Search

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.

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.

Microbeads have wide applications in biomedical engineering field that include drug delivery, encapsulation of biomolecules, tissue padding and tissue regeneration. In this paper, we report a simple, yet efficient, flicking technique to produce microcapsules of calcium alginate at a narrow distribution of size. The system consists of an infusion pump and a customised flicker that taps the syringe needle for dispersing microcapsules of sodium alginate that polymerised in the calcium chloride solution. The flow rate of the syringe pump and the velocity of the flicker were studied to achieve a well controlled and tunable size distribution of microbeads ranging from 200 to 400 μm. At a flow rate of 4 μl/min and flicking rate of 80 rpm, a narrow size distribution of microbeads were produced. Via this technique, HaCaT cells were encapsulated in calcium alginate microbeads that grown into microtissues with a size ranging from 100 to 300 μm after two weeks of culture. These microtissues could be potentially useful for pharmacological application.

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.

Cell migration is a key contributor to wound repair. This study presents findings indicating that the liquid crystal based cell traction force transducer (LCTFT) system can be used in conjunction with a bespoke cell traction force mapping (CTFM) software to monitor cell/surface traction forces from quiescent state in real time. In this study, time-lapse photo microscopy allowed cell induced deformations in liquid crystal coated substrates to be monitored and analyzed. The results indicated that the system could be used to monitor the generation of cell/surface forces in an initially quiescent cell, as it migrated over the culture substrate, via multiple points of contact between the cell and the surface. Future application of this system is the real-time assaying of the pharmacological effects of cytokines on the mechanics of cell migration.

Growing three dimensional (3D) cells is an emerging research in tissue engineering. Biophysical properties of the 3D cells regulate the cells growth, drug diffusion dynamics and gene expressions. Scaffold based or scaffoldless techniques for 3D cell cultures are rarely being compared in terms of the physical features of the microtissues produced. The biophysical properties of the microtissues cultured using scaffold based microencapsulation by flicking and scaffoldless liquid crystal (LC) based techniques were characterized. Flicking technique produced high yield and highly reproducible microtissues of keratinocyte cell lines in alginate microcapsules at approximately 350 ± 12 pieces per culture. However, microtissues grown on the LC substrates yielded at lower quantity of 58 ± 21 pieces per culture. The sizes of the microtissues produced using alginate microcapsules and LC substrates were 250 ± 25 μm and 141 ± 70 μm, respectively. In both techniques, cells remodeled into microtissues via different growth phases and showed good integrity of cells in field-emission scanning microscopy (FE-SEM). Microencapsulation packed the cells in alginate scaffolds of polysaccharides with limited spaces for motility. Whereas, LC substrates allowed the cells to migrate and self-stacking into multilayered structures as revealed by the nuclei stainings. The cells cultured using both techniques were found viable based on the live and dead cell stainings. Stained histological sections showed that both techniques produced cell models that closely replicate the intrinsic physiological conditions. Alginate microcapsulation and LC based techniques produced microtissues containing similar bio-macromolecules but they did not alter the main absorption bands of microtissues as revealed by the Fourier transform infrared spectroscopy. Cell growth, structural organization, morphology and surface structures for 3D microtissues cultured using both techniques appeared to be different and might be suitable for different applications.

Cells encapsulation is a micro-technology widely applied in cell and tissue research, tissue transplantation, and regenerative medicine. In this paper, we proposed a growth of microtissue model for the human keratinocytes (HaCaT) cell line and an oral squamous cell carcinoma (OSCC) cell line (ORL-48) based on a simple aerosol microencapsulation technique. At an extrusion rate of 20 μL/min and air flow rate of 0.3 L/min programmed in the aerosol system, HaCaT and ORL-48 cells in alginate microcapsules were encapsulated in microcapsules with a diameter ranging from 200 to 300 μm. Both cell lines were successfully grown into microtissues in the microcapsules of alginate within 16 days of culture. The microtissues were characterized by using a live/dead cell viability assay, field emission-scanning electron microscopy (FE-SEM), fluorescence staining, and cell re-plating experiments. The microtissues of both cell types were viable after being extracted from the alginate membrane using alginate lyase. However, the microtissues of HaCaT and ORL-48 demonstrated differences in both nucleus size and morphology. The microtissues with re-associated cells in spheroids are potentially useful as a cell model for pharmacological studies.

