Search

Biophysical stimulation regulates stem cell functions, including proliferation and differentiation. Matrix nanotopography and external forces, such as electromagnetic fields (EMF), can enhance this stimulation. Here, it is demonstrated that biophysical multiple cues coordinated from electromagnetized Au‐nanoparticles‐decorated polymer nanofiber under EMF significantly regulate the adhesion, alignment, proliferation, and lineage commitment of hMSCs. Without EMF, matrix cues of electrical conductivity and nanodotted fibrous topography accelerate the anchorage and spreading of hMSCs. Of note, EMF synergizes with the matrix cues to enhance cellular behaviors, resulting in elongated and aligned cells along the field direction. Microtubules are highly polymerized, acetylated, and aligned, playing an active role in these events. Actin filaments also develop in parallel with the microtubules, facilitating actin‐microtubule crosstalks. These phenomena lead to changes in the nuclear mechanics of hMSCs, including elongated nuclear shape and decondensed chromatins with histone acetylation. The EMF+matrix‐stimulated hMSCs express genes related to microtubule organization and euchromatin, as revealed by RNA sequencing, and show chromatin accessibility with enrichment of genes related to mechanotransduction and lineage specification, as analyzed by ATAC sequencing. The EMF+matrix biophysical stimulation further increases the capacity for lineage specification (predominantly towards osteogenic, myogenic, and tenogenic), offering a promising bioengineering platform for stem cell engineering and therapies. [ABSTRACT FROM AUTHOR]

Ample proof showed that non‐coding RNAs (ncRNAs) play a crucial role in proliferation and differentiation of osteoblasts and bone marrow stromal cells (BMSCs). Varied forms of biophysical stimuli like mechanical strain, fluid shear stress (FSS), microgravity and vibration are verified to regulate ncRNAs expression in osteogenic differentiation and influence the expression of target genes associated with osteogenic differentiation and ultimately regulate bone formation. The consequences of biophysical stimulation on osteogenic differentiation validate the prospect of exercise for the prevention and treatment of osteoporosis. In this review, we tend to summarize the studies on regulation of osteogenic differentiation by ncRNAs beneath biophysical stimulation and facilitate to reveal the regulatory mechanism of biophysical stimulation on ncRNAs, and provide an update for the prevention of bone metabolism diseases by exercise. [ABSTRACT FROM AUTHOR]

Objective: Chronic nerve compression (CNC) injuries occur when peripheral nerves are subjected to sustained mechanical forces, with increasing evidence implicating Schwann cells as key mediators. Integrins, a family of transmembrane adhesion molecules that are capable of intracellular signaling, have been implicated in a variety of biological processes such as myelination and nerve regeneration. In this study, we seek to define the physical stimuli mediating demyelination and to determine whether integrin plays a role in the demyelinating response. Methods: We used a previously described in vitro model of CNC injury where myelinating neuron-Schwann cell cocultures were subjected to independent manipulations of hydrostatic pressure, hypoxia, and glucose deprivation in a custom bioreactor. We assessed whether demyelination increased in response to applied manipulation and determined whether integrin-associated signaling cascades are upregulated. Results: Biophysical stimulation of neural tissue induced demyelination and Schwann cell proliferation without neuronal or glial cytotoxicity or apoptosis. Although glucose deprivation and hypoxia independently had minor effects on myelin stability, together they potentiated the demyelinating effects of hydrostatic compression, and in combination, significantly destabilized myelin. Biophysical stimuli transiently increased phosphorylation of the integrin-associated tyrosine kinase Src within Schwann cells. Silencing this integrin signaling cascade blocked Src activation and prevented pressure-induced demyelination. Colocalization analysis indicated that Src is localized within Schwann cells. Interpretation: These results indicate that myelin is sensitive to CNC injury and support the novel concept that myelinating cocultures respond directly to mechanical loading via activating an integrin signaling cascade. ANN NEUROL 2012;72:112-123 [ABSTRACT FROM AUTHOR]

A plethora of antimicrobial strategies are being developed to address prosthetic infection. The currently available methods for implant infection treatment include the use of antibiotics and revision surgery. Among the bacterial strains, Staphylococcus species pose significant challenges particularly, with regard to hospital acquired infections. In order to combat such life threatening infectious diseases, researchers have developed implantable biomaterials incorporating nanoparticles, antimicrobial reinforcements, surface coatings, slippery/non-adhesive and contact killing surfaces. This review discusses a few of the biomaterial and biophysical antimicrobial strategies, which are in the developmental stage and actively being pursued by several research groups. The clinical efficacy of biophysical stimulation methods such as ultrasound, electric and magnetic field treatments against prosthetic infection depends critically on the stimulation protocol and parameters of the treatment modality. A common thread among the three biophysical stimulation methods is the mechanism of bactericidal action, which is centered on biophysical rupture of bacterial membranes, the generation of reactive oxygen species (ROS) and bacterial membrane depolarization evoked by the interference of essential ion-transport. Although the extent of antimicrobial effect, normally achieved through biophysical stimulation protocol is insufficient to warrant therapeutic application, a combination of antibiotic/ROS inducing agents and biophysical stimulation methods can elicit a clinically relevant reduction in viable bacterial numbers. In this review, we present a detailed account of both the biomaterial and biophysical approaches for achieving maximum bacterial inactivation. Summarizing, the biophysical stimulation methods in a combinatorial manner with material based strategies can be a more potent solution to control bacterial infections. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 2174-2190, 2017. [ABSTRACT FROM AUTHOR]

The effect of pulsed electromagnetic fields (PEMFs) on the integration of osteochondral autografts was evaluated in sheep. After osteochondral grafts were performed, the animals were treated with PEMFs for 6 h/day or sham-treated. Six animals were sacrificed at 1 month. Fourteen animals were treated for 2 months and sacrificed at 6 months. At 1 month, the osteogenic activity at the transplant-host subchondral bone interface was increased in PEMF-treated animals compared to controls. Articular cartilage was healthy in controls and stimulated animals. At 6 months, complete resorption was observed in four control grafts only. Cyst-like resorption areas were more frequent within the graft of sham-treated animals versus PEMF-treated. The average volume of the cysts was not significantly different between the two groups; nevertheless, analysis of the variance of the volumes demonstrated a significant difference. The histological score showed no significant differences between controls and stimulated animals, but the percentage of surface covered by fibrous tissue was higher in the control group than in the stimulated one. Interleukin-1 and tumor necrosis factor-α concentration in the synovial fluid was significantly lower, and transforming growth factor-β1 was significantly higher, in PEMF-treated animals compared to controls. One month after osteochondral graft implantation, we observed larger bone formation in PEMF-treated grafts which favors early graft stabilization. In the long term, PEMF exposure limited the bone resorption in subchondral bone; furthermore, the cytokine profile in the synovial fluid was indicative of a more favorable articular environment for the graft. © 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 26:631-642, 2008 [ABSTRACT FROM AUTHOR]

