Search

Bioelectronics presents a promising future in the field of embedded and implantable electronics, providing a range of functional applications, from personal health monitoring to bioactuators. However, due to the intrinsic difficulties present in producing and optimizing bioelectronics, recent research has focused on utilizing machine learning (ML) to reliably mitigate such issues and aid in process development. This review focuses on the recent developments of integrating ML into bioelectronics, aiding in a multitude of areas, such as material development, fabrication process optimization, and system integration. First, discussing how ML has aided in the material development by identifying complex relationships between process input parameters and desired outputs, such as product design. Second, examine the advancements in ML to accurately optimize fabrication precision and stability for various 3D printing technologies. Third, provide an overview of how ML can greatly assist in the analysis of complex, nonlinear relationships in data obtained from bioelectronics. Lastly, a summary of the challenges present with utilizing ML with bioelectronics and any other developments in this field. Such advancements in the field of bioelectronics and ML could hopefully build a strong foundation for this research field, promoting smart optimization together with effective use of ML to further enhance the effectiveness of such applications.

PURPOSE: To assess baseline differences and longitudinal rate of change in retinal and choroidal imaging parameters between APOE ε4 carriers and non-carriers with normal cognition. DESIGN: Prospective study. SUBJECTS: 413 eyes of 218 individuals with normal cognition aged ≥55 years with known APOE status (98 ε4 carriers, 120 non-carriers). Exclusion criteria included diabetes mellitus, uncontrolled hypertension, glaucoma, and vitreoretinal or neurodegenerative disease. METHODS: Optical coherence tomography (OCT) and OCT angiography (OCTA) was performed at baseline and at 2 years [Zeiss Cirrus HD-OCT 5000 with AngioPlex (Zeiss Meditec, Dublin, CA)]. Groups were compared using sex- and age-adjusted generalized estimating equations. MAIN OUTCOME MEASURES: OCT: retinal nerve fiber layer thickness, macular ganglion cell-inner plexiform layer thickness, central subfield thickness (CST), choroidal vascularity index. OCTA: foveal avascular zone area, perfusion density (PD), vessel density, peripapillary capillary perfusion density and capillary flux index (CFI). Rate of change per year was calculated. RESULTS: At baseline, ε4 carriers had lower CST (p=0.018), PD in the 6mm Early Treatment Diabetic Retinopathy Study (ETDRS) circle (p=0.049), and temporal CFI (p=0.047). Seventy-one ε4 carriers and 78 non-carriers returned at 2 years; at follow-up, the 6mm ETDRS circle (p=0.05) and outer ring (p=0.049) showed lower PD in ε4 carriers, with no differences in rates of change between groups (all p>0.05). CONCLUSIONS: There was exploratory evidence of differences in CST, PD, and peripapillary CFI between APOE ε4 carriers and non-carriers, both with normal cognition. Larger and longer-term studies may further elucidate the potential value of these findings.

Introduction To elucidate the perceptions on eye care of patients affected by the disruption of outpatient and surgical ophthalmological services during the COVID-19 pandemic. Methods A cross-sectional questionnaire-based survey was conducted during the reopening of outpatient services at two tertiary eye care centres in Singapore and North India. Consecutive patients were recruited from general and specialist eye clinics in June 2020. Results A total of 326 patients were recruited, 200 patients from Singapore and 126 patients from New Delhi, India. The most common eye conditions were diabetic retinopathy and uveitis or ocular inflammatory conditions in the Indian centre, whereas the most common in the Singaporean centre were cataract in the pre- or postoperative stage and glaucoma. For patients from the Indian centre, 61.9% felt that COVID-19 had negatively impacted their eye disease, 58.7% were more distressed by their eye disease, 70.8% could not access appropriate eye care, 66.6% were afraid of contracting COVID-19 in the clinic, and 61.9% were accepting of teleconsultations. For patients from the Singaporean centre, 13.5% felt that COVID-19 had negatively impacted their eye disease, 19.5% were more distressed by their eye disease, 21.5% could not access appropriate eye care, 35% were afraid of contracting COVID-19 in the clinic, and only 31% were accepting of teleconsultations. Conclusion Patients from India appear to have been more negatively affected by the pandemic compared to patients from Singapore. This study highlights patients’ perceptions of the impact of COVID-19 on eye care, perceived risks, ease of access to care and attitudes towards eye care during the pandemic. Patients’ perceptions are integral in developing strategies for the best care possible. There were heterogeneous responses amongst our patients; hence, there may be a role for more individualized healthcare strategies in the future. Supplementary Information The online version contains supplementary material available at 10.1007/s40123-021-00444-0.

