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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 (N p), 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 N p = 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.

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 July 1st 2022. A meta-analysis was then performed. The quality of studies was assessed using the Newcastle-Ottawa Scale (NOS). 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 finally 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.

Three-dimensional (3D) printed hydrogel scaffolds enhanced with ceramics have shown potential applications for cartilage regeneration, but leaving biological and mechanical properties to be desired. This paper presents our study on the development of chitosan /alginate scaffolds with nano hydroxyapatite (nHA) by combining 3D printing and impregnating techniques, forming a hybrid, yet novel, structure of scaffolds for potential cartilage regeneration. First, we incorporated nHA into chitosan scaffold printing and studied the printability by examining the difference between the printed scaffolds and their designs. Then, we impregnated alginate with nHA into the printed chitosan scaffolds to forming a hybrid structure of scaffolds; and then characterized the scaffolds mechanically and biologically, with a focus on identifying the influence of nHA and alginate for potential cartilage regeneration. The results of compression tests on the scaffolds showed that the inclusion of nHA increased the elastic moduli of scaffolds; while the live/dead assay illustrated that nHA had a great effect on improving attachment and viability of ATCD5 cells on the scaffolds. Also, our results illustrated scaffolds with nHA impregnated in alginate hydrogel enhanced the cell viability and attachment. Furthermore, antibacterial activity of hybrid scaffolds was characterized with results indicating that the chitosan scaffolds had favourable antibacterial ability, which was further enhanced with the impregnated nHA. Taken together, our study has illustrated that chitosan/HA/alginate hybrid scaffolds are promising for cartilage regeneration and the methods developed to create hybrid scaffolds based on 3D printing and impregnating techniques, which can also be extended to fabricating scaffolds for other tissue engineering applications.

Dental enamel is the hardest tissue in the human body, providing external protection for the tooth against masticatory forces, temperature changes and chemical stimuli. Once enamel is damaged/altered by genetic defects, dental caries, trauma, and/or dental wear, it cannot repair itself due to the loss of enamel producing cells following the tooth eruption. The current restorative dental materials are unable to replicate physico-mechanical, esthetic features and crystal structures of the native enamel. Thus, development of alternative approaches to repair and regenerate enamel defects is much needed but remains challenging due to the structural and functional complexities involved. This review paper summarizes the clinical aspects to be taken into consideration for the development of optimal therapeutic approaches to tackle dental enamel defects. It also provides a comprehensive overview of the emerging acellular and cellular approaches proposed for enamel remineralization and regeneration. Acellular approaches aim to artificially synthesize or re-mineralize enamel, whereas cell-based strategies aim to mimic the natural process of enamel development given that epithelial cells can be stimulated to produce enamel postnatally during the adult life. The key issues and current challenges are also discussed here, along with new perspectives for future research to advance the field of regenerative dentistry.

Distinguishing from other traditional imaging, synchrotron radiation microcomputed tomography (SR-μCT) imaging allows for the visualization of three-dimensional objects of interest in a nondestructive and/or

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., Graphical abstract Image 1, Highlights • Focusing on one of the critical challenges in 3D bioprinting called “printability”. • Investigating factors, including those associated with bioink, printing process, and scaffold design affecting printability. • Highlights the recent development in the discovery of printability for the extrusion bioprinting. • Providing a systematic review on “how printability is measured and characterized”. • Identifying key challenges in the printability discovery.

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.

Hydrogel-based three-dimensional (3D) bioprinting has been illustrated as promising to fabricate tissue scaffolds for regenerative medicine. Notably, bioprinting of hydrated and soft 3D hydrogel scaffolds with desired structural properties has not been fully achieved so far. Moreover, due to the limitations of current imaging techniques, assessment of bioprinted hydrogel scaffolds is still challenging, yet still essential for scaffold design, fabrication, and longitudinal studies. This paper presents our study on the bioprinting of hydrogel scaffolds and on the development of a novel noninvasive imaging method, based on synchrotron propagation-based imaging with computed tomography (SR-PBI-CT), to study the structural properties of hydrogel scaffolds and their responses to environmental stimuli both in situ and in vivo. Hydrogel scaffolds designed with varying structural patterns were successfully bioprinted through rigorous printing process regulations and then imaged by SR-PBI-CT within physiological environments. Subjective to controllable compressive loadings, the structural responses of scaffolds were visualized and characterized in terms of the structural deformation caused by the compressive loadings. Hydrogel scaffolds were later implanted in rats as nerve conduits for SR-PBI-CT imaging, and the obtained images illustrated their high phase contrast and were further processed for the 3D structure reconstruction and quantitative characterization. Our results show that the scaffold design and printing conditions play important roles in the printed scaffold structure and mechanical properties. More importantly, our obtained images from SR-PBI-CT allow us to visualize the details of hydrogel 3D structures with high imaging resolution. It demonstrates unique capability of this imaging technique for noninvasive, in situ characterization of 3D hydrogel structures pre- and post-implantation in diverse physiological milieus. The established imaging platform can therefore be utilized as a robust, high-precision tool for the design and longitudinal studies of hydrogel scaffold in tissue engineering.

