Biomedical Engineering Research Articles

Applying Spatiotemporal Modeling of Cell Dynamics to Accelerate Drug Development.

Cells act as physical computational programs that utilize input signals to orchestrate molecule-level protein-protein interactions (PPIs), generating and responding to forces, ultimately shaping all of the physiological and pathophysiological behaviors. Genome editing and molecule drugs targeting PPIs hold great promise for the treatments of diseases. Linking genes and molecular drugs with protein-performed cellular behaviors is a key yet challenging issue due to the wide range of spatial and temporal scales involved. Building predictive spatiotemporal modeling systems that can describe the dynamic behaviors of cells intervened by genome editing and molecular drugs at the intersection of biology, chemistry, physics, and computer science will greatly accelerate pharmaceutical advances. Here, we review the mechanical roles of cytoskeletal proteins in orchestrating cellular behaviors alongside significant advancements in biophysical modeling while also addressing the limitations in these models. Then, by integrating generative artificial intelligence (AI) with spatiotemporal multiscale biophysical modeling, we propose a computational pipeline for developing virtual cells, which can simulate and evaluate the therapeutic effects of drugs and genome editing technologies on various cell dynamic behaviors and could have broad biomedical applications. Such virtual cell modeling systems might revolutionize modern biomedical engineering by moving most of the painstaking wet-laboratory effort to computer simulations, substantially saving time and alleviating the financial burden for pharmaceutical industries.

A novel tetra hybrid bio-nanofluid model with stenosed artery

Abstract For treating and diagnosing cardiovascular diseases, the field of biomedical engineering is significant because it develops new ways and techniques. Stenosis is the narrowing of an artery, and it leads reduction in the flow rate of blood. This study investigates the blood flow mechanism in an artery using a mathematical model of Carreau nanofluid with four distinct nanoparticles. Tetra nanofluid model produces significant advancement in the simulation of blood flow through the stenosed arteries. The model is capable of predicting the pressure drop and velocity distribution for diagnosing and treating stenosis. The spectral relaxation approach is used to present the model's efficiency and effectiveness, which makes it a suitable method for solving the governing equations of this study. The findings of this study have important implications for the development of new treatments and diagnostic techniques for stenosis and other cardiovascular diseases.

The Influence of the Gap Phenomenon on the Occurrence of Consecutive Discharges in WEDM Through High-Speed Video Camera Observation

The Wire Electrical Discharge Machining (WEDM) process is an accurate method for manufacturing high-added-value components for industry. Continuous developments in the process have resulted in specialized machines used in sectors such as aerospace and biomedical engineering. However, some fundamental aspects of the discharge process remain unresolved. This work aims to study the influence of discharge location and bubble expansion on the occurrence of subsequent discharges. A high-speed video camera observation system was constructed to capture images of each discharge. From the acquired images, an algorithm was devised to determine the discharge location based on grayscale analysis. Moreover, the voltage and current waveforms of the discharges and the framing signals of the high-speed video camera were then obtained using an oscilloscope. Synchronizing the observation images and signals allowed for calculating the delay time for each single discharge. The results indicate that most of the discharges occurred near the boundary of the bubble and during bubble expansion. This finding has been observed for a variety of machining conditions and can be explained by the effect of the debris particles concentrated at the bubble boundary. This study provides useful information for better understanding the discharge process in WEDM.

A Planar Darkfield Illuminator for Wide‐Field High‐Contrast Imaging of Specimens in Microfluidic Chips

AbstractDarkfield microscopy is an effective technique and well suited for use involving live and unstained biological samples, where a bulky condenser should be precisely aligned in the optical path to produce a cone of illumination light. Here, a compact darkfield illuminator is invented that has a planar shape and can work at broadband wavelengths. It can be easily incorporated into a conventional microscope as a substrate to produce hollow cones of light for large‐area darkfield illumination, resulting in a high‐contrast high‐sensitivity widefield microscopy images. Taking advantages of its planar and compact structure, this darkfield illuminator is successfully integrated with a microfluidic chip; thus, the actions and reactions of biological and chemical specimens flowing inside micrometer‐sized channels, can be real‐time imaged with high contrast and sensitivity in a large field‐of‐view (FoV). For the first time, the work integrates a compact darkfield illuminator with microfluidic chips, which produces a new platform for applications in biology, chemistry, and biomedical engineering.