The present study reports the impact of the interplay between electroactive properties of the biomaterials and electrical stimulation (ES) toward the cell proliferation, migration and maturation of osteoprogenitors (preosteoblasts; MC3T3‐E1) on the electroactive poly (vinylidene difluoride) (PVDF)‐based composites. The barium titanate (BaTiO3; BT; 30 wt%) and multiwalled carbon nanotubes (MWCNT; 3 wt%) were introduced into the PVDF via melt mixing, which led to an enhancement of the dielectric permittivity, electrical conductivity, and surface roughness. We also present the design and development of an in‐house customized 12‐well plate‐based device for providing different types (DC, square, biphasic) of ES to cells in culture in a programmable manner. In the presence of ES of 1 V cm−1, biophysical stimulation experiments performed using 12‐well plate‐based device revealed that PVDF composite (PVDF/30BT/3MWCNT) can facilitate the enhanced adhesion and proliferation of the MC3T3‐E1 in non‐osteogenic media, with respect to non‐stimulated conditions. Importantly, MC3T3‐E1 cells demonstrated significantly better migration and differentiation on the PVDF/30BT/3MWCNT under ES when compared to ES‐free culture conditions. Similar enhancement with respect to alkaline phosphatase activity, intracellular Ca2+ concentration, and calcium deposition in MC3T3‐E1 cells was recorded, when pre‐osteoblasts were grown for 21 days on electroactive substrates. All these observations supported the activation of osteo‐differentiation fates, which were further promoted in the osteogenic medium. The present study demonstrates that the synergistic interactions of ES with piezoelectric PVDF‐based polymer composite can potentially enhance the proliferation, migration, and osteogenesis of the pre‐osteoblast cells, rendering it a promising bioengineering strategy for bone tissue engineering. [ABSTRACT FROM AUTHOR]

Background and Purpose Exogenous electromagnetic fields (EMFs) affect bone metabolism, but the mechanisms responsible for this phenomenon are unclear. Pulsed EMFs (PEMFs) can be effective in the management of congenital pseudarthrosis or delayed union or non-union of fractures. We investigated the effects of PEMFs used in clinical practice on human osteoblast cultures. Methods Primary osteoblastic cells were isolated from a human femoral head. Cultures were exposed to the PEMF stimulation for 72 hours, 7 and 10 days and compared with a control group of primary osteoblastic cells non-exposed to PEMF. Cell growth and alkaline phosphatase activity were evaluated in the osteoblast cell cultures at each observation time. Results At each observation time, the differences in cell numbers between PEMF-exposed cells and control group were statistically significant ( p < 0.05). The alkaline phosphatase-specific activity of PEMF-exposed osteoblast cultures showed a statistically significant ( p < 0.05) increase when compared with the control group after 7 and 10 days of exposure. Conclusions The application of PEMF stimulation on human osteoblasts accelerates cellular proliferation when compared with a control group of non-PEMF-exposed cells. Copyright © 2012 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Administration of exogenous hyaluronic acid (HA) by liquid jet injection is considered as a beneficial therapy for dermatology conditions. This paper reviews variety of the factors which would optimize the clinical output of hyaluronic acid in this treatment modality. A pneumatically accelerated jet penetrates the epidermis and spherically spreads micro‐droplets of HA in the dermis without significant damage to the tissue and blood vessels. Kinetic energy of the jet activates two parallel mechanisms of action—mechanical and biological—which act synergistically to initiate and augment the regenerative effect. Jet‐induced micro‐trauma stimulates collagen synthesis and tissue repair without inflammation. Aside from the biophysical stimulation of dermal fibroblast, the biomolecular properties of exogenous HA provide excellent clinical results for skin atrophy, remodeling of dermal scarring, and reverse formation of fibrotic tissue. The effect is mediated by HA‐specific cell receptors and depends on molecular weight and the rheological properties of HA polymer. Skin mechanical properties play a key role in predicting HA dispersion patterns. Tolerability and safety of the treatment approach are determined by the jet's physical impact on the tissue and/or by the safety profile of the injected material. Although pneumatic jet delivery of a hyaluronic acid has a limited use in clinical practice, this treatment approach has a strong potential for extended implementation in esthetic dermatology. The synergistic mechanism has significant advantages of predictable and rapid clinical outcomes with a low discomfort. Additional well‐designed investigations are required for establishing a scientific foundation and guidelines for this treatment modality. [ABSTRACT FROM AUTHOR]

Aims: To explore the distribution of site‐specific volumetric bone mineral density (vBMD) and analyze the mechanism of vertebral compression fractures with type 2 diabetes mellitus (T2DM) subjects using quantitative computed tomography (QCT). Materials and Methods: 304 postmenopausal women without T2DM and 274 postmenopausal women with T2DM underwent QCT scan, and all divided into three age subgroups. L1 vertebra was segmented into nine zones based on the corresponding position to the human body. Results: Whether in the T2DM or non‐T2DM of each age group, from the ventral to the dorsal side of L1 vertebra, the posterior third zones were the highest, and from the head to the foot of L1 vertebra, the middle third zones were the highest (p < 0.05). Global and most zonal vBMDs of T2DM were higher than those of non‐T2DM in the age group of 50–59 years old, vBMD‐mp of T2DM was higher in the age group of 60‐59 years old, and vBMD‐mm of T2DM was higher in the age group of 70–80 years old (p < 0.05). Zonal vBMDs in T2DM were higher than non‐T2DM and the difference decreases with age especially in the upper third of L1 vertebra and the lower third of L1 vertebra. Conclusions: Vertebral compression fractures and the confusion between T2DM and vBMD may be all caused by the heterogeneous distribution of vBMDs. The higher risk of T2DM with vertebral compression fractures may be associated with the different loss rate of global and site‐specific vBMD, independent of vBMD itself. [ABSTRACT FROM AUTHOR]

Nowadays, a high-induction magnetic stimulation is starting to be increasingly applied as a biophysical stimulation in the conservative treatment of the degenerative locomotor system diseases. These are mainly in correlation with the changes in soft tissue elasticity, which should be positively influenced by the flow-induced electrical currents of high current density during high-induction magnetic stimulation. This assumption was verified within the interventional and prospective study using the ultrasound elastography. The group consisted of 6 volunteers, whose elasticity of the patellar tendons was measured using the 2D shear-wave ultrasound elastography. The volunteers were then exposed to a 20-minute high-induction magnetic stimulation session with a frequency of 20 Hz, in 2 s package intervals, with a 5 s pause, and a induced electric current density of 100 Am−2 in the tendons area. A tendon tension was measured five times for all volunteers, where mean tension at the marked area of the tendon, as well as the highest point tension indicated by the Q-Box, was monitored. The measurement results show that high-induction magnetic stimulation has an influence on the patellar tendon tension change, which occurred in the case of all involved volunteers when the patellar tension was decreased. [ABSTRACT FROM AUTHOR]

The escalating demands for smart biomedical systems ignite a significantly growing influence of three‐dimensional (3D) printing technology. Recognized as a revolutionary and potent fabrication tool, 3D printing possesses unparalleled capabilities for generating customized functional devices boasting intricate and meticulously controlled architectures while enabling the integration of multiple functional materials. These distinctive advantages arouse a growing inclination toward customization and miniaturization, thereby facilitating the development of cutting‐edge biomedical systems. In this comprehensive review, the prevalent 3D printing technologies employed in biomedical applications are presented. Moreover, focused attention is paid to the latest advancements in harnessing 3D printing to fabricate smart biomedical systems, with specific emphasis on exemplary ongoing research encompassing biomedical examination systems, biomedical treatment systems, as well as veterinary medicine. In addition to illuminating the promising potential inherent in 3D printing for this rapidly evolving field, the prevailing challenges impeding its further progression are also discussed. By shedding light on recent achievements and persisting obstacles, this review aims to inspire future breakthroughs in the realm of smart biomedical systems. [ABSTRACT FROM AUTHOR]