Transient global amnesia (TGA) is a neurological disorder characterized by sudden onset of anterograde amnesia with or without retrograde amnesia, lasting less than 24 hours, without other clinical neurological dysfunction. TGA with short duration and benign prognosis is usually neglected in clinical practice. Transient total amnesia after radiofrequency ablation is rare and its etiology is unknown. We report a case of 27-year-old man who experienced TGA after radiofrequency catheter ablation of supraventricular tachycardia. The patient had no other cognitive and motor impairment except for memory impairment. The symptom lasted for about six hours and relieved without recurrence. Nervous system examination showed that 12 pairs of cranial nerves were normal, the muscle strength and muscle tone of the limbs were normal, physiological reflexes existed, and no pathological reflexes were elicited. Tests were performed immediately and normally including blood routine examination, liver and kidney function, electrolyte, blood glucose, thyroid function, blood coagulation function, D-dimer, myocardial injury markers, blood gas analysis and other hematological. There is no abnormality in electrocardiogram (ECG), chest X-ray, cervical vascular ultrasound, and cardiac color Doppler ultrasound examination. Head magnetic resonance examination magnetic resonance imaging (MRI) showed dots in right frontal lobe and bilateral ventricles in T2-weighted images. There was no cerebral infarction and cerebral hemorrhage. The patient received low flow oxygen inhalation and aspirin 300mg orally. The outcome of patient with TGA is benign. There are still many unsolved mysteries worthy of long-term follow-up.

Spermatogenic failure is believed to be a major cause of male infertility. The establishment of a testis organoid model would facilitate the study of such pathological mechanisms and open the possibility of male fertility preservation. Because of the complex structures and cellular events occurring within the testis, the establishment of a compartmentalized testis organoid with a complete spermatogenic cycle remains a challenge in all species. Since the late 20th century, a great variety of scaffold-based and scaffold-free testis cell culture systems have been established to recapitulate de novo testis organogenesis and in vitro spermatogenesis. The utilization of the hydrogel scaffolds provides a 3D microenvironment for testis cell growth and development, facilitating the reconstruction of de novo testis tissue-like structures and spermatogenic differentiation. Using a combination of different strategies, including the use of various scaffolding biomaterials, the incorporation of the living cells with high self-assembling capacity, and the integration of the advanced fabrication techniques, a scaffold-based testis organoid with a compartmentalized structure that supports in vitro spermatogenesis may be achieved. This article briefly reviews the current progress in the development of scaffold-based testis organoids while focusing on the scaffolding biomaterials (hydrogels), cell sources, and scaffolding approaches. Key challenges in current organoid studies are also discussed along with recommendations for future research.

Microfluidic devices, such as the tumor-on-a-chip (ToC), allow for the delivery of multiple drugs as desired for various therapies such as cancer treatment. Due to the complexity involved, visualizing, and gaining knowledge of the performance of such devices through experimentation alone is difficult if not impossible. In this paper, we performed a numerical simulation study on ToC performance, which focuses on the ability to combine multiple nanodrugs and optimized ToC performance. The numerical simulations of the chip performance were performed based on the typical chip design and operating parameters, as well as the established governing equations, boundary conditions, and fluid-structure interaction. The effect of cell injection time and position, inlet flow rate, number of inlets, medium viscosity, and cell concentration on the chip performance in terms of shear stress and cell distribution were examined. The results illustrate the profound effect of operation parameters, thus allowing for rigorously determining operational parameters to prevent spheroids ejection from microwells and to restrict the shear stresses within a physiological range. Also, the results show that triple-inlets can increase the uniformity of cell distribution in comparison with single or double inlets. Based on the simulation results, the architecture of the primary ToC was further optimized, resulting in a novel design that enables applying multiple, yet simultaneous, nanodrugs with optimal drug combination as desired for an individual patient. Furthermore, our simulations on the optimized chip showed a uniform cell distribution required for uniform-sized tumor spheroids generation, and complete medium exchange. Taken together, this study not only illustrates that numerical simulations are effective to visualize the ToCs performance, but also develops a novel ToC design optimized for nanodrug-based combination therapy.

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.