Unlocking Intracellular Protein Delivery by Harnessing Polymersomes Synthesized at Microliter Volumes using Photo-PISA.

Efficient delivery of therapeutic proteins and vaccine antigens to intracellular targets is challenging due to generally poor cell membrane permeation and endolysosomal entrapment causing degradation. Herein, these challenges are addressed by developing an oxygen-tolerant photoinitiated polymerization-induced self-assembly (Photo-PISA) process, allowing for the microliter-scale (10µL) synthesis of protein-loaded polymersomes directly in 1536-well plates. High-resolution techniques capable of analysis at a single particle level are employed to analyze protein encapsulation and release mechanisms. Using confocal microscopy and super-resolution stochastic optical reconstruction microscopy (STORM) imaging, their ability to deliver proteins into the cytosol following endosomal escape is subsequently visualized. Lastly, the adaptability of these polymersomes is exploited to encapsulate and deliver a prototype vaccine antigen, demonstrating its ability to activate antigen-presenting cells and support antigen cross-presentation for applications in subunit vaccines and cancer immunotherapy. This combination of ultralow volume synthesis and efficient intracellular delivery holds significant promise for unlocking the high throughput screening of a broad range of otherwise cost-prohibitive or early-stage therapeutic protein and vaccine antigen candidates that can be difficult to obtain in large quantities. The versatility of this platform for rapid screening of intracellular protein delivery can result in significant advancements across the fields of nanomedicine and biomedical engineering.

Recent Advances in Degradable Biomedical Polymers for Prevention, Diagnosis and Treatment of Diseases.

Biomedical polymers play a key role in preventing, diagnosing, and treating diseases, showcasing a wide range of applications. Their unique advantages, such as rich source, good biocompatibility, and excellent modifiability, make them ideal biomaterials for drug delivery, biomedical imaging, and tissue engineering. However, conventional biomedical polymers suffer from poor degradation in vivo, increasing the risks of bioaccumulation and potential toxicity. To address these issues, degradable biomedical polymers can serve as an alternative strategy in biomedicine. Degradable biomedical polymers can efficiently relieve bioaccumulation in vivo and effectively reduce patient burden in disease management. This review comprehensively introduces the classification and properties of biomedical polymers and the recent research progress of degradable biomedical polymers in various diseases. Through an in-depth analysis of their classification, properties, and applications, we aim to provide strong guidance for promoting basic research and clinical translation of degradable biomedical polymers.

Design and Applications of Supramolecular Peptide Hydrogel as Artificial Extracellular Matrix.

Supramolecular peptide hydrogels (SPHs) consist of peptides containing hydrogelators and functional epitopes, which can first self-assemble into nanofibers and then physically entangle together to form dynamic three-dimensional networks. Their porous structures, excellent bioactivity, and high dynamicity, similar to an extracellular matrix (ECM), have great potential in artificial ECM. The properties of the hydrogel are largely dependent on peptides. The noncovalent interactions among hydrogelators drive the formation of assemblies and further transition into hydrogels, while bioactive epitopes modulate cell-cell and cell-ECM interactions. Therefore, SPHs can support cell growth, making them ideal biomaterials for ECM mimics. This Review outlines the classical molecular design of SPHs from hydrogelators to functional epitopes and summarizes the recent advancements of SPHs as artificial ECMs in nervous system repair, wound healing, bone and cartilage regeneration, and organoid culture. This emerging SPH platform could provide an alternative strategy for developing more effective biomaterials for tissue engineering.

Effectiveness of Acupuncture in Improving Quality of Life for Patients with Advanced Cancer: A Systematic Review and Meta-Analysis.

