Biomedical Applications Research Articles

Global trends in clinical trials involving engineered biomaterials.

Engineered biomaterials are materials specifically designed to interact with biological systems for biomedical applications. This paper offers the comprehensive analysis of global clinical trial trends involving such materials. We surveyed 834 studies in the ClinicalTrials.gov database and explored biomaterial types, their initiation points, and durations in clinical trials. Predominantly, synthetic and natural polymers, particularly silicone and collagen, are used. Trials, focusing on ophthalmology, dentistry, and vascular medicine, are primarily conducted in the United States, Canada, and Italy. These trials encompass a broad demographic, and trials enrolled fewer than 100 participants. The study duration varied ranging from 0.5 to 4.5 years. These biomaterials are mainly bioresorbable or bioinert, with the integration of cells in biomaterials remaining an underexplored area. Our findings shed light on current practices and future potentials of engineered biomaterials in clinical research, offering insights for advancing this dynamic field globally.

Introducing PCL-Based Electrospun Nanocomposite Wound Dressings: Synergistic Effects of Curcumin and Reduced Graphene Oxide

ABSTRACT The development of effective wound dressings is critical for enhancing patient outcomes in both acute and chronic wound care scenarios. In this research, electrospun nanofibrous scaffolds were fabricated from poly(ε-caprolactone) (PCL), enhanced with curcumin and reduced graphene oxide (RGO) to optimize their biomedical applications, particularly in wound healing. The resulting scaffolds were rigorously characterized through scanning electron microscopy, contact angle measurements, water uptake capacity, and water vapor transmission rate assays. The biocompatibility of these novel nanofibers was affirmed through MTT assays. Antibacterial tests confirmed the scaffolds’ ability to inhibit both Gram-negative and Gram-positive bacteria, with inhibition zones measuring up to 9.9 mm for S. aureus and 9.2 mm for E. coli. Additionally, scaffolds containing curcumin exhibited significant antioxidant activity, achieving up to 40% radical scavenging efficiency. The study further revealed the scaffolds’ capability for sustained drug release, with an initial burst release within the first 12 hours followed by a gradual release over 168 hours. Overall, the PCL-curcumin-RGO electrospun mats demonstrated considerable potential for biomedical applications, notably in the field of wound dressings, due to their enhanced antibacterial, antioxidant, and biocompatible properties.

Graphitic Carbon Nitride Enters the Scene: A Promising Versatile Tool for Biomedical Applications.

Graphitic carbon nitride (g-C3N4), since the pioneering work on visible-light photocatalytic water splitting in 2009, has emerged as a highly promising advanced material for environmental and energetic applications, including photocatalytic degradation of pollutants, photocatalytic hydrogen generation, and carbon dioxide reduction. Due to its distinctive two-dimensional structure, excellent chemical stability, and distinctive optical and electrical properties, g-C3N4 has garnered a considerable amount of interest in the field of biomedicine in recent years. This review focuses on the fundamental properties of g-C3N4, highlighting the synthesis and modification strategies associated with the interfacial structures of g-C3N4-based materials, including heterojunction, band gap engineering, doping, and nanocomposite hybridization. Furthermore, the biomedical applications of these materials in various domains, including biosensors, antimicrobial applications, and photocatalytic degradation of medical pollutants, are also described with the objective of spotlighting the unique advantages of g-C3N4. A summary of the challenges faced and future prospects for the advancement of g-C3N4-based materials is presented, and it is hoped that this review will inspire readers to seek further new applications for this material in biomedical and other fields.