Researchers have looked to cartilage tissue engineering to address the lack of cartilage regenerative capability related to cartilage disease/trauma. For this, a promising approach is extrusion-based three-dimensional (3D) printing technique to deliver cells, biomaterials, and growth factors within a scaffold to the injured site. This paper evaluates the printability of chitosan scaffolds for a cartilage tissue engineering, with a focus on identifying the influence of drying technique implemented before crosslinking on the improvement of chitosan printability. First, the printability of chitosan with concentrations of 8%, 10%, and 12% (w/v) was evaluated and 10% chitosan was selected for further studies. Then, different drying methods, including air drying, warm drying, and vacuum drying followed by crosslinking, were used to study their effect on the mechanical properties of the 10% chitosan scaffolds. Our compression testing results showed the highest elastic modulus for the scaffolds crosslinked with the air-drying technique; as a major part of experiemtn, pore sizes were studies and scaffolds with smaller pore sizes showed higher elastic modulus. Additionally, the geometrical features of scaffolds were examined using a scanning electron microscopy (SEM) technique. The morphology of scaffolds, dried with the aformentioned methods, was assess using SEM images to evaluate the dimensional stability of scaffolds. Chondrocyte cells cultured on the 3D-printed chitosan scaffolds dried using the air-drying technique showed high cell attachment while retaining round cellular morphology. Also, the results of the cytotoxicity test indicated that there was proper biocompatibility of the chitosan for the ATDC5 cells. Results showed that the drying method plays a decisive role in the mechanical and biological behavior of chitosan scaffolds. Considering biological and mechanical properties, the proposed 3D-printed chitosan scaffold can be of a potential structure for cartilage tissue engineering applications.

The capability to hinder microbial growth on the implant surfaces is of great interest in medical applications. This paper presents our study on the synthesis of zeolite/silver-graphene oxide (Zeo/...

Electrospinning polyurethane has been utilized as skin wound dressing for protecting skin wounds from infection and thus facilitating their healings, but also limited by its imperfect biocompatibility, mechanical and antibacterial properties. This paper presents our study on the addition of graphene oxide to electrospinning polyurethane for improved properties, as well as its in vitro characterization. Polyurethane/graphene oxide wound dressing was electrospun with varying amount of graphene oxide (from 0.0% to 2.0%); and in vitro tests was carried out to characterize the wound dressing properties and performance from the structural, mechanical, and biological perspectives. Scanning electron microscopy and Fourier-transform infrared spectroscopy were used to confirm the interaction between graphene oxide particles and polyurethane fibers, while the scanning electron microscopy images further illustrated that the wound dressing was of a porous structure with fibre diameters depending on the amount of graphene oxide added; specifically, 20 to 180 nm were for composite polyurethane/graphene oxide fibers and 600 to 900 nm for pure polyurethane. Our results also revealed that the hydrophilicity and swelling properties of the wound dressing could be regulated by the amount of graphene oxide added to the polyurethane/graphene oxide composites. Mechanical, antibacterial, and cytotoxicity properties of the composite polyurethane/graphene oxide wound dressing were examined with the results illustrating that the addition of graphene oxide could improve the properties of the electrospun wound dressing. Combined together, our study illustrates that electrospinning polyurethane/graphene oxide composite is promising as skin wound dressing.

Skin and soft tissue infections are major concerns with respect to wound repair. Recently, anti-bacterial wound dressings have been emerging as promising candidates to reduce infection, thus accelerating the wound healing process. This paper presents our work to develop and characterize poly(vinyl alcohol) (PVA)/chitosan (CS)/silk sericin (SS)/tetracycline (TCN) porous nanofibers, with diameters varying from 305 to 425 nm, both in vitro and in vivo for potential applications as wound dressings. The fabricated nanofibers possess a considerable capacity to take up water through swelling (~325–650%). Sericin addition leads to increased hydrophilicity and elongation at break while decreasing fiber diameter and mechanical strength. Moreover, fibroblasts (L929) cultured on the nanofibers with low sericin content (PVA/CS/1-2SS) displayed greater proliferation compared to those on nanofibers without sericin (PVA/CS). Nanofibers loaded with high sericin and tetracycline content significantly inhibited the growth of Escherichia coli and Staphylococcus aureus. In vivo examination revealed that PVA/CS/2SS-TCN nanofibers enhance wound healing, re-epithelialization, and collagen deposition compared to traditional gauze and nanofibers without sericin. The results of this study demonstrate that the PVA/CS/2SS-TCN nanofiber creates a promising alternative to traditional wound dressing materials.

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.