To investigate the effect of acupuncture on advanced cancer patients by meta-analysis. Nine databases (the Cochrane Central Register of Controlled Trials, MEDLINE, Web of Science, Embase, China National Knowledge Infrastructure, the Cumulative Index to Nursing and Allied Health Literature, Chinese Biomedical Literature Database, China Science and Technology Journal Database, and WanFang Data) were searched for randomized controlled trials (RCTs) on acupuncture in advanced cancer patients published from inception to February 13, 2023 and updated to June 1, 2023. Primary outcomes were quality of life (QOL), while secondary outcomes were pain, fatigue, and adverse events (side effects). Data synthesis was performed using RevMan V.5.3 to calculate pooled effect sizes. RoB-2 was used for the risk of bias, and the quality of evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) tool. Totally 17 RCTs involving 1,178 participants were included, 15 of which were pooled for meta-analysis. Most studies demonstrated some concern for the overall risk of bias. The pooled data indicated that acupuncture was associated with improved QOL [mean difference (MD)=6.67, 95% confidence interval (CI): 5.09 to 8.26], pain (MD=-1.18, 95% CI -2.28 to -0.08), and adverse events (risk ratio=0.30, 95% CI: 0.26 to 0.57) compared with control groups. Fatigue outcome was not included. Heterogeneity was substantial, and GRADE evidence was very low for both QOL and pain. Acupuncture could benefit patients with advanced cancer and is considered safe compared with usual care. However, the evidence regarding QOL and pain outcomes requires further validation. It is crucial to encourage the development of high-quality studies to strengthen this evidence. (Registry No. CRD42023423539).

Time-frequency analysis of speech signals using the Stockwell transform for the detection of upper respiratory tract infection

The acoustic properties of speech demonstrate modifications in the presence of different health states. Biomedical engineering has great promise for creating non-invasive diagnostic processes that use speech as a biomarker. The use of speech indications to screen for upper respiratory tract infections (URTIs), such as the common cold, may have potential advantages in terms of limiting transmission. In this study, we have employed the Stockwell transform -based time-frequency (TF) analysis of speech signals for URTI detection. The Stockwell transform is applied on speech signals to derive their TF representation. Using a TF matrix, the various statistics of magnitude and phase are calculated and used as features for classifying speech of healthy speakers and speakers with URTI. The URTIC database is employed for evaluating the proposed features. The utilization of an ensemble of support vector machines (SVM) is proposed as a classification approach to address the issue of class imbalance. The results show that the proposed method produces comparable outcomes to state-of-the-art approaches. The proposed features obtain 66.53% and 64.65% UARs on the development and test partitions of the URTIC database.

Metal‐Free, Light‐Catalyzed ATRP For the Synthesis of Functional PVDF‐Based Block Copolymers and Their Characterization

AbstractThe synthesis and characterization of poly(vinylidene fluoride) (PVDF)‐based block copolymers using a metal‐free light‐catalyzed atom transfer radical polymerization (ATRP) approach are described. A PVDF macroinitiator with C─Br bonds at both ends of the chain is synthesized, and an organic photoredox catalyst (OPRC) is used to control the process. The metal‐free process expands the possibilities for the synthesis and application of PVDF‐based block copolymers, as it allows the use of monomers that is previously incompatible with classical ATRP due to their interaction with metal catalysts. The synthesized block copolymers are characterized structurally and thermally as powder materials and in thin films. Fourier‐transform infrared spectroscopy (FT‐IR) analysis revealed that the crystalline phase of PVDF changes when thin films are formed. Specifically, the disappearance of the FT‐IR peaks related to the gamma phase and the presence of characteristic peaks related to the alpha and beta phases indicate that film formation rearranged the PVDF chains, leading to changes in their crystalline phases. These PVDF‐based block copolymers have unique properties, including high thermal stability, chemical resistance, and piezoelectricity, making them potential candidates for use in various fields, such as biomedical engineering, energy storage, and electronic devices.