ABSTRACT In vitro manipulation of human stem cells is a critical process in regenerative medicine and cellular therapies. Strategies and methods to maintain stem cells and direct them into specific lineages are ongoing challenges in these fields. To date, a number of studies have reported that besides biochemical stimulation, biophysical cues in the form of surface patterning and external stimulation also influence stem cell attachment, proliferation, and differentiation, and can be used in cell reprogramming and the maintenance of pluripotency. While biochemical cues are generally effective and easy to deliver, biophysical cues have many other advantages for scalability as they are cost efficient, have a longer lifetime, and can be easily defined. However, different protocols and cell sources utilized in a variety of studies have led to difficulties in obtaining clear conclusions about the effects of the biophysical environment on stem cells. In addition, the examination of different types of external stimulation is time consuming and limited by available fabrication techniques, resulting in a delay in commercialization and clinical applications. In this review, we aim to summarize the most important biophysical cues and methods for the culture of human stem cells, including mesenchymal and pluripotent stem cells, to facilitate their adoption in stem cell biology. The standard classical protocols of using biochemical cues will also be discussed for comparison. We believe that combining biochemical and biophysical stimulation has the greatest potential to generate functionally mature cells at a scalable and inexpensive rate for diverse applications in regenerative medicine and cell therapy. Biotechnol. Bioeng. 2017;114: 260-280. © 2016 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

The extracellular matrix (ECM) regulates carcinogenesis by interacting with cancer cells via cell surface receptors. Discoidin Domain Receptor 2 (DDR2) is a collagen‐activated receptor implicated in cell survival, growth, and differentiation. Dysregulated DDR2 expression has been identified in various cancer types, making it as a promising therapeutic target. Additionally, cancer cells exhibit mechanosensing abilities, detecting changes in ECM stiffness, which is particularly important for carcinogenesis given the observed ECM stiffening in numerous cancer types. Despite these, whether collagen‐activated DDR2 signaling and ECM stiffness‐induced mechanosensing exert similar effects on cancer cell behavior and whether they operate through analogous mechanisms remain elusive. To address these questions, we performed bulk RNA sequencing (RNA‐seq) on human SH‐SY5Y neuroblastoma cells cultured on collagen‐coated substrates. Our results show that DDR2 downregulation induces significant changes in the cell transcriptome, with changes in expression of 15% of the genome, specifically affecting the genes associated with cell division and differentiation. We validated the RNA‐seq results by showing that DDR2 knockdown redirects the cell fate from proliferation to senescence. Like DDR2 knockdown, increasing substrate stiffness diminishes cell proliferation. Surprisingly, RNA‐seq indicates that substrate stiffness has no detectable effect on the transcriptome. Furthermore, DDR2 knockdown influences cellular responses to substrate stiffness changes, highlighting a crosstalk between these two ECM‐induced signaling pathways. Based on our results, we propose that the ECM could activate DDR2 signaling and mechanosensing in cancer cells to orchestrate their cell fate through distinct mechanisms, with or without involving gene expression, thus providing novel mechanistic insights into cancer progression. [ABSTRACT FROM AUTHOR]

Affecting millions of individuals worldwide, neurodegenerative diseases (NDDs) pose a significant and growing health concern in people over the age of 60 years. Contributing to this trend are the steady increase in the aging population coupled with a persistent lack of disease‐altering treatment strategies targeting NDDs. The absence of efficient therapeutics can be attributed to high failure rates in clinical trials and the ineptness of animal models in preceding preclinical studies. To that end, in recent years, significant research effort has been dedicated to the development of human cell‐based preclinical disease models characterized by a higher degree of predictive validity. However, a key requirement of any in vitro model constitutes the precise knowledge and replication of the target tissues' (patho‐)physiological microenvironment. Herein, microphysiological systems have demonstrated superiority over conventional static 2D/3D in vitro cell culture systems, as they allow for the emulation and continuous monitoring of the onset, progression, and remission of disease‐associated phenotypes. This review provides an overview of recent advances in the field of NDD research using organ‐on‐a‐chip platforms. Specific focus is directed toward non‐invasive sensing strategies encompassing electrical, electrochemical, and optical sensors. Additionally, promising on‐ and integrable off‐chip sensing strategies targeting key analytes in NDDs will be presented and discussed in detail. [ABSTRACT FROM AUTHOR]

Skeletal tissues respond to the physical demands of their environment by altering the synthesis and organization of the extracellular matrix. These observations have major implications for how physical environmental demands result in the clinical observations of atrophy and hypertrophy, and how manipulation of the physical environment can be used therapeutically to stimulate repair. Electrical stimulation will be considered as a paradigm of how musculoskeletal tissues respond to physical stimuli. A model of demineralized bone matrix-induced endochondral ossification has been used because it epitomizes the cell biology of endochondral bone formation in a temporally consistent way. We have studied cartilage and bone matrix production, the temporal locus of cell responsiveness, signal dosimetry, and the synthesis of signaling cytokines (TGF-β) using biochemical, immunohistochemical, and molecular techniques. Exposure to certain electrical environments enhances chondrocyte differentiation reflected as a temporal acceleration and quantitative increase of cartilage extracellular matrix, earlier onset of osteogenesis, and more mature trabecular bone. The cell pool competent to respond resides in the mesenchymal stage. The enhancement in chondrogenesis is associated with an increase in TGF-β synthesis mediated at least in part by binding of the transcription factor AP-1 and may be modulated specifically by phosphorylation of JNK. The clinical practice of orthopedics has empirically created a variety of biophysical environments in attempts to optimize skeletal repair. We are beginning to understand the biological effects of biophysical stimulation and are now poised to replace empiricism with treatment paradigms based upon physiologic understandings of dose and biologic response. [ABSTRACT FROM AUTHOR]

The generation of tissue from stem cells is an alluring concept as it holds a number of potential applications in clinical therapeutics and regenerative medicine. Mesenchymal stromal/stem cells (MSCs) can be isolated from a number of different somatic sources, and have the capacity to differentiate into adipogenic, osteogenic, chondrogenic, and myogenic lineages. Although the first three have been extensively investigated, there remains a paucity of literature on the latter. This review looks at the various strategies available in vitro to enhance harvested MSC commitment and differentiation into the myogenic pathway. These include chemical inducers, myogenic‐enhancing cell culture substrates, and mechanical and dynamic culturing conditions. Drawing on information from embryonic and postnatal myogenesis from somites, satellite, and myogenic progenitor cells, the mechanisms behind the chemical and mechanical induction strategies can be studied, and the sequential gene and signaling cascades can be used to monitor the progression of myogenic differentiation in the laboratory. Increased understanding of the stimuli and signaling mechanisms in the initial stages of MSC myogenic commitment will provide tools with which we can enhance their differentiation efficacy and advance the process to clinical translation. [ABSTRACT FROM AUTHOR]