The design of scaffolds for tissue engineering has to consider two trade-off properties: mechanical and mass-transport properties. This is particularly true for additively manufactured scaffolds with the structures of minimal surfaces, and notably, the influence of the surface curvature of the structure on the mechanical and mass-transport properties remains unclear. This work presents our study on the scaffolds designed with the structure of triply periodic minimal surfaces (TPMS), with a focus on discovering the influence of surface curvature on the mechanical response and the mass-transport property or permeability of the scaffolds. Based on the entropy weight fuzzy comprehensive evaluation method, a model representative of both mechanical and permeable properties of scaffolds was developed; scanning electron microscopy (SEM) and finite element analysis (FEA) were also used to reveal the influence mechanism of curvature on structural fracture and deformation behavior. AlSi10Mg samples of scaffolds designed with different surface curvatures were manufactured using selective laser melting (SLM), and their mechanical and permeable properties were examined and characterized by both experiments and simulations. Our results illustrate that at the same porosity, the more concentrated the curvature distribution of the same type of unit, the better trade-off mechanical and mass-transport properties the scaffolds have. Particularly, at the porosity of 55%, the compressive elastic modulus and permeability of the Dte structure are increased by 2.03 times and 1.95 times compared with the Diamond unit, respectively. The fusion structure can greatly improve permeability performance at the cost of mechanical properties. Our results also show that porosity has the greatest influence on mechanical and permeable properties, followed by the surface curvature. The study illustrates that the surface curvature has a significant influence on the mechanical and permeable properties of scaffolds, and that the developed scaffold performance evaluation scheme is an effective means for the optimization and evaluation of scaffold performance.

The advent of endovascular therapy for acute large vessel occlusion has revolutionized stroke treatment. Timely access to endovascular therapy, and the ability to restore intracranial flow in a safe, efficient, and efficacious manner has been critical to the success of the thrombectomy procedure. The stentriever has been a mainstay of endovascular stroke therapy, and current guidelines recommend the usage of stentrievers in the treatment of large vessel occlusion stroke. Despite the success of existing stentrievers, there continues to be significant development in the field, with newer stentrievers attempting to improve on each of the three key aspects of the thrombectomy procedure. Here, we elucidate the technical requirements that a stentriever must fulfill. We then review the basic variables of stent design, including the raw material and its form, fabrication method, geometric configuration, and further additions. Lastly, a selection of stentrievers from successive generations are reviewed using these engineering parameters, and clinical data is presented. Further avenues of stentriever development and testing are also presented.

The goal of cartilage tissue engineering (CTE) is to regenerate new hyaline cartilage in joints and treat osteoarthritis (OA) using cell-impregnated hydrogel constructs. However, the production of an extracellular matrix (ECM) made of fibrocartilage is a potential outcome within hydrogel constructs when in vivo. Unfortunately, this fibrocartilage ECM has inferior biological and mechanical properties when compared to native hyaline cartilage. It was hypothesized that compressive forces stimulate fibrocartilage development by increasing production of collagen type 1 (Col1), an ECM protein found in fibrocartilage. To test the hypothesis, 3-dimensional (3D)-bioprinted hydrogel constructs were fabricated from alginate hydrogel impregnated with ATDC5 cells (a chondrogenic cell line). A bioreactor was used to simulate different in vivo joint movements by varying the magnitude of compressive strains and compare them with a control group that was not loaded. Chondrogenic differentiation of the cells in loaded and unloaded conditions was confirmed by deposition of cartilage specific molecules including glycosaminoglycans (GAGs) and collagen type 2 (Col2). By performing biochemical assays, the production of GAGs and total collagen was also confirmed, and their contents were quantitated in unloaded and loaded conditions. Furthermore, Col1 vs. Col2 depositions were assessed at different compressive strains, and hyaline-like cartilage vs. fibrocartilage-like ECM production was analyzed to investigate how applied compressive strain affects the type of cartilage formed. These assessments showed that fibrocartilage-like ECM production tended to reduce with increasing compressive strain, though its production peaked at a higher compressive strain. According to these results, the magnitude of applied compressive strain governs the production of hyaline-like cartilage vs. fibrocartilage-like ECM and a high compressive strain stimulates fibrocartilage-like ECM formation rather than hyaline cartilage, which needs to be addressed by CTE approaches.

Triply periodic minimal surface (TPMS) has a promising application in the design of bone scaffolds due to its relevance in bone structure. Notably, the mechanical properties of TPMS scaffolds can be affected by many factors, including the spatial angle and surface curvature, which, however, remain to be discovered. This paper illustrates our study on the mechanical properties of tissue scaffolds consisting of TPMS structures (Primitive and I-WP) by considering the influence of spatial angle and surface curvature. Also, the development of a novel model representative of the mechanical properties of scaffolds based on the entropy weight fuzzy comprehensive evaluation method is also presented. For experimental investigation and validation, we employed the selective laser melting technology to manufacture scaffolds with varying structures from AlSi10Mg powder and then performed mechanical testing on the scaffolds. Our results show that for a given porosity, the Gaussian curvature of the stretched TPMS structures is more concentrated and have a higher elastic modulus and fatigue life. At the spatial angle θ = 27°, the shear modulus of the primitive unit reaches its largest value; the shear modulus of the I-WP unit is positively correlated with the spatial angle. Additionally, it is found that the comprehensive mechanical properties of TPMS structures can be significantly improved after changing the surface curvature. Taken together, the identified influence of spatial angle and surface curvature and the developed models of scaffold mechanical properties would be of significant advance and guidance for the design and development of bone scaffolds.

