Bilateral optic nerve infiltration and leukemic retinopathy as initial signs of leukemia relapse with central nervous system involvement in an adult: a case report.

BACKGROUND: We describe a case in which bilateral optic nerve infiltration and leukemic retinopathy were the initial signs of disease relapse in a patient with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+-ALL) with central nervous system (CNS) involvement. CASE PRESENTATION: A 65-year-old Asian female with Ph+-ALL in complete remission presented at our institution with symptoms of visual disturbance, central scotoma and pain with eye movement in both eyes for a 1-month duration. Ophthalmic examination revealed remarkable optic disc swelling with multiple flame-shaped peripapillary hemorrhages, retinal venous dilation and retinal hemorrhages in both eyes. She was subsequently referred to the treating oncologist and diagnosed with Ph+-ALL relapse with multiple relapsed diseases involving the bone marrow and CNS. After intrathecal (IT) therapy, her visual acuity dramatically improved, and her leukemic infiltrates decreased. CONCLUSIONS: To the best of our knowledge, this is the first case report of ALL relapse with CNS involvement presenting as bilateral optic nerve infiltration and leukemic retinopathy in an adult. Hence, we highlight the priority and sensitivity of ophthalmic examinations, as they are noninvasive methods for detecting leukemia relapse.

Polyacrylamide/sodium alginate/sodium chloride photochromic hydrogel with high conductivity, anti-freezing property and fast response for information storage and electronic skin.

Photochromic hydrogels have promising prospects in areas such as wearable device, information encryption technology, optoelectronic display technology, and electronic skin. However, there are strict requirements for the properties of photochromic hydrogels in practical engineering applications, especially in some extreme application environments. The preparation of photochromic hydrogels with high transparency, high toughness, fast response, colour reversibility, excellent electrical conductivity, and anti-freezing property remains a challenge. In this study, a novel photochromic hydrogel (PAAm/SA/NaCl-Mo7) was prepared by loading ammonium molybdate (Mo7) and sodium chloride (NaCl) into a dual-network hydrogel of polyacrylamide (PAAm) and sodium alginate (SA) using a simple one-pot method. PAAm/SA/NaCl-Mo7 hydrogel has excellent conductivity (175.9 S/cm), water retention capacity and anti-freezing properties, which can work normally at a low temperature of -28.4 °C. In addition, the prepared PAAm/SA/NaCl-Mo7 hydrogel exhibits fast response (<15 s), high transparency (>70 %), good toughness (maximum elongation up to 1500 %), good cyclic compression properties at high compressive strains (60 %), good biocompatibility (78.5 %), stable reversible discolouration and excellent sensing properties, which can be used for photoelectric display, information storage and motion monitoring. This work provides a new inspiration for the development of flexible electronic skin devices.

A High-Stretching, Rapid-Self-Healing, and Printable Composite Hydrogel Based on Poly(Vinyl Alcohol), Nanocellulose, and Sodium Alginate.

Hydrogels with excellent flexibility, conductivity, and controllable mechanical properties are the current research hotspots in the field of biomaterial sensors. However, it is difficult for hydrogel sensors to regain their original function after being damaged, which limits their practical applications. Herein, a composite hydrogel (named SPBC) of poly(vinyl alcohol) (PVA)/sodium alginate (SA)/cellulose nanofibers (CNFs)/sodium borate tetrahydrate was synthesized, which has good self-healing, electrical conductivity, and excellent mechanical properties. The SPBC0.3 hydrogel demonstrates rapid self-healing (<30 s) and achieves mechanical properties of 33.92 kPa. Additionally, it exhibits high tensile strain performance (4000%). The abundant internal ions and functional groups of SPBC hydrogels provide support for the good electrical conductivity (0.62 S/cm) and electrical response properties. In addition, the SPBC hydrogel can be attached to surfaces such as fingers and wrists to monitor human movements in real time, and its good rheological property supports three-dimensional (3D) printing molding methods. In summary, this study successfully prepared a self-healing, conductive, printable, and mechanically superior SPBC hydrogel. Its suitability for 3D-printing personalized fabrication and outstanding sensor properties makes it a useful reference for hydrogels in wearable devices and human motion monitoring.

Advancements in Soft Robotics: A Comprehensive Review on Actuation Methods, Materials, and Applications.