This study aimed to describe the topographic variation of the macula’s choroidal angioarchitecture using three-dimensional (3D) choroidal vascularity index (CVI) of healthy eyes from an Asian population and to investigate the associations of CVI. 50 participants were recruited via stratified randomisation based on subfoveal choroidal thickness from the Singapore Epidemiology of Eye Diseases Study. Macular volume scans were acquired using spectral-domain optical coherence tomography with enhanced depth imaging. CVI was assessed based on B-scan binarisation and choroid segmentation. The 3D CVI of the whole, superior, central, and inferior macula were 62.92 ± 1.57%, 62.75 ± 1.93%, 63.35 ± 1.72%, and 62.66 ± 1.70%, respectively, pairwise comparisons P all > 0.05). 3D CVI (Whole Macula) and 2D CVI (Subfoveal) were associated only with each other and not with other ocular and systemic factors. 2D CVI (Subfoveal) had a moderate agreement with 3D CVI (Central Macula) [intraclass corelation coefficient (ICC) = 0.719], and had poorer agreement with 3D CVI of the whole macula, superior, and inferior macula (ICC = 0.591, 0.483, and 0.394, respectively). Scanning volume did not influence 3D CVI measurements. In conclusion, 3D CVI demonstrated no significant topographic variation. CVI was not correlated with demographic or ocular structural features. 2D CVI of the fovea is partially representative of 3D CVI of the macula.

To evaluate differences in the retinal microvasculature and structure and choroidal structure among men and women with Alzheimer's disease (AD) compared with age-matched cognitively normal male and female controls.Case-control study of participants ≥ 50 years of age.A total of 202 eyes of 139 subjects (101 cases and 101 controls).All participants and controls underwent OCT and OCT angiography (OCTA), and parameters of subjects with AD were compared with those of cognitively normal controls.The foveal avascular zone (FAZ) area, vessel density (VD), and perfusion density (PD) in the superficial capillary plexus within the 3- and 6-mm circle and ring using Early Treatment Diabetic Retinopathy Study (ETDRS) grid overlay on OCTA; central subfield thickness (CST), retinal nerve fiber layer (RNFL) thickness, ganglion cell-inner plexiform layer (GCIPL) thickness, and choroidal vascularity index (CVI) on OCT.No significant sex differences in VD or PD were found in the AD or control cohorts; however, there were greater differences in VD and PD among AD female participants than AD male participants compared with their respective controls. The CST and FAZ area were not different between male and female AD participants. Among controls, men had a thicker CST (There may be a loss of the physiologic sex-related differences in retinal structure and microvasculature in those with AD compared with controls. Further studies are needed to elucidate the pathophysiological basis for these findings.

The choroidal vascularity index (CVI) is a relatively new parameter, calculated off optical coherence tomography (OCT) images, for the quantitative evaluation of choroid vascularity. It is defined as the ratio of vascular area to the total choroidal area, presented as a percentage. The choroid is an important vascular bed, often implicated in ocular and systemic conditions. Since the introduction of CVI, multiple studies have evaluated its efficacy as a tool for disease prognostication and monitoring progression, with promising results. The CVI was born out of the need for more robust and accurate evaluations of choroidal vasculature, as prior parameters such as choroidal thickness and choroidal vessel diameter had their limitations. In this review, we summarise current literature on the CVI, explain how the CVI is derived and explore its potential integration into future research and translation into clinical care. This includes the application of CVI in various disease states, and ongoing attempts to produce an automated algorithm which can calculate CVI from OCT images.