Effect of the lattice structures on mechanical characterisation of additively manufactured Ti-6Al-4V for biomedical application

ABSTRACT In the last decades, most investigations in titanium bone implantology have applied lattice structures instead of dense materials to reduce weight and obtain the mechanical properties similar to human bones. However, there is still a need for more research on the optimal design of lattice titanium implants with proper mechanical behaviour and heat treatment investigations, which directly affects the mechanical, microstructural, and morphological characteristics. The present study aims to examine the effect of densities and unit cell sizes for Selective Laser Melting (SLM)-printed lattice structures created by MSLattice. TPMS lattice structures including Diamond, Gyroid, and Primitive generated by MSLattice software were subsequently printed using Ti-6Al-4 V ELI. Tensile testing of DTi (dense) produced an ultimate tensile strength of 1241.58 ± 23.92 MPa and a Yield strength of 1151 ± 8.6 MPa, while its compression test resulted in an ultimate value of 1424.8 ± 20.13 MPa. The increase in density from 20% to 30% has resulted in a doubling of some mechanical properties. The lattice structure of the Gyroid at 30% density presented a UCS value of 143.96 ± 0.89 MPa as the highest, while that of the Diamond at 20% density presented the lowest with 46.89 ± 0.43 MPa. The values for energy absorption and plateau stress follow in a precise sequence.

Engineering a Self-Assembled Protein Cage for Targeted Dual Functionalization.

Self-assembled protein cages are attractive scaffolds for organizing various proteins of interest (POIs) toward applications in synthetic biology and medical science. However, specifically attaching multiple POIs to a single protein cage remains challenging, resulting in diversity among the functionalized particles. Here, we present the engineering of a self-assembled protein cage, DTMi3ST, capable of independently recruiting two different POIs using SpyCatcher (SC)/SpyTag (ST) and DogCatcher (DC)/DogTag (DT) chemistries, thereby reducing variability between assemblies. Using fluorescent proteins as models, we demonstrate controlled targeting of two different POIs onto DTMi3ST protein cages both in vitro and inside living cells. Furthermore, dual functionalization of the DTMi3ST protein cage with a membrane-targeting peptide and β-galactosidase resulted in the construction of membrane-bound enzyme assemblies in Escherichia coli, leading to a 69.6% enhancement in substrate utilization across the membrane. This versatile protein cage platform provides dual functional nanotools for biological and biomedical applications.

Magnetically Actuated Nanomaterials in Biomedical Applications

Magnetically Actuated Nanomaterials in Biomedical Applications

The Horizons of Medical Mineralogy: Structure-Bioactivity Relationship and Biomedical Applications of Halloysite Nanoclay.

Medical mineralogy explores the interactions between natural minerals and living organisms such as cells, tissues, and organs and develops therapeutic and diagnostic applications in drug delivery, medical devices, and healthcare materials. Many minerals (especially clays) have been recognized for pharmacological activities and therapeutic potential. Halloysite clay (Chinese medicine name: Chishizhi), manifested as one-dimensional aluminum silicate nanotubes (halloysite nanotubes, HNTs), has gained applications in hemostasis, wound repair, gastrointestinal diseases, tissue engineering, detection and sensing, cosmetics, and daily chemicals formulations. Various biomedical applications of HNTs are derived from hollow tubular structures, high mechanical strength, good biocompatibility, bioactivity, and unique surface characteristics. This natural nanomaterial is safe, abundantly available, and may be processed with environmentally safe green chemistry methods. This review describes the structure and physicochemical properties of HNTs relative to bioactivity. We discuss surface area, porosity and surface defects, hydrophilicity, heterogeneity and charge of external and internal surfaces, as well as biosafety. The paper provides comprehensive guidance for the development of this tubule nanoclay and its advanced biomedical applications for clinical diagnosis and therapy.

Direct Functionalization of Polyethylene Surfaces with High-Density Polymer Brushes.

