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Tissue-mimetic hybrid bioadhesives for the repair of intervertebral disc after nucleotomy is proposed, comprising a viscoelastic glue for delivering cells to fill the cavity and a tough adhesive sealant to prevent re-herniation post-nucleotomy.

Reinforced extracellular matrix (ECM)-based hydrogels recapitulate several mechanical and biochemical features found in the tumor microenvironment (TME) in vivo. While these gels retain several critical structural and bioactive molecules that promote cell-matrix interactivity, their mechanical properties tend toward the viscous regime limiting their ability to retain ordered structural characteristics when considered as architectured scaffolds. To overcome this limitation characteristic of pure ECM hydrogels, we present a composite material containing alginate, a seaweed-derived polysaccharide, and gelatin, denatured collagen, as rheological modifiers which impart mechanical integrity to the biologically active decellularized ECM (dECM). After an optimization process, the reinforced gel proposed is mechanically stable and bioprintable and has a stiffness within the expected physiological values. Our hydrogel's elastic modulus has no significant difference when compared to tumors induced in preclinical xenograft head and neck squamous cell carcinoma (HNSCC) mouse models. The bioprinted cell-laden model is highly reproducible and allows proliferation and reorganization of HNSCC cells while maintaining cell viability above 90% for periods of nearly 3 weeks. Cells encapsulated in our bioink produce spheroids of at least 3000 μm2 of cross-sectional area by day 15 of culture and are positive for cytokeratin in immunofluorescence quantification, a common marker of HNSCC model validation in 2D and 3D models. We use this in vitro model system to evaluate the standard-of-care small molecule therapeutics used to treat HNSCC clinically and report a 4-fold increase in the IC50 of cisplatin and an 80-fold increase for 5-fluorouracil compared to monolayer cultures. Our work suggests that fabricating in vitro models using reinforced dECM provides a physiologically relevant system to evaluate malignant neoplastic phenomena in vitro due to the physical and biological features replicated from the source tissue microenvironment.

A growing number of circular RNAs (circRNAs) have been identified and verified in several cancers. However, highly efficient therapeutic methods based on circRNAs in lung cancer remain largely unexplored. In the present study, we identified a novel circular RNA, hsa_circ_103820, based on Gene Expression Omnibus (GEO) data. Functionally, overexpression of hsa_circ_103820 showed significant inhibitory effects on the proliferation, migration and invasion of lung cancer cells, and knockdown of hsa_circ_103820 played promoting roles. Regarding the mechanism, we revealed that miR-200b-3p was a direct target of hsa_circ_103820 and that LATS2 and SOCS6 were the downstream target genes of miR-200b-3p. Therefore, we identified a novel potential tumor suppressive function of hsa_circ_103820 in lung cancer.

Injectable hydrogels are increasingly used for in situ tissue regeneration and wound healing. Ideally, an injectable implant should promote the recruitment of cells from the surrounding native tissue and allow cells to migrate freely as they generate a new extracellular matrix network. Nanocomposite hydrogels such as carbon nanotube (CNT)-loaded hydrogels have been hypothesized to promote cell recruitment and cell migration relative to unloaded ones. To investigate this, CNT-glycol chitosan hydrogels were synthesized and studied. Chemoattractant-induced cell migration was studied using a modified Boyden Chamber experiment. Migrated cells were counted using flow cytometry. Cell adhesion was inferred from the morphology of the cells via an image segmentation method. Cell migration and recruitment results confirmed that small concentrations of CNT significantly increase cell migration in hydrogels, thereby accelerating tissue regeneration and wound healing in situations where there is insufficient migration in the unloaded matrix.

Cell-laden scaffolds of architecture and mechanics that mimic those of the host tissues are important for a wide range of biomedical applications but remain challenging to bioprint. To address these challenges, we report a new method called triggered micropore-forming bioprinting. The approach can yield cell-laden scaffolds of defined architecture and interconnected pores over a range of sizes, encompassing that of many cell types. The viscoelasticity of the bioprinted scaffold can match that of biological tissues and be tuned independently of porosity and stiffness. The bioprinted scaffold also exhibits superior mechanical robustness despite high porosity. The bioprinting method and the resulting scaffolds support cell spreading, migration, and proliferation. The potential of the 3D bioprinting system is demonstrated for vocal fold tissue engineering and as an in vitro cancer model. Other possible applications are foreseen for tissue repair, regenerative medicine, organ-on-chip, drug screening, organ transplantation, and disease modeling.

