Min-Ho Kim

Gallium-based antimicrobials have historically shown their strongest activity against Gram-negative pathogens, particularly P. aeruginosa, while exhibiting limited efficacy against S. aureus. Here, we demonstrate that ligand design can profoundly alter the antibacterial spectrum of gallium complexes. Among six structurally distinct Ga(III) complexes evaluated, gallium tris(8-hydroxyquinolinate), Ga(8HQ)₃, emerged as the only compound displaying potent anti-staphylococcal activity. Ga(8HQ)₃ exhibited low MIC values (2.5-5.0 μg/mL) against methicillin-susceptible S. aureus (MSSA), methicillin-resistant S. aureus (MRSA), vancomycin-intermediate S. aureus (VISA), and multiple clinical isolates, and demonstrated rapid bactericidal activity with MBC/MIC ratios ≤2. The complex also effectively inhibited MRSA biofilm formation and restored susceptibility of a mupirocin-resistant MRSA strain, reducing the mupirocin MIC by 64-fold. The crystallographic, computational, and biological data together support a mechanistic model in which ligand coordination enhances intracellular gallium delivery. Consistent with this model, Ga(8HQ)₃ produced substantially greater intracellular gallium accumulation than gallium nitrate, accompanied by increased oxidative stress and membrane permeabilization. In serial-passage studies, Ga(8HQ)₃ exhibited a low propensity for resistance development and retained activity against mupirocin-resistant MRSA, indicating minimal cross-resistance.,Collectively, these findings demonstrate that rational ligand selection can reprogram the biological behavior of gallium complexes, transforming a traditionally anti-Gram-negative metallodrug platform into a potent anti-staphylococcal agent and identifying Ga(8HQ)₃ as a promising candidate for treating drug-resistant and biofilm-associated S. aureus infections.

Background/Objectives: The widespread use of mupirocin and fusidic acid for the treatment and decolonization of Staphylococcus aureus (SA) skin infections has led to a rapid emergence of resistant strains, limiting the effectiveness of the few topical agents currently available for clinical use. Methods: In this study, we evaluate Fe(tropo)₃, a neutral and lipophilic iron(III)–tropolone complex, as a non-antibiotic topical antimicrobial candidate for the management of drug-resistant SA skin and soft tissue infections. Results: Fe(tropo)₃ exhibits potent in vitro activity against methicillin-susceptible SA, methicillin-resistant SA (MRSA), vancomycin-intermediate SA, and strains with high-level resistance to mupirocin and fusidate, with minimum inhibitory concentrations of 2 µg/mL across all tested isolates. The compound effectively penetrates bacterial cells, induces intracellular iron accumulation, and triggers dose-dependent reactive oxygen species generation, resulting in rapid bacterial killing and significant antibiofilm activity. Importantly, Fe(tropo)₃ shows a slower development of resistance compared with ciprofloxacin and displays synergistic activity with oxacillin against MRSA. When formulated as a 1% topical ointment, Fe(tropo)₃ significantly reduces bacterial burden in a murine excisional wound infection model, achieving a 98% ± 1% reduction in SA load without detectable hemolysis or skin irritation. Conclusions: These pilot study results support Fe(tropo)₃ as a clinically relevant, mechanism-distinct topical antimicrobial with potential utility in settings where resistance to existing topical antibiotics compromises standard care.

Background: Carbapenem-resistant Acinetobacter baumannii (CRAB) is a critical public health threat, particularly in hospital environments where treatment options are limited. Drug repurposing offers a rapid and cost-effective strategy to address antimicrobial resistance. This study evaluates KP46 (tris(8-quinolinolato)gallium(III)), an orally bioavailable gallium-based anticancer agent, for its antimicrobial potential against CRAB. Methods: KP46 was synthesized and characterized using spectroscopic and crystallographic techniques. Its antibacterial activity was assessed against planktonic and biofilm-associated CRAB strains, including multidrug-resistant clinical isolates. Mechanistic studies included intracellular reactive oxygen species (ROS) quantification, membrane integrity assays, and resistance development profiling. Results: KP46 exhibited potent antibacterial activity against both susceptible and carbapenem-resistant A. baumannii strains. It inhibited planktonic growth and disrupted early biofilm formation. KP46 induced intracellular oxidative stress, leading to membrane damage and cell death. Resistance development was significantly slower compared to meropenem, and KP46 retained efficacy against meropenem-resistant isolates. Conclusions: KP46 demonstrates dual-action antimicrobial activity and a low propensity for resistance development, positioning it as a promising candidate for repurposing against CRAB infections. These findings support further preclinical evaluation of KP46 as an orally active therapeutic agent targeting both planktonic and biofilm-associated bacterial populations. resistance development and retained efficacy against meropenem-resistant strains.