Tissue engineering offers a great potential in regenerative dentistry and to this end, three dimensional (3D) bioprinting has been emerging nowadays to enable the incorporation of living cells into the biomaterials (such a mixture is referred as a bioink in the literature) to create scaffolds. However, the bioinks available for scaffold bioprinting are limited, particularly for dental tissue engineering, due to the complicated, yet compromised, printability, mechanical and biological properties simultaneously imposed on the bioinks. This paper presents our study on the development of a novel bioink from carboxymethyl chitosan (CMC) and alginate (Alg) for bioprinting scaffolds for enamel tissue regeneration. CMC was used due to its antibacterial ability and superior cell interaction properties, while Alg was added to enhance the printability and mechanical properties as well as to regulate the degradation rate. The bioinks with three mixture ratios of Alg and CMC (2–4, 3–3 and 4–2) were prepared, and then printed into the calcium chloride crosslinker solution (100 mM) to form a 3D structure of scaffolds. The printed scaffolds were characterized in terms of structural, swelling, degradation, and mechanical properties, followed by their in vitro characterization for enamel tissue regeneration. The results showed that the bioinks with higher concentrations of Alg were more viscous and needed higher pressure for printing; while the printed scaffolds were highly porous and showed a high degree of printability and structural integrity. The hydrogels with higher CMC ratios had higher swelling ratios, faster degradation rates, and lower compressive modulus. Dental epithelial cell line, HAT-7, could maintain high viability in the printed constructs after 1, 7 and 14 d of culture. HAT-7 cells were also able to maintain their morphology and secrete alkaline phosphatase after 14 d of culture in the 3D printed scaffolds, suggesting the capacity of these cells for mineral deposition and enamel-like tissue formation. Among all combinations Alg4%–CMC2% and in a less degree 2%Alg–4%CMC showed the higher potential to promote ameloblast differentiation, Ca and P deposition and matrix mineralization in vitro. Taken together, Alg-CMC has been illustrated to be suitable to print scaffolds with dental epithelial cells for enamel tissue regeneration.

Cell-laden cardiac patches have recently been emerging to renew cellular sources for myocardial infarction (MI, commonly know as a heart attack) repair. However, the fabrication of cell-laden patches with porous structure remains challenging due to the limitations of currently available hydrogels and existing processing techniques. The present study utilized a bioprinting technique to fabricate hydrogel patches and characterize them in terms of printability, mechanical and biological properties. Cell-laden hydrogel (or bio-ink) was formulated from alginate dialdehyde (ADA) and gelatin (GEL) to improve the printability, degradability as well as bioactivity. Five groups of hydrogel compositions were designed to investigate the influence of the oxidation degree of ADA and hydrogels concentration on the properties of printed scaffolds. ADA–GEL hydrogels have generally shown favorable for living cells (EA.hy926 cells and hybrid human umbilical vein endothelial cell line). The hydrogel with an oxidation degree of 10% and a concentration ratio of 70/30 (or 10%ADA70–GEL30) demonstrated the best printability among the groups examined. Formulated hydrogels were also bioprinted with the living cells (EA.hy926), and the scaffolds printed were then subject to the cell culture for 7 days. Our results illustrate that the scaffolds bioprinted from 10%ADA70–GEL30 hydrogels had the best homogenous cell distribution and also the highest cell viability. Taken together, in the present study we synthesized a newly formulated bio-ink from ADA and GEL and for the fist time, used them to bioprint cardiac patches, which have the potential to be used in MI repair.

Creating scaffolds for skin tissue engineering remain challenging in terms of their mechanical and biological properties. In this paper, we present a study on the nanocomposite polyurethane (PU)/polycaprolactone (PCL) scaffolds with graphene oxide (GO), which were fabricated by using electrospinning method, for potential skin tissue engineering. For this, homogenous and soft PU nanofibers containing varying percent of polycaprolactone (12% and 15%) and nano GO (0.5-4%) were electrospun, respectively, and then characterized by different techniques/assays in vitro. For the scaffold characterization, scanning electron microscopy (SEM) and Fourier-transform infrared spectroscopy (FTIR) were used. The SEM results show the spun scaffolds have 3D porous structure (90%) with the fiber diameter increased with the GO concentration, while the FTIR results confirmed the presence of PU, PCL, and Go in the scaffolds. Also, the biocompatibility, via the cytotoxicity, of the scaffolds was examined by MTT assay with the human skin fibroblast cells, along with their wettability in terms of contact angle. Our results show that the scaffolds are biocompatible to the skin fibroblast cell, illustrating their potential use in skin tissue engineering. Also, our results illustrate that the addition of GO to the PU/PCL composite can increase the wettability (or hydrophilicity) and biocompatibility of scaffolds. Combined together, the nanocomposite PU/PCL scaffolds with GO are promising as biocompatible constructs for skin tissue engineering.

