Advanced Biomedical Applications Research Articles

Chitosan-2D Nanomaterial-Based Scaffolds for Biomedical Applications

Chitosan (CS) and two-dimensional nanomaterial (2D nanomaterials)-based scaffolds have received widespread attention in recent times in biomedical applications due to their excellent synergistic potential. CS has garnered much attention as a biomedical scaffold material either alone or in combination with some other material due to its favorable physiochemical properties. The emerging 2D nanomaterials, such as black phosphorus (BP), molybdenum disulfide (MoS2), etc., have taken huge steps towards varying biomedical applications. However, the implementation of a CS-2D nanomaterial-based scaffold for clinical applications remains challenging for different reasons such as toxicity, stability, etc. Here, we reviewed different types of CS scaffold materials and discussed their advantages in biomedical applications. In addition, a different CS nanostructure, instead of a scaffold, has been described. After that, the importance of 2D nanomaterials has been elaborated on in terms of physiochemical properties. In the next section, the biomedical applications of CS with different 2D nanomaterial scaffolds have been highlighted. Finally, we highlighted the existing challenges and future perspectives of using CS-2D nanomaterial scaffolds for biomedical applications. We hope that this review will encourage a more synergistic biomedical application of the CS-2D nanomaterial scaffolds and their utilization clinical applications.

Developing machine learning models with metaheuristic algorithms for droplet size prediction in a microfluidic microchannel

Droplet-based microfluidics holds promise for advanced biomedical applications due to its enhanced accuracy, throughput, rapid reaction time, and minimal reagent consumption. However, achieving droplets with the desired radius often entails costly design iterations. In this paper, we propose a novel approach that combines machine learning algorithms with metaheuristic algorithms to leverage their respective strengths in speed and accuracy. Specifically, we demonstrate the effectiveness of the Rain Optimization Algorithm (ROA) in enhancing the accuracy of five machine learning models. Additionally, we introduce a hybrid model, optimized by ROA, for predicting droplet generation in a cross-junction microfluidic channel, achieving a coefficient of determination (R2) of 0.937, reflecting a 3.6 % increase in accuracy. We employ symbolic regression to validate the hybrid model, yielding an R2 value of 0.987, indicating strong agreement with real data. Furthermore, we utilize the SHAP method in Explainable AI to interpret the hybrid model's performance. Notably, the proposed hybrid model requires only four seconds to solve the prediction problem, significantly reducing computational time compared to the numerical model and experimental method. This approach facilitates the study of each input parameter's impact on droplet size prediction, offering otherwise challenging and costly insights to obtain experimentally.

Non‐Covalent Functionalization of Magnetic Carbon Nanotubes with Fmoc Amino Acid‐Modified Polyethylene Glycol

Once dispersion and cytotoxicity issues are resolved, it has been proven that carbon nanotubes (CNTs) have great advantages in biomedical applications due to their unique properties. In this study, the superiority of carbon nanotubes was combined with magnetic targeting strategies, and a solution to the distribution problem in the aqueous media of the resulting CNTs decorated with iron oxide (mCNTs) was sought. A non‐covalent functionalization approach has been utilized to overcome this fundamental drawback of mCNTs. Conjugates of polyethylene glycol monomethyl ether and 9‐fluorenyl methyl chloroformate (Fmoc) amino acids were used to coat the lateral surfaces of mCNTs, making them more water‐soluble. The selected Fmoc amino acids have different numbers of aromatic rings, which is known to affect the coating efficiency in non‐covalent functionalization and therefore, the dispersion behavior of the CNTs. Their coating yields, dispersion behaviors, magnetism, charge, and size properties have been determined. All coated mCNT samples displayed superparamagnetic behavior. Dispersion tests showed a promise to increase the stability of mCNTs with this approach. Moreover, we demonstrated that the functionalization of mCNTs affects cell viability in a dose‐dependent manner. The main finding of this study is that mCNTs can be successfully functionalized with Fmoc amino acid‐modified polyethylene glycol.