Electrochemical impedance spectroscopy (EIS), one of the techniques for electrochemical analysis, has been used for a wide range of applications especially chemical- and bio-sensing. Besides, EIS is one of the few techniques that has been proven useful for membrane fouling detection. Electrodes are some of the most essential components for analytes detection applications with EIS. With the advances in printing technology, the fabrication of advanced printed electrode systems with miniature designs and improved sensitivity for electrochemical sensing is made possible. This review addresses recent advances in printed electrodes for electrochemical impedance spectroscopy with the emphasis placed on discussing the use of printed electrodes for membrane fouling detection. Common electrode designs and materials for electrochemical impedance spectroscopy are discussed, along with practical examples of these printed electrodes. The commonly used printing techniques for the fabrication of printed electrodes are also deliberated. The successful realization of printed electrodes for EIS requires careful design of electrodes, proper selection of electrode materials, as well as optimization of the printing process. It is expected that printed electrodes will be widely accepted for EIS sensing applications and will facilitate the creation of low-cost high-performance sensing devices. Economic Development Board (EDB) National Research Foundation (NRF) Public Utilities Board (PUB) Accepted version This research is supported by PUB, Singapore’s National Water Agency under its Urban Solutions & Sustainability (Competitive Research Programme (CRP)(Water) Scheme, PUB-1804-0075) and the National Research Foundation, Prime Minister’s Oce, Singapore under its Medium-Sized Centre funding scheme. The financial support of the Economic Development Board (EDB) of Singapore to the Singapore Membrane Technology Centre (SMTC), Nanyang Environment & Water Research Institute (NEWRI) is greatly appreciated

Heart disease is the leading cause of death worldwide. Due to the limited regenerative ability of native myocardium, damaged myocardium cannot be restored. Advanced therapeutic approaches such as tissue engineering and regenerative medicine provides potential biological solutions to restore the function of damaged myocardium. Despite progresses in cardiac tissue engineering over the past decades, it is still far from mimicking the native myocardium. Some design considerations for engineering cardiac tissue includes inducing cell alignment, and attaining high cell density within a construct. Bioprinting, a computer-assisted technology, can potentially achieve the abovementioned considerations. In the native myocardium, fibre and cell orientation varies across different planar level. Bioprinting can potentially recapture this complexity through designing print path. The purpose of this project is to fabricate an engineered cardiac tissue via bioprinting. Extrusion-based bioprinting was investigated in terms of printing parameters and material properties to achieve required print resolution for efficient nutrient exchange in bioprinted cell-hydrogel construct. Next, a design framework was developed to characterize and formulate materials for bioprinting. The design framework was applied for material formulation in extrusion printing of C2C12 cells. Following which, a bioprinting strategy, termed support-assisted bioprinting, was established to produce three dimensionally defined constructs. Support-assisted bioprinting is a bioprinting strategy that uses a secondary material (support material) to provide mechanical stability for the primary material (build material) prior to crosslinking of the build material. Support-assisted bioprinting has demonstrated printing of three dimensionally defined cell-hydrogel, where hydrogel struts showed distinct 0o-90o angular difference at different height level. Cell alignment was achieved along the longitudinal axis of printed construct. The mechanism of cell-hydrogel remodelling process towards cell alignment in bioprinted construct was mapped for inducing cell alignment along strut orientation. Lastly, enabling technologies in data and cell processing were developed as translational measures towards organ printing. In data processing, machine readable print path using G-code was generated to reflect the differences in fibre orientation of left ventricle wall. This shows the feasibility of fabricating bioprinted construct that better mimics the architecture of myocardium. In cell processing towards high throughput cell aggregates formation, the use of 3D printed microfluidics was studied. These findings ascertained the potential of bioprinting towards directing cell alignment in a dimensionally defined construct. Doctor of Philosophy (MAE)