The flexibility and adaptability of soft robots enable them to perform various tasks in changing environments, such as flower picking, fruit harvesting, in vivo targeted treatment, and information feedback. However, these fulfilled functions are discrepant, based on the varied working environments, driving methods, and materials. To further understand the working principle and research emphasis of soft robots, this paper summarized the current research status of soft robots from the aspects of actuating methods (e.g., humidity, temperature, PH, electricity, pressure, magnetic field, light, biological, and hybrid drive), materials (like hydrogels, shape-memory materials, and other flexible materials) and application areas (camouflage, medical devices, electrical equipment, and grippers, etc.). Finally, we provided some opinions on the technical difficulties and challenges of soft robots to comprehensively comprehend soft robots, lucubrate their applications, and improve the quality of our lives.

Three-dimensional bioprinting of tissue-engineered skin: Biomaterials, fabrication techniques, challenging difficulties, and future directions: A review.

As an emerging new manufacturing technology, Three-dimensional (3D) bioprinting provides the potential for the biomimetic construction of multifaceted and intricate architectures of functional integument, particularly functional biomimetic dermal structures inclusive of cutaneous appendages. Although the tissue-engineered skin with complete biological activity and physiological functions is still cannot be manufactured, it is believed that with the advances in matrix materials, molding process, and biotechnology, a new generation of physiologically active skin will be born in the future. In pursuit of furnishing readers and researchers involved in relevant research to have a systematic and comprehensive understanding of 3D printed tissue-engineered skin, this paper furnishes an exegesis on the prevailing research landscape, formidable obstacles, and forthcoming trajectories within the sphere of tissue-engineered skin, including: (1) the prevalent biomaterials (collagen, chitosan, agarose, alginate, etc.) routinely employed in tissue-engineered skin, and a discerning analysis and comparison of their respective merits, demerits, and inherent characteristics; (2) the underlying principles and distinguishing attributes of various current printing methodologies utilized in tissue-engineered skin fabrication; (3) the present research status and progression in the realm of tissue-engineered biomimetic skin; (4) meticulous scrutiny and summation of the extant research underpinning tissue-engineered skin inform the identification of prevailing challenges and issues.

Ferulic acid, ligustrazine, and tetrahydropalmatine display the anti-proliferative effect in endometriosis through regulating Notch pathway.

AIMS: With an ambiguous anti-proliferative mechanism, the combination of ferulic acid, ligustrazine, and tetrahydropalmatine (FLT) shows good anti-endometriosis (EMS) activity. In EMS, the expression of Notch pathway and its role in proliferation are not yet unclear. In this study, we sought to uncover the role of Notch pathway's effect and FLT's anti-proliferative mechanism on EMS proliferation. MAIN METHODS: In autograft and allograft EMS models, the proliferating markers (Ki67, PCNA), Notch pathway, and the effect of FLT on them were detected. Then, the anti-proliferative influence of FLT was measured in vitro. The proliferating ability of endometrial cells was investigated with a Notch pathway activator (Jagged 1 or VPA) or inhibitor (DAPT) alone, or in combination with FLT separately. KEY FINDINGS: FLT presented the inhibitory effect on ectopic lesions in 2 EMS models. The proliferating markers and Notch pathway were promoted in ectopic endometrium, but FLT showed the counteraction. Meantime, FLT restrained the endometrial cell growth and clone formation along with a reduction in Ki67 and PCNA. Jagged 1 and VPA stimulated the proliferation. On the contrary, DAPT displayed the anti-proliferating effect. Furthermore, FLT exhibited an antagonistic effect on Jagged 1 and VPA by downregulating Notch pathway and restraining proliferation. FLT also displayed a synergistic effect on DAPT. SIGNIFICANCE: This study indicated that the overexpressing Notch pathway induced EMS proliferation. FLT attenuated the proliferation by inhibiting Notch pathway.

Comprehensive Review on Fabricating Bioactive Ceramic Bone Scaffold Using Vat Photopolymerization.

In recent years, bioactive ceramic bone scaffolds have drawn remarkable attention as an alternative method for treating and repairing bone defects. Vat photopolymerization (VP) is a promising additive manufacturing (AM) technique that enables the efficient and accurate fabrication of bioactive ceramic bone scaffolds. This review systematically reviews the research progress of VP-printed bioactive ceramic bone scaffolds. First, a summary and comparison of commonly used bioactive ceramics and different VP techniques are provided. This is followed by a detailed introduction to the preparation of ceramic suspensions and optimization of printing and heat treatment processes. The mechanical strength and biological performance of the VP-printed bioactive ceramic scaffolds are then discussed. Finally, current challenges and future research directions in this field are highlighted.

Editorial on the Special Issue "Modification of Hydrogels and Their Applications in Biomedical Engineering".

