Bioelectric medicine: unveiling the therapeutic potential of micro-current stimulation.

Bioelectric medicine (BEM) refers to the use of electrical signals to modulate the electrical activity of cells and tissues in the body for therapeutic purposes. In this review, we particularly focused on the microcurrent stimulation (MCS), because, this can take place at the cellular level with sub-sensory application unlike other stimuli. These extremely low-level currents mimic the body's natural electrical activity and are believed to promote various physiological processes. To date, MCS has limited use in the field of BEM with applications in several therapeutic purposes. However, recent studies provide hopeful signs that MCS is more scalable and widely applicable than what has been used so far. Therefore, this review delves into the landscape of MCS, shedding light on the multifaceted applications and untapped potential of MCS in the realm of healthcare. Particularly, we summarized the hierarchical mediation from cell to whole body responses by MCS including its physiological applications. Our final objective of this review is to contribute to the growing body of literature that unveils the captivating potential of BEM, with MCS poised at the intersection of technological innovation and the intricacies of the human body.

Micro-Current Stimulation Suppresses Inflammatory Responses in Peptidoglycan-Treated Raw 264.7 Macrophages and Propionibacterium acnes-Induced Skin Inflammation via TLR2/NF-κB Signaling Pathway.

Acne is a common inflammatory disorder of the human skin and a multifactorial disease caused by the sebaceous gland and Propionibacterium acnes (P. acnes). This study aimed to evaluate the anti-inflammatory effect of micro-current stimulation (MC) on peptidoglycan (PGN)-treated raw 264.7 macrophages and P. acnes-induced skin inflammation. To specify the intensity with anti-inflammatory effects, nitric oxide (NO) production was compared according to various levels of MC. As the lowest NO production was shown at an intensity of 50 µA, subsequent experiments used this intensity. The changes of expression of the proteins related to TLR2/NF-κB signaling were examined by immunoblotting. Also, immunofluorescence analysis was performed for observing NF-κB p65 localization. All of the expression levels of proteins regarding TLR2/NF-κB signaling were decreased by the application of MC. Moreover, the application of MC to PGN-treated raw 264.7 cells showed a significant decrease in the amount of nuclear p65-protein. In the case of animal models with P. acnes-induced skin inflammation, various pro-inflammatory cytokines and mediators significantly decreased in MC-applied mice. In particular, the concentration of IL-1ß in serum decreased, and the area of acne lesions, decreased from the histological analysis. We suggest for the first time that MC can be a novel treatment for acne.

Micro-Current Stimulation Has Potential Effects of Hair Growth-Promotion on Human Hair Follicle-Derived Papilla Cells and Animal Model.

Recently, a variety of safe and effective non-pharmacological methods have been introduced as new treatments of alopecia. Micro-current electrical stimulation (MCS) is one of them. It is generally known to facilitate cell proliferation and differentiation and promote cell migration and ATP synthesis. This study aimed to investigate the hair growth-promoting effect of MCS on human hair follicle-derived papilla cells (HFDPC) and a telogenic mice model. We examined changes in cell proliferation, migration, and cell cycle progression with MCS-applied HFDPC. The changes of expression of the cell cycle regulatory proteins, molecules related to the PI3K/AKT/mTOR/Fox01 pathway and Wnt/ß-catenin pathway were also examined by immunoblotting. Subsequently, we evaluated the various growth factors in developing hair follicles by RT-PCR in MCS-applied (MCS) mice model. From the results, the MCS-applied groups with specific levels showed effects on HFDPC proliferation and migration and promoted cell cycle progression and the expression of cell cycle-related proteins. Moreover, these levels significantly activated the Wnt/ß-catenin pathway and PI3K/AKT/mTOR/Fox01 pathway. Various growth factors in developing hair follicles, including Wnts, FGFs, IGF-1, and VEGF-B except for VEGF-A, significantly increased in MCS-applied mice. Our results may confirm that MCS has hair growth-promoting effect on HFDPC as well as telogenic mice model, suggesting a potential treatment strategy for alopecia.

Characteristics of Sodium Polyacrylate/Nano-Sized Carbon Hydrogel for Biomedical Patch.

Conductive hydrogels were prepared for biomedical patch in order to improve the electrical conductivity. Sodium polyacrylate and nano-sized carbon were mixed and fabricated by aqueous solution gelation process in various contents of nano-sized carbon with 0.1, 0.5, 1.0 and 2.0 wt%. Sodium polyacrylate/nano-sized carbon conductive hydrogels were investigated by molecular structure, surface morphology and electrical conductivity. The conductivity of the hydrogel/nano-sized carbon conductive hydrogel proved to be 10% higher than conductive hydrogel without nano-sized carbon. However, it was founded that conductive hydrogels with nano-sized carbon content from 0.5 up to 2.0 wt% were remarkably decreased. This may be due to the non-uniform distribution of nano-sized carbon, resulting from agglomerates of nano-sized carbon. The developed hydrogel is intended for use in the medical and cosmetic fields that is applicable to supply micro-current from device to human body.