Aligned cells provide direction-dependent mechanical properties that influence biological and mechanical function in native tissues. Alignment techniques such as casting and uniaxial stretching cannot fully replicate the complex fibre orientation of native tissue such as the heart. In this study, bioprinting is used to direct the orientation of cell alignment. A 0°-90° grid structure was printed to assess the robustness of the support-assisted bioprinting technique. The variation in the angles of the grid pattern is designed to mimic the differences in fibril orientation of native tissues, where angles of cell alignment vary across the different layers. Through bioprinting of a cell-hydrogel mixture, C2C12 cells displayed directed alignment along the longitudinal axis of printed struts. Cell alignment is induced through firstly establishing structurally stable constructs (i.e. distinct 0°-90° structures) and secondly, allowing cells to dynamically remodel the bioprinted construct. Herein reports a method of inducing a macroscale level of controlled cell alignment with angle variation. This was not achievable both in terms of methods (i.e. conventional alignment techniques such as stretching and electrical stimulation) and magnitude (i.e. hydrogel features with less than 100 µm features). Nanyang Technological University National Research Foundation (NRF) This research is supported by the National Research Foundation, Prime Minister’s Office, Singapore under its Medium-Sized Centre funding scheme. This work is also supported by NTU start up grant and is funded by the Research Student Scholarship (NTU).

Silver nanoparticle based microelectrodes embedded between layers of hydrogel material were successfully fabricated. 3D bioprinting is employed to print the entire bioelectronics platform comprising of conducting silver ink and Gelatin methacryloyl (GelMA) hydrogel. The additive manufacturing technique of bioprinting gives design freedom for the circuit, saves material and shortens the time to fabricate the bioelectronics platform. The silver platform shows excellent electrical conductivity, structural flexibility and stability in wet environment. It is tested for biocompatibility using C2C12 murine myoblasts cell line. The work demonstrates the potential of the fabricated platform for the realization of practical bioelectronic devices. NRF (Natl Research Foundation, S’pore) Published version

Bioelectronics platforms are gaining widespread attention as they provide a template to study the interactions between biological species and electronics. Decoding the effect of the electrical signals on the cells and tissues holds the promise for treating the malignant tissue growth, regenerating organs and engineering new-age medical devices. This work is a step forward in this direction, where bio- and electronic materials co-exist on one platform without any need for post processing. We fabricate a freestanding and flexible hydrogel based platform using 3D bioprinting. The fabrication process is simple, easy and provides a flexible route to print materials with preferred shapes, size and spatial orientation. Through the design of interdigitated electrodes and heating coil, the platform can be tailored to print various circuits for different functionalities. The biocompatibility of the printed platform is tested using C2C12 murine myoblasts cell line. Furthermore, normal human dermal fibroblasts (primary cells) are also seeded on the platform to ascertain the compatibility. NRF (Natl Research Foundation, S’pore)

The use of hydrogels enables the encapsulation and patterning of living cells within 3-D environment that closely mimic the physical, chemical, and biological aspects of the native extracellular matrix (ECM). This chapter first reviews the developments, key characteristics, and applications of some commonly used and emerging hydrogels. It then discusses the compatibility between hydrogels and the bioprinting processes and highlights some of the recent emerging trends in hydrogel research.

Over the years, the field of bioprinting has attracted attention for its highly automated fabrication system that enables the precise patterning of living cells and biomaterials at pre-defined positions for enhanced cell-matrix and cell-cell interactions. Notably, vat polymerization (VP)-based bioprinting is an emerging bioprinting technique for various tissue engineering applications due to its high fabrication accuracy. Particularly, different photo-initiators (PIs) are utilized during the bioprinting process to facilitate the crosslinking mechanism for fabrication of high-resolution complex tissue constructs. The advancements in VP-based printing have led to a paradigm shift in fabrication of tissue constructs from cell-seeding of tissue scaffolds (non-biocompatible fabrication process) to direct bioprinting of cell-laden tissue constructs (biocompatible fabrication process). This paper, presenting a first-time comprehensive review of the VP-based bioprinting process, provides an in-depth analysis and comparison of the various biocompatible PIs and highlights the important considerations and bioprinting requirements. This review paper reports a detailed analysis of its printing process and the influence of light-based curing modality and PIs on living cells. Lastly, this review also highlights the significance of VP-based bioprinting, the regulatory challenges and presents future directions to transform the VP-based printing technology into imperative tools in the field of tissue engineering and regenerative medicine. The readers will be informed on the current limitations and achievements of the VP-based bioprinting techniques. Notably, the readers will realize the importance and value of highly-automated platforms for tissue engineering applications and be able to develop objective viewpoints towards this field. Accepted version