During normal urination, smooth muscle cells (SMCs) in the lower urinary tract (LUT) are exposed to mechanical signals that have a critical impact on tissue structure and function. Nevertheless, the mechanisms underlying the maintenance of the contractile phenotype of SMCs remain poorly understood. This is due, in part, to a lack of studies that have examined the effects of mechanical loading using three‐dimensional (3D) models. In this study, surface modifications of polydimethylsiloxane (PDMS) membrane were evaluated to investigate the effects of cyclic mechanical stimulation on SMC maturation in 3D constructs. Commercially available cell stretching plates were modified with amino or methacrylate groups to promote adhesion of 3D constructs fabricated by bioprinting. After 6 days of stimulation, the effects of mechanical stimulation on the expression of contractile markers at the mRNA and protein levels were analyzed. Methacrylate‐modified surfaces supported stable adhesion of the 3D constructs to the membrane and facilitated cyclic mechanical stimulation, which significantly increased the expression of contractile markers at the mRNA and protein levels. These effects were found to be mediated by activation of the p38 MAPK pathway, as inhibition of this pathway abolished the effects of stimulation in a dose‐dependent manner. These results provide valuable insights into the role of mechanical signaling in maintaining the contractile phenotype of bladder SMCs, which has important implications for the development of future treatments for LUT diseases. [ABSTRACT FROM AUTHOR]

Cartilage damage caused by trauma or osteoarthritis is a common joint disease that can increase the social and economic burden in society. Due to its avascular characteristics, the poor migration ability of chondrocytes, and a low number of progenitor cells, the self‐healing ability of cartilage defects has been significantly limited. Hydrogels have been developed into one of the most suitable biomaterials for the regeneration of cartilage because of its characteristics such as high‐water absorption, biodegradation, porosity, and biocompatibility similar to natural extracellular matrix. Therefore, the present review article presents a conceptual framework that summarizes the anatomical, molecular structure and biochemical properties of hyaline cartilage located in long bones: articular cartilage and growth plate. Moreover, the importance of preparation and application of hyaluronic acid – gelatin hydrogels for cartilage tissue engineering are included. Hydrogels possess benefits of stimulating the production of Agc1, Col2α1‐IIa, and SOX9, molecules important for the synthesis and composition of the extracellular matrix of cartilage. Accordingly, they are believed to be promising biomaterials of therapeutic alternatives to treat cartilage damage. [ABSTRACT FROM AUTHOR]

Cell encapsulation has been studied for various applications ranging from cell transplantation to biological production. However, current encapsulation technologies focus on cell protection rather than cell regulation that is essential to most if not all cell‐based applications. Here we report a method for cell nanoencapsulation and regulation using an ultrathin biomimetic extracellular matrix as a cell nanocapsule to carry nanoparticles (CN2). This method allows high‐capacity nanoparticle retention at the vicinity of cell surfaces. The encapsulated cells maintain high viability and normal metabolism. When gold nanoparticles (AuNPs) are used as a model to decorate the nanocapsule, light irradiation transiently increases the temperature, leading to the activation of the heat shock protein 70 (HSP70) promoter and the regulation of reporter gene expression. As the biomimetic nanocapsule can be decorated with any or multiple NPs, CN2 is a promising platform for advancing cell‐based applications. [ABSTRACT FROM AUTHOR]

Triboelectric nanogenerators (TENGs) are new energy collection devices that have the characteristics of high efficiency, low cost, miniaturization capability, and convenient manufacture. TENGs mainly utilize the triboelectric effect to obtain mechanical energy from organisms or the environment, and this mechanical energy is then converted into and output as electrical energy. Bioelectricity is a phenomenon that widely exists in various cellular processes, including cell proliferation, senescence, apoptosis, as well as adjacent cells' communication and coordination. Therefore, based on these features, TENGs can be applied in organisms to collect energy and output electrical stimulation to act on cells, changing their activities and thereby playing a role in regulating cellular function and interfering with cellular fate, which can further develop into new methods of health care and disease intervention. In this review, we first introduce the working principle of TENGs and their working modes, and then summarize the current research status of cellular function regulation and fate determination stimulated by TENGs, and also analyze their application prospects for changing various processes of cell activity. Finally, we discuss the opportunities and challenges of TENGs in the fields of life science and biomedical engineering, and propose a variety of possibilities for their potential development direction. [ABSTRACT FROM AUTHOR]

Autologous human adipose tissue-derived mesenchymal stem cells (MSCs) have the potential for clinical translation through their induction into osteoblasts for regeneration. Bone healing can be driven by biophysical stimulation using electricity for activating quiescent adult stem cells. It is hypothesized that application of electric current will enhance their osteogenic differentiation, and addition of conductive carbon nanotubes (CNTs) to the cell substrate will provide increased efficiency in current transmission. Cultured MSCs were seeded and grown onto fabricated silicone-based composites containing collagen and CNT fibers. Chemical inducers, namely, glycerol phosphate, dexamethasone, and vitamin C, were then added to the medium, and pulsatile submilliampere electrical currents (about half mA for 5 cycles at 4 mHz, twice a week) were applied for two weeks. Calcium deposition indicative of MSC differentiation and osteoblastic activity was quantified through Alizarin Red S and spectroscopy. It was found that pulsed current significantly increased osteodifferentiation on silicone-collagen films without CNTs. Under no external current, the presence of 10% (m/m) CNTs led to a significant and almost triple upregulation of calcium deposition. Both CNTs and current parameters did not appear to be synergistic. These conditions of enhanced osteoblastic activities may further be explored ultimately towards future therapeutic use of MSCs. [ABSTRACT FROM AUTHOR]

It is essential to design a multifunctional well‐controlled platform to transfer mechanical cues to the cells in different magnitudes. This study introduces a platform, a miniaturized bioreactor, which enables to study the effect of shear stress in microsized compartmentalized structures. In this system, the well‐established cell encapsulation system of liquefied capsules (LCs) is used as microbioreactors in which the encapsulated cells are exposed to variable core viscosities to experience different mechanical forces under a 3D dynamic culture. The LC technology is joined with electrospraying to produce such microbioreactors at high rates, thus allowing the application of microcapsules for high‐throughput screening. Using this platform for osteogenic differentiation as an example, shows that microbioreactors with higher core viscosity which produce higher shear stress lead to significantly higher osteogenic characteristics. Moreover, in this system the forces experienced by cells in each LC are simulated by computational modeling. The maximum wall shear stress applied to the cells inside the bioreactor with low, and high core viscosity environment is estimated to be 297 and 1367 mPa, respectively, for the experimental setup employed. This work outlines the potential of LC microbioreactors as a reliable in vitro customizable platform with a wide range of applications. [ABSTRACT FROM AUTHOR]