Ionotronic hydrogels find wide applications in flexible electronics, wearable/implantable devices, soft robotics, and human-machine interfaces. Their performance and practical translation have been bottlenecked by poor adhesiveness, limited mechanical properties, and the lack of biological functions. The remedies are often associated with complex formulations and sophisticated processing. Here, we report a rational design and facile synthesis of ionotronic tough adhesives (i-TAs), which have excellent mechanical, physical, electrical, and biological properties and promise high scalability and translational potential. They consist of an interpenetrating network with high-density amine groups and highly mobile chains, which enable intrinsic adhesiveness, self-healing, ionic stability, cytocompatibility, and antimicrobial functions. The i-TAs in both pristine and swollen states possess high toughness, stretchability, and strong adhesion to diverse substrates such as tissues and elastomers. The superior mechanical performance is achieved simultaneously with high ionic conductivity and stability in electrolyte solutions. We further demonstrate the use of i-TAs as wearable devices, strain sensors, and sensory sealants. This work is expected to open avenues for new ionotronics with novel functions and stimulate the development and translation of ionotronics.

A bioinspired surface functionalization strategy is proposed to fabricate sutures with robust hydrogel sheath with multifunctions., Sutures pervade surgeries, but their performance is limited by the mechanical mismatch with tissues and the lack of advanced functionality. Existing modification strategies result in either deterioration of suture’s bulk properties or a weak coating susceptible to rupture or delamination. Inspired by tendon endotenon sheath, we report a versatile strategy to functionalize fiber-based devices such as sutures. This strategy seamlessly unites surgical sutures, tough gel sheath, and various functional materials. Robust modification is demonstrated with strong interfacial adhesion (>2000 J m−2). The surface stiffness, friction, and drag of the suture when interfacing with tissues can be markedly reduced, without compromising the tensile strength. Versatile functionalization of the suture for infection prevention, wound monitoring, drug delivery, and near-infrared imaging is then presented. This platform technology is applicable to other fiber-based devices and foreseen to affect broad technological areas ranging from wound management to smart textiles.

Tissue adhesives can form appreciable adhesion with tissues and have found clinical use in a variety of medical settings such as wound closure, surgical sealants, regenerative medicine, and device attachment. The advantages of tissue adhesives include ease of implementation, rapid application, mitigation of tissue damage, and compatibility with minimally invasive procedures. The field of tissue adhesives is rapidly evolving, leading to tissue adhesives with superior mechanical properties and advanced functionality. Such adhesives enable new applications ranging from mobile health to cancer treatment. To provide guidelines for the rational design of tissue adhesives, here, existing strategies for tissue adhesives are synthesized into a multifaceted design, which comprises three design elements: the tissue, the adhesive surface, and the adhesive matrix. The mechanical, chemical, and biological considerations associated with each design element are reviewed. Throughout the report, the limitations of existing tissue adhesives and immediate opportunities for improvement are discussed. The recent progress of tissue adhesives in topical and implantable applications is highlighted, and then future directions toward next-generation tissue adhesives are outlined. The development of tissue adhesives will fuse disciplines and make broad impacts in engineering and medicine.

OBJECTIVE Most acellular injectable biomaterials for vocal fold (VF) wound treatment have limited regenerative potential due to their fast enzymatic degradation and limited recruitment of native cells postinjection. The injection of cells as therapeutic treatment often results in apoptosis due to stresses within the needle and the immune response of the host. Degradable microspheres may improve treatment effectiveness by increasing cell residence time, shielding cells during injection, and offering early protection against the immune system response. The objective of the present study was to investigate the potential of human VF fibroblasts encapsulated in polymeric microspheres as an injectable therapeutic treatment in vitro. METHODS Alginate, alginate-poly-L-lysine, and alginate-chitosan microspheres were fabricated using electrospraying and characterized in terms of biocompatibility, swelling, and mechanical properties as well as cytokine production. RESULTS Alginate microspheres were found to have the most desirable properties for VF regeneration. They were resistant to mechanical challenges. They were found to have a stiffness similar to that reported for native VF-lamina propria. They were found to be biocompatible and increased the proliferation of fibroblasts. Human VF fibroblasts encapsulated in alginate microspheres induced the production of interleukin (IL)-8 and IL-4 at 24 hours. CONCLUSION The alginate microspheres fabricated in this study were found to offer potential advantages, as cell delivery tool. This study highlights the importance of combining biomaterials and cells to expedite the wound-healing process through cytokine production. Future work is aimed to further analysis of the wound-healing properties the microspheres. LEVEL OF EVIDENCE NA Laryngoscope, 131:1828-1834, 2021.