Multimaterials deposition, a distinct advantage in bioprinting, overcomes material's limitation in hydrogel-based bioprinting. Multimaterials are deposited in a build/support configuration to improve the structural integrity of three-dimensional bioprinted construct. A combination of rapid cross-linking hydrogel has been chosen for the build/support setup. The bioprinted construct was further chemically cross-linked to ensure a stable construct after print. This paper also proposes a file segmentation and preparation technique to be used in bioprinting for printing freeform structures. NRF (Natl Research Foundation, S’pore) Published version

Spatial distribution of biological cells plays a key role in tissue engineering for reconstituting the cellular microenvironment, and recently, acoustofluidics are explored as a viable tool for controlling structures in tissue fabrication because of its good biocompatibility, low-power consumption, automation capability, nature of non-invasive, and non-contact. Herein, a reusable acoustofluidic device is developed using surface acoustic waves for manipulating microparticles/cells to form a 3D matrix pattern inside a scaffold-based hydrogel contained in a millimetric chamber. The 3D patterned and polymerized hydrogel construct can be easily and safely removed from the chamber using a proposed lifting technique, which prevent any physical damages or contaminations and promote the reusability of the chamber. The generated 3D patterns of microparticles and cells are numerically studied using a finite-element method, which is well validated by the experimental results. The proposed acoustofluidic device is a useful tool for in vitro engineering 3D scaffold-based artificial tissues for drug and toxicity testing and building organs-on-chip applications. Ministry of Education (MOE) Nanyang Technological University The authors gratefully acknowledge the support of 1) Nanyang Technological University and the Ministry of Education of Singapore through a Ph.D. Scholarship and AcRF Tier 1 research grant (RG 96/18); 2) the UK Engineering and Physical Sciences Research Council (EPSRC) grants (EP/P018998/1); and 3) Special Interesting Group of Acoustofluidics funded by UK Fluids Network (EP/N032861/1).

Bioprinting is an emerging technology that allows the assembling of both living and non-living biological materials into an ideal complex layout for further tissue maturation. Bioprinting aims to produce engineered tissue or organ in a mechanized, organized, and optimized manner. Various biomaterials and techniques have been utilized to bioprint biological constructs in different shapes, sizes and resolutions. There is a need to systematically discuss and analyze the reported strategies employed to fabricate these constructs. We identified and discussed important design factors in bioprinting, namely shape and resolution, material heterogeneity, and cellular-material remodeling dynamism. Each design factors are represented by the corresponding process capabilities and printing parameters. The process-design map will inspire future biomaterials research in these aspects. Design considerations such as data processing, bio-ink formulation and process selection are discussed. Various printing and crosslinking strategies, with relevant applications, are also systematically reviewed. We categorized them into 5 general bioprinting strategies, including direct bioprinting, in-process crosslinking, post-process crosslinking, indirect bioprinting and hybrid bioprinting. The opportunities and outlook in 3D bioprinting are highlighted. This review article will serve as a framework to advance computer-aided design in bioprinting technologies.

Collagen is the most abundant extracellular matrix protein that is widely used in tissue engineering (TE). There is little research done on printing pure collagen. To understand the bottlenecks in printing pure collagen, it is imperative to understand collagen from a bottom-up approach. Here it is aimed to provide a comprehensive overview of collagen printing, where collagen assembly in vivo and the various sources of collagen available for TE application are first understood. Next, the current printing technologies and strategy for printing collagen-based materials are highlighted. Considerations and key challenges faced in collagen printing are identified. Finally, the key research areas that would enhance the functionality of printed collagen are presented. Nanyang Technological University National Research Foundation (NRF) This research was supported by the National Research Foundation, Prime Minister’s Office, Singapore under its Medium-Sized Centre funding scheme. This work was also supported by NTU start-up grant. This research was conducted in collaboration with HP Inc. and supported/partially supported by the Singapore Government through the Industry Alignment Fund-Industry Collaboration Projects Grant.