Mechanistic insights on stabilization and destabilization effect of ionic liquids on type I collagen fibrils

Tuned assembly of collagen has tremendous applications in the field of biomedical and tissue engineering owing to its targeted biological functionalities. In this study, ionic liquids choline dihydrogen citrate (CDHC) and diethyl methyl ammonium methane sulfonate (AMS) have been used to regulate the self-assembly of collagen at its physiological pH by probing the assembled systems at certain concentration ratios of ionic liquids and the systems were studied using various characterization methods. Due to interaction with collagen, choline dihydrogen citrate causes delay in the collagen fibrillisation process showing no binding interactions with collagen. In contrast, diethyl methyl ammonium methane sulfonate shows crosslinking effect on collagen fibrillisation due to the electrostatic interaction with the tetrahedral hydration shell of collagen moieties. From rheological studies it was observed that the AMS treated collagen fibril at 1:1 % (w/v) has highest linear viscoelastic range, this can bear the stress under high strain compare to native collagen fibril as well as all CDHC composites. For a sustainable biomaterial or bio-scaffold, mechanical property plays pivotal role on it and from our experimental analysis we found certain composites of ionic liquid treated collagen fibrillar assembly which may act as a sustainable biomaterial or bio-scaffold. It was also evolved that, how the structure-function relationship of ionic force modulated fibrillar assembly controlling the mechanical properties of the tuned system. This self-assembled, ionic-liquid treated collagen-fibrillar system would accelerate various force modulated fibrillar network study, for mimicking the ECM and tissue engineering application.

Prediction of puncturing events through LSTM for multilayer tissue

Recognizing penetration events in multilayer tissue is critical for many biomedical engineering applications, including surgical procedures and medical diagnostics. This paper presents a unique method for detecting penetration events in multilayer tissue using Long Short-Term Memory (LSTM) networks. LSTM networks, a form of recurrent neural network (RNN), excel at analyzing sequential data because of their ability to hold long-term dependencies. The suggested method collects time-series insertion force data from sensors integrated from a 1-DOF prismatic robot as it penetrates tissue. This data is then processed by the LSTM network, which has been trained to recognize patterns indicating penetration events through various tissue layers. The effectiveness of this approach is validated through experimental setups, demonstrating high accuracy and reliability in detecting penetration events. This technique offers significant improvements over traditional methods, providing a non-invasive, real-time solution that enhances the precision and safety of medical procedures involving multilayer tissue interaction.

Advancements in Hydrogels for Corneal Healing and Tissue Engineering.

Hydrogels have garnered significant attention for their versatile applications across various fields, including biomedical engineering. This review delves into the fundamentals of hydrogels, exploring their definition, properties, and classification. Hydrogels, as three-dimensional networks of crosslinked polymers, possess tunable properties such as biocompatibility, mechanical strength, and hydrophilicity, making them ideal for medical applications. Uniquely, this article offers original insights into the application of hydrogels specifically for corneal tissue engineering, bridging a gap in current research. The review further examines the anatomical and functional complexities of the cornea, highlighting the challenges associated with corneal pathologies and the current reliance on donor corneas for transplantation. Considering the global shortage of donor corneas, this review discusses the potential of hydrogel-based materials in corneal tissue engineering. Emphasis is placed on the synthesis processes, including physical and chemical crosslinking, and the integration of bioactive molecules. Stimuli-responsive hydrogels, which react to environmental triggers, are identified as promising tools for drug delivery and tissue repair. Additionally, clinical applications of hydrogels in corneal pathologies are explored, showcasing their efficacy in various trials. Finally, the review addresses the challenges of regulatory approval and the need for further research to fully realize the potential of hydrogels in corneal tissue engineering, offering a promising outlook for future developments in this field.

