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MXenes are novel 2-D materials which have been extensively investigated for use in advanced biocomposites, water purification, biosensors, bioimaging and antibacterial systems. However, the knowledge associated with the mechanism of cytotoxic response is still limited to lack of verification against 3D spheroid-type cultures. Herein, we present a report on the in vitro cytotoxicity of Ti2CTx MXene against cervical cancer cell lines (HeLa) in a form of 3D spheroid with comparison to 2D cell culture system. Ti2CTx MXenes can be characterized by their multi-layered structure that is produced by the efficient elimination of Al and appearance of the surface functional groups. The biological results with 2D and 3D HeLa indicated that the Ti2CTx MXene was moderately cytotoxic to cells and the cytotoxicity was dose dependent. Our results showed that the toxicity of MXenes is potentially due to direct contact of the Ti2CTx MXene with the cell membrane wall. The Raman spectra suggested that the Ti2CTx MXenes interfered with the cytoplasmic proteins’ conformation and the surrounding microenvironment. This inherently modified the biochemistry of the cell membrane and caused cell apoptosis. This paper contributes to the pool of knowledge regarding the biocompatibility and biophysical properties of Ti2CTx MXene.

Generating a tissue model mimicking the cervix could be useful for studying treatment of precancerous lesions. In this work, bioprinting of hexagon shaped alginate-gelatin scaffolds laden with HeLa spheroids was presented. The three-dimensional (3D) printing system was designed to extrude alginate-gelatin bioink of different viscosities at an extrusion rate of 1–5 mL/min and printing speed from 10 to 50 mm/s. The biophysical properties of the bioink were characterized using dynamic mechanical analysis, viscometer, degradation test, contact angle measurement, Fourier transform infrared spectroscopy (FTIR), live/dead cell stainings and Raman spectroscopy. The bioink formulated with 10% w/v of alginate and 50% w/v of gelatin (ALG10-Gel50) enabled high fidelity printing for the construction of a multilayered 3D structure. The viscosity of the bioink within 12 Pa s and viscoelasticity of the polymerized bioink (G′ = 0.074 MPa > G″ = 0.028 MPa) exhibited mechanical properties close to the in-vivo system. The scaffolds degraded 35% on the day 16 of culture. The polymerized bioinks exhibited hydrophilicity and contained amino groups as characterized by contact angles and FTIR measurements, respectively. In addition, the 3D microtissues laden in the scaffold were indicated with high cell viability at 95.25 ± 1.75% based on the live/dead cell stainings. The printed microtissues were characterized with the presence of deoxyribonucleic acid, lipids and amino acids associated with the collagen. This paper demonstrated the success in the bioprinting of multilayer hexagon shaped tissue model which is potentially useful for development of an in-vitro cervical cancer model.

Bioinks of 3D bioprinting have significant potential application in the field of tissue engineering to support cell attachment and proliferation. In this work, the alginate-gelatin-CELC (AGLC) bioink based on different compositions of alginate-gelatin (AG) hydrogel and cholesteryl ester liquid crystals (CELC) was prepared. Primarily, the alginate-gelatin hydrogel with certain concentration of Gelatin (10-50%w/v) was investigated. The printability of the hydrogel reached a minimum width of 1.8 mm at a flow rate of 1 mL/min when the Gelatin concentration was increased to 50 % w/v (AG1050). Subsequently, the respective polymers with 10% w/v Alginate and50% w/v Gelatin blended with 1%, 5%, 10%, 20%, 40%, and 60% w/v of CELC in the preparation of the alginate-gelatin-CELC bioink was further investigated. The printability of the bioink was examined by micro-extrusion based 3D bioprinter. The printability of the bioink enhanced by 27.8% as compared to AG1050 and reached a minimum width of 1.3 mm at a flow rate of 1 mL/min when the CELC concentration was increased to 40% and 60%. The tested properties of the bioink show that the CELC improve shear-thinning and lipid moieties properties to the composite bioink and hence, enhances its printability.