This white paper is the outcome of the seventh UC Davis Cardiovascular Research Symposium on Systems Approach to Understanding Cardiovascular Disease and Arrhythmia. This biannual meeting aims to bring together leading experts in subfields of cardiovascular biomedicine to focus on topics of importance to the field. The theme of the 2022 Symposium was 'Cell Diversity in the Cardiovascular System, cell‐autonomous and cell–cell signalling'. Experts in the field contributed their experimental and mathematical modelling perspectives and discussed emerging questions, controversies, and challenges in examining cell and signal diversity, co‐ordination and interrelationships involved in cardiovascular function. This paper originates from the topics of formal presentations and informal discussions from the Symposium, which aimed to develop a holistic view of how the multiple cell types in the cardiovascular system integrate to influence cardiovascular function, disease progression and therapeutic strategies. The first section describes the major cell types (e.g. cardiomyocytes, vascular smooth muscle and endothelial cells, fibroblasts, neurons, immune cells, etc.) and the signals involved in cardiovascular function. The second section emphasizes the complexity at the subcellular, cellular and system levels in the context of cardiovascular development, ageing and disease. Finally, the third section surveys the technological innovations that allow the interrogation of this diversity and advancing our understanding of the integrated cardiovascular function and dysfunction. [ABSTRACT FROM AUTHOR]

Cellular homeostasis is assumed to be regulated by the coordination of dynamic behaviors. Lack of efficient methods for synchronizing large quantities of cells makes studying cell culture strategies for bioprocess development challenging. Here, we demonstrate a novel application of botulinum hemagglutinin (HA), an E‐cadherin function‐blocking agent, to synchronize behavior‐driven mechanical memory in human induced pluripotent stem cell (hiPSC) cultures. Application of HA to hiPSCs resulted in a decrease in actin bundling and disruption of colony formation in a concentration‐and time‐dependent manner. Interestingly, cytoskeleton rearrangement in cells with prolonged exposure to HA resulted in mechanical memory synchronization with Yes‐associated protein, which increased pluripotent cell homogeneity. Synchronized hiPSCs have higher capability to differentiate into functional hepatocytes than unsynchronized hiPSCs, resulting in improved efficiency and robustness of hepatocyte differentiation. Thus, our strategy for cell behavior synchronization before differentiation induction provides an approach against the instability of differentiation of pluripotent cells. [ABSTRACT FROM AUTHOR]

The inner ear is a complex organ that encodes sound, motion, and orientation in space. Given the complexity of the inner ear, it is not surprising that treatments are relatively limited despite the fact that, in 2015, hearing loss was the fourth leading cause of years lived with disability worldwide. Inner ear organoid models are a promising tool to advance the study of multiple aspects of the inner ear to aid the development of new treatments and validate drug‐based therapies. The blood supply of the inner ear plays a pivotal role in growth, maturation, and survival of inner ear tissues and their physiological functions. This vasculature cannot be ignored in order to achieve a truly in vivo‐like model that mimics the microenvironment and niches of organ development. However, this aspect of organoid development has remained largely absent in the generation of inner ear organoids. The current review focuses on three‐dimensional inner ear organoid and how recent technical progress in generating in vitro vasculature can enhance the next generation of these models. [ABSTRACT FROM AUTHOR]

Objective: This study explores LncRNA TM1‐3P effects on the proliferation, apoptosis, and inflammatory response of fibroblasts in osteoarthritis (OA) and its underlying mechanism. Methods: Bioinformatics was performed to analyze OA disease‐related genes, miRNA profiles, and function. The targeted regulation of LncRNA TM1‐3P and miR‐144‐3p, ONECUT2 and miR‐144‐3p were analyzed by dual luciferase reporter gene assay, RNA Binding Protein Immunoprecipitation (RIP), and RNA pull down. Histopathological morphology of the knee joint was observed by hematoxylin–eosin (HE) and Annona Red O/Fast Green. The expressions of mRNAs and proteins were detected by RT‐qPCR, Western blot, and immunohistochemistry. Unpaired T test was used between groups, and the one‐way analysis of variance of repeated measurement data was applied for multi‐group comparison, following Tukey's post‐test. Results: ONECUT2 and Smurf2 genes were significantly elevated in the osteoarthritis group compared with the normal group (P < 0.001, P < 0.001). Expressions of ONECUT2 and LncRNA TM1‐3P were increased, and expression of miR‐144‐3p was decreased in interleukin (IL)‐1β‐induced human fibroblast synovial cells (hFSCs) (mRNA: 1.06 ± 0.24 vs. 3.29 ± 0.73, proteins: 0.22 ± 0.03 vs. 0.46 ± 0.22, 1.23 ± 0.22 vs. 3.76 ± 0.73, 1.06 ± 0.25 vs. 0.37 ± 0.13, P < 0.01, P < 0.001, P < 0.01, P < 0.05). Overexpression of miR‐144‐3p down‐regulated the ONECUT2 expression, reduced cell proliferation, promoted apoptosis in hFSCs induced by IL‐1β (mRNA: 0.89 ± 0.14 vs. 0.15 ± 0.01, P < 0.05; proteins: 0.46 ± 0.01 vs. 0.23 ± 0.01, P < 0.001; CCK8: 1.88 ± 0.07 vs. 1.65 ± 0.07; P < 0.05; EDU: 55.82 ± 1.44 vs 40.57 ± 2.24, P < 0.05; apoptosis: 10.57 ± 0.79 vs 16.36 ± 0.35, P < 0.0001). Overexpression of LncRNA TM1‐3P up‐regulated the expression of ONECUT2, promoted cell proliferation, and inhibited apoptosis (mRNA: 0.9 ± 0.09 vs 1.94 ± 0.12, P < 0.05; proteins: 0.61 ± 0.05 vs 0.76 ± 0.03, P > 0.05; CCK8: 2.07 ± 0.05 vs 2.47 ± 0.06; P < 0.01; EDU: 52.67 ± 1.17 vs 60.06 ± 3.24, P < 0.05; apoptosis: 10.57 ± 0.79 vs 16.36 ± 0.35, P < 0.001), which were reversed by the overexpression of miR‐144‐3p treatment (mRNA: 1.82 ± 0.07 vs 0.31 ± 0.07, P < 0.0001; proteins: 0.74 ± 0.02 vs 0.35 ± 0.01, P < 0.01; CCK8: 2.41 ± 0.01 vs 1.67 ± 0.02; P < 0.0001; EDU: 66.85 ± 2.86 vs 44.68 ± 1.97, P < 0.0001; apoptosis: 7.19 ± 0.19 vs 13.36 ± 0.53, P < 0.0001). Silencing LncRNA TM1‐3P attenuated the injury of knee joint tissue, down‐regulated the expression of ONECUT2, Smurf2, IL‐1β, IL‐6, TNF‐α, and improved the expression of Rap1 in rats (0.71 ± 0.04 vs 0.48 ± 0.02, 0.68 ± 0.06 vs 0.36 ± 0.02, 0.74 ± 0.03 vs 0.49 ± 0.04, 0.78 ± 0.01 vs 0.54 ± 0.03, 0.68 ± 0.02 vs 0.4 ± 0.04, 0.24 ± 0.01 vs 0.4 ± 0.03, P < 0.05, P < 0.05, P < 0.05, P < 0.01, P < 0.01, P < 0.05). Conclusion: LncRNA TM1‐3P improved inflammation and damage of knee joints in OA rats through miR‐144‐3p/ONECUT2 axis, providing a new theoretical basis for gene therapy of OA. [ABSTRACT FROM AUTHOR]