A Novel Intrauterine Device for the Spatio-Temporal Release of Norethindrone Acetate as a Counter-Estrogenic Intervention in the Genitourinary Syndrome of Menopause

The genitourinary syndrome of menopause (GSM) is a widely occurring condition affecting millions of women worldwide. The current treatment of GSM involves the use of orally or vaginally administered estrogens, often with the risk of endometrial hyperplasia. The utilization of progestogens offers a means to counteract the effects of estrogen on the endometrial tissue, decreasing unwanted side effects and improving therapeutic outcomes. In this study, a norethindrone acetate (NETA)-loaded, hollow, cylindrical, and sustained release platform has been designed, fabricated, and optimized for implantation in the uterine cavity as a counter-estrogenic intervention in the treatment of GSM. The developed system, which comprises ethyl cellulose (EC) and polycaprolactone (PCL), has been statistically optimized using a two-factor, two-level factorial design, with the mechanical properties, degradation, swelling, and in vitro drug release of NETA from the device evaluated. The morphological characteristics of the platform were further investigated through scanning electron microscopy in addition to cytocompatibility studies using NIH/3T3 cells. Results from the statistical design highlighted the platform with the highest NETA load and the EC-to-PCL ratio that exhibited favorable release and weight loss profiles. The drug release data for the optimal formulation were best fitted with the Peppas–Sahlin model, implicating both diffusion and polymer relaxation in the release mechanism, with cell viability results noting that the prepared platform demonstrated favorable cytocompatibility. The significant findings of this study firmly establish the developed platform as a promising candidate for the sustained release of NETA within the uterine cavity. This functionality serves as a counter-estrogenic intervention in the treatment of GSM, with the platform holding potential for further advanced biomedical applications.

Computational Analysis of Biodegradable Polyester Materials for Biomedical Applications: Investigating Molecular Weight Change due to Hydrolysis.

Biopolymers have gained significant importance in the field of biomedicine, particularly in addressing organ and tissue loss in living organisms. These polymers exhibit temporary functionality during treatment and undergo biodegradation once their intended purpose is fulfilled. The diverse characteristics of these biopolymers expand their range of applications, albeit necessitating extensive experimentation and a time commitment for thorough investigation. Computational models have emerged as a promising avenue for predictive analysis, complementing traditional experimental methods. In this study, we delve into the degradation dynamics of polyester materials with a specific emphasis on the hydrolysis process. We employed an appropriate reaction diffusion model to unveil the underlying mechanisms governing material weight loss and erosion within a two-dimensional framework for a rectangular slice of the implant. By bridging computational modeling with empirical research, this study provides valuable insights into the behavior of biopolymers, contributing to a deeper understanding of these materials and their potential for advanced biomedical applications. To illustrate this framework's effectiveness, we conducted a case study using experimental data from the literature, focusing on poly(d,l-lactic acid) material.

High-Specificity Imaging Mass Spectrometry.

Imaging mass spectrometry (IMS) enables highly multiplexed, untargeted tissue mapping for a broad range of molecular classes, facilitating in situ biological discovery. Yet, challenges persist in molecular specificity, which is the ability to discern one molecule from another, and spatial specificity, which is the ability to link untargeted imaging data to specific tissue features. Instrumental developments have dramatically improved IMS spatial resolution, allowing molecular observations to be more readily associated with distinct tissue features across spatial scales, ranging from larger anatomical regions to single cells. High-performance mass analyzers and systems integrating ion mobility technologies are also becoming more prevalent, further improving molecular coverage and the ability to discern chemical identity. This review provides an overview of recent advancements in high-specificity IMS that are providing critical biological context to untargeted molecular imaging, enabling integrated analyses, and addressing advanced biomedical research applications.