Biofabrication has been extensively explored in tissue engineering over the past two decades. It uses bioactive materials and live cells as the building blocks to create spatially defined geometries. The goal of biofabrication is to create engineered tissue constructs to replace damaged or diseased human tissues with full functionality. The advantage is that it can rapidly fabricate tissue constructs to meet customized needs. The biomaterials used for biofabrication are called bioinks and usually comprise hydrogel precursor solutions or biocompatible thermal plastics. In this review, we review the commonly used biofabrication methods and critical aspects for creating scaffolds for tissue regeneration. We discuss the criteria for developing and selecting suitable biomaterials as the bioinks. Commonly used biomaterials and their applications are summarized to present the versatility of biofabrication. We also aim to highlight the challenges of this technology and initiate new ideas and opportunities in the future developments in the bioprinting approach and bioinks. The refinement in fabrication techniques, exploration in biology, and development in new bioinks are essential elements toward the advancement of biofabrication.

Scars composed of fibrous connective tissues are natural consequences of injury upon incisional wound healing in soft tissues. Hydrogels that feature a sustained presentation of immunomodulatory cytokines are known to modulate wound healing. However, existing immunomodulatory hydrogels lack interconnected micropores to promote cell ingrowth. Other limitations include invasive delivery procedures and harsh synthesis conditions that are incompatible with drug molecules. Here, hybrid nanocomposite microgels containing interleukin-10 (IL-10) are reported to modulate tissue macrophage phenotype during wound healing. The intercalation of laponite nanoparticles in the polymer network yields microgels with tissue-mimetic elasticity (Young's modulus in the range of 2-6 kPa) and allows the sustained release of IL-10 to promote the differentiation of macrophages toward proregenerative phenotypes. The porous interstitial spaces between microgels promote fibroblast proliferation and fast trafficking (an average speed of ≈14.4 µm h

Biological tissues hinge on blood perfusion and mechanical toughness to function. Injectable hydrogels that possess both high permeability and toughness have profound impacts on regenerative medicine but remain a long‐standing challenge. To address this issue, injectable, pore‐forming double‐network hydrogels are fabricated by orchestrating stepwise gelation and phase separation processes. The interconnected pores of the resulting hydrogels enable direct medium perfusion through organ‐sized matrices. The hydrogels are amenable to cell encapsulation and delivery while promoting cell proliferation and spreading. They are also pore insensitive, tough, and fatigue resistant. When tested in biomimetic perfusion bioreactors, the hydrogels maintain physical integrity under prolonged, high‐frequency biomechanical stimulations (>6000 000 cycles at 120 Hz). The excellent biomechanical performance suggests the great potential of the new injectable hydrogel technology for repairing mechanically dynamic tissues, such as vocal folds, and other applications, such as tissue engineering, biofabrication, organs‐on‐chips, drug delivery, and disease modeling., A design and methodology to form injectable, in situ pore‐forming, tough, and cytocompatible hydrogels are reported. Such hydrogels combine superior permeability and toughness, enabling direct medium perfusion through organ‐sized matrices. They are immune against extreme biomechanical loads and auspicious to cells. This work advances the injectable hydrogel technology and opens new opportunities in tissue engineering, drug/cell delivery, biofabrication, microfluidics, and organs‐on‐chips.

Bioprinting, within the emerging field of biofabrication, aims at the fabrication of functional biomimetic constructs. Different three-dimensional bioprinting techniques have been adapted to bioprint cell-laden bioinks. However, single-material bioprinting techniques oftentimes fail to reproduce the complex compositions and diversity of native tissues. Multi-material bioprinting as an emerging approach enables the fabrication of heterogeneous multi-cellular constructs that replicate their host microenvironments better than single-material approaches. Here, we briefly review bioprinting modalities, discuss how they are being adapted to multi-material bioprinting, as well as analyze their advantages and challenges, encompassing both custom-designed and commercially available technologies. The review offers a perspective of how multi-material bioprinting opens up new opportunities for tissue engineering, tissue model engineering, therapeutics development, and personalized medicine.