Effect of erythrocyte aggregation at pathological levels on NO/O2 transport in small arterioles.

This study examined the effects of red blood cell (RBC) aggregation at pathological levels on NO/O2 transport in small arterioles. Transient gas diffusion simulations were performed with in vivo cell-free layer (CFL) widths data obtained from arteriolar flows in the rat cremaster muscle. The CFL data were measured at physiological and pathological levels of aggregation under reduced flow conditions (pseudoshear rate = 31.4 ± 10.5 s-1). Our results showed that the mean peak NO concentration significantly decreased with increasing the aggregation level from non-aggregating to normal-aggregating (P < 0.05) and to hyper-aggregating (P < 0.01) conditions. In contrast, the partial O2 pressure (PO2) in pathological aggregating conditions significantly increased from those under non-aggregating (P < 0.001) and normal-aggregating (P < 0.05) conditions. Although the NO scavenging by RBCs could be impaired with a thicker CFL at higher levels of aggregation, the overall decrease in NO production due to reduction of wall shear stress with the thicker CFL dominantly limited the NO availability in tissue. On the other hand, the O2 availability in tissue increased due to the relatively high core hematocrit in the blood lumen with the thicker CFL.

A review of numerical methods for red blood cell flow simulation.

In this review, we provide an overview of the simulation techniques employed for modelling the flow of red blood cells (RBCs) in blood plasma. The scope of this review omits the fluid modelling aspect while focusing on other key components in the RBC-plasma model such as (1) describing the RBC deformation with shell-based and spring-based RBC models, (2) constitutive models for RBC aggregation based on bridging theory and depletion theory and (3) additional strategies required for completing the RBC-plasma flow model. These include topics such as modelling fluid-structure interaction with the immersed boundary method and boundary integral method, and updating the variations in multiphase fluid property through the employment of index field methods. Lastly, we summarily discuss the current state and aims of RBC modelling and suggest some research directions for the further development of this field of modelling.

Effects of cell-free layer formation on NO/O2 bioavailability in small arterioles.

We developed a new time-dependent computational model for coupled NO/O(2) transport in small arterioles that incorporates potential physiological responses (temporal changes in NO scavenging rate and O(2) partial pressure in blood lumen and NO production rate in endothelium) to the temporal cell-free layer width variations. Two relations between wall shear stress (WSS) and NO production rate based on the linear and sigmoidal functions were considered in this simulation study. The cell-free layer data used for the simulation were acquired from arteriolar flows (D=48.3 ± 1.9 µm) in the rat cremaster muscles under normal flow conditions (WSS=3.4-5.6 Pa). For both cases of linear and sigmoidal relations, temporal layer width variations were found to be capable of significantly enhancing NO bioavailability and this effect was more pronounced in the latter (P<0.0005) than the former (P<0.005). In contrast, O(2) bioavailability in the arteriolar wall was not considerably altered by the temporal layer width variations, irrespective of the relation. Prominent enhancement (P<0.005) of soluble guanylyl cyclase (sGC) activation in the smooth muscle by the temporal layer width variations were predicted for both relations. The extent of sGC activation was generally lower (P<0.01) in the case of the sigmoidal relation than that of the linear relation, suggesting a lesser tendency for arterioles to dilate with the former.

Suggestion of potential stent design parameters to reduce restenosis risk driven by foreshortening or dogboning due to non-uniform balloon-stent expansion.

The foreshortening or dogboning of a stent that occurs due to transient non-uniform balloon-stent expansion can induce a vascular injury, resulting in restenosis of the coronary artery. However, previous studies rarely considered the effects of transient non-uniform balloon expansion on analysis of the mechanical properties and behaviors of stents during stent deployment, nor did they determine design parameters to minimize the restenosis risk driven by foreshortening or dogboning. The aim of the current study was, therefore, to suggest potential design parameters capable of reducing the possibility of restenosis risk driven by foreshortening or dogboning through a comparative study of seven commercial stents using finite element (FE) analyses of a realistic transient non-uniform balloon-stent expansion process. The results indicate that using stents composed of opened unit cells connected by bend-shaped link structures, in particular the MAC Plus stent, and controlling the geometrical and morphological features of the unit cell strut or the link structure at the distal ends of stent may prevent restenosis risk caused by foreshortening or dogboning. This study provides a first look at the realistic transient non-uniform balloon-stent expansion by investigating the mechanical properties, behaviors, and design parameters capable of reducing the possibility of restenosis risk induced by the foreshortening or the dogboning.