The effect of porcelain filler particulates madar fiber reinforced epoxy composite – A comprehensive study for biomedical applications

Environmental consciousness motivates scientists to devise an alternative method for producing natural fiber composite materials in order to decrease the demand for synthetic fibers. This study explores the potential of a novel composite material derived from madar fiber-reinforced epoxy with porcelain filler particulates, designed specifically for biomedical instrumentation applications. The primary focus is to assess the material's structural, mechanical, and antibacterial properties. X-ray Diffraction analysis was employed to discern the crystalline nature of the composite, revealing enhanced crystallinity due to the inclusion of porcelain particulates. Fourier-Transform Infrared Spectroscopy confirmed the chemical interactions and bonding mechanisms between madar fiber, epoxy matrix, and porcelain filler. Mechanically, the composite exhibited superior properties when addition of porcelain fillers, maximum results obtain in tensile strength of 51.28 MPa, flexural strength of 54.21 MPa, and impact strength of 0.0155 kJ/m2, making it ideal for robust biomedical applications. Scanning Electron Microscopy provided detailed insights into the morphology and distribution of the reinforcing agents within the epoxy matrix, emphasizing the fibrillated structure of madar fiber and the uniform dispersion of porcelain particulates. Importantly, antibacterial assays demonstrated the composite's potential resistance against common pathogenic bacteria, which is crucial for biomedical instrumentation. Collectively, this research underscores the promising attributes of the madar fiber reinforced epoxy composite with porcelain particulates, suggesting its suitability for advanced biomedical applications.

Recent advances in biomedical applications of carbon and graphene quantum dots: A review.

The carbon-based nanostructures have led to the development of theranostic nanoplatforms for simultaneous diagnosis and therapy due to their effective cell membrane-penetration ability, low degree of cytotoxicity, excellent pore volume, substantial chemical stability, and reactive surface. In the last few years, extensive efforts were made to design multifunctional nanoplatform strategies based on carbon nanostructures, involving multimodal imaging, controlled drug release capabilities, sensing in vitro, efficient drug loading capacity, and therapy. Carbon and graphene quantum dots (CQDs and GQDs) were the recent entrants, contingently being assessed for drug delivery and bioimaging. With the advancements, these quantum dots have ignited remarkable research interest and are now widely evaluated for diagnosis, bioimaging, sensing, and drug delivery applications. The last decade has witnessed their remarkable electrical, optical, and biocompatible properties since their inception. It is presumed that both of them have high potential as drug carriers and would serve as the next generation of approaches to address numerous unresolved therapeutic challenges. This review examined the recent advances of CQD and GQD based drug delivery applications, challenges, and future perspectives to pave the way for further studies in the future.

Advancements in Biomedical Applications of Calcium Phosphate Glass and Glass-Based Devices-A Review.

Calcium phosphate (CaP) glass has recently gained popularity as a promising material for a wide range of biomedical applications. Recent developments have seen CaP glasses moving from a passive implant material to an active degradable material, particularly as a major constituent of bioresorbable photonic devices. This holds great promise in advanced biomedical applications, since the main constituents of CaP glasses are present in the human body. In this review, the progressive advancements in the biomedical applications of calcium phosphate glass-based devices over the past 50 years are discussed. An overview of their role as reinforcing agents and the studies on doping their matrices for ion releasing and drug and gene delivery are reviewed. Recent applications of CaP glass and fibers in soft-tissue engineering and their potential for optical quality bioresorbable devices are then discussed along with the current challenges and potential future directions, emphasizing the promising role of CaP glass in the next generation of biomaterials. Considering their progress and potential in performing several biomedical functionalities over time, CaP glass-based devices hold promise for becoming enabling tools as an implantable, bioresorbable, multifunctional class of devices in future biomedicine.

Tailored binary polymer system PCL-PEO for advanced biomedical applications: Optimization, characterization and in vitro analysis

Combining a hydrophobic polymer such as polycaprolactone (PCL) with a hydrophilic polymer polyethylene oxide (PEO) in a binary polymer system can enable a range of novel applications in biomedical engineering by permitting exceptional therapeutic release, antimicrobial possibilities, and heterogeneous tissue engineering scaffolds. In this work, both PCL and PEO were dissolved in chloroform at 15 w/v % at six different ratios to prepare binary polymer solutions. The rheological properties of the singular and binary polymer solutions were measured, and fibers were spun using pressurized gyration. The fiber morphologies of the prepared materials were studied using scanning electron microscopy (SEM). By immersing samples in deionized water, binary polymeric fibers with varying swelling behaviors were developed and analyzed using optical microscopy. The results were used to identify an optimum PCL:PEO binary mixture in chloroform. Chemical compositions of singular/binary polymer composites loaded with ibuprofen (IBP) were characterized by Fourier-transform infrared spectroscopy (FTIR) and thermal analysis was examined using differential scanning calorimetry (DSC). In vitro studies on PEO–IBP exhibited an instant release rate of 90 % in 40 s, whereas PCL–IBP and PCL:PEO–IBP revealed a sustained release of 87–96 % in 72 h, respectively. The results were used to discuss the potential use of binary polymer systems in biomedical applications.