The multiphase Eulerian-Eulerian approach was applied to investigate heat transfer through an immersed tube in a turbulent fluidized bed computationally. Heat transfer occurred in the turbulent fluidized bed via four mechanisms: particle-tube conduction, particle-particle conduction, gas-tube convection and gas-particle convection. A strong correlation between heat transfer performance and particle distribution around the immersed tube was observed. Replacement of hot particles around the tube with cold particles promoted heat transfer. Three parametric studies on effects of fluidization regime, particle size and pulsed flow were conducted. It was observed that the heat transfer performance of a bubbling fluidized bed was superior to that of a turbulent fluidized bed. The size of gas pocket increased with increasing particle size. As the tube was enveloped by gas pockets for a longer period of time, particle-tube conduction was hindered and average heat transfer coefficient around the tube decreased. Two key weaknesses of a turbulent fluidized bed were identified to be formation of large gas pockets and presence of a stagnant zone above the tube. The novelty of the current study is the application of pulsed flow to address these weaknesses. It was observed that there existed an optimal pulsating frequency at which heat transfer in a turbulent fluidized bed was enhanced. When the pulsating amplitude was selected such that the fluidized bed oscillated between two different fluidization regimes, the heat transfer performance of the turbulent fluidized bed became comparable to that of a bubbling fluidized bed.

Water-in-water (W/W) emulsion is an interesting template for microentrapment of hydrophilic compounds due to biocompatible nature of its aqueous media. W/W emulsification can be established from a destabilised aqueous two-phase system (ATPS). In this study, binodal data of ATPSs comprising polyethylene glycol (PEG) and gelatin were generated. Binodal curves of PEG + gelatin + water systems were successfully correlated using non-linear empirical Merchuk equation, and the tie lines were constructed using lever-arm rule. The effects of temperature, type of gelatin, and molecular weight of PEG on the binodal curves were evaluated. Notably, a higher molecular weight of PEG decreased the concentration of gelatin required for two-phase formation. ATPSs made of gelatin bovine has a larger biphasic region than that of gelatin porcine. Gelatin microgel was successfully synthesized from the PEG + gelatin emulsion system via rapid cooling of the dispersed phase of gelatin. The size of gelatin microgel was reduced by a higher stirring speed, while a temperature as high as 333.15 K increased the size distribution of gelatin microgel. Lastly, the microentrapment of model protein, green fluorescent protein, was demonstrated. PEG/Gelatin system holds good potential for food engineering and delivery system.

This article aims to provide further classification of cell-compatible bioprinting processes and examine the concept of 3D bioprinting within the general technology field of 3D printing. These technologies are categorized into four distinct process categories, namely material jetting, vat photopolymerization, material extrusion and free-form spatial printing. Discussion will be presented on the definition of classification with example of techniques grouped under the same category. The objective of this article is to establish a basic framework for standardization of process terminology in order to accelerate the implementation of bioprinting technologies in research and commercial landscape. Published version

This study examines why non-financial publicly traded firms knowingly issue wealth destroying Rule 144A debt, which is associated with a negative announcement return and a higher yield. We provide a plausible ‘demand-side’ explanation (i.e. last-resort debt financing) for the motivation for issuing such debt. We also provide evidence as to what drives this negative reaction. Our findings suggest that the negative market impact is mainly driven by short-selling pressure from convertible bond arbitrageurs.

In recent years, computer-assisted technology has been adopted into the field of tissue engineering. The ability to control the input of cell/material using computer technology has spun an active field termed bioprinting. Of the three different types of bioprinting techniques, extrusion-based bioprinting allows deposition of material with varying viscosity range. Several studies optimise the bioprinting process to study the effect of extrusion printing and material parameters in relation to formation quality and cell viability. This article aims to develop a model for a time-pressure extrusion-based biodispensing system, providing a platform for future correlation studies.