Ti alloy has been widely employed in the creation of implants for various dentistry and orthopedic applications, but is limited by its inadequate bioactivity. This paper presents our study ...

Biodegradable magnesium (Mg) alloys have drawn considerable attention for use in orthopedic implants, but their antibacterial activity and corrosion resistance still require improvement. In the present work, functional Ta2O5 (tantalum pentoxide) compact layers and PCL/MgO-Ag (poly (e-caprolactone)/magnesium oxide-silver) nanofiber porous layers were subsequently deposited on Mg alloys via reactive magnetron sputtering and electrospinning, respectively, to improve anticorrosion and antibacterial performance. Sputter coating of the Ta2O5 resulted in a thick layer (∼1 μm) with an amorphous structure and high adhesive strength. The nanostructure exhibited bubble-like patterns with no obvious nano-cracks, nano-porosities, or pinholes. The electrospun PCL/MgO-Ag nanofiber coating was porous, smooth, and plain with no obvious beads. In vitro corrosion tests demonstrated the PCL/MgO-Ag nanofiber-coated alloy had greater corrosion resistance than a Ta2O5 sputter-coated alloy or uncoated Mg alloy. The additional electrospun PCL/MgO-Ag nanofiber coating also had greater antibacterial behavior toward Gram-negative (Escherichia coli) and Gram-positive (Staphylococcus aureus) bacteria than the Ta2O5-coated or uncoated alloy specimens. Increasing the MgO-Ag concentration of the nanofibers from 1 to 3 wt% increased antibacterial activity. The combination of Ta2O5 and PCL/MgO-Ag nanofiber coatings on Mg alloys may therefore have potential applications for reducing bone infection as related to orthopedic implants for bone repair.

Three-dimensional (3D) bioprinting is a promising technique used to fabricate scaffolds from hydrogels with living cells. However, the printability of hydrogels in bioprinting has not been adequately studied. The aim of this study was to quantitatively characterize the printability and cell viability of alginate dialdehyde (ADA)-gelatin (Gel) hydrogels for bioprinting. ADA-Gel hydrogels of various concentrations were synthesized and characterized using Fourier transform infrared spectroscopy, along with rheological tests for measuring storage and loss moduli. Scaffolds (with an area of 11 × 11 mm) of 1, 2, and 13 layers were fabricated from ADA-Gel hydrogels using a 3D-bioplotter under printing conditions with and without the use of cross-linker, respectively, at room temperature and at 4 °C. Scaffolds were then quantitatively assessed in terms of the minimum printing pressure, quality of strands and pores, and structural integrity, which were combined together for the characterization of ADA-Gel printability. For the assessment of cell viability, scaffolds were bioprinted from ADA-Gel hydrogels with human umbilical vein endothelial cells (HUVECs) and rat Schwann cells and were then examined at day 7 with live/dead assay. HUVECs and Schwann cells were used as models to demonstrate biocompatibility for potential angiogenesis and nerve repair applications, respectively. Our results illustrated that ADA-Gel hydrogels with a loss tangent (ratio of loss modulus over storage modulus) between 0.24 and 0.28 could be printed in cross-linker with the best printability featured by uniform strands, square pores, and good structural integrity. Additionally, our results revealed that ADA-Gel hydrogels with an appropriate printability could maintain cell viability over 7 days. Combined together, this study presents a novel method to characterize the printability of hydrogels in bioprinting and illustrates that ADA-Gel hydrogels can be synthesized and bioprinted with good printability and cell viability, thus demonstrating their suitability for bioprinting scaffolds in tissue engineering applications.

Treatment of bone defects requires materials or bone cement with superior mechanical properties and favorable biological properties, but this remains unachievable to date. To address this issue, the present study aimed to synthesize and characterize a novel poly(methyl methacrylate) (PMMA) bone cement containing monticellite (Mon) and carbon nanotubes (CNTs) for bone defect treatment. Considerably better mechanical properties were noted in the PMMA-Mon-CNT vs. PMMA and PMMA-Mon bone cements due to the unique resistance of CNTs to crack formation and propagation. Favorable bioactivity was also found in the bone cements containing Mon and CNTs, whereas the PMMA bone cement presented poor bioactivity. Specifically, the incorporation of Mon and CNTs into the PMMA matrix promoted the attachment of MG63 cells compared to the PMMA cement. Thus, the PMMA-Mon-CNT bone cements developed are good potential candidates for filling bone defects in orthopedic surgeries.