Engineering aggregates of julolidine-substituted aza-BODIPY nanoparticles for NIR-II photothermal therapy

Near infrared-II (NIR-II) dyes have unique advantages in biomedical applications owing to the powerful ability in penetrating biological tissues. Herein, NIR-II aza-BODIPY dye, QLD-BDP, was developed with julolidine at 1,7-sites and p-dimethylaminophenyl group at 3,5-sites. According to X-ray analysis, QLD-BDP exhibits significant distortion, and this molecule appears a bowl shaped structure. The photothermal conversion efficiency of the self-assembled QLD-BDP nanoparticles (QLD-BDP-NPs) can reach 50.5%, with maximum emission at 998 nm by the aggregate. QLD-BDP-NPs can cause the complete destruction of 4T1 multicellular spheroids (MCSs), indicating a photothermal therapy (PTT) effect.

[Research progress of methylcellulose-based thermosensitive hydrogels applied in biomedical field].

Methylcellulose is a semi-flexible cellulose ether derivative, whose hydrogels are thermosensitive and reversible, with good biocompatibility and adjustable function, and its application has attracted much attention in the biomedical field. In this paper, the application of methylcellulose-based thermo-sensitive hydrogels in biomedical field was reviewed. Based on the mechanism of gelation and influencing factors of methylcellulose, this paper focused on the recent advances in biomedical applications of methylcellulose-based hydrogels, including drug delivery, regenerative medicine, and other related fields. The current achievements in these fields were summarized in the form of lists in this paper to provide ideas and tendencies for future research. Finally, the future development of multifunctional methylcellulose-based hydrogel materials with improved performance was also discussed.

Recent Advances in Biomedical Applications of Mannans and Xylans.

Plant-based phytochemicals, including flavonoids, alkaloids, tannins, saponins, and other metabolites, have attracted considerable attention due to their central role in synthesizing nanomaterials with various biomedical applications. Hemicelluloses are the second most abundant among naturally occurring heteropolymers, accounting for one-third of all plant constituents. In particular, xylans, mannans, and arabinoxylans are structured polysaccharides derived from hemicellulose. Mannans and xylans are characterized by their linear configuration of β-1,4-linked mannose and xylose units, respectively. At the same time, arabinoxylan is a copolymer of arabinose and xylose found predominantly in secondary cell walls of seeds, dicotyledons, grasses, and cereal tissues. Their widespread use in tissue engineering, drug delivery, and gene delivery is based on their properties, such as cell adhesiveness, cost-effectiveness, high biocompatibility, biodegradability, and low immunogenicity. Moreover, it can be easily functionalized, which expands their potential applications and provides them with structural diversity. This review comprehensively addresses recent advances in the field of biomedical applications. It explores the potential prospects for exploiting the capabilities of mannans and xylans in drug delivery, gene delivery, and tissue engineering.

Extrusion-Based 3D Printing of Photocrosslinkable Chitosan Inks.