Blood clots are naturally derived bioadhesives that adhere to tissues, plug vascular damage and stop bleeding. Their function of hemostasis hinges on their resistance against rupture (toughness). Despite the relevance, fracture mechanics of blood clots remains largely unexplored, particularly the toughness and critical length scales governing clot fracture have not been reported. Here, we study the fracture behavior of human whole blood clots and platelet-poor plasma clots. The fracture energy of whole blood clots and platelet-poor plasma clots determined using modified lap-shear method is 5.90 ± 1.18 J/m2 and 0.96 ± 0.90 J/m2, respectively. We find that the measured toughness is independent of the specimen geometry and loading conditions. These results reveal an important contribution of blood cells to the clot fracture, as well as the dissipative length scale and nonlinear elastic length scale governing clot fracture. This study will motivate the investigation on blood clot fracture and inspire the development of clot-mimicking bioadhesives.

The cause of cabin odors is usually hard to be identified when there is no specific crew alerts or indications, which could have a catastrophic effect on civil aircrafts. Fault analysis has been conducted based on FTA (Fault Tree Analysis) in this paper to locate fault sources of cabin odors. A checklist is recommended to be performed during the flight or ground tests afterwards, which could provide quantitative references. An actual case applying the troubleshooting and analysis method above is shared at the end.

The ejection theory is widely used in industrial fields such as drainage, cooling, vacuum. Many ejection devices are applied in civil aircraft due to their simple design and easy layout. This article introduces several types of ejection applications in multiple systems of civil aircrafts. Then a CFD simulation of the APU (Auxiliary Power Unit) compartment drainage ejector is conducted to analyse the influence on the drainage function by different arrangements.

Injectable hydrogels are increasingly used for in situ tissue regeneration and wound healing. Ideally, an injectable implant should promote the recruitment of cells from the surrounding native tissue and allow cells to migrate freely as they generate a new extracellular matrix network. Nanocomposite hydrogels such as carbon nanotube (CNT)-loaded hydrogels have been hypothesized to promote cell recruitment and cell migration relative to unloaded ones. To investigate this, CNT-glycol chitosan hydrogels were synthesized and studied. Chemoattractant-induced cell migration was studied using a modified Boyden Chamber experiment. Migrated cells were counted using flow cytometry. Cell adhesion was inferred from the morphology of the cells via an image segmentation method. Cell migration and recruitment results confirmed that small concentrations of CNT significantly increase cell migration in hydrogels, thereby accelerating tissue regeneration and wound healing in situations where there is insufficient migration in the unloaded matrix.

Porous composite hydrogels were prepared using glycol chitosan as the matrix, glyoxal as the chemical crosslinker, and carbon nanotubes (CNTs) as the fibers. Both carboxylic and hydroxylic functionalized CNTs were used. The homogeneity of CNTs dispersion was evaluated using scanning electron microscopy. Human vocal fold fibroblasts were cultured and encapsulated in the composite hydrogels with different CNT concentrations to quantify cell viability. Rheological tests were performed to determine the gelation time and the storage modulus as a function of CNT concentration. The gelation time tended to decrease for low concentrations and increase at higher concentrations, reaching a local minimum value. The storage modulus obeyed different trends depending on the functional group. The porosity of the hydrogels was found to increase by 120% when higher concentrations of carboxylic CNTs were used. A high porosity may promote cell adhesion, migration, and recruitment from the surrounding native tissue, which will be investigated in a future work aiming at applying this injectable biomaterial for vocal fold tissue regeneration.

A lack of relevant disease models for Campylobacter jejuni has long been an obstacle to research into this common enteric pathogen. Here we used an infant rabbit to study C. jejuni infection, which enables us to define several previously unknown but key features of the organism. C. jejuni is capable of systemic invasion in the rabbit, and developed a diarrhea symptom that mimicked that observed in many human campylobacteriosis. The large intestine was the most consistently colonized site and produced intestinal inflammation, where specific cytokines were induced. Genes preferentially expressed during C. jejuni infection were screened, and acs, cj1385, cj0259 seem to be responsible for C. jejuni invasion. Our results demonstrates that the infant rabbit can be used as an alternative experimental model for the study of diarrheagenic Campylobacter species and will be useful in exploring the pathogenesis of other related pathogens.