In 3D bioprinting, printing resolution represents the deposited material in the x- and y-axes, while dimensionality defines the structural resolution of printed constructs. Dimensionality in 3D bioprinting can be defined as the resolution in the z-axis. The printing resolution, together with dimensionality, contributes to the overall shape fidelity of the bioprinted constructs. The in-depth understanding of physical processes for different printing technologies is imperative in controlling the print resolution and definition. In this article, bioprinting technologies are classified according to the physical processes that deposit or form the bioprinted construct. Due to the different fabrication processes in forming fundamental printed units (voxels), the definition of printability differs for each bioprinting technique. Another aspect of resolution is the spatial positioning of cells within each fundamental building unit. The proximity of cells in the bioprinted construct affects the physiological outcomes. The second aspect of 3D bioprinting technologies is the ability to control shape fidelity. Different strategies have been used to improve the construction of a 3D engineered tissue or organ. Lastly, moving toward complex tissue printing involves adding functionalities to the bioprinted construct. Data processing, material formulations, and integration of different fabrication technologies are key areas in bioprinting that can recapture the different hierarchical aspects of native tissues. This article presents a comprehensive overview of enhancing the resolution of the bioprinting construct and identifying methods to improve functionalities of bioprinted tissues. NRF (Natl Research Foundation, S’pore) Published version

Bioprinting is an emerging research field that has attracted tremendous attention for various applications; it offers a highly automated, advanced manufacturing platform for the fabrication of complex bioengineered constructs. Different bio-inks comprising multiple types of printable biomaterials and cells are utilized during the bioprinting process to improve the homology to native tissues and/or organs in a highly reproducible manner. This paper, presenting a first-time comprehensive yet succinct review of microvalve-based bioprinting, provides an in-depth analysis and comparison of different drop-on-demand bioprinting systems and highlights the important considerations for microvalve-based bioprinting systems. This review paper reports a detailed analysis of its printing process, bio-ink properties and cellular components on the printing outcomes. Lastly, this review highlights the significance of drop-on-demand bioprinting for various applications such as high-throughput screening, fundamental cell biology research, in situ bioprinting and fabrication of in vitro tissue constructs and also presents future directions to transform the microvalve-based bioprinting technology into imperative tools for tissue engineering and regenerative medicine.

Responsive nanomaterials have emerged as promising candidates as drug delivery vehicles in order to address biomedical diseases such as cancer. In this work, polymer-based responsive nanoparticles prepared by a supramolecular approach are loaded with doxorubicin (DOX) for the cancer therapy. The nanoparticles contain disulfide bonds within the polymer network, allowing the release of the DOX payload in a reducing environment within the endoplasm of cancer cells. In addition, the loaded drug can also be released under acidic environment. In vitro anticancer studies using redox and pH dual responsive nanoparticles show excellent performance in inducing cell death and apoptosis. Zebrafish larvae treated with DOX-loaded nanoparticles exhibit an improved viability as compared with the cases treated with free DOX by the end of a 3 d treatment. Confocal imaging is utilized to provide the daily assessment of tumor size on zebrafish larva models treated with DOX-loaded nanoparticles, presenting sustainable reduction of tumor. This work demonstrates the development of functional nanoparticles with dual responsive properties for both in vitro and in vivo drug delivery in the cancer therapy.

Fabrication techniques for cardiac tissue engineering have been evolving around scaffold-based and scaf-fold-free approaches. Conventional fabrication approaches lack control over scalability and homogeneous cell distribu-tion. Bioprinting provides a technological platform for controlled deposition of biomaterials, cells, and biological fac-tors in an organized fashion. Bioprinting is capable of alternating heterogeneous cell printing, printing anatomical rele-vant structure and microchannels resembling vasculature network. These are essential features of an engineered cardiac tissue. Bioprinting can potentially build engineered cardiac construct that resembles native tissue across macro to na-noscale.