Purpose: Despite substantial animal evidence, cell therapy in humans remains in its infancy. The purpose of this study was to examine the potential therapeutic effects and safety of cell therapy in the treatment of tendon disorders. Methods: According to the PRISMA guideline, a systematic review was performed on clinical studies concerning cell therapy in tendon disorders. A comprehensive search including the 5 databases of MEDLINE, Embase, Scopus, Web of Science, and Cochrane Library until December 2021 was carried out and associated with hand searching. The quality of the eligible studies was assessed using the tools suggested by Cochrane recommendations. Qualitative synthesis was performed in 2 tables and discussed separately for rotator cuff, elbow, patella, Achilles, and gluteal tendons. Results: Through 6017 records, 22 studies were included in the qualitative synthesis, including 658 patients. All the studies administered autologous cells, except one that used allogenic adipose-derived mesenchymal stem cells (Allogenic AD-MSC). Almost all studies demonstrated the safety of cell injection in their follow-up period with no serious side effects or immunologic reactions, with only a few related minor adverse events in some cases. The included studies showed the effectiveness of cell injection in tendinopathies of different sites, rotator cuff, elbow, patella, Achilles, and gluteal tendons. Among the rotator cuff studies, 4 comparative studies claimed that cell therapy is a more efficient treatment with a lower retear rate and pain level compared to the control group. However, one study found no differences between the groups. No controlled study has been performed on elbow tendinopathies, but 5 case series demonstrated the effectiveness of cell injection in elbow tendon disorders. For Achilles tendinopathies, only one randomized controlled trial (RCT) found that both cell therapy and control groups showed significant pain reduction and functional improvement with no statistical differences at the 6 months follow-up, but the cell therapy group had improved faster at earlier follow-ups. Patellar tendinopathy was studied in 2 RCTs, one did not show a significant difference and the other showed superior improvement compared to controls. Conclusion: Cell therapy showed promising results and the available evidence suggests that it is safe at several sites of tendon disease. Based on available evidence, cell therapy should be suggested in specific conditions at each site. To approve cell therapy for tendon diseases, randomized clinical trials are required with a large sample size and long-term follow-ups. Level of evidence: IV [ABSTRACT FROM AUTHOR]

The effect of titanium scaffold geometry on the bone regeneration ability of the scaffold remains unclear. Here, selective laser melting as a 3D printing technology was used to create porous titanium alloy scaffolds with two unit structures: a hollow hexagonal prism (group A) and a hollow triangular prism (group B). The structures and morphologies of the scaffolds were characterized before mechanical properties were simulated. Cell adhesion behaviors, osteoblast activity and proliferation, and alkaline phosphatase (ALP) activity were evaluated, in addition to in vivo testing in an animal model. The results showed that the two scaffolds made of Ti6Al4V had compression moduli similar to that of human cortical bone (116.91 ± 0.01 and 174.29 ± 2.21 MPa vs. 89–164 MPa). The two scaffolds were nontoxic to cells and had good biocompatibility, while group A scaffolds facilitated cell adhesion. The number of cells increased gradually in culture. The ALP activity of cells on group A scaffolds demonstrated higher osteogenic ability than that of group B scaffolds. The in vivo tests showed that all scaffolds retained their shape well after implantation, and no obvious inflammatory reaction or infection in surrounding tissues was found. Based on fluorescence staining, mature new bone formation was found at week 12. Group A scaffolds showed better bone integration ability compared with group B scaffolds. The percentage of new bone area in group A (7.5%) was higher than that in group B (6.5%). This research suggests that the hollow hexagonal prism structure of porous scaffolds can promote osteogenic differentiation and osseointegration better than the triangular prism structure. [ABSTRACT FROM AUTHOR]

In the past decades, bone tissue engineering developed and exploited many typologies of bioreactors, which, besides providing proper culture conditions, aimed at integrating those bio‐physical stimulations that cells experience in vivo, to promote osteogenic differentiation. Nevertheless, the highly challenging combination and deployment of many stimulation systems into a single bioreactor led to the generation of several unimodal bioreactors, investigating one or at mostly two of the required biophysical stimuli. These systems miss the physiological mimicry of bone cells environment, and often produced contrasting results, thus making the knowledge of bone mechanotransduction fragmented and often inconsistent. To overcome this issue, in this study we developed a perfusion and electroactive‐vibrational reconfigurable stimulation bioreactor to investigate the differentiation of SaOS‐2 bone‐derived cells, hosting a piezoelectric nanocomposite membrane as cell culture substrate. This multimodal perfusion bioreactor is designed based on a numerical (finite element) model aimed at assessing the possibility to induce membrane nano‐scaled vibrations (with ~12 nm amplitude at a frequency of 939 kHz) during perfusion (featuring 1.46 dyn cm−2 wall shear stress), large enough for inducing a physiologically‐relevant electric output (in the order of 10 mV on average) on the membrane surface. This study explored the effects of different stimuli individually, enabling to switch on one stimulation at a time, and then to combine them to induce a faster bone matrix deposition rate. Biological results demonstrate that the multimodal configuration is the most effective in inducing SaOS‐2 cell differentiation, leading to 20‐fold higher collagen deposition compared to static cultures, and to 1.6‐ and 1.2‐fold higher deposition than the perfused‐ or vibrated‐only cultures. These promising results can provide tissue engineering scientists with a comprehensive and biomimetic stimulation platform for a better understanding of mechanotransduction phenomena beyond cells differentiation. [ABSTRACT FROM AUTHOR]

Despite the recent advances in reconstructive orthopedics; fracture union is a challenge to bone regeneration. Concurrent angiogenesis is a complex process governed by events, delicately entwined with osteogenesis. However, poorly perfused scaffolds have lower success rates; necessitating the need for a better vascular component, which is important for the delivery of nutrients, oxygen, waste elimination, recruitment of cells for optimal bone repair. This review highlights the latest strategies to promote biomaterial‐based scaffold vascularization by incorporation of cells, growth factors, inorganic ions, etc. into natural or synthetic polymers, ceramic materials, or composites of organic and inorganic compounds. Furthermore, it emphasizes structural modifications, biophysical stimuli, and natural molecules to fabricate scaffolds aiding the genesis of dense vascularization following their implantation to manifest a compatible regenerative microenvironment without graft rejection. [ABSTRACT FROM AUTHOR]