Gorlin equation has been applied in clinical practice for evaluating the aortic valve area (AVA) of vascular and aortic valve stenosis for past sixty years [1]. It was derived using the Bernoulli equation across the stenosis with the assumption that the velocity of the fluid behind the stenosis is much greater than the velocity upstream of the stenosis. Because of this assumption, the calculated stenosed area may have large error if the flow rate across the valve is low or the stenosis is mild [2]. In a recent paper, Okpara and Agarwal [3] proposed a new equation (Agarwal – Okpara equation) which significantly decreases the evaluation error compared to the Gorlin Equation. The purpose of this paper is to modify the Agarwal – Okpara equation to generalize its applicability based on additional data calculated from the commercial CFD software FLUENT as well as the clinical data obtained from the literature. A total of ten cases are computed using CFD to assess the range of validity of the Gorlin equation and the Agarwal – Okpara equation. In addition, eighty clinical data points were obtained from the papers of Minners et al. [4] and Hakii et al. [5] covering a large range of severity of stenosis. The error in AVA computed from Gorlin equation and Agarwal – Okpara equation varied from 7.44 to 82.14% and 0.06 to 27.26% respectively compared to the CFD simulation data, and 41.47 to 83.60% and 8.88 to 33.98% respectively compared to the clinical data; however, AVA calculated using the Agarwal – Okpara – Bao equation presented in this paper gives results within 0.42 to 9.6% error compared to the exact AVA used in FLUENT simulations, and from 4.76 to 24.13% compared to the clinical data. The Agarwal – Okpara – Bao equation agrees with the clinical data for all relevant flow rates and full range of severity of stenosis. Thus, the use of Agarwal – Okpara – Bao equation to evaluate AVA in clinical practice is suggested.Copyright © 2015 by ASME

Arteriovenous fistula (AVF) is one type of vascular access which is a surgically created vein used to remove and return blood during hemodialysis [1]. It is a long-term treatment for kidney failure. Although clinical treatment and technology have both achieved great improvements in recent years, the vascular access for hemodialysis still has significant early failure rates after the insertion of AVF in patients [2]. Studies have shown that stenosis in the vascular access circuit is the single major cause for access morbidity. Majority of efforts to understand the mechanisms of stenosis formation, and its prevention and management have largely focused on understanding and managing this complication based on the pathophysiology, tissue histology and molecular biology; however these efforts have not resulted in significant progress to date. We believe that the major impact in this area will come from continued and accurate understanding of the hemodynamics, and by development of techniques of intervention to modulate factors such as flow rates, pressures and compliance of the circuit. The goal of this paper is to study anastomotic models of AV access using Computational Fluid Dynamics (CFD) and optimize them to minimize the wall shear stress (WSS). In order to achieve this goal, the commercial CFD software FLUENT [3] is employed in conjunction with a single objective genetic algorithm [4]. Computations for two types of AVF currently in use in clinical practice are performed. AVF with 25° angle/3–4mm diameter and 90° angle/3–5mm diameter are selected to conduct the optimization. A single-objective genetic algorithm is employed in the optimization process and a k-kl-ω turbulence model is employed in CFD simulations; this model can accurately compute transitional/turbulent flows. In order to optimize for the same flow conditions, a fixed boundary condition is used during the optimization process. Computations for 16 to 20 generations of the selected AVFs are obtained from the genetic algorithm solver. The maximum WSS in the two AVFs considered are 6997.8 and 7750 dynes/cm2; however, the maximum WSS in the shape-optimized AVFs are reduced to 3511.2 and 4293.9 dynes/cm2 respectively, which have decreased by 49.82% and 44.59% respectively. Thus, the probability of the formation of stenosis in AVFs and early failure rates of vascular access are reduced by using the optimized AVFs.

The components of situational awareness for the grid information network are analyzed, and models for evaluating the ability of situational awareness are established both in the information domain and the cognitive domain. In the information domain, three aspects of information quantity including completeness, accuracy and timeliness are proposed to evaluate the situational awareness ability. In the cognitive domain, the Logistic equation is established in combination with the quantitative analyses of the information domain in order to describe the change of the situational awareness from time to time. Keywords-the grid information network; situational awareness; completeness; accuracy; timeliness; Logistic.

