Electrical stimulation (ES) is an attractive field among clinicians in the topic of wound healing, which is common yet complicated and requires multidisciplinary approaches. The conventional dressing and skin graft showed no promise on complete wound closure. These urge the need for the exploration of electrical stimulation to supplement current wound care management. This review aims to provide an overview of electrical stimulation in wound healing. The mechanism of galvanotaxis related to wound repair will be reviewed at the cellular and molecular levels. Meanwhile, different modalities of externally applied electricity mimicking a physiologic electric field will be discussed and compared in vitro, in vivo, and clinically. With the emerging of tissue engineering and regenerative medicine, the integration of electroconductive biomaterials into modern miniaturised dressing is of interest and has become possible with the advancing understanding of smart biomaterials.
In this work, the dielectrophoretic force (FDEP) response of Aluminium Microelectrode Arrays with tapered profile is investigated through experimental measurements and numerical simulations. A standard CMOS processing technique with a step for the formation of a tapered profile resist is implemented in the fabrication of Tapered Aluminium Microelectrode Arrays (TAMA). The FDEP is investigated through analysis of the Clausius-Mossotti factor (CMF) and cross-over frequency (fxo). The performance of TAMA with various side wall angles is compared to that of microelectrodes with a straight cut sidewall profile over a wide range of frequencies through FEM numerical simulations. Additionally, electric field measurement (EFM) is performed through scanning probe microscopy (SPM) in order to obtain the region of force focus in both platforms. Results showed that the tapered profile microelectrodes with angles between 60° and 70° produce the highest electric field gradient on the particles. Also, the region of the strongest electric field in TAMA is located at the bottom and top edge of microelectrode while the strongest electric field in microelectrodes with straight cut profile is found at the top corner of the microelectrode. The latter property of microelectrodes improves the probability of capturing/repelling the particles at the microelectrode’s side wall.
Biopolymers that mimic the extracellular matrix are favourable in tissue engineering. However, the rapid degradation and the lack of mechanical and enzymatic stabilities of these biopolymers prompt researchers to composite different biopolymers. In this study, we aim to develop an acellular gelatin-chitosan-cellulose nanocrystal (GCCNC) scaffold as a potential wound dressing. The GCCNC mixture was homogenised via ultrasonication and the genipin crosslinking was performed by magnetic stirring. The mixture was then frozen at − 80 °C for 6 h and freeze-dried. The effects of different ratios of gelatin and chitosan with cellulose nanocrystals on the physiochemical properties, mechanical properties, and cellular biocompatibility were studied. Our results herein showed that G3C7CNC demonstrated a homogenous interconnected porous structure with a good porosity (67.37 ± 9.09%) and pore size (148.46 ± 48.68 µm), acceptable swelling ratio (1071.11 ± 140.26%), adequate water vapour transmission rate (315.59 ± 25.27 g/m2/day), low contact angle (70.21 ± 6.79°), and sufficient mechanical strength (modulus of 64.67 ± 12.42 MPa). The lower biodegradation rate in the G3C7CNC (0.06 ± 0.01 mg/hr) compared to G10CNC (0.48 ± 0.07 mg/hr) together with the absence of glass transition phenomenon indicated an increase in both enzymatic and thermal stabilities. Furthermore, G3C7CNC was non-cytotoxic and biocompatible with human epidermal keratinocytes (HEKs) and human dermal fibroblasts (HDFs). The presence of collagen type I and α-smooth muscle actin expression in HDFs, together with the expression of cytokeratin-14 in HEKs, demonstrated our scaffold’s ability to maintain normal skin physiological functions. Therefore, this study proposes that the fabricated GCCNC scaffold could serve as a potential acellular skin substitute in managing chronic wounds.
Discussing the topic of the capability of dielectrophoresis (DEP) devices in terms of the selective detection and rapid manipulation of particles based on the DEP force (FDEP) via contactless methods is challenging in medical research, drug discovery and delivery. Nonetheless, the process of the selective detection and rapid manipulation of particles via contactless DEP based on dielectric particles and the surrounding medium can reduce the effects of major issues, including physical contact with the particles and medium contamination to overcome operational difficulties. In this review, DEP microelectromechanical system (MEMS) microelectrodes with a tapered profile for the selective detection and rapid manipulation of particles were studied and compared with those of conventional designs with a straight-cut profile. The main objective of this manuscript is to review the versatile mechanism of tapered DEP MEMS microelectrodes for the purpose of selective detection and rapid manipulation. Thus, this review provides a versatile filtration mechanism with the potential for a glomerular-based membrane in an artificial kidneys’ development solution for implementing engineered particles and cells by lateral attraction as well as vertical repulsion in the development of lab-on-a-chip applications. For tapered DEP MEMS microelectrodes, the scope of this study methodology involved the characterisation of DEP, modelling of the polarisation factor and the dynamic dielectric changes between the particles and medium. Comprehensive discussions are presented on the capability of tapered DEP microelectrodes to drive the selected particles and the simulation, fabrication and testing of the tapered profile. This study revealed an outstanding performance with the capability of producing two regions of high electric field intensity at the bottom and top edges of the side wall of tapered microelectrodes. Observations on particle separation mainly by the lateral attraction force of particles with positive DEP on the y-axis and vertical repulsion force of particles with negative DEP on the z-axis proved an efficient and uniform FDEP produced by tapered electrodes. In conclusion, this study confirmed the reliability and efficiency of the tapered DEP microelectrodes in the process of selective detection and rapid manipulation at a higher efficiency rate than straight-cut microelectrodes, which is significant in DEP technology applications.