Assessment of a Structurally Modified Alternanthera Mosaic Plant Virus as a Delivery System for Sarcoma Cells

The virions of plant viruses and their structurally modified particles (SP) represent valuable platforms for recombinant vaccine epitopes and antitumor agents. The possibility of modifying their surface with biological compounds makes them a tool for developing medical biotechnology applications. Here, we applied a new type of SP derived from virions and virus-like particles (VLP) of Alternanthera mosaic virus (AltMV) and well-studied SP from Tobacco mosaic virus (TMV). We have tested the ability of SP from AltMV (AltMV SPV) and TMV virions also as AltMV VLP to bind to and penetrate Ewing sarcoma cells. The adsorption properties of AltMV SPV and TMV SP are greater than those of the SP from AltMV VLP. Compared to normal cells, AltMV SPV adsorbed more effectively on patient-derived sarcoma cells, whereas TMV SP were more effective on the established sarcoma cells. The AltMV SPV and TMV SP were captured by all sarcoma cell lines. In the established Ewing sarcoma cell line, the effectiveness of AltMV SPV penetration was greater than that of TMV SP. The usage of structurally modified plant virus particles as a platform for drugs and delivery systems has significant potential in the development of anticancer agents.

Integration of nanomaterials in FDM for enhanced surface properties: Optimized manufacturing approaches

This article presents a comprehensive review of advanced techniques for integrating nanomaterials into fused deposition modeling (FDM) processes, addressing prevalent challenges such as limited surface quality and wear resistance in traditional FDM-printed parts. The integration of nanomaterials offers potential solutions to these issues by enhancing surface properties. This review explores key methodologies, including direct nanoparticle mixing with polymer filaments, in-situ polymerization, and surface coating techniques, and demonstrates their impact on improving surface roughness and wear resistance. Specifically, nanomaterial-enhanced composites achieve up to a 30% reduction in surface roughness and a 40% improvement in wear resistance compared to conventional materials. To optimize manufacturing processes, we apply the Taguchi method to identify critical process parameters such as extrusion temperature, print speed, layer thickness, and nanoparticle concentration that influence surface properties. Our simulations and analysis of variance (ANOVA) indicate that optimal settings can enhance surface quality by 25% and improve wear resistance by 35%. The proposed methodologies and theoretical framework lay the groundwork for experimental validation, which will involve testing the optimized parameters and assessing their practical impact. This research advances the field of additive manufacturing by providing novel insights into nanomaterial integration, paving the way for improved FDM technology with applications spanning aerospace, biomedical engineering, and beyond. The findings contribute significantly to overcoming existing limitations and enhancing the performance of FDM-printed parts.

Mechanical behavior of shape memory alloys considering the effects of body fluids corrosion for biomedical applications

Abstract Shape memory alloys (SMAs) are widely used in biomedical engineering, including cardiovascular stents, artificial skeletons, and orthodontic implants. For the above applications, the body fluids corrosion processes will inevitably cause deterioration in the mechanical properties of the SMAs actuator during its service life, which will threaten the safety of human health. To analyze such problems, experimental measurements have been carried out to investigate the influence of body fluid corrosion on the mechanical properties of SMAs. Changes in the mechanical properties, such as Young’s modulus and phase transformation temperatures of SMAs under body fluids corrosion were tested firstly in the simulated body environment with the 0.9 wt. % NaCl solution at 37. With an increase of the immersion time, the results show that the Ti (titanium) percentage, austenitic (reverse) transformation start temperature, austenitic (reverse) transformation finish temperature, and maximum residual strain all increase, the Ni (nickel) percentage, martensitic transformation finish temperature, tensile strength, and yield strength decrease, and the martensitic transformation start temperature first decreases and then increases. The research in this work can provide an experimental basis for further study of the SMAs materials in biomedicine applications.