Introducing functionality onto PE surfaces is a longstanding challenge in polymer science, driven by the need for polymer materials with improved adhesion and antifouling properties. Herein, we report surface-initiated hydrogen atom transfer-reversible addition-fragmentation chain transfer (SI HAT-RAFT) as a robust method to grow high-density brush polymers from PE surfaces. We demonstrate that, under mild conditions, direct initiation from the C-H bonds of PE surfaces allows for the graft polymerization of a variety of (meth)acrylate monomers. The resulting polymer brushes reached several hundred nanometers in thickness with densities of ca. 0.62 chains/nm2, compared to the current standard of ∼0.28 chains/nm2. Finally, we show that our method is capable of dramatically improving the adhesive properties of PE surfaces. This work enables the preparation of PE with diverse surface functionalities for potential use in biomedical, industrial, and battery applications.

High-throughput screening for cell binding and repulsion peptides on multifunctionalized surfaces

The adhesion of cells to the extracellular matrix engages cell surface receptors such as integrins, proteoglycans and other types of cell adhesion molecules such as CD44. To closely examine the determinants of cell adhesion, herein we describe the generation of high-density peptide arrays and test the growth of cells on these multifunctionalized surfaces. The peptide library used consists of over 11,000 different sequences, either random or derived from existing proteins. By applying this screen to SW620 mCherry colorectal cancer cells, we select for peptides with both maximum cell adhesion and maximum cell repulsion. All of these extreme properties are based on unique combinations of amino acids. Here, we identify peptides with maximum cell repulsion on secreted frizzled- and Dickkopf-related proteins. Peptides with strong cell repulsion are found at the poles of the TNF-alpha homotrimer. The formation of cellular patterns on alternating highly repulsive and adhesive peptides are examined. Our screen allows the identification of peptides suitable for biomedical and tissue engineering applications.

Biocompatible Hybrid Graphenic Thin Coatings on Flexible Substrates through Matrix-Assisted Pulsed Laser Evaporation (MAPLE).

This work reports the production of biocompatible thin layers for biomedical applications based on a graphene-like material (GL), a graphene-related material (GRM) obtained from carbon black. GL was combined in a hybrid fashion with polydopamine (pDA), a mussel-inspired water-resistant wet adhesive bonding obtained by the oxidative polymerization of dopamine (DA), and polyvinyl pyrrolidinone (PVP), a nontoxic synthetic polymer with intrinsic adhesion properties, to obtain a tighter adhesion of the thin layer to the substrate (silicone slices). Matrix-assisted pulsed laser evaporation (MAPLE) was used to coat PDMS slices with thin films of GL-pDA and GL-PVP directly from their frozen suspensions in water. The results indicate that the relevant chemical-physical characteristics of both thin films (evidenced by FTIR and AFM) were maintained after MAPLE deposition and that the films exhibit uniformity also at the nanometric level. After deposition, the GL-pDA and GL-PVP films underwent a biological survey toward murine fibroblasts (NIH3T3), human keratinocytes (HaCAT), and human cervical adenocarcinoma epithelial-like (HeLa) cells to assess the feasibility of this approach. Results indicate that both the GL-pDA and GL-PVP films did not perturb the biological parameters evaluated, including cytoskeleton alterations. Both hybrid films enhanced the effects of GL on cellular vitality across all cell lines. Specifically, the GL-pDA film exhibited a more stable effect over time (up to 72 h), whereas the GL-PVP film behaved similarly to the GL film in NIH3T3 and HeLa cell lines after long-term exposure. These promising results make the GL-pDA and GL-PVP films potential candidates for the manufacture of coated flexible devices for biomedical applications.

3D printing assisted surface patterning process on acrylated hydrogels for contact guidance of fibroblasts

