Key biomarkers in type 2 diabetes patients: A systematic review.

Type 2 diabetes mellitus (T2DM) is not just a local health issue but a significant global health burden, affecting patient outcomes and clinical management worldwide. Despite the wealth of studies reporting T2DM biomarkers, there is an urgent need for a comparative review. This review aims to provide a comprehensive analysis based on the reported T2DM biomarkers and how these are linked with other conditions, such as inflammation and wound healing. A comparative review was conducted on 24 001 study participants, including 10 024 T2DM patients and 13 977 controls (CTL; age 30-90 years). Four main profiles were extracted and analysed from the clinical reports over the past 11 years: haematological (1084 cases vs. 1458 CTL), protein (6753 cases vs. 9613 CTL), cytokine (975 cases vs. 1350 CTL) and lipid (1212 cases vs. 1556 CTL). This review provides a detailed analysis of the haematological profile in T2DM patients, highlighting fundamental changes such as increased white blood cells and platelet counts, accompanied by decreases in red blood cell counts and iron absorption. In the serum protein profile, a reduction in albumin and anti-inflammatory cytokines was noted along with an increase in globulin levels and pro-inflammatory cytokines. Furthermore, changes in lipid profiles were discussed, specifically the decreases in high-density lipoprotein (HDL) and the increases in low-density lipoprotein (LDL) and triglycerides. Understanding the changes in these four biomarker profiles is essential for developing innovative strategies to create diagnostic and prognostic tools for diabetes management.

Surface Chemistry Induced IgG Unfolding and Modulation of Immune Responses.

Immunoglobulin G (IgG) comprises a significant portion of the protein corona that forms on biomaterial surfaces and holds a pivotal role in modulating host immune responses. To shed light on the important relationship between biomaterial surface functionality, IgG adsorption, and innate immune responses, we prepared, using plasma deposition, four surface coatings with specific chemistries, wettability, and charge. We found that nitrogen-containing coatings such as these deposited from allylamine (AM) and 2-methyl-2-oxazoline (POX) cause the greatest IgG unfolding, while hydrophilic acrylic acid (AC) surfaces allowed for the retention of the protein structure. Structural changes in IgG significantly modulated macrophage attachment, migration, polarization, and the expression of pro- and anti-inflammatory cytokines. Unfolded IgG on the POX and AM surfaces enhanced macrophage attachment, migration, extracellular trap release, and pro-inflammatory factors production such as IL-6 and TNF-α. Retention of IgG structure on the AC surface downregulated inflammatory responses. The findings of this study demonstrate that the retention of protein structure is an essential factor that must be taken into consideration when designing biomaterial surfaces. Our study indicates that using hydrophilic surface coatings could be a promising strategy for designing immune-modulatory biomaterials for clinical applications.

Antibacterial Electrospun Membrane with Hierarchical Bead-on-String Structured Fibres for Wound Infections.

Chronic wounds often result in multiple infections with various kinds of bacteria and uncontrolled wound exudate, resulting in several healthcare issues. Advanced medicated nanofibres prepared by electrospinning have gained much attention for their topical application on infected chronic wounds. The objective of this work is to enhance the critical variables of ciprofloxacin-loaded polycaprolactone-silk sericin (PCL/SS-PVA-CIP) nanofibre production via the process of electrospinning. To examine the antibacterial effectiveness of PCL/SS-PVA-CIP nanocomposites, the material was tested against P. aeruginosa and S. aureus. The combination of PCL/SS-PVA-CIP exhibited potent inhibitory properties, with the most effective concentrations of ciprofloxacin (CIP) being 3 µg/g and 7.0 µg/g for each bacterium, respectively. The biocompatibility was evaluated by conducting cell reduction and proliferation studies using the human epidermal keratinocyte (HaCaT) cells and human gingival fibroblasts (HGFs) in vitro cell lines. The PCL/SS-PVA-CIP showed good cell compatibility with HaCaT and HGF cells, with effective proliferation even at antibiotic doses of up to 7.0 µg/g. The drug release effectiveness of the nanocomposites was assessed at various concentrations of CIP, resulting in a maximum cumulative release of 76.5% and 74.4% after 72 h for CIP concentrations of 3 µg/g and 7 µg/g, respectively. In summary, our study emphasizes the possibility of combining silk sericin (SS) and polycaprolactone (PCL) loading with CIP nanocomposite for wound management.

