Electrical stimulation of titanium to promote stem cell orientation, elongation and osteogenesis

Electrical stimulation of cells allows exogenous electric signals as stimuli to manipulate cell growth, preferential orientation and bone remodelling. In this study, commercially pure titanium discs were utilised in combination with a custom-built bioreactor to investigate the cellular responses of human mesenchymal stem cells via in-vitro functional assays. Finite element analysis revealed the homogeneous delivery of electric field in the bioreactor chamber with no detection of current density fluctuation in the proposed model. The custom-built bioreactor with capacitive stimulation delivery system features long-term stimulation with homogeneous electric field, biocompatible, sterilisable, scalable design and cost-effective in the manufacturing process. Using a continuous stimulation regime of 100 and 200 mV/mm on cp Ti discs, viability tests revealed up to an approximately 5-fold increase of cell proliferation rate as compared to non-stimulated controls. The human mesenchymal stem cells showed more elongated and differentiated morphology under this regime, with evidence of nuclear elongation and cytoskeletal orientation perpendicular to the direction of electric field. The continuous stimulation did not cause pH fluctuations and hydrogen peroxide production caused by Faradic reactions, signifying the suitability for long-term toxic free stimulation as opposed to the commonly used direct stimulation regime. An approximate of 4-fold increase in alkaline phosphatase production and approximately 9-fold increase of calcium deposition were observed on 200 mV/mm exposed samples relative to non-stimulated controls. It is worth noting that early stem cell differentiation and matrix production were observed under the said electric field even without the presence of chemical inductive growth factors. STATEMENT OF SIGNIFICANCE: This manuscript presents a study on combining pure titanium (primarily preferred as medical implant materials) and electrical stimulation in a purpose-built bioreactor with capacitive stimulation delivery system. A continuous capacitive stimulation regime on titanium disc has resulted in enhanced stem cell orientation, nuclei elongation, proliferation and differentiation as compared to non-stimulated controls. We believe that this manuscript creates a paradigm for future studies on the evolution of healthcare treatments in the area of targeted therapy on implantable and wearable medical devices through tailored innovative electrical stimulation approach, thereby influencing therapeutic conductive and electroactive biomaterials research prospects and development

The global research of artificial intelligence in lung cancer: a 20-year bibliometric analysis

BackgroundLung cancer (LC) is the second-highest incidence and the first-highest mortality cancer worldwide. Early screening and precise treatment of LC have been the research hotspots in this field. Artificial intelligence (AI) technology has advantages in many aspects of LC and widely used such as LC early diagnosis, LC differential classification, treatment and prognosis prediction.ObjectiveThis study aims to analyze and visualize the research history, current status, current hotspots, and development trends of artificial intelligence in the field of lung cancer using bibliometric methods, and predict future research directions and cutting-edge hotspots.ResultsA total of 2931 articles published between 2003 and 2023 were included, contributed by 15,848 authors from 92 countries/regions. Among them, China (40%) with 1173 papers,USA (24.80%) with 727 papers and the India(10.2%) with 299 papers have made outstanding contributions in this field, accounting for 75% of the total publications. The primary research institutions were Shanghai Jiaotong University(n=66),Chinese Academy of Sciences (n=63) and Harvard Medical School (n=52).Professor Qian Wei(n=20) from Northeastern University in China were ranked first in the top 10 authors while Armato SG(n=458 citations) was the most co-cited authors. Frontiers in Oncology(121 publications; IF 2022,4.7; Q2) was the most published journal. while Radiology (3003 citations; IF 2022, 19.7; Q1) was the most co-cited journal. different countries and institutions should further strengthen cooperation between each other. The most common keywords were lung cancer, classification, cancer, machine learning and deep learning. Meanwhile, The most cited papers was Nicolas Coudray et al.2018.NAT MED(1196 Total Citations).ConclusionsResearch related to AI in lung cancer has significant application prospects, and the number of scholars dedicated to AI-related research on lung cancer is continually growing. It is foreseeable that non-invasive diagnosis and precise minimally invasive treatment through deep learning and machine learning will remain a central focus in the future. Simultaneously, there is a need to enhance collaboration not only among various countries and institutions but also between high-quality medical and industrial entities