Generating stable and customizable topography on hydrogel surfaces with contact guidance potential is critical as it can direct/influence cell growth. This necessitates the development of new techniques for surface patterning of the hydrogels. We report on the design of a square grid template for surface patterning hydrogels. The template was 3-D printed and has the diameter of a well in a 24-well plate. Hyaluronic acid methacrylate (HA) hydrogel precursor solutions were cast on the 3D printed template's surface, which generated 3D square shape topographies on the HA hydrogel surface upon demolding. The 3D Laser Microscopy has shown the formation of a periodic array of 3D topographies on hydrogel surfaces. 3D Laser and Electron Microscopy Imaging have revealed that this new method has increased the surface area and exposed the underlying pore structure of the HA hydrogels. To demonstrate the method's versatility, we have successfully applied this technique to generate 3D topography on two more acrylate hydrogel formulations, gelatin Methacrylate and polyethylene glycol dimethacrylate. Human neonatal dermal fibroblast cells were used as a model cell line to evaluate the cell guidance potential of patterned HA hydrogel. Confocal fluorescence microscopy imaging has revealed that the 3D surface topographies on HA hydrogels can guide and align the actin filaments of the fibroblasts presumably due to the contact guidance mechanism. The newly developed methodology of 3D topography generation in acrylate hydrogels may influence the cell responses on hydrogel surfaces which can impact biomedical applications such as tissue engineering, wound healing, and disease modeling.

Resin-based dental pulp capping restoration enclosing silica and portlandite nanoparticles from natural resources

Natural-based materials represent green choices for biomedical applications. In this study, resin pulp capping restoration enclosing strengthening silica and bioactive portlandite nanofillers were prepared from industrial wastes. Silica nanoparticles were isolated from rice husk by heat treatment, followed by dissolution/precipitation treatment. Portlandite nanoparticles were prepared by calcination of carbonated lime waste followed by ultrasonic treatment. Both were characterized using x-ray diffraction, energy dispersive x-ray, and transmission electron microscopy. For preparing pulp capping restoration, silica (after silanization) and/or portlandite nanoparticles were mixed with 40/60 weight ratio of bisphenol A-glycidyl methacrylate and triethylene glycol dimethacrylate. Groups A, B, and C enclosing 50 wt.% silica, 25 wt.% silica + 25 wt.% portlandite, and 50 wt.% portlandite, respectively, were prepared. All groups underwent microhardness, compressive strength, calcium release, pH, and apatite forming ability inspection in comparison to mineral trioxide aggregate (MTA) positive control. In comparison to MTA, all experimental groups showed significantly higher compressive strength, group B showed comparable microhardness, and group C showed significantly higher calcium release. Groups B and C showed prominent hydroxyapatite formation. Thus, the preparation of economic, silica-fortified, bioactive pulp capping material from under-utilized agricultural residues (rice husk) and zero-value industrial waste (carbonated lime from sugar industry) could be achieved.

Recent Progress and Challenges in Graphene Quantum Dots as Multifunctional Nanoplatforms for Biomedical Applications

Recent Progress and Challenges in Graphene Quantum Dots as Multifunctional Nanoplatforms for Biomedical Applications

Facile Synthesis of Hemin Derivatives with Modulated Aggregation Behaviour and Enhanced Nitric‐Oxide Scavenging Properties as New Therapeutics for Breast Cancer

Nitric oxide (•NO) plays various pathophysiological roles in breast cancer, significantly influencing the migration of tumour cells through concentration gradients. Therefore, modulating •NO levels via selective scavenging presents a promising approach to treating aggressive •NO‐dependent cancers, such as triple‐negative breast cancer (TNBC). Hemin emerges as a potential scavenger of •NO; however, its metalloporphyrin molecules tend to aggregate in physiological solutions, which limits its biomedical applications. To address this, a modification strategy is employed to minimize aggregation and protect against physiological oxidative degradation while preserving •NO‐scavenging properties. This is achieved through a simple chemical transformation that involves hemin conjugation to aromatic residues, tyrosine, and tyramine via carbodiimide reactions. These derivatives exhibit altered electronic properties and oxidation potential compared to hemin, alongside reduced aggregation tendencies and retained •NO‐binding affinity in aqueous solutions. Furthermore, depending on the type of hemin derivative, there is an associated inhibition of TNBC cell migration. These model hemin compounds demonstrate varying •NO‐binding affinities and resistance levels to oxidative degradation and aggregation, offering insights into the design of •NO‐scavenging molecules with enhanced properties for cancer treatment.