Photocuring of chitosan has shown great promise in the extrusion-based 3D printing of scaffolds for advanced biomedical and tissue engineering applications. However, the poor mechanical stability of methacrylated chitosan photocuring ink restricts its applicability. The inclusion of co-networks by means of simultaneous polycomplex formation is an effective method by which to solve this drawback, but the formed hydrogel inks are not printable. This work aims to develop new photocurable chitosan inks based on the simultaneous photocrosslinking of methacrylated chitosan (CHIMe) with N,N'-methylenebisacrylamide, polyethylene glycol diacrylate, and acrylic acid to be applied in extrusion 3D printing. Interestingly, the polycomplex co-network corresponding to the acrylic-acid-based ink could be successfully printed by the here-presented simultaneous photocuring strategy. Further, the conversion of photocrosslinking was studied via photo-DSC analyses that revealed a clear dependence on the chemical structure of the employed crosslinking agents (from 40 to ~100%). In addition, the mechanical and rheological properties of the photocured hydrogels were comparatively studied, as well as the printing quality of the extruded scaffolds. The newly developed chitosan photocurable inks demonstrated extrusion printability (squareness ~0.90; uniformity factor ~0.95) and tunable mechanical properties (Young modulus 14-1068 Pa) by means of different crosslinking approaches according to the chemical architecture of the reactive molecules employed. This work shows the great potential of photocrosslinkable chitosan inks.

Flexible Ag2Se Thermoelectric Films Enable the Multifunctional Thermal Perception in Electronic Skins.

Skin is critical for shaping our interactions with the environment. The electronic skin (E-skin) has emerged as a promising interface for medical devices to replicate the functions of damaged skin. However, exploration of thermal perception, which is crucial for physiological sensing, has been limited. In this work, a multifunctional E-skin based on flexible thermoelectric Ag2Se films is proposed, which utilizes the Seebeck effect to replicate the sensory functions of natural skin. The E-skin can enable capabilities including temperature perception, tactile perception, contactless perception, and material recognition by analyzing the thermal conduction behaviors of various materials. To further validate the capabilities of constructed E-skins, a wearable device with multiple sensory channels was fabricated and tested for gesture recognition. This work highlights the potential for using flexible thermoelectric materials in advanced biomedical applications including health monitoring and smart prosthetics.

Optimisation of processing parameters for wear properties of polylactic acid biopolymer parts in FDM process

ABSTRACT Currently, additive manufacturing (AM) technology has been expanding in advanced engineering and biomedical applications. The fused deposition modelling (FDMTM) method, also known as fused filament fabrication (FFF), is one of the most extensively used AM methods owing to its simple operation, reliability and potential to manufacture intricate components. The mechanical and wear properties of these components depend mainly on the proper selection of processing parameters. This study aims to determine the optimum parameters for low wear rate, less frictional force and good surface roughness. To achieve this aim, a hybrid approach based on user preference ranking is adopted to evaluate the effect of the four processing parameters including nozzle temperature, fill density, layer thickness and printing speed, on the wear behaviour, frictional force and surface roughness. The study procedure includes Taguchi L27 experiment design, finding the weight ratios, calculating utility index (UI) values and optimising UI values using Taguchi methodology for maximum utilisation. The results found that at 220°C of nozzle temperature, 100% fill density, 0.24 mm layer thickness and a printing speed of 60 mm/s are optimal parameters for the maximum utility index value. From the results, the percentage of contribution of fill density, nozzle temperature, layer thickness and printing speed were observed as 69.071%, 15.974%, 5.431% and 2.306%, respectively.

Self-Assembled DNA Nanospheres Driven by Carbon Dots for MicroRNAs Imaging in Tumor via Logic Circuit.

DNA nanostructures with diverse biological functions have made significant advancements in biomedical applications. However, a universal strategy for the efficient production of DNA nanostructures is still lacking. In this work, a facile and mild method is presented for self-assembling polyethylenimine-modified carbon dots (PEI-CDs) and DNA into nanospheres called CANs at room temperature. This makes CANs universally applicable to multiple biological applications involving various types of DNA. Due to the ultra-small size and strong cationic charge of PEI-CDs, CANs exhibit a dense structure with high loading capacity for encapsulated DNA while providing excellent stability by protecting DNA from enzymatic hydrolysis. Additionally, Mg2+ is incorporated into CANs to form Mg@CANs which enriches the performance of CANs and enables subsequent biological imaging applications by providing exogenous Mg2+ . Especially, a DNAzyme logic gate system that contains AND and OR Mg@CANs is constructed and successfully delivered to tumor cells in vitro and in vivo. They can be specifically activated by endogenic human apurinic/apyrimidinic endonuclease 1 and recognize the expression levels of miRNA-21 and miRNA-155 at tumor sites by logic biocomputing. A versatile pattern for delivery of diverse DNA and flexible logic circuits for multiple miRNAs imaging are developed.