A simple in vitro biomimetic perfusion system for mechanotransduction study

In mechanotransduction studies, flow-induced shear stress (FSS) is often applied to two-dimensional (2D) cultured cells with a parallel-plate flow chamber (PPFC) due to its simple FSS estimation. However, cells behave differently under FSS inside a 3D scaffold (e.g. 10 mPa FSS was shown to induce osteogenesis of human mesenchymal stem cells (hMSC) in 3D but over 900 mPa was needed for 2D culture). Here, a simple in vitro biomimetic perfusion system using borosilicate glass capillary tubes has been developed to study the cellular behaviour under low-level FSS that mimics 3D culture. It has been shown that, compared to cells in the PPFC, hMSC in the capillary tubes had upregulated Runx-2 expression and osteogenic cytoskeleton actin network under 10 mPa FSS for 24 h. Also, an image analysis method based on Haralick texture measurement has been used to identify osteogenic actin network. The biomimetic perfusion system can be a valuable tool to study mechanotransduction in 3D for more clinical relevant tissue-engineering applications

Electrical stimulation of titanium to promote stem cell orientation, elongation and osteogenesis.

From PubMed via Jisc Publications RouterHistory: received 2021-02-27, revised 2021-07-06, accepted 2021-08-06Publication status: aheadofprintElectrical stimulation of cells allows exogenous electric signals as stimuli to manipulate cell growth, preferential orientation and bone remodelling. In this study, commercially pure titanium discs were utilised in combination with a custom-built bioreactor to investigate the cellular responses of human mesenchymal stem cells via in-vitro functional assays. Finite element analysis revealed the homogeneous delivery of electric field in the bioreactor chamber with no detection of current density fluctuation in the proposed model. The custom-built bioreactor with capacitive stimulation delivery system features long-term stimulation with homogeneous electric field, biocompatible, sterilisable, scalable design and cost-effective in the manufacturing process. Using a continuous stimulation regime of 100 and 200 mV/mm on cp Ti discs, viability tests revealed up to an approximately 5-fold increase of cell proliferation rate as compared to non-stimulated controls. The human mesenchymal stem cells showed more elongated and differentiated morphology under this regime, with evidence of nuclear elongation and cytoskeletal orientation perpendicular to the direction of electric field. The continuous stimulation did not cause pH fluctuations and hydrogen peroxide production caused by Faradic reactions, signifying the suitability for long-term toxic free stimulation as opposed to the commonly used direct stimulation regime. An approximate of 4-fold increase in alkaline phosphatase production and approximately 9-fold increase of calcium deposition were observed on 200 mV/mm exposed samples relative to non-stimulated controls. It is worth noting that early stem cell differentiation and matrix production were observed under the said electric field even without the presence of chemical inductive growth factors. STATEMENT OF SIGNIFICANCE: This manuscript presents a study on combining pure titanium (primarily preferred as medical implant materials) and electrical stimulation in a purpose-built bioreactor with capacitive stimulation delivery system. A continuous capacitive stimulation regime on titanium disc has resulted in enhanced stem cell orientation, nuclei elongation, proliferation and differentiation as compared to non-stimulated controls. We believe that this manuscript creates a paradigm for future studies on the evolution of healthcare treatments in the area of targeted therapy on implantable and wearable medical devices through tailored innovative electrical stimulation approach, thereby influencing therapeutic conductive and electroactive biomaterials research prospects and development. [Abstract copyright: Copyright © 2021. Published by Elsevier Ltd.