Splittable systems in biomedical applications.

Splittable systems have emerged as a powerful approach for the precise spatiotemporal control of biological processes. This concept relies on splitting a functional molecule into inactive fragments, which can be reassembled under specific conditions or stimuli to regain activity. Several binding pairs and orthogonal split fragments are introduced by fusing with other modalities to develop more complex and robust designs. One of the pillars of these splittable systems is modularity, which involves decoupling targeting, activation, and effector functions. Challenges, such as off-target effects and overactivation, can be addressed through precise control. This review provides an overview of the design principles, strategies, and applications of splittable systems across diverse fields including immunotherapy, gene editing, prodrug activation, biosensing, and synthetic biology.

Modulating the Thermoresponsive Characteristics of PLGA-PEG-PLGA Hydrogels via Manipulation of PLGA Monomer Sequences.

Hydrogels are promising materials for biomedical applications, particularly in drug delivery and tissue engineering. This study highlights thermoresponsive hydrogels, specifically poly(lactic-co-glycolic acid) (PLGA)-poly(ethylene glycol) (PEG)-PLGA triblock copolymers, and introduces a feed rate-controlled polymerization (FRCP) method. By utilizing an organic catalyst and regulating the monomer feed rate, the sequence distribution of PLGA within the triblock copolymer is controlled. Various analyses, including 13C NMR and rheological measurements, were conducted to investigate the impact of sequence distribution. Results show that altering sequence distribution significantly influences the sol-gel transition, hydrophobicity-hydrophilicity balance, and drug release profile. Increased sequence uniformity lowers the glass transition temperature, raises the sol-gel transition temperature due to enhanced hydrophilicity, and promotes a more uniform drug (curcumin) distribution within the PLGA domain, resulting in a slower release rate. This study emphasizes the importance of PLGA sequence distribution in biomedical applications and the potential of FRCP to tailor thermoresponsive hydrogels for biomedical advancements.

Preliminary phytochemical and biological activity screening of Sargassum lapazeanum

Algae are exposed to substantial stress. In response, these organisms have developed efficient defense systems, such as protective secondary metabolite synthesis, making algae a primary source of bioactive compounds with a wide spectrum of biological activities. Thus, algae show potential for use in treatments of thrombotic, infectious, and chronic degenerative diseases. Therefore, the objective of this study was to evaluate the phytochemical compounds and pharmacological activity of an extract obtained from Sargassum lapazeanum. Algae were collected in the intertidal zone of Tarabillas beach (Bahía de La Paz, BCS). The biological activities of an ethanolic extract and its fractions were evaluated using chromatographic techniques. In addition, a bioautographic assay of hemolytic activity was conducted, and phytochemical profiles and acute toxicity in Artemia franciscana were evaluated. The relationships among the main extract components were also determined. The ethanolic extract exhibited significant antioxidant and hemolytic activity, which was mainly attributed to its content of anthrones, anthraquinones, and unsaturated triterpenes. Its toxicological activity reached an LC50 value of 225.1 μg mL-1, which was mainly attributed to alkaloids, flavonoids, anthrones, and saponins. The results suggest that Sargassum lapazeanum, which is endemic to the Gulf of California, has great pharmacological potential with biomedical applications.