Monitoring of Carbonated Hydroxyapatite Growth on Modified Polycrystalline CVD-Diamond Coatings on Titanium Substrates

Production of diamond coatings on titanium substrates has demonstrated as a promising strategy for applications ranging from biosensing to hard tissue engineering. The present study focuses on monitoring the nucleation and growth of bone-like carbonated-hydroxyapatite (C-HA) on polycrystalline diamond (PCD) synthetized on titanium substrate by means of a hot filament chemical vapor deposition (HF-CVD) method. The surface terminations of diamond coatings were selectively modified by oxidative treatments. The process of the C-HA deposition, accomplished by precipitation from simulated body fluid (SBF), was monitored from 3 to 20 days by Raman spectroscopy analysis. The coupling of morphological and structural investigations suggests that the modulation of the PCD surface chemistry enhances the bioactivity of the produced materials, allowing for the formation of continuous C-HA coatings with needle-like texture and chemical composition typical of those of the bone mineral. Specifically, after 20 days of immersion in SBF the calculated carbonate weight percent and the Ca/P ratio are 5.5% and 2.1, respectively. Based on these results, this study brings a novelty in tailoring the CVD-diamond properties for advanced biomedical and technological applications.

Chemical and Structural Engineering of Gelatin-Based Delivery Systems for Therapeutic Applications: A Review.

As a biodegradable and biocompatible protein derived from collagen, gelatin has been extensively exploited as a fundamental component of biological scaffolds and drug delivery systems for precise medicine. The easily engineered gelatin holds great promise in formulating various delivery systems to protect and enhance the efficacy of drugs for improving the safety and effectiveness of numerous pharmaceuticals. The remarkable biocompatibility and adjustable mechanical properties of gelatin permit the construction of active 3D scaffolds to accelerate the regeneration of injured tissues and organs. In this Review, we delve into diverse strategies for fabricating and functionalizing gelatin-based structures, which are applicable to gene and drug delivery as well as tissue engineering. We emphasized the advantages of various gelatin derivatives, including methacryloyl gelatin, polyethylene glycol-modified gelatin, thiolated gelatin, and alendronate-modified gelatin. These derivatives exhibit excellent physicochemical and biological properties, allowing the fabrication of tailor-made structures for biomedical applications. Additionally, we explored the latest developments in the modulation of their physicochemical properties by combining additive materials and manufacturing platforms, outlining the design of multifunctional gelatin-based micro-, nano-, and macrostructures. While discussing the current limitations, we also addressed the challenges that need to be overcome for clinical translation, including high manufacturing costs, limited application scenarios, and potential immunogenicity. This Review provides insight into how the structural and chemical engineering of gelatin can be leveraged to pave the way for significant advancements in biomedical applications and the improvement of patient outcomes.

Injectable smart stimuli-responsive hydrogels: pioneering advancements in biomedical applications.

Hydrogels have established their significance as prominent biomaterials within the realm of biomedical research. However, injectable hydrogels have garnered greater attention compared with their conventional counterparts due to their excellent minimally invasive nature and adaptive behavior post-injection. With the rapid advancement of emerging chemistry and deepened understanding of biological processes, contemporary injectable hydrogels have been endowed with an "intelligent" capacity to respond to various endogenous/exogenous stimuli (such as temperature, pH, light and magnetic field). This innovation has spearheaded revolutionary transformations across fields such as tissue engineering repair, controlled drug delivery, disease-responsive therapies, and beyond. In this review, we comprehensively expound upon the raw materials (including natural and synthetic materials) and injectable principles of these advanced hydrogels, concurrently providing a detailed discussion of the prevalent strategies for conferring stimulus responsiveness. Finally, we elucidate the latest applications of these injectable "smart" stimuli-responsive hydrogels in the biomedical domain, offering insights into their prospects.