AFM for Nanomechanical Assessment of Polymer Overcoatings on Nanoparticle-Decorated Biomaterials.

Nanoparticle adhesion to polymer and similar substrates may be prone to low nano-Newton forces, disrupting the surface bonds and patterning, potentially reducing the functionality of complex surface patterns. Testing this, a functionalised surface reported for biological and medical applications, consisting of a thin plasma-derived oxazoline-based film with 68 nm diameter covalently bound colloidal gold nanoparticles attached within an aqueous solution, underwent nanomechanical analysis. Atomic Force Microscopy nanomechanical analysis was used to quantify the limits of various adaptations to these nanoparticle-featured substrates. Regular and laterally applied forces in the nano-Newton range were shown to de-adhere surface-bound gold nanoparticles. Applying a nanometre-thick overcoating anchored the nanoparticles to the surface and protected the underlying base substrate in a one-step process to improve the overall stability of the functionalised substrate against lower-range forces. The thickness of the oxazoline-based overcoating displayed protection from forces at different rates. Testing overcoating thickness ranging from 5 to 20 nm in 5 nm increments revealed a significant improvement in stability using a 20 nm-thick overcoating. This approach underscores the importance of optimising overcoating thickness to enhance nanoparticle-based surface modifications' durability and functional integrity.

Manipulation of Serum Protein Adsorption by Nanoengineered Biomaterials Influences Subsequent Immune Responses.

The adsorption of serum proteins on biomaterial surfaces is a critical determinant for the outcome of medical procedures and therapies, which involve inserting materials and devices into the body. In this study, we aimed to understand how surface topography at the nanoscale influences the composition of the protein corona that forms on the (bio)material surface when placed in contact with serum proteins. To achieve that, we developed nanoengineered model surfaces with finely tuned topography of 16, 40, and 70 nm, overcoated with methyl oxazoline to ensure uniform outermost chemistry across all surfaces. Our findings revealed that within the studied height range, surface nanotopography had no major influence on the overall quantity of adsorbed proteins. However, significant alterations were observed in the composition of the adsorbed protein corona. For instance, clusterin adsorption decreased on all the nanotopography-modified surfaces. Conversely, there was a notable increase in the adsorption of ApoB and IgG gamma on the 70 nm nanotopography. In comparison, the adsorption of albumin was greater on surfaces that had a topography scale of 40 nm. Analysis of the gene enrichment data revealed a reduction in protein adsorption across all immune response-related biological pathways on nanotopography-modified surfaces. This reduction became more pronounced for larger surface nanoprotrusions. Macrophages were used as representative immune cells to assess the influence of the protein corona composition on inflammatory outcomes. Gene expression analysis demonstrated reduced inflammatory responses on the nanotopographically modified surface, a trend further corroborated by cytokine analysis. These findings underscore the potential of precisely engineered nanotopography-coated surfaces for augmenting biomaterial functionality.

Exploring the Challenges of Characterising Surface Topography of Polymer-Nanoparticle Composites.

Nanomechanical testing plays a crucial role in evaluating surfaces containing nanoparticles. Testing verifies surface performance concerning their intended function and detects any potential shortcomings in operational standards. Recognising that nanostructured surfaces are not always straightforward or uniform is essential. The chemical composition and morphology of these surfaces determine the end-point functionality. This can entail a layered surface using materials in contrast to each other that may require further modification after nanomechanical testing to pass performance and quality standards. Nanomechanical analysis of a structured surface consisting of a poly-methyl oxazoline film base functionalised with colloidal gold nanoparticles was demonstrated using an atomic force microscope (AFM). AFM nanomechanical testing investigated the overall substrate architecture's topographical, friction, adhesion, and wear parameters. Limitations towards