Microfluidics has found ubiquitous presence in biological applications such as tissue spheroid fabrication and pharmacology investigation. The increasing prevalence and complexity demand a highly adaptable fabrication method for the rapid and convenient production of these microfluidic systems. 3D printing, as an emerging fabrication technique, was investigated in this paper. Microfluidic features were fabricated using two most widely used 3D printing technologies namely the inkjet printing and filament deposition techniques. The printing resolution, accuracy, repeatability, surface roughness, wetting ability, and biocompatibility of the printed microfluidic chips were characterized. The capability of 3D printing was demonstrated by printing a number of microfluidic devices such as rotational flow device and gradient generator. Results showed that 3D printing techniques were successful in making intricate microscale architectures and have the potential of greatly simplifying the manufacturing process.

Hydrogels are 3D networks that have a high water content. They have been widely used as cell carriers and scaffolds in tissue engineering due to their structural similarities to the natural extracellular matrix. Among these, smart hydrogels refer to a group of hydrogels that is responsive to various external stimuli such as pH, temperature, light, electric, and magnetic field. Combining the potential of 3D printing and smart hydrogels is an exciting new paradigm in the fabrication of a functional 3D tissue. In this article, we provide a state-of-the-art review on smart hydrogels and bioprinting. We identify the critical material properties needed for the most commonly used bioprinting techniques, namely extrusion-based, inkjet-based, and laser-based techniques. The latest progress in different smart hydrogel systems and their applications in bioprinting are presented. The challenges of printing these hydrogel systems are also highlighted. Lastly, we present the potentials and the future perspectives of smart hydrogels in 3D bioprinting.

Bioprinting, a computer-aided printing, is an emerging field in tissue engineering. The ability to print biological models from scanned medical images allows customizability in printed construct. Identifying input printing factors that affects dimensions of printed biological construct is important as it enables control over geometry of structure. Biocompatible hydrogel is used in bioprinting to incorporate cells into printing process. In this experiment, a time-pressure dispensing system is used. This article investigatesdifferent factors such as pressure of system, nozzle inner diameter, moving speed, and viscoelastic material that define the dimensions of printed construct. It is identified printed hydrogel achieves finer resolution at higher concentration, faster moving speed, smaller nozzle inner diameter and lower pressure. Published version

The purpose of this study is to develop a measurement instrument for customer satisfaction with internet banking (IBCS). A web survey was used with the subjects being internet banking users of Taiwanese banks. A total of 226 valid questionnaires were obtained with an 85% response rate. For the development of a standardised instrument, an exploratory factor analysis was used. The study demonstrates that all the items in the Doll and Torkzadeh instrument for end-user computing satisfaction measures are still valid in the context of internet banking, and that IBCS depends heavily on security and trust considerations on the internet.

Three-dimensional (3D) bioprinting strategies use computer-aided processes to enable automated simultaneous spatial patterning of cells and/or biomaterials. These technologies are suitable for a broad range of biomedical applications owing to their capability to produce structurally sophisticated and functionally relevant tissue constructs. Extrusion-based 3D bioprinting strategies were among the first modalities developed and are now arguably the most widely used for producing 3D tissue constructs. These technologies have rapidly evolved over the past two decades, providing a powerful tool set for the biofabrication of tissues that can facilitate translational efforts in the field. In this Primer, we describe the methodology of 3D extrusion bioprinting, focusing on the selection of hardware, software and bioinks. We expand upon recent advances in 3D extrusion bioprinting by illustrating the key variations that promote its biofabrication abilities. Finally, we provide an outlook on possible future refinements of the technology., 3D extrusion bioprinting methods can be used to produce tissue constructs in vitro and in situ and are arguably the most commonly used bioprinting strategies. In this Primer, Zhang and colleagues describe the variants of 3D extrusion bioprinting methods and their specific applications, considerations for the formulation of bioinks and strategies for assessing print quality. The authors conclude by looking to recent and upcoming developments in 4D printing and artificial intelligence-assisted dynamic printing strategies.