The internally driven 24-h cycle in humans, called circadian rhythm, controls physiological, metabolic, and hormonal processes, and is tied to the circadian clocks ticking in most of the cells and tissues. The central clock, located in suprachiasmatic nuclei of the hypothalamus, is directly influenced by external cues, particularly light, and entrains the peripheral clocks through neural and hormonal pathways to the external light-dark cycle. However, peripheral clocks also have self-sustained circadian rhythmicity and feeding is the potent synchronizer. The internal clock system regulates the sleep-wake cycle and maintains stress responses through the hypothalamus-pituitary-adrenal axis and autonomic pathways. Any misalignment in this complex network could lead to circadian clock disruption and endocrine and metabolic dysfunction that may induce inflammatory responses. The detrimental consequences of such dysfunction are broad and can lead to serious health problems; however, the extent of the circadian disruption is difficult to assess. New promising techniques based on biosensors and point-of-care devices using aptamers - single-stranded DNA or RNA biorecognition molecules that can measure biomarkers of stress, sleep, and circadian rhythms in bodily fluids such as saliva with high sensitivity and specificity - can provide timely and accurate diagnosis and allow for effective implementation of behavioral and therapeutic interventions. This review provides detailed insight into the complex crosstalk between stress, sleep, and circadian rhythm, their relationship with the body's homeostasis, and the consequences of circadian dysregulation. The review also summarizes the mechanisms of aptamer-based biosensors and/or point-of-care devices developed to date for the detection of salivary biomarkers linked to stress, sleep, and circadian rhythm. Lastly, the review outlines the knowledge gaps in the literature related to the detection of lower concentrations of biomarkers in saliva and discusses the prospects of aptamer-based detection of salivary biomarkers from a high-precision perspective that is crucial for clinical diagnosis, at a time when circadian disruption is evident in unprecedented proportions across the globe.

Objective: Myonectin, a recently found myokine, has a role of inhibiting inflammation. The aim of this research is to see if myonectin levels are linked to the occurrence of atrial fibrillation (AF).Methods: We examined serum myonectin in a population of 194 patients with AF who were then classified into three subgroups: paroxysmal AF, persistent AF, and permanent AF. Atrial remolding was assessed using left atrial diameter (LAD). Results: Serum myonectin was significantly lower in AF group compared with healthy controls. Logistic regression analysis demonstrated that serum myonectin concentrations were correlated with a decreased risk of AF. Patients with permanent AF displayed decreased serum myonectin than in persistent and paroxysmal AF groups. Serum myonectin was lower in persistent AF group than in paroxysmal AF group. Serum myonectin concentrations in AF patients were negatively associated with body mass index (BMI), systolic blood pressure, diastolic blood pressure, and LAD. BMI and LAD stayed to be correlated with serum myonectin according to multiple stepwise regression analysis. Conclusion: Our study demonstrated a correlation between serum myonectin and AF.

Enamel is the highest mineralized tissue in the body protecting teeth from external stimuli, infections, and injuries. Enamel lacks the ability to self-repair due to the absence of enamel-producing cells in the erupted teeth. Here, we reported a novel approach to promote enamel-like tissue formation via the delivery of a key ameloblast inducer, T-box1 gene, into a rat dental epithelial stem cell line, HAT-7, using non-viral gene delivery systems based on cationic lipids. We comparatively assessed the lipoplexes prepared from glycyl-lysine-modified gemini surfactants and commercially available 1,2-dioleoyl-3-trimethylammonium-propane lipids at three nitrogen-to phosphate (N/P) ratios of 2.5, 5 and 10. Our findings revealed that physico-chemical characteristics and biological activities of the gemini surfactant-based lipoplexes with a N/P ratio of 5 provide the most optimal outcomes among those examined. HAT-7 cells were transfected with T-box1 gene using the optimal formulation then cultured in conventional 2D cell culture systems. Ameloblast differentiation, mineralization, bio-enamel interface and structure were assessed at different time points over 28 days. Our results showed that our gemini transfection system provides superior gene expression compared to the benchmark agent, while keeping low cytotoxicity levels. T-box1-transfected HAT-7 cells strongly expressed markers of secretory and maturation stages of the ameloblasts, deposited minerals, and produced enamel-like crystals when compared to control cells. Taken together, our gemini surfactant-based T-box1 gene delivery system is effective to accelerate and guide ameloblastic differentiation of dental epithelial stem cells and promote enamel-like tissue formation. This study would represent a significant advance towards the tissue engineering and regeneration of dental enamel.