Neurological disorders including gliomas and neurodegenerative diseases are characterized by dysregulation of the central nerve system (CNS). Despite recent advances in disease-modifying treatments, pharmacological approaches for neurological disorders still face limitations due to the complexity of these diseases and the challenges in targeting the underlying mechanisms. Magnetic hyperthermia, an approach that utilizes magnetic nanoparticles (MNPs) to generate localized heat in target cells and tissues by responding to an alternating magnetic field (AMF), has been developed as a non-pharmacological treatment approach for targeting tumor cells or pathogens, primarily through thermal inactivation. Recently, beyond its traditional application in thermal therapies, magnetic hyperthermia has been increasingly explored for neurological diseases. Importantly, recent studies demonstrate the ability of magnetic hyperthermia in eliciting various biological effects by means of triggering heat shock protein (HSP) signaling, enhancing immune responses, and activating heat-sensitive ion channels in neurons. This review highlights the current understanding of magnetic hyperthermia in stimulating molecular and cellular effects on brain tissue and further discusses its potential in the treatment of neurological disorders including Glioblastoma Multiforme (GBM), Alzheimer's Disease (AD), Parkinson's Disease (PD). The studies discussed in this review were selected by using the search tool on PubMed with the suggested key words.

Copper nanoparticles, when properly combined with vitamin C, can synergistically enhance antibacterial activity against broad spectrum of bacteria through the increased generation of ROS in bacterial cells.

The principle of magnetic hyperthermia is to generate localized heating on target proteins, cells and tissue that are targeted by magnetic nanoparticles (MNPs) upon stimulation by remotely applied high frequency alternating magnetic field (AMF). Beyond its traditional applications in hyperthermia therapy, recent studies demonstrated the feasibility of magnetic hyperthermia as a new strategy for neural stimulation. The objective of this study is to examine the feasibility of localized magnetic hyperthermia (i.e. MNP/AMF hyperthermia) as a new strategy for brain stimulation, especially in modulating microglia activity and behaviors in vivo. This was examined by correlating a varying degree of MNP/AMF-induced thermal dose with the extent of microglial activation in the mouse brain. The MNP/AMF hyperthermia stimulation applied at a mild thermal dose to the mouse hippocampus significantly increased the infiltration of microglia and altered their morphology towards reactive and ameboid-like phenotypes in a thermal dose-dependent manner. Importantly, these responses were associated with increased expression of heat shock protein 70 (HSP70), a molecular chaperon protein, and LC3II, a marker of autophagic activity. Our findings support the feasibility of developing mild magnetic hyperthermia as a new strategy for localized stimulation of brain tissue.

Durability of bonded restorations (Li et al., 2024).Another contribution reported by Rangel et al. focuses on the pivotal role of cellinstructive biomaterials in tissue engineering and regenerative medicine (Rangel et al., 2024). Over the past three decades, significant strides have been made in regenerating diseased or damaged tissues by integrating innovations in biomaterials, signaling molecules, and cell therapies. Despite these advancements, challenges such as material property limitations, the need for advanced manufacturing technologies, and clinical translation hurdles persist. The article highlights breakthroughs in selfhealing and modular biomaterials, 3D bioprinting, and emerging research technologies like multi-omics and spatial biology. The perspective offered underscores the critical contributions of clinician-scientists in driving innovation, clinical validation, and adoption of next-generation biomaterials, emphasizing their transformative potential in tissue and organ engineering (Rangel et al., 2024).Additionally, a study on pneumatic, fabric-reinforced inflatable soft actuators made of Dragon Skin 30 silicone provides insights into material endurance and variability (Bui et al., 2023). The research elucidates how material properties affect actuator performance over time by examining repeatability, durability, and failure pressure.These findings contribute to a deeper understanding of the real-world behavior of soft actuators and their material constraints, enabling improved design and control in practical applications (Bui et al., 2023).The overarching aim of this Research Topic was to provide a platform for early career scientists to share their innovative contributions while fostering an understanding of their work within the larger scientific community. The articles included here reflect the broad applicability and interdisciplinary nature of biomaterials and bio-inspired materials, emphasizing their importance in creating sustainable and functional solutions. The collective findings illustrate significant progress in the synthesis, design, and application of these materials, demonstrating their potential to address pressing global needs in healthcare, environmental sustainability, and beyond.The compilation of studies in this Research Topic exemplifies innovative approaches to biomaterial development, such as the pH-responsive dentin adhesives and cellinstructive biomaterials, which address both performance enhancement and sustainability in practical applications. Early career scientists are uniquely positioned to lead this charge, leveraging their creativity and openness to novel approaches. The insights shared in this Research Topic highlight their essential role in shaping the field's future and provide a glimpse into the directions that biomaterials research is likely to take. However, the insights shared also illuminate persistent challenges, such as the scalability of self-healing biomaterials, the durability and stability of soft actuators, and the clinical translation of tissue engineering technologies. Addressing these challenges requires precise understanding of the structure and function of biological systems to translate them into bioinspired materials effectively as well as interdisciplinary collaborations and advancements in manufacturing techniques, such as 3D bioprinting and high-throughput material characterization methods.For early career scientists, there are vast opportunities in exploring areas such as bioinspired 3D printing, the development of multifunctional biomaterials, and the application of machine learning in material design. Collaborations across disciplines and with industry partners can accelerate the translation of these materials into realworld applications. By focusing on underexplored niches like low-cost sustainable biomaterials or modular designs for regenerative medicine, early career researchers can carve impactful pathways for future advancements.The editorial team extends its gratitude to the authors, reviewers, and collaborators who contributed to this Research Topic. Their collective efforts have ensured that the work presented here reflects the highest standards of scientific rigor and relevance. This Research Topic stands as a testament to the ingenuity and dedication of early career researchers, serving as both a snapshot of current advancements and a catalyst for future innovations in biomaterials and bio-inspired materials research.As editors, we believe that the findings presented here underscore the transformative potential of biomaterials and bio-inspired materials in addressing global challenges.The pioneering work of early career scientists featured in this Research Topic serves as a beacon for future research. The integration of innovative material properties, sustainable practices, and interdisciplinary approaches is not just a necessity but a pathway to breakthroughs that can redefine the field. We hope this compilation inspires