Diabetes patients are at risk of having chronic wounds, which would take months to years to resolve naturally. Chronic wounds can be countered using the electrical stimulation technique (EST) by dielectrophoresis (DEP), which is label-free, highly sensitive, and selective for particle trajectory. In this study, we focus on the validation of polystyrene particles of 3.2 and 4.8 μm to predict the behavior of keratinocytes to estimate their crossover frequency (fXO) using the DEP force (FDEP) for particle manipulation. MyDEP is a piece of java-based stand-alone software used to consider the dielectric particle response to AC electric fields and analyzes the electrical properties of biological cells. The prototypic 3.2 and 4.8 μm polystyrene particles have fXO values from MyDEP of 425.02 and 275.37 kHz, respectively. Fibroblast cells were also subjected to numerical analysis because the interaction of keratinocytes and fibroblast cells is essential for wound healing. Consequently, the predicted fXO from the MyDEP plot for keratinocyte and fibroblast cells are 510.53 and 28.10 MHz, respectively. The finite element method (FEM) is utilized to compute the electric field intensity and particle trajectory based on DEP and drag forces. Moreover, the particle trajectories are quantified in a high and low conductive medium. To justify the simulation, further DEP experiments are carried out by applying a non-uniform electric field to a mixture of different sizes of polystyrene particles and keratinocyte cells, and these results are well agreed. The alive keratinocyte cells exhibit NDEP force in a highly conductive medium from 100 kHz to 25 MHz. 2D/3D motion analysis software (DIPP-MotionV) can also perform image analysis of keratinocyte cells and evaluate the average speed, acceleration, and trajectory position. The resultant NDEP force can align the keratinocyte cells in the wound site upon suitable applied frequency. Thus, MyDEP estimates the Clausius–Mossotti factors (CMF), FEM computes the cell trajectory, and the experimental results of prototypic polystyrene particles are well correlated and provide an optimistic response towards keratinocyte cells for rapid wound healing applications.
Purpose: – The purpose of this study is to design and characterize the dielectrophoretic (DEP) microelectrodes with various array structure arrangements in order to produce optimum non-uniform electric field for particle capture. The DEP-electrodes with 2D electrode structure was fabricated and characterized to see the effect of electrode structure configuration on the capture capability of the cells suspending in the solution. Design/methodology/approach: – The presented microelectrode array structures are made of planar conductive metal structure having same size and geometry. Dielectrophoretic force (FDEP) generated in the fluidic medium is initially simulated using COMSOL Multi-physics performed on two microelectrodes poles, which is then continued on three-pole microelectrodes. The proposed design is fabricated using standard MEMS fabrication process. Furthermore, the effect of different sinusoidal signals of 5, 10 and 15 volt peak to peak voltage (Vpp) at fixed frequency of 1.5 MHz on capturing efficiency of microelectrodes were also investigated using graphite metalloids particles as the suspended particles in the medium. The graphite particles that are captured at the microelectrode edges are characterized over a given time period. Findings: – Based on analysis, the capturing efficiency of microelectrodes at the microelectrode edges is increased as voltage input increases, confirming its dependency to the FDEP strength and direction of non-uniform electric field. This dependency to field consequently increases the surface area of the accumulated graphite. It is also showed that the minimum ratio of the surface accumulated area of captured graphite is 1, 2.75 and 9 μm2 for 5, 10 and 15 Vpp, respectively. The simulation result also indicates a significant improvement on the performance of microelectrodes by implementing third pole in the design. The third pole effect the particles in the medium by creating stronger non-uniform electric field as well as more selective force toward the microelectrodes’ edges. Originality/value: – The microelectrode array arrangement is found as a reliable method to increase the strength and selectivity of non-uniform electric field distribution that affect FDEP. The presented findings are verified through experimental test and simulation results.