Microencapsulation technology had been widely used in biological study, drug delivery, cosmetic and also food industry. Previous methods developed for microencapsulation is complex in terms of their design and handling. A simple micro extruder device with vibration mode was developed to microencapsulate HaCaT cells in calcium alginate capsules at 10 to 60 Hz. The microencapsulated cells proliferated and formed into microtissues. Alginate lyase was applied to remove the microtissues from the encapsulation and for studying the cell adhesion in the microtissues. DAPI and live/dead cell stainings were applied to study the organisation and viability of cells, respectively. Via the nuclei staining, it was found that the distance between cells reduced as the incubation period increased. After 15 days of culture, the cells were viable as indicated by the fluorescence green expression of Calcein-AM. Replating experiment indicated that the cells from the microtissues were able to migrate and has the tendency to form monolayer of cells on the culture flask.

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.

Microencapsulation of cells for various applications is attracting increasing interest. A variety of microencapsulation technology has been developed to produce cells encapsulation. However, previous microencapsulation systems were associated with complex design, high voltage supply, requirements of post cleaning process and large volume of reagents. In this paper, we proposed the development of a flicking device for generating a 3D cell model in calcium alginate microbeads that has potential for pharmacological test and tissue implants. A flicking system based on a flicking device and a syringe pump has been developed for generation of calcium alginate microbeads. The size of the microbeads produced using this system can be controlled by changing the flow rate (5 to 15 µl/min) of the syringe pump and fixing the motor rotation speed of the flicking device at 90 rpm. The calcium alginate microbeads produced using the flicking device were shown to be size controllable (270 to 430 µm) and suitable for microencapsulation.

The encapsulation of living cells in a variety of soft polymers or hydrogels is important, particularly for the generation of microtissues. Various techniques have been developed for the production of microcapsules to encapsulate cells but presented threat to the cells due to the harsh treatment during the encapsulation process. In this paper, we propose a simple, economic and compact design of aerosol electronic system for producing different sizes of microcapsules. The aerosol system was developed with the incorporation of a conventional syringe pump and a customised air pump. The syringe pump purged the droplets of sodium alginate and air pump dispersed the droplets into microdroplets of sodium alginate which was then polymerised in the calcium chloride solution. In this system, the air flow rate from the air pump was controlled by a programmed microcontroller that received input instructions from a potentiometer. The suitable air flow rates that worked synchronously with the speed of the syringe pump were characterised. At 0.2 and 0.3 L/min of air flow and 20 µl/min of alginate solution flow, this device successfully generated round microcapsules with various sizes ranging from 100 to 350 µm.

Microtissues can be cultured on the hydrogel, liquid crystal substrate and scaffolds. Therefore, a cleaner has been developed to clean the microtissue extracted from the culture substrate such as the cholesteryl ester liquid crystal (CELC). Clean microtissue samples were required for the precise experimental output. The cleaner performance was verified by observing the CELC’s birefringence properties around microtissue through cross-polarising microscope. In addition, the effects of mechanical vibration that generated by the microtissue cleaner onto the microtissue sample were investigated by live/dead cells assay. Based on the results, 3D microtissue cleaner was effectively cleaned microtissue after three replicated cleaning steps. Two minutes of continuous vibration frequency at 148 Hz and acceleration of 0.89 Grms were suitable to clean the microtissue.

This paper presents the design and development of an electrical above knee prosthesis, which works as a passive knee prosthesis in part of gait cycle phases and as an active knee prosthesis during other portions. During the passive mode, the system works as a non-holonomic system, and the dynamic coupling between the thigh segment and the knee prosthesis is used to control the prosthesis. Therefore, this knee prosthesis is designed to be back-drivable in passlve mode. In order to present a proper design for the knee prosthesis, the mechanism synthesis and analysis for the proposed back-drivable semi-active knee prosthesis are covered in this paper.