Hydrogels and hydrophilic polymer networks play an important role in biomedical engineering due to their good biocompatibility, biodegradability, hydrophilicity, and mechanical properties, similarly to some soft tissues [...].

Enhancing Conductivity and Self-Healing Properties of PVA/GEL/OSA Composite Hydrogels by GO/SWNTs for Electronic Skin.

The use of flexible, self-healing conductive hydrogels as a type of typical electronic skin with the function of transmitting sensory signals has attracted wide attention in the field of biomaterials. In this study, composite hydrogels based on polyvinyl alcohol (PVA), gelatin (GEL), oxidized sodium alginate (OSA), graphene oxide (GO), and single-walled carbon nanotubes (SWNTs) were successfully prepared. The hydrogen and imine bonding of the composite hydrogels gives them excellent self-healing properties. Their self-healing properties restore 68% of their breaking strength and over 95% of their electrical conductivity. The addition of GO and SWNTs enables the PGO-GS hydrogels to achieve a compressive modulus and conductivity of 42.2 kPa and 29.6 mS/m, which is 8.2 times and 1.5 times that of pure PGO, respectively. Furthermore, the PGO-GS hydrogels can produce profound feedback signals in response to deformation caused by external forces and human movements such as finger flexion and speech. In addition, the PGO-GS hydrogels exhibit superior biocompatibility compared to PGO. All of these results indicate that the PGO-GS hydrogels have great potential with respect to future applications in the field of electronic skin.

Modification, 3D printing process and application of sodium alginate based hydrogels in soft tissue engineering: A review.

Sodium alginate (SA) is an inexpensive and biocompatible biomaterial with fast and gentle crosslinking that has been widely used in biological soft tissue repair/regeneration. Especially with the advent of 3D bioprinting technology, SA hydrogels have been applied more deeply in tissue engineering due to their excellent printability. Currently, the research on material modification, molding process and application of SA-based composite hydrogels has become a hot topic in tissue engineering, and a lot of fruitful results have been achieved. To better help readers have a comprehensive understanding of the development status of SA based hydrogels and their molding process in tissue engineering, in this review, we summarized SA modification methods, and provided a comparative analysis of the characteristics of various SA based hydrogels. Secondly, various molding methods of SA based hydrogels were introduced, the processing characteristics and the applications of different molding methods were analyzed and compared. Finally, the applications of SA based hydrogels in tissue engineering were reviewed, the challenges in their applications were also analyzed, and the future research directions were prospected. We believe this review is of great helpful for the researchers working in biomedical and tissue engineering.

A 3D printable, highly stretchable, self-healing hydrogel-based sensor based on polyvinyl alcohol/sodium tetraborate/sodium alginate for human motion monitoring.

Self-healing hydrogels have great application potential in the field of bio-sensors due to their self-healing, flexibility and excellent tensile properties. However, most hydrogel-based sensors are processed by template method, which is unable to fabricate complex three-dimensional (3D) structures, and limits the development of hydrogel-based sensor devices. A simple yet efficient one-pot method was proposed to fabricate polyvinyl alcohol/sodium tetraborate/sodium alginate hydrogel inks (SPB), also a fabricating process of self-healing hydrogel based on 3D printing technology has been proposed. The SPB hydrogel rapidly healed (<30 s) at room temperature, while its mechanical properties and conductivity also recovered quickly after healing. Besides, it could be used as wearable strain sensors, whose high stretchability (>2800 % strain) and sensitivity (gauge factor: 18.56 at 2000 % strain) could not only detect very large stretch deformations, but also detect the tiny pressure changes in the human body, such as finger flexion, knee flexion, and respiration. This study provides a method for the rapid fabrication of complex-structured hydrogel-based sensors, which is helpful for the hydrogel-based sensor applications in human motion detection and wearable devices.

Numerical Simulation and Experimental Study the Effects of Process Parameters on Filament Morphology and Mechanical Properties of FDM 3D Printed PLA/GNPs Nanocomposite.