In tissue engineering, three-dimensional (3D) printing is an emerging approach to producing functioning tissue constructs to repair wounds and repair or replace sick tissue/organs. It allows for precise control of materials and other components in the tissue constructs in an automated way, potentially permitting great throughput production. An ink made using one or multiple biomaterials can be 3D printed into tissue constructs by the printing process; though promising in tissue engineering, the printed constructs have also been reported to have the ability to lead to the emergence of unforeseen illnesses and failure due to biomaterial-related infections. Numerous approaches and/or strategies have been developed to combat biomaterial-related infections, and among them, natural biomaterials, surface treatment of biomaterials, and incorporating inorganic agents have been widely employed for the construct fabrication by 3D printing. Despite various attempts to synthesize and/or optimize the inks for 3D printing, the incidence of infection in the implanted tissue constructs remains one of the most significant issues. For the first time, here we present an overview of inks with antibacterial properties for 3D printing, focusing on the principles and strategies to accomplish biomaterials with anti-infective properties, and the synthesis of metallic ion-containing ink, chitosan-containing inks, and other antibacterial inks. Related discussions regarding the mechanics of biofilm formation and antibacterial performance are also presented, along with future perspectives of the importance of developing printable inks.

Scaffolds are used in bone tissue engineering to provide a temporary structural template for cell seeding and extracellular matrix formation. However, tissue formation on scaffold outer edges after implantation due to insufficient interconnectivity may restrict cell infiltration and mass transfer to/from the scaffold center, leading to bone regeneration failure. To address this problem, we prepared nanohydroxyapatite/polyamide66 (n-HA/PA66) anisotropic scaffolds with axially aligned channels (300 μm) with the aim to enhance pore interconnectivity and subsequent cell and tissue infiltration throughout the scaffold. Anisotropic scaffolds with axially aligned channels had better mechanical properties and a higher porosity (86.37%) than isotropic scaffolds produced by thermally induced phase separation (TIPS). The channels in the anisotropic scaffolds provided cells with passageways to the scaffold center and thus facilitated cell attachment and proliferation inside the scaffolds. In vivo studies showed that the anisotropic scaffolds could better facilitate new bone ingrowth into the inner pores of the scaffold compared to the isotropic scaffolds. The anisotropic scaffolds also had improved vascular invasion into their inner parts, increasing the supply of oxygen and nutrients to the cells and thus facilitating revascularization and bone ingrowth. Enhanced cell and tissue penetration to the scaffold center was observed in the anisotropic scaffolds both in vitro and in vivo, indicating the axially aligned channels positively influenced cell and tissue infiltration. Thus, such scaffolds have great potential for applications in bone tissue engineering.

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The ongoing coronavirus disease 2019 (COVID-19) pandemic is a rapidly evolving situation. New discoveries about COVID-19 and its causative virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), continue to deepen the understanding of this novel disease. As there is currently no COVID-19 specific treatment, isolation is the most effective method to prevent transmission. Moreover, development of a safe and effective COVID-19 vaccine will be instrumental in reinstating pre-COVID-19 conditions. As of 31 July 2020, there are at least 139 vaccine candidates from around the globe in preclinical evaluation, with another 26 undergoing clinical evaluation. This paper aims to review the basics of COVID-19, including epidemiology, basic biology of SARS-CoV-2, and transmission. We also review COVID-19 vaccine development, including animal models, platforms under development, and vaccine development in Canada.

Extrusion bioprinting has been widely used to extrude continuous filaments of bioink (or the mixture of biomaterial and living cells), layer-by-layer, to build three-dimensional constructs for biomedical applications. In extrusion bioprinting, printability is an important parameter used to measure the difference between the designed construct and the one actually printed. This difference could be caused by the extrudability of printed bioink and/or the structural formability and stability of printed constructs. Although studies have reported in characterizing printability based on the bioink properties and printing process, the concept of printability is often confusingly and, sometimes, conflictingly used in the literature. The objective of this perspective is to define the printability for extrusion bioprinting in terms of extrudability, filament fidelity, and structural integrity, as well as to review the effect of bioink properties, bioprinting process, and construct design on the printability. Challenges related to the printability of extrusion bioprinting are also discussed, along with recommendations for improvements.

Occlusion of coronary artery and subsequent damage or death of myocardium can lead to myocardial infarction (MI) and even heart failure-one of the leading causes of deaths world wide. Notably, myocardium has extremely limited regeneration potential due to the loss or death of cardiomyocytes (i.e., the cells of which the myocardium is comprised) upon MI. A variety of stem cells and stem cell-derived cardiovascular cells, in situ cardiac fibroblasts and endogenous proliferative epicardium, have been exploited to provide renewable cellular sources to treat injured myocardium. Also, different strategies, including direct injection of cell suspensions, bioactive molecules, or cell-incorporated biomaterials, and implantation of artificial cardiac scaffolds (e.g., cell sheets and cardiac patches), have been developed to deliver renewable cells and/or bioactive molecules to the MI site for the myocardium regeneration. This article briefly surveys cell sources and delivery strategies, along with biomaterials and their processing techniques, developed for MI treatment. Key issues and challenges, as well as recommendations for future research, are also discussed.