Although the antibacterial properties of MXene nanosheets containing Ti3C2Tx are known, their antifungal properties have not been well studied. Herein, we present for the first time a report on the antifungal properties of Ti3C2Tx MXene. The Ti3C2Tx MXene was obtained by first exfoliating MAX phase of Ti3AlC2 with concentrated hydrofluoric acid, then the Ti3C2Tx was intercalated and deliminated by ethanol treatment and ultrasonication process. The delaminated Ti3C2Tx MXene nanosheets (d-Ti3C2Tx) were characterized using field emission scanning electron microscopy (FE-SEM), energy dispersive X-ray (EDX), X-ray diffraction spectroscopy (XRD), and Raman spectroscopy. It was found that Ti3C2Tx MXene was characterized by lamellar structure alternating with layers of Ti, Al and C. The EDX results revealed that the delaminated Ti3C2Tx MXene nanosheets were composed of Ti, C, Si, O, F, and a trace amount of Al. The XRD and Raman spectra further indicated the elimination of Al and the formation of two-dimensional Ti3C2Tx MXene nanosheets. The antifungal activity of the delaminated Ti3C2Tx MXene was determined against Trichoderma reesei using the modified agar disc method. Observation using inverted phase contrastmicroscopy revealed inhibited fungus growth with the absence of hyphae around the discs treated wtih MXene. The surrounding of the control groups without an inclusion of MXene was found with large number of hyphae and spores. In addition, the spores of the fungi treated with the samples containing d-Ti3C2Tx MXene nanosheets did not germinate even after 11 days of culture. The results demonstrated disruption to the hemispheric structural formation of fungi colony, inhibition of hyphae growth and cell damage for fungi grown on the d-Ti3C2Tx MXene nanosheets. These new findings suggest that d-Ti3C2Tx MXene nanosheets developed in this work could be a promising anti-fungi material.

MXene based nanomaterial is an uprising two-dimensional material gaining tremendous scientific attentions due to its versatile properties for the applications in electronic devices, power generation, sensors, drug delivery, and biomedicine. However, the cytotoxic effects of MXene still remained a huge concern. Therefore, stringent analysis of biocompatibility of MXene is an essential requirement before introduction to human physiological system. Several in vitro and in vivo toxicological studies have been reported to investigate the interactions between MXenes with living organisms such as microbes, mammalian cells and animal models. The biological response and cytotoxicity reported were dependent on the physicochemical properties of MXene. The biocompatibility and cytotoxicity of MXene were dependent on size, dose, and surface coating. This review demystifies the in vitro and in vivo biocompatibility studies associated with MXene. Various methods proposed to mitigate the cytotoxicity of MXene for in vivo applications were revealed. The machine learning methods were developed to predict the cytotoxicity of experimentally synthesized MXene compounds. Finally, we also discussed the current research gaps of applying MXenes in biomedical interventions.

MXene is a recently emerged multifaceted two-dimensional (2D) material that is made up of surface-modified carbide, providing its flexibility and variable composition. They consist of layers of early transition metals (M), interleaved with n layers of carbon or nitrogen (denoted as X) and terminated with surface functional groups (denoted as Tx/Tz) with a general formula of Mn+1XnTx, where n = 1–3. In general, MXenes possess an exclusive combination of properties, which include, high electrical conductivity, good mechanical stability, and excellent optical properties. MXenes also exhibit good biological properties, with high surface area for drug loading/delivery, good hydrophilicity for biocompatibility, and other electronic-related properties for computed tomography (CT) scans and magnetic resonance imaging (MRI). Due to the attractive physicochemical and biocompatibility properties, the novel 2D materials have enticed an uprising research interest for application in biomedicine and biotechnology. Although some potential applications of MXenes in biomedicine have been explored recently, the types of MXene applied in the perspective of biomedical engineering and biomedicine are limited to a few, titanium carbide and tantalum carbide families of MXenes. This review paper aims to provide an overview of the structural organization of MXenes, different top-down and bottom-up approaches for synthesis of MXenes, whether they are fluorine-based or fluorine-free etching methods to produce biocompatible MXenes. MXenes can be further modified to enhance the biodegradability and reduce the cytotoxicity of the material for biosensing, cancer theranostics, drug delivery and bio-imaging applications. The antimicrobial activity of MXene and the mechanism of MXenes in damaging the cell membrane were also discussed. Some challenges for in vivo applications, pitfalls, and future outlooks for the deployment of MXene in biomedical devices were demystified. Overall, this review puts into perspective the current advancements and prospects of MXenes in realizing this 2D nanomaterial as a versatile biological tool.

In a conventional three-dimensional (3D) cell culture system based on microencapsulation, the calcium alginate microcapsules tend to rupture within 7 days of culture, causing unwanted cell leakage. The microencapsulation based on flicking model of calcium-alginate-polyethylene glycol (Ca-alg-PEG) was proposed to rectify this problem. An analytical model to simulate the flicking process based on the deflection of a needle cantilever was also successfully developed and used to predict the size of the microbeads. The size of the microbeads were ranged from 300 to 500 μm and it is controlled by varying the liquid flow rate from 4.8 to 366 μL/min and flicking speed from 70 to 120 rpm. Under a flicking force of 0.58 N, uniform sized and spherical shaped Ca-alginate-PEG microbeads were produced at a liquid flow rate of 40 μL/min and a flicking rate of 100 rpm. The microbeads were characterized by Field Emission Scanning Microscopy, Atomic Force Microscopy, Raman Spectroscopy and Nanoindentation, and the results indicated improved bio-physical properties of the ca-alginate microbeads after added with PEG. The cell viability test demonstrated that Ca-alginate-PEG microbeads were able to support the growth of viable HeLa cells into spheroids. Resilient calcium-alginate-polyethylene glycol (Ca-alg-PEG) microbeads were found to be able to last up to 15 days before rupturing and greatly reduced the cell leakage problem.