Articular distal femur fractures represent 4% to 6% of femur fractures. Locking compression plates (LCPs) are the main treatment option. Nevertheless, a reoperation rate of 12.9% has been reported; nonunion is reported at 4.8%, delayed union at 1.6%, and malunion at 0.6%. Treatment of nonunions can be challenging as no unanimous consensus regarding the best surgical technique has been reached. The aim of this study was to evaluate and compare two types of revision surgery as treatment of LCP-treated articular distal femoral fracture nonunion: retrograde nail or replating. A retrospective cohort study of patients admitted from January 2015 to February 2017 for nonunion of AO/OTA 33C2 fractures previously treated with a lateral LCP was conducted. Patients were treated either with intramedullary nailing (Group A) or with replating (Group B). One independent observer performed clinically and radiographically followed up at 1, 3, 6, 9, 12, 24, and 36 months after surgery. The nonunion scoring system (NUSS) was used. Nine patients were included in our study. The mean follow-up was 2 years. Five patients were treated with intramedullary nailing and four with replating. The NUSS score was 24.2 ± 6.8 in the nailing group and 37.3 ± 3 in the replating group (P = 0.03). In the nailing group, radiographic consolidation was obtained in all cases. In the replating group, nonunion was found in 3 patients and failure of osteosynthesis in one patient. Therefore, four patients (Group B) underwent implant removal and retrograde femoral nailing, obtaining radiological healing. The union time was 7.6 months in the nailing group. Retrograde intramedullary nailing can be used as an effective treatment of aseptic AO-33C distal femoral nonunion following primary locking plating. [ABSTRACT FROM AUTHOR]

There is a clear clinical need for efficient cartilage healing strategies for treating cartilage defects which burdens millions of patients physically and financially. Different strategies including microfracture technique, osteochondral transfer, and scaffold-based treatments have been suggested for curing cartilage injuries. Although some improvements have been achieved in several facets, current treatments are still less than satisfactory. Recently, different hydrogel-based biomaterials have been suggested as a therapeutic candidate for cartilage tissue regeneration due to their biocompatibility, high water content, and tunability. Specifically, magnetic hydrogels are becoming more attractive due to their smart response to magnetic fields remotely. We seek to outline the context-specific regenerative potential of magnetic hydrogels for cartilage tissue repair. In this review, first, we explained conventional techniques for cartilage repair and then compared them with new scaffold-based approaches. We illustrated various hydrogels used for cartilage regeneration by highlighting the magnetic hydrogels. Also, we gathered in vitro and in vivo studies of how magnetic hydrogels promote chondrogenesis as well as studied the biological mechanism which is responsible for cartilage repair due to the application of magnetic hydrogel. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this systematic review is to explore the current available knowledge about tendon disorders and orthobiologics derived by preclinical experiments to evaluate their role and efficacy in the different stages and conditions related to the tendon healing processes. Methods: The systematic review was performed according to the PRISMA guidelines. Different electronic databases (MEDLINE, Web of Science, EMBASE) were searched for studies investigating orthobiologics (PRP and cell-based products from adipose tissue or bone marrow) in animal models or veterinary clinical trials for tendon pathologies (complete/partial tendon ruptures, rotator cuff tears, tendinopathy, enthesis-related injuries). Data regarding the specific product used, the treatment site/pathology, the host and the model were collected. The results were classified into the following categories: histological, biomechanical, molecular and imaging. Results: A large pool of preclinical studies on tendon disorders have been found on platelet-rich plasma (PRP), while data about stromal vascular fraction (SVF) and bone marrow concentrate (BMAC) are still limited and frequently focused on expanded cells, rather than orthobiologics prepared at the point of care. The effect of PRP is related to an acceleration of the healing process, without improvements in the final structure and properties of repaired tendon. Cell-based products have been reported to produce more durable results, but the level of evidence is currently insufficient to draw clear indications. Conclusions: The preclinical results about orthobiologics applications to tendon pathologies would support the rationale of their clinical use and encourage the performance of clinical trials aimed to confirm these data in human subjects. [ABSTRACT FROM AUTHOR]

Bone cells respond to mechanical stimulation via mechanoreceptors and convert biophysical stimulation into biochemical signals that alter gene expression and cellular adaptation. Pulsed acoustic energy treatment raises membrane potential and induces osteogenic activity. How membrane-bound osteoblast mechanoreceptors convert physical ultrasound (US) stimuli into osteogenic responses is not fully understood. We demonstrated that low-intensity pulsed US treatment (200-μs pulse, 1 kHz, 30 mW/cm2) elevated Cbfa1/Runx2 mRNA expression and progressively promoted osteocalcin mRNA expression in human osteoblasts. Pretreatment with pertussis toxin (PTX), but not with cholera toxin, suppressed US-augmented osteogenic transcription. This indicated that Gi proteins, but not Gs proteins, were involved in US promotion of osteogenic transcription. Further studies demonstrated US treatment could rapidly increase PTX-sensitive Gαi protein levels and subsequently enhanced phosphorylation of extracellular signal-regulated kinase (ERK). PTX pretreatment significantly reduced US promotion of ERK activation. Moreover, inhibition of ERK activity by PD98059 suppressed US augmentation of Cbfa1/Runx2 and osteocalcin mRNA expression. Membranous Gαi proteins and cytosolic ERK pathways acted as potent mechanosensitive signals in the response of osteoblasts to pulsed US stimulation. [Copyright &y& Elsevier]

Impaired apoptosis is one of the hallmarks of cancer, and almost all of the non‐surgical approaches of eradicating tumour cells somehow promote induction of apoptosis. Indeed, numerous studies have stated that non‐ionizing non‐thermal extremely low‐frequency magnetic fields (ELF‐MF) can modulate the induction of apoptosis in exposed cells; however, much controversy exists in observations. When cells are exposed to ELF‐EMF alone, very low or no statistically significant changes in apoptosis are observed. Contrarily, exposure to ELF‐EMF in the presence of a co‐stressor, including a chemotherapeutic agent or ionizing radiation, can either potentiate or inhibit apoptotic effects of the co‐stressor. In our idea, the main point neglected in interpreting these discrepancies is "the cellular stress responses" of cells following ELF‐EMF exposure and its interplay with apoptosis. The main purpose of the current review was to outline the triangle of ELF‐EMF, the cellular stress response of cells and apoptosis and to interpret and unify discrepancies in results based on it. Therefore, initially, we will describe studies performed on identifying the effect of ELF‐EMF on induction/inhibition of apoptosis and enumerate proposed pathways through which ELF‐EMF exposure may affect apoptosis; then, we will explain cellular stress response and cues for its induction in response to ELF‐EMF exposure; and finally, we will explain why such controversies have been observed by different investigators. [ABSTRACT FROM AUTHOR]

Nanoscience has been considered as one of the most substantial research in modern science. The utilization of nanoparticle (NP) materials provides numerous advantages in biomedical applications due to their unique properties. Among various types of nanoparticles, the magnetic nanoparticles (MNPs) of iron oxide possess intrinsic features, which have been efficiently exploited for biomedical purposes including drug delivery, magnetic resonance imaging, Magnetic‐activated cell sorting, nanobiosensors, hyperthermia, and tissue engineering and regenerative medicine. The size and shape of nanostructures are the main factors affecting the physicochemical features of superparamagnetic iron oxide nanoparticles, which play an important role in the improvement of MNP properties, and can be controlled by appropriate synthesis strategies. On the other hand, the proper modification and functionalization of the surface of iron oxide nanoparticles have significant effects on the improvement of physicochemical and mechanical features, biocompatibility, stability, and surface activity of MNPs. This review focuses on popular methods of fabrication, beneficial surface coatings with regard to the main required features for their biomedical use, as well as new applications. [ABSTRACT FROM AUTHOR]