Fruit Wastes and Crop Residues as Nutrient Sources for Bacterial Nanocellulose Production: A Review

Nanocellulose has been developed and used as a bio-based advanced material in modern biotechnology. Lately, bacterial nanocellulose (BNC) emerged as a prominent biopolymer because of its multi-functional application in various industries, such as food, biomedical, cosmetics, and environmental. The emerging concern for large-scale BNC production is the high fermentation costs, low productivity, and expensive culture medium. To minimise this issue, agro-industrial wastes can be used as feedstock. Recently, many studies have investigated the utilization of agro-industrial wastes as potential nutrient sources for BNC production. However, a comprehensive review of BNC production from fruit wastes and crop residues is lacking. To address this gap, the current review focuses on the utilization of fruit wastes and crop residues for BNC production, including its advantages and disadvantages. This study contributes to the scientific community by (a) providing an insight into fruit waste and crop residue utilization for BNC synthesis (b) an overview on its advantages and disadvantages (c) providing recommendations and future perspectives on BNC production from agro-industrial waste utilization. The sustainable concept of BNC production utilizing agro-industrial wastes opens a way for industries to produce BNC on a larger scale.

Development and Biomedical Application of Non-Noble Metal Nanomaterials in SERS.

Surface-enhanced Raman scattering (SERS) is vital in many fields because of its high sensitivity, fast response, and fingerprint effect. The surface-enhanced Raman mechanisms are generally electromagnetic enhancement (EM), which is mainly based on noble metals (Au, Ag, etc.), and chemical enhancement (CM). With more and more studies on CM mechanism in recent years, non-noble metal nanomaterial SERS substrates gradually became widely researched and applied due to their superior economy, stability, selectivity, and biocompatibility compared to noble metal. In addition, non-noble metal substrates also provide an ideal new platform for SERS technology to probe the mechanism of biomolecules. In this paper, we review the applications of non-noble metal nanomaterials in SERS detection for biomedical engineering in recent years. Firstly, we introduce the development of some more common non-noble metal SERS substrates and discuss their properties and enhancement mechanisms. Subsequently, we focus on the progress of the application of SERS detection of non-noble metal nanomaterials, such as analysis of biomarkers and the detection of some contaminants. Finally, we look forward to the future research process of non-noble metal substrate nanomaterials for biomedicine, which may draw more attention to the biosensor applications of non-noble metal nanomaterial-based SERS substrates.

Computational study of micromagnetorotation on the micropolar flow characteristics in a rectangular channel with continuous applied shear

The aim of this investigation is to computationally analyse the effect of micromagnetorotation on flow characteristics within magneto-micropolar flows. To the authors' knowledge such consideration has not been discussed in the literature in present context. The assumption in literature that the magnetization is parallel to the applied magnetic field is incorrect due to the anisotropic nature of micropolar flows. This allows to re-investigate the micropolar flows in the present of micromagnetorotation. To this end, the theory of magneto-micropolar flows is briefly described and a computational model governing the system dynamics is presented. Finite element code in FreeFem++ is developed and validated through an exact solution. It turns out that the numerical findings obtained are in strong agreement with the analytical results. The results obtained are significant because they can assist researchers in allied fields of electronics, materials science and biomedical engineering in finding solutions to a variety of real-world issues.

Enhanced Sensitivity of Cell Identification in Complex Environments Using Chirally Inverted L-DNA-Based Logic Devices.

Accurate identification and isolation of target cells are crucial for precision diagnosis and treatment. DNA aptamer-based logic devices provide a distinct advantage in this context, as they can logically analyze multiple cell surface markers with high efficiency. However, the susceptibility of natural DNA (D-DNA) to degradation can compromise the sensitivity and specificity of these devices, potentially leading to false-positive and false-negative results, particularly in complex biological environments. To address this issue, dual- and triple-aptamer-based cell-surface logic devices are designed and developed using mirror-image L-DNA, a chiral molecule of D-DNA with high biostability. These devices allow for simultaneous analysis of multiple cell surface proteins, achieving greater specificity in cell identification and isolation than D-DNA-based logic devices. The L-DNA probes realized 98.7% and 70.5% sensitivities in FBS buffer with dual- and triple-aptamer-based logic devices for target cell identification, while D-DNA probes only showed 27.9% and 0.1%. It is believed that the high stability of L-DNA and the high efficiency of the devices for labeling cell subpopulations will have broad applications in the life sciences, biomedical engineering, and personalized medicine.