8-Hydroxyquinoline (8-hq) exhibits potent antimicrobial activity against Staphylococcus aureus (SA) bacteria with MIC = 16.0–32.0 µM owing to its ability to chelate metal ions such as Mn²⁺, Zn^2+, and Cu²⁺ to disrupt metal homeostasis in bacterial cells. We demonstrate that Fe(8-hq)₃, the 1:3 complex formed between Fe(III) and 8-hq, can readily transport Fe(III) across the bacterial cell membrane and deliver iron into the bacterial cell, thus, harnessing a dual antimicrobial mechanism of action that combines the bactericidal activity of iron with the metal chelating effect of 8-hq to kill bacteria. As a result, the antimicrobial potency of Fe(8-hq)₃ is significantly enhanced in comparison with 8-hq. Resistance development by SA toward Fe(8-hq)₃ is considerably delayed as compared with ciprofloxacin and 8-hq. Fe(8-hq)₃ can also overcome the 8-hq and mupirocin resistance developed in the SA mutant and MRSA mutant bacteria, respectively. Fe(8-hq)₃ can stimulate M1-like macrophage polarization of RAW 264.7 cells to kill the SA internalized in such macrophages. Fe(8-hq)₃ exhibits a synergistic effect with both ciprofloxacin and imipenem, showing potential for combination therapies with topical and systemic antibiotics for more serious MRSA infections. The in vivo antimicrobial efficacy of a 2% Fe(8-hq)₃ topical ointment is confirmed by the use of a murine model with skin wound infection by bioluminescent SA with a reduction of the bacterial burden by 99 ± 0.5%, indicating that this non-antibiotic iron complex has therapeutic potential for skin and soft tissue infections (SSTIs).

Although it has no known biochemical role in living organisms, bismuth has been used to treat syphilis, diarrhea, gastritis and colitis for almost a century due to its nontoxic nature to mammalian cells. When prepared via a top-down sonication route from a bulk sample, bismuth subcarbonate (BiO)₂CO₃ nanoparticles (NPs) with an average size of 5.35 ± 0.82 nm exhibit broad-spectrum potent antibacterial activity against both the gram-positive and gram-negative bacteria including methicillin-susceptible Staphylococcus aureus (DSSA), methicillin-resistant Staphylococcus aureus (MRSA), drug-susceptible Pseudomonas aeruginosa (DSPA) and multidrug-resistant Pseudomonas aeruginosa (DRPA). Specifically, the minimum inhibitory concentrations (MICs) are 2.0 µg/mL against DSSA and MRSA and 0.75 µg/mL against DSPA and DRPA. In sharp contrast to ciprofloxacin, AgNPs and meropenem, (BiO)₂CO₃ NPs show no sign of developing Bi-resistant phenotypes after 30 consecutive passages. On the other hand, such NPs can readily overcome the resistance to ciprofloxacin, AgNPs and meropenem in DSPA. Finally, the combination of (BiO)₂CO₃ NPs and meropenem shows a synergistic effect with the fractional inhibitory concentration (FIC) index of 0.45.

The crawling behavior of leukocytes is driven by the cell morphology transition, which is a direct manifestation of molecular motor machinery. The topographical anisotropy and mechanical stiffness of the substrates are the main physical cues that affect leukocytes’ shape generation and migratory responses. However, their combined effects on the cell morphology and motility have been poorly understood, particularly for neutrophils, which are the fastest reacting leukocytes against infections and wounds. Here, spatiotemporally correlated physical parameters are shown, which determine the neutrophil shape change during migratory processes, in response to surface topography and elasticity. Guided crawling and shape generation of individual neutrophils, activated by a uniform concentration of a chemoattractant, are analyzed by adopting elasticity‐tunable micropatterning and live cell imaging techniques. Whole cell‐level image analysis is performed based on a planar geometric quantification of cell shape and motility. The findings show that the pattern anisotropy and elastic modulus of the substrate induce synergic effects on the shape anisotropy, deformability, and polarization/alignment of crawling neutrophils. How the morphology–motility relationship is affected by different surface microstructures and stiffness is demonstrated. These results imply that the neutrophil shape‐motility correlations can be utilized for controlling the immune cell functions with predefined physical microenvironments.