardiomyocytes in adult mammals proliferate at an extremely low rate and thus, a major challenge in MI treatment is supplementing exogenous cells and keeping them viable in MI areas. To address this challenge, injecting hydrogels encapsulating cells into MI areas, to compensate for the loss of cardiomyocytes, shows promise. This study synthesized two types of alginate hydrogels, based on self-crosslinking (SCL) and calcium ion crosslinking (Ca2+) in varying formulations. The hydrogels encapsulated living muscle-derived stem cells (MDSCs) and their performance was evaluated in terms of optimizing cell viability during the injection process, as well as the live/dead rate after long-term cultivation. The morphology of the hydrogel-encapsulated cells was characterized by scanning electronic microscopy (SEM) and live/dead cells were examined using an MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide staining) assay. The mechanical properties of the hydrogels were also determined via a rheometer, to identify their influence on cell viability during the injection process and with respect to long-term cultivation. The SCL hydrogel with a 0.8% alginate and 20% gelatin formulation resulted in the highest cell viability during the injection process, and the Ca2+ hydrogel composed of 1.1% alginate and 20% gelatin maintained the highest cell survival rate after two months in culture.

An aneurysm is a balloon-like bulge in the wall of blood vessels, occurring in major arteries of the heart and brain. Biodegradable polymeric stent-assisted coiling is expected to be the ideal treatment of wide-neck complex aneurysms. This paper presents the development of methods to fabricate and optimally design biodegradable polymeric stents for aneurysms treatment. Firstly, a dispensing-based rapid prototyping (DBRP) system was developed to fabricate coil and zigzag structures of biodegradable polymeric stents. Then, compression testing was carried out to characterize the radial deformation of the stents fabricated with the coil or zigzag structure. The results illustrated the stent with a zigzag structure has a stronger radial stiffness than the one with a coil structure. On this basis, the stent with a zigzag structure was chosen for the development of a finite element model for simulating the real compression tests. The result showed the finite element model of biodegradable polymeric stents is acceptable within a range of radial deformation around 20%. Furthermore, the optimization of the zigzag structure was performed with ANSYS DesignXplorer, and the results indicated that the total deformation could be decreased by 35.7% by optimizing the structure parameters, which would represent a significant advance of the radial stiffness of biodegradable polymeric stents.

Mechanical properties of a scaffold play an important role in its in vivo performance in bone tissue engineering, due to the fact that implanted scaffolds are typically subjected to stress including compression, tension, torsion, and shearing. Unfortunately, not all the materials used to fabricate scaffolds are strong enough to mimic native bones. Extensive research has been conducted in order to increase scaffold strength and mechanical performance by incorporating nanoparticles and/or coatings. An incredible improvement has been achieved; and some outstanding examples are the usage of nanodiamond, hydroxyapatite, bioactive glass particles, SiO2, MgO, and silver nanoparticles. This review paper aims to present the results, to summarize significant findings, and to give perspective for future work, which could be beneficial to future bone tissue engineering.

Abstract Background: The influence of pulmonary vein (PV) anatomy on cryo kinetics during cryoballoon (CB) ablation is unclear. Objective: To investigate the relationship between PV anatomy and cryo kinetics during CB ablation for atrial fibrillation (AF). Methods: Sixty consecutive patients were enrolled. PV anatomy, including ostial diameters (long, short and corrected), ratio between short and long diameters, ostium shape (round, oval, triangular, and narrow), and drainage pattern (typical, with common trunk, common antrum, ostial branch and supernumerary PV) were evaluated on multi-detector computed tomography (MDCT) images pre-procedure. Cryo kinetics parameters [balloon freeze time from 0 to -30ºC (BFT), balloon nadir temperature (BNT) and balloon warming time from -30 to +15ºC (BWT)] were recorded during procedure. All p values are two-sided, with values of p < 0.05 considered to be statistically significant. Results: 606 times of freezing cycle were accomplished. Moderate negative correlation was documented between BNT and corrected PV diameter (r = -0.51, p < 0.001) when using 23-mm CBs, and mild negative correlation (r = - 0.32, p = 0.001) was found when using 28-mm CBs. Multivariate logistic regression analysis revealed that PV corrected ostial diameter (OR, 1.4; p = 0.004) predicted a BNT < -51ºC when using 23-mm CBs, while PV ostium oval shape (OR, 0.3; p = 0.033) and PV locations (left inferior PV: OR, 0.04; p = 0.005; right superior PV: OR, 4.3; p = 0.025) predicted BNT < -51ºC when using 28-mm CBs. Conclusions: MDCT can provide PV anatomy accurate evaluation prior CB ablation. PV anatomy is associated with cryo kinetics during ablation.