The human locomotion is studied through gait analysis and is best observed instrumentally rather than observing visually. Thus, a portable insole pressure mapping system is built to assist in studying the human gait cycle. The pressure distribution is determined by instrumentally mapping the insole using force sensitive resistive sensors that are connected to Arduino UNO via cables. The values are saved into a secure digital card that could be post processed. Hardware and software design phase are executed for the development of this project. The outcomes match to the knowledge of human gait definitions in static posture and normal walking.

Over the last two decades, design and fabrication of micromixer have been an emerging trend in research field of microfluidic. Micromixers are generally categorised into two types which are the passive micromixer dependent on pumping energy and active micromixer that relies on external energy to achieve fluid mixing in desired parameters. This paper presents the micromixing simulation of two fluids of different concentrations from two inlets to generate four distinguished concentration gradient of output in four outlets. The blueprint of the micromixer was designed using Solidworks, computer-aided design software. The 2D model design was imported to COMSOL Multiphysics 4.2 to simulate the fluid mixing. The suggested physic modules were applied on the 2D model to aid the fluids dilution and mixing process. Linear dilution was achieved by applying low flow rates to the micromixer.

Microfabrication technique based on microelectronic technology is commonly used to produce microfluidic devices but this technique involves with costly and toxic chemicals. In this paper, we proposed the use of patterned adhesive vinyl template to produce a poly-dimethylsiloxane (PDMS) microfluidic device that was applied to generate microbeads of calcium alginate for microencapsulation of cells. In the microfluidic system, an infusion pump of high flow rate (2000 µl/min) and a commercial syringe pump were used to emulsify the continuous and disperse phases of liquids in forming the microbeads. Microbeads of calcium alginate in the range of 438 ± 38–799 ± 20 µm were successfully produced using this environmental friendly technique.

Micromixing technology has drastically advanced in the past few decades. Micromixers are one of the elements in integrated microfluidic systems for chemical, analytical chemistry, pharmaceutical, and biological applications. In this study, two tier micromixer was used to mix and dilute two solutions of similar and different concentration in order to investigate performance of micromixer's mixing. This paper presents the fabrication of a designed micromixer using polydimethylsiloxane (PDMS) and vinyl tape methods which reduce time, cost and complexity of prototyping. The serpentine structure of the microchannels was designed to enhance both mixing and dilution. Two types of food dyes and distilled water were used to investigate the mixing performance of the micromixer followed by spectrophotometry analysis. It is observed that the single dye solution and distilled water shows better mixing performance compared to the micromixing of two dye solutions which was supported by the diffusion theory. 2.00 ml/min was the optimum flow rate that allow optimum mixing and dilution between two different concentrated liquids.

With the advancement in microfluidic technology, fluid flow control for syringe pump is always essential. In this paper, a mechatronic syringe pump will be developed and customized to control the fluid flow in a poly-dimethylsiloxane (PDMS) microfluidic device based on a polyimide laminating film. The syringe pump is designed to drive fluid with flow rates of 100 and 1000 μl/min which intended to drive continuous fluid in a polyimide based microfluidic device. The electronic system consists of an Arduino microcontroller board and a uni-polar stepper motor. In the system, the uni-polar stepper motor was coupled to a linear slider attached to the plunger of a syringe pump. As the motor rotates, the plunger pumps the liquid out of the syringe. The accuracy of the fluid flow rate was determined by adjusting the number of micro-step/revolution to drive the stepper motor to infuse fluid into the microfluidic device. With the precise control of the electronic system, the syringe pump could accurately inject fluid volume at 100 and 1000 μl/min into a microfluidic device.

Microtissue can be grown on soft substrates of hydrogel or liquid crystal gel. These gels are adherent to the microtissues and they may interfere fluorescence imaging as background noise due to their absorbance property. A microfluidic vibrational cleaner with polydimethylsiloxane (PDMS) microfluidic chip platform was proposed and developed to remove the residual gel of liquid crystal adhered to the microtissues. The microtissues were placed in a microfluidic chip attaching to a microfluidic vibrational platform. In the system design, two motorised vibrators vibrating attached to a microfluidic platform and generating vibration signals at 148 Hz and 0.89 Grms to clean the microtissues. The acceleration of the vibration increased gradually from 0 to 0.96 Grms when the duty cycle of PWM pulses increased from 50 - 90%. It dropped slightly to 0.89 Grms at 100% duty cycle. Irrigation water valve was designed to control the fluid flow from water pump during cleaning process. Water pumps were included to flush the channels of the microfluidic device. The signals in controlling the pump, motor and valve were linearly proportional to the duty cycles of the pulse width modulation signals generated from a microcontroller.