Delayed union and nonunion fractures are clinical challenges for orthopedic surgeons. The development of fracture complications, such as delayed union and nonunion fractures, is still difficult to predict. Various methods are being investigated to improve fracture healing and prevent complications in patients. There are various methods to promote fracture healing, broadly divided into biological, chemical, and physical methods. One of the most widely used physical methods to promote fracture healing is the pulsed electromagnetic field (PEMF). This study aimed to evaluate the healing process of delayed union fracture after being stimulated by PEMF. Twenty-four rats were randomly divided into two groups: the control group (n = 12) and the PEMF group (n = 12). Delayed union fracture was performed on the left femur of all rats. Subsequently, the PEMF group was given PEMF stimulus with a magnetic field intensity of 1.6 mT and a frequency of 50 Hz for 4 hours/day and 7 days/week. The fracture healing process was evaluated on days 5, 10, 18, and 28 based on the bone callus histology using safranin O fast green (SOFG) staining. The results of the histological analysis showed that bone cartilage was higher in the PEMF group than in the control group throughout the observation period. In addition, the PEMF group had less fibrous tissue at the beginning of the healing. This finding indicates PEMF stimulation has an effect on inducing osteogenesis on fracture healing and reducing the risk of delayed union. [ABSTRACT FROM AUTHOR]

As 2D surfaces fail to resemble the tumoral milieu, current discussions are focused on which 3D cell culture strategy may better lead the cells to express in vitro most of the malignant hints described in vivo. In this study, this question is assessed by analyzing the full genetic profile of MCF7 cells cultured either as 3D spheroids-considered as "gold standard" for in vitro cancer research- or immobilized in 3D tumor-like microcapsules, by RNA-Seq and transcriptomic methods, allowing to discriminate at big-data scale, which in vitro strategy can better resemble most of the malignant features described in neoplastic diseases. The results clearly show that mechanical stress, rather than 3D morphology only, stimulates most of the biological processes involved in cancer pathogenicity, such as cytoskeletal organization, migration, and stemness. Furthermore, cells entrapped in hydrogel-based scaffolds are likely expressing other physiological hints described in malignancy, such as the upregulated expression of metalloproteinases or the resistance to anticancer drugs, among others. According to the knowledge, this study represents the first attempt to answer which 3D experimental system can better mimic the neoplastic architecture in vitro, emphasizing the relevance of confinement in cancer pathogenicity, which can be easily achieved by using hydrogel-based matrices. [ABSTRACT FROM AUTHOR]

To overcome the negative contrast limitations, and to improve the sensitivity of the magnetic resonance signals, the mesoporous silica coated Fe/Mn multilayered nanowires (NWs) were used as a T1–T2 dual‐mode contrast agents (CAs). The single component Fe and Mn NWs, and Fe/Mn multilayer NWs were synthesized by electrodeposition in the homemade anodic aluminum oxide (AAO) templates with the aperture of about 30 nm. The structural characterization and morphology of single component and multisegmented NWs was done by X‐ray diffraction and transmission electron microscopy. The elemental composition of Fe/Mn multilayerd NWs was confirmed by energy‐dispersive X‐ray and energy‐dispersive spectrometer. Vibrating sample magnetometer was used to test the magnetic properties, and 1.5 T magnetic resonance imaging (MRI) scanner was used to measure the relaxation efficiency. Importantly, the MRI study indicated that the Fe/Mn multilayer NWs showed a significant T1–T2 imaging effect, and have longitudinal relaxivity (r1) value, that is, 1.25 ± 0.0329 × 10−4 μM−1 s−1 and transverse relaxivity (r2), that is, 5.13 ± 0.123 × 10−4 μM−1 s−1, which was two times of r1 value (0.654 ± 0.00899 × 10−4 μM−1 s−1) of Mn NWs, and r2 value (2.96 ± 0.0415 × 10−4 μM−1 s−1) of Fe NWs. Hence, Fe/Mn multilayer NWs have potential to be used as T1–T2 dual‐mode CAs. [ABSTRACT FROM AUTHOR]

Synovial fluid is dynamic in vivo with biological components changing in ratio and size depending on the health of the joint space, making it difficult to model in vitro. Previous efforts to develop synthetic synovial fluid have typically focused on single organic‐tribological interactions with implant surfaces, thus ignoring interplay between multiple solution components. Using a Taguchi orthogonal array, we were able to isolate the individual effects of five independent synovial fluid composition variables: ratios of (1) hyaluronic acid to phospholipids (HA:PL) and (2) albumin to globulin (A:G), and concentrations of (3) hydrogen peroxide (H2O2), (4) cobalt (Co2+) and (5) chromium (Cr3+) ions on macrophage viability and reduced glutathione production, local solution pH and the comprehensive CoCrMo alloy electrochemical response. While no single synovial fluid variable significantly affected the collective response, HA:PL ratio resulted in the largest impact factor (Δ) on 12 of the 13 measured responses with significant effects (p <.05) on the average macrophage survival rate and electrochemical capacitive state of the CoCrMo surface. Cluster analysis separated significant responses from all trials into three groups, corresponding to healthy, mild, or severely inflamed fluids, respectively; with the healthy synovial fluid composition having mid‐range HA:PL ratios with no Co2+ ions, and the severely inflamed fluids consisting of low and high HA:PL ratios with H2O2 and Co2+ ions. By utilizing the Taguchi approach in combination with cluster analysis, we were able to advance our knowledge of complex multivariate synthetic synovial fluids influence on macrophage and electrochemical behavior at the cell‐solution‐metal interface. [ABSTRACT FROM AUTHOR]

This study aims to determine the effect of laser puncture shooting on the reproductive acupuncture points of Japanese quail (Coturnix coturnix japonica) egg quantity (egg production) and internal egg quality (Haugh unit, yolk index, and yolk colour). This research was conducted for 30 days using a sample of Japanese quail aged 4 weeks because for the first 2 weeks, the quail did not produce and it was in production in the last 2 weeks. There were 4 treatments and 25 replications each. So, there were a total of 100 quails. Laser puncture shooting was carried out at 3-day intervals at the Ova point and 6-day intervals at Hu Men, Bei Ji, and Wei Gen points. So, on the first day, laser puncture shooting was carried out at 4 points, on the 4th day, only at 1 point, and then, on the 7th day, it returned to 4 points. And so, it was carried out for 4 weeks. T0 (−) was considered as a negative control because quails are not given laser puncture shooting; T0 (+) was considered as a positive control because quails are treated with laser puncture shooting which is deactivated or a dose of 0 Joule; T1 was a group treated with laser puncture shooting at a dose of 0.2 Joule, and T2 was a group treated with laser puncture shooting at a dose of 0.5 Joule. Then, the research results were analyzed using Analysis of Variance and followed by Duncan's Multiple Range Test. Laser puncture shooting at the reproductive acupuncture point of Japanese quail (Coturnix coturnix japonica) can increase the quantity of eggs (p < 0.05). While the results of the egg internal quality in the form of the Haugh unit value and the yolk index increased (p < 0.05), the value of the yolk colour did not change compared to the control (p > 0.05). Laser puncture shooting at the reproductive acupuncture point of Japanese quail (Coturnix coturnix japonica) can increase egg quantity (egg production) and internal egg quality (Haugh unit and yolk index) with the best dose of 0.5 Joule. [ABSTRACT FROM AUTHOR]