The selection of optimal process parameters has a decisive effect on the quality of 3D printing. In this work, the numerical and experimental methods were employed to investigate the FDM printing deposition process of PLA/GNPs nanocomposite. The effect of process parameters on cross-sectional morphology and dimension of the deposited filament, as well as the mechanical property of the FDM printed specimens were studied. The extrusion and the deposition process of the molten PLA/GNPs nanocomposite was simulated as a fluid flow by the paradigm of CFD, the effects of printing temperature and shear rate on thermal-physical properties, such as viscosity and surface tension, were considered in models. Under the assumptions of non-Newtonian fluid and creep laminar flow, the deposition flow was controlled by two key parameters: the nozzle temperature and the nozzle velocity. The numerical model was verified by experiments from four aspects of thickness, width, area, and compactness of the deposited PLA/GNPs nanocomposite filament cross-section. Both the numerical simulation and experiment results show that with the increase of nozzle temperature and nozzle velocity, the thickness, area, and compactness of the deposited filament decreases. While the width of deposited filament increased with the increase of nozzle temperature and decrease of nozzle velocity. The decrease in thickness and the increase in width caused by the change of process parameters reached 10.5% and 24.7%, respectively. The tensile strength of the printed PLA/GNPs specimen was about 61.8 MPa under the higher nozzle temperatures and velocity condition, an improvement of 18.6% compared to specimen with the tensile strength of 52.1 MPa under the lower nozzle temperatures and velocity condition. In addition, the experimental results indicated that under the low nozzle velocity and nozzle temperature condition, dimensional standard deviation of the printed specimens decreased by 52.2%, 62.7%, and 68.3% in X, Y, and Z direction, respectively.

Application and development of 3D bioprinting in cartilage tissue engineering.

Articular cartilage defects are one of the most common clinical diseases of bone articulation. Early repair of damaged joint cartilage can effectively stop the progression of arthritis and restore health to the patient. In recent years, various therapeutic strategies have been developed to repair cartilage defects and make them available for clinical transplantation. However, cartilage defect repair remains a clinically unsolved challenge to date. Although there have been numerous breakthroughs in cartilage defect repair, the limited spatial complexity of tissue-engineered implants in terms of cells, materials, and active factors has limited the success of engineered cartilage so far. Bioprinting technology allows for the construction of three-dimensional tissues drop by drop and layer by layer, where cells, matrices, and active materials can be deposited on demand while maintaining high precision. Therefore, adopting the bioprinting technology in cartilage tissue engineering promises to develop the next generation of engineered cartilage and address the cartilage defect/regeneration problem. In this paper, we reviewed the bioinks and bioprinting technologies used in cartilage tissue engineering, outlined the recent advances of 3D bioprinting technologies in cartilage tissue engineering, and prospected the development direction of next-generation engineered cartilage.

Success Factors of Additive Manufactured Root Analogue Implants.

Dental implantation is an effective method for the treatment of loose teeth, but the threaded dental implants used in the clinic cannot match with the tooth extraction socket. A root analogue implant (RAI) has the congruence shape, which reduces the damage to bone and soft tissue. Additive manufacturing (AM) technologies have the advantages of high precision, flexibility, and easy operation, becoming the main manufacturing method of RAI in basic research. The purpose of this systematic review is to summarize AM technologies used for RAI manufacturing as well as the factors affecting successful implantation. First, it introduces the AM technologies according to different operating principles and summarizes the advantages and disadvantages of each method. Then the influences of materials, structure design, surface characteristics, implant site, and positioning are discussed, providing reference for designers and dentists. Finally, it addresses the gap between basic research and clinical application for additive manufactured RAIs and discusses the current challenges and future research directions for this field.

Base-Induced Highly Regioselective Synthesis of N2-Substituted 1,2,3-Triazoles under Mild Conditions in Air.

We developed a highly regioselective base-induced synthesis of N2-substituted 1,2,3-triazoles from N-sulfonyl-1,2,3-triazoles and alkyl bromides/alkyl iodides at room temperature. We propose an SN2-like mechanistic pathway to explain the high N2-regioselectivity. The protocol features a broad substrate scope and generates products in good to excellent yields (72-90%).

Novel 2-phenyl-3-(Pyridin-2-yl) thiazolidin-4-one derivatives as potent inhibitors for proliferation of osteosarcoma cells in vitro and in vivo.

Due to unknown pathogenesis and unidentified drug target, no drug for the treatment of osteosarcoma (OS) has been launched to the market. Herein, thiazolidinone 1a was discovered as a hit compound by phenotypic screening with an in-house patrimonial collection of structural diversity. The following SAR (Structure-Activity Relationship) study affords the final water-soluble lead compound (R)-8i as a potential inhibitor for the proliferation of OS cells by the modulation of solubility of the compounds with remarkable cellular potency (IC50 = 21.9 nM for MNNG/HOS cells) and in vivo efficacy (52.9% inhibition OS growth in mice), as well as pharmacokinetic properties. (R)-8i also significantly suppresses OS cell migration in vitro and showed to be well-tolerated. Our preliminary investigation shows that the effects of (R)-8i are not dependent on p53 and myoferlin (MYOF). These results suggest that (R)-8i might be a potential drug candidate for OS treatment.

Self-Healing Mechanism and Conductivity of the Hydrogel Flexible Sensors: A Review.

Sensors are devices that can capture changes in environmental parameters and convert them into electrical signals to output, which are widely used in all aspects of life. Flexible sensors, sensors made of flexible materials, not only overcome the limitations of the environment on detection devices but also expand the application of sensors in human health and biomedicine. Conductivity and flexibility are the most important parameters for flexible sensors, and hydrogels are currently considered to be an ideal matrix material due to their excellent flexibility and biocompatibility. In particular, compared with flexible sensors based on elastomers with a high modulus, the hydrogel sensor has better stretchability and can be tightly attached to the surface of objects. However, for hydrogel sensors, a poor mechanical lifetime is always an issue. To address this challenge, a self-healing hydrogel has been proposed. Currently, a large number of studies on the self-healing property have been performed, and numerous exciting results have been obtained, but there are few detailed reviews focusing on the self-healing mechanism and conductivity of hydrogel flexible sensors. This paper presents an overview of self-healing hydrogel flexible sensors, focusing on their self-healing mechanism and conductivity. Moreover, the advantages and disadvantages of different types of sensors have been summarized and discussed. Finally, the key issues and challenges for self-healing flexible sensors are also identified and discussed along with recommendations for the future.

Design and Fabrication of Sodium Alginate/Carboxymethyl Cellulose Sodium Blend Hydrogel for Artificial Skin.

Tissue-engineered skin grafts have long been considered to be the most effective treatment for large skin defects. Especially with the advent of 3D printing technology, the manufacture of artificial skin scaffold with complex shape and structure is becoming more convenient. However, the matrix material used as the bio-ink for 3D printing artificial skin is still a challenge. To address this issue, sodium alginate (SA)/carboxymethyl cellulose (CMC-Na) blend hydrogel was proposed to be the bio-ink for artificial skin fabrication, and SA/CMC-Na (SC) composite hydrogels at different compositions were investigated in terms of morphology, thermal properties, mechanical properties, and biological properties, so as to screen out the optimal composition ratio of SC for 3D printing artificial skin. Moreover, the designed SC composite hydrogel skin membranes were used for rabbit wound defeat repairing to evaluate the repair effect. Results show that SC4:1 blend hydrogel possesses the best mechanical properties, good moisturizing ability, proper degradation rate, and good biocompatibility, which is most suitable for 3D printing artificial skin. This research provides a process guidance for the design and fabrication of SA/CMC-Na composite artificial skin.

Combination of ferulic acid, ligustrazine and tetrahydropalmatine inhibits invasion and metastasis through MMP/TIMP signaling in endometriosis.

BACKGROUND: The design of the combination of ferulic acid, ligustrazine and tetrahydropalmatine (FLT) is inspired by the Chinese herbal prescription Foshou San. Previous work has shown that FLT inhibited endometriosis growth in rat autograft models. However, the mechanism behind this is unclear. MMP/TIMP signaling is considered as the vital pathway of metastasis and invasion in endometriosis. In this study, we aim to disclose effects of FLT on MMP/TIMP signaling in invasion and metastasis during endometrial cells and xenograft endometriosis. METHODS: In vivo, effect of FLT on endometriosis was evaluated in a xenogeneic mice model. In vitro, cell viability assay was performed with an IC50 measurement of FLT in hEM15A and HEC1-B cells. The effect of FLT on invasion and metastasis was analyzed in scratch wound and transwell assay. Gene and protein expression of MMP/TIMP signaling were detected by qPCR and Western blotting. RESULTS: In xenograft endometriosis, FLT reduced ectopic volume without effect on weight. FLT inhibitory effects on cell growth exhibited a dose-dependent manner in hEM15A and HEC1-B cells. IC50s of FLT in hEM15A cells were 839.30 ± 121.11 or 483.53 ±156.91 µg·ml-1 after the treatment for 24 or 48 h, respectively. In HEC1-B cells, IC50 values of 24 or 48 h were 625.20 ± 59.52 or 250.30 ± 68.12 µg·ml-1. In addition, FLT significantly inhibited invasion and metastasis in scratch wound and transwell assay. Furthermore, FLT inactivated MMP/TIMP signaling with decreasing expression of MMP-2/9, and an enhancing expression of TIMP-1. CONCLUSIONS: MMP/TIMP inactivation is a reasonable explanation for the inhibition of FLT on invasion and metastasis in endometriosis. This result reveals a potential mechanism on the role of FLT in endometriosis and may benefit for its further application.