Osteochondral Tissue Co‐Culture: An In Vitro and In Silico Approach

Osteochondral tissue engineering aims to regenerate functional tissue mimicking physiological properties of injured cartilage and its subchondral bone. Given the distinct structural and biochemical difference between bone and cartilage, bi-layered scaffolds and bioreactors are commonly employed. We present an osteochondral culture system which co-cultured ATDC5 and MC3T3-E1 cells on an additive manufactured bi-layered scaffold in a dual-chamber perfusion bioreactor. Also, finite element models (FEM) based on the micro-computed tomography (μCT) image of the manufactured scaffold as well as on the computer aided design (CAD) were constructed; the microenvironment inside the two FEM was studied and compared. In vitro results showed that the co-culture system supported osteochondral tissue growth in terms of cell viability, proliferation, distribution and attachment. In silico results showed that the CAD and the actual manufactured scaffold had significant differences in the flow velocity, differentiation media mixing in the bioreactor and fluid-induced shear stress (FSS) experienced by the cells. This system was shown to have desired microenvironment for ostechondral tissue engineering and it can potentially be used as an inexpensive tool for testing newly developed pharmaceutical products for osteochondral defects. This article is protected by copyright. All rights reserved

Changes in the extracellular microenvironment and osteogenic responses of mesenchymal stem/stromal cells induced by in vitro direct electrical stimulation

Electrical stimulation (ES) has potential to be an effective tool for bone injury treatment in clinics. However, the therapeutic mechanism associated with ES is still being discussed. This study aims to investigate the initial mechanism of action by characterising the physical and chemical changes in the extracellular environment during ES and correlate them with the responses of mesenchymal stem/stromal cells (MSCs). Computational modelling was used to estimate the electrical potentials relative to the cathode and the current density across the cell monolayer. We showed expression of phosphorylated ERK1/2, c-FOS, c-JUN, and SPP1 mRNAs, as well as the increased metabolic activities of MSCs at different time points. Moreover, the average of 2.5 μM of HO and 34 μg/L of dissolved Pt were measured from the electrically stimulated media (ES media), which also corresponded with the increases in SPP1 mRNA expression and cell metabolic activities. The addition of sodium pyruvate to the ES media as an antioxidant did not alter the SPP1 mRNA expression, but eliminated an increase in cell metabolic activities induced by ES media treatment. These findings suggest that HO was influencing cell metabolic activity, whereas SPP1 mRNA expression was regulated by other faradic by-products. This study reveals how different electrical stimulation regime alters cellular regenerative responses and the roles of faradic by-products, that might be used as a physical tool to guide and control cell behaviour.BBSRC grant (BB/M013545/1). It also receives funding from The Royal Thai Government Scholarship (ST 4729) and Rosetrees Trust (M48

Capacitive electrical stimulation of a conducting polymeric thin film induces human mesenchymal stem cell osteogenesis

Electroactive materials based on conductive polymers are promising options for tissue engineering and regenerative medicine applications. In the present work, the conducting copolymers of poly (3,4-ethylenedioxythiophene) and poly (d, l-lactic acid) (PEDOT-co-PDLLA) with PEDOT:PDLLA molar ratios of 1:50, 1:25, and 1:5 were synthesized and compared to the insulating macromonomer of EDOT-PDLLA as an experimental control. Bone marrow-derived human mesenchymal stem cells (hMSC-BM) were cultured on the copolymers and the macromonomer thin films inside a bioreactor that induced a capacitive electrical stimulation (CES) with an electric field of 100 mV/mm for 2 h per day for 21 days. Under CES, the copolymers exhibited good cell viability and promoted the differentiation from hMSC-BM to osteogenic lineages, revealed by higher mineralization mainly when the contents of conducting segments of PEDOT (i.e., copolymer with 1:25 and 1:5 PEDOT:PDLLA ratios) were increased. The results indicate that the intrinsic electrical conductivity of the substrates is an important key point for the effectiveness of the electric field generated by the CES, intending to promote the differentiation effect for bone cells