Operational stability study of lactate biosensors: modeling, parameter identification, and stability analysis

IntroductionThis paper investigates the operational stability of lactate biosensors, crucial devices in various biomedical and biotechnological applications. We detail the construction of an amperometric transducer tailored for lactate measurement and outline the experimental setup used for empirical validation.MethodsThe modeling framework incorporates Brown and Michaelis–Menten kinetics, integrating both distributed and discrete delays to capture the intricate dynamics of lactate sensing. To ascertain model parameters, we propose a nonlinear optimization method, leveraging initial approximations from the Brown model’s delay values for the subsequent model with discrete delays.ResultsStability analysis forms a cornerstone of our investigation, centering on linearization around equilibrium states and scrutinizing the real parts of quasi-polynomials. Notably, our findings reveal that the discrete delay model manifests marginal stability, occupying a delicate balance between asymptotic stability and instability. We introduce criteria for verifying marginal stability based on characteristic quasi-polynomial roots, offering practical insights into system behavior.DiscussionQalitative examination of the model elucidates the influence of delay on dynamic behavior. We observe a transition from stable focus to limit cycle and period-doubling phenomena with increasing delay values, as evidenced by phase plots and bifurcation diagrams employing Poincaré sections. Additionally, we identify limitations in model applicability, notably the loss of solution positivity with growing delays, underscoring the necessity for cautious interpretation when employing delayed exponential function formulations. This comprehensive study provides valuable insights into the design and operational characteristics of lactate biosensors, offering a robust framework for understanding and optimizing their performance in diverse settings.

Insights into metachronal propulsion's influence on Ellis fluid flow across tri‐layers amid dynamic thermal transport: Theoretical study

AbstractCilia‐based therapies are emerging for treating ciliopathies, such as inhalable drugs to propel mucus out of the lungs of patients with cystic fibrosis. This has motivated scientists and researchers to investigate cilia motion mechanics and viscoelastic fluid properties for biomedical engineering applications and disease treatments. In line with the diverse biological implications, this study focuses on the mass and heat transfer flow of tri‐layered non‐Newtonian fluids propelled by ciliary beating in a cylindrical tube. The fluid remains incompressible, with distinct layers that do not mix. The study considers the impact of mass and heat transfer in three distinct regimes, ensuring continuity at the interfaces. Mathematical modeling incorporating the lubrication approximation, small Reynolds number, and long wavelength approximation is employed for simplification. The resulting differential equations, along with boundary conditions, yield accurate solutions for temperature, velocity, and concentration fields in the three fluid layers and are discussed graphically. Key findings demonstrate that velocity and temperature fields are most pronounced in the inner fluid layer (PCL), while the concentration profile is most prominent in the outer layers (ACL), with moderate behavior in the central region. The implications of this research extend to diverse fields, including mucus clearance from the respiratory tract, microfluidics, esophageal transport, biofluid mechanics, and other areas of physiology. The insights gained from this study have promising applications in developing new treatments and biomedical engineering solutions.

FRESH-based 3D bioprinting of complex biological geometries using chitosan bioink

Traditional three-dimensional (3D) bioprinting has always been associated with the challenge of print fidelity of complex geometries due to the gel-like nature of the bioinks. Embedded 3D bioprinting has emerged as a potential solution to print complex geometries using proteins and polysaccharides-based bioinks. This study demonstrated the Freeform Reversible Embedding of Suspended Hydrogels (FRESH) 3D bioprinting method of chitosan bioink to 3D bioprint complex geometries. 4.5% chitosan was dissolved in an alkali solvent to prepare the bioink. Rheological evaluation of the bioink described its shear-thinning nature. The power law equation was fitted to the shear rate-viscosity plot. The flow index value was found to be less than 1, categorizing the material as pseudo-plastic. The chitosan bioink was extruded into another medium, a thermo-responsive 4.5% gelatin hydrogel. This hydrogel supports the growing print structures while printing. After this, the 3D bioprinted structure was crosslinked with hot water to stabilize the structure. Using this method, we have 3D bioprinted complex biological structures like the human tri-leaflet heart valve, a section of a human right coronary arterial tree, a scale-down outer structure of the human kidney, and a human ear. Additionally, we have shown the mechanical tunability and suturability of the 3D bioprinted structures. This study demonstrates the capability of the chitosan bioink and FRESH method for 3D bioprinting of complex biological models for biomedical applications.