The study was performed to analyze the proteomic profiling of doxorubicin-treated H9c2 cardiomyocytes in order to identify novel protein biomarkers associated with doxorubicin-induced cardiomyopathy. The protein profiling of H9c2 cells in response to doxorubicin at an apoptosis-induced concentration of 0.5 μM were compared using iTRAQ analysis. Western-blot analysis was used to confirm differentially expressed proteins identified in the proteomic study. A total of 22 differently expressed proteins were identified in doxorubicin-treated H9c2 cells including 15 up-regulated and 7 down-regulated proteins. Gene Ontology (GO) analysis revealed that 10 altered proteins were enriched in the process of apoptosis. We further validated the expression of cathepsin B and its possible regulator nuclear factor kappa B (NF-κB) in H9c2 cells were increased during doxorubicin treatment using Western-blots. Differentially expressed proteins might provide clues to clarify novel mechanisms underlying doxorubicin-induced cardiomyopathy. Our results also suggest that increased cathepsin B expression might be associated with NF-κB up-regulation, and the exact mechanisms need to be clarified.

Recently, engender mechanism for combat capability of system-of-systems based on information systems have been highlighted in the field of military theory research. The goal of this paper is to research on aggregation mechanism which is one of important aspects of engender mechanism. From the complex systems theory angle, the characteristic of the system-of-systems aggregation is analyzed, and the viewpoint that aggregation can be divided into index aggregation and system aggregation is suggested. On the basis of analyzing the aggregation relation of index aggregation, the analytic aggregation model is established. Using the CAS theory, the simulation modeling process and method of the system aggregation are proposed.

To evaluate Siglec-1 protein (CD169) and mRNA levels in peripheral blood monocytes of patients with primary biliary cirrhosis (PBC) and investigate its role in PBC pathogenesis by looking for correlations between Siglec-1 expression and key PBC associated biochemical indices.FACS analysis was used to identify the percentage of peripheral blood monocytes positive for both CD14 and Siglec-1 in (a) 45 PBC patients, (b) 40 patients with liver cirrhosis after hepatitis B infection and (c) 36 healthy controls. Siglec-1 mRNA was measured by real-time RT-PCR and serum biomarkers by routine biochemistry.The percentage of CD14-Siglec-1 double positive cells was significantly higher (p0.01) in PBC patients than in healthy controls or cirrhosis post-hepatitis patients (13.68 +/- 2.44%, 1.0 +/- 0.2 %, and 4.1 +/- 0.5 %, respectively). Siglec-1 mRNA expression in the PBC group was 3.42 times higher than in healthy controls (p0.01).We investigated the role of Siglec-1 in PBC by assessing its expression in mononuclear cells of PBC patients and levels of secreted cytokines in cell supernatants after Siglec-1 RNA interference. It is possible that elevated Siglec-1 expression in peripheral blood monocytes of PBC patients is correlated with monocyte-mediated inflammatory responses during the development of PBC.

Simulation experiment is one of the main approaches of the measure of effectiveness of C4ISR systems. Different phase of the construction of C4ISR system results different requirements of simulation and evaluation experimental methods. Six typical applying modes are summarized here and it is pointed out that the traditional method has to construct different environments and simulation systems for each mode separately. A new method is proposed to act as an overall and general experimental method and process, which can satisfy the different requirements of the traditional C4ISR system simulation experiment and evaluation. According, a platform and a suite of tools are developed to make an environment to support this method.

This study was intended to establish a method of purification of HPV16 L1 protein expressed in a prokaryotic system and to obtain the purified protein. The prokaryotic expression vector pGEX-4T-1-HPV16 L1 was constructed and transformed into E. coli BL21 cell, and induced by 1 mM IPTG to express HPV16L1 protein. The inclusion bodies were isolated and solubilized with 8 M urea. After the urea was removed by gradual dialysis, the denatured L1 protein were renatured and then were purified by affinity chromatography. The results showed that HPV16L1 protein formed inclusion bodies in bacterial expression system, suggesting that this assay can be used to purify HPV16L1 protein and hence provide a basis for studying the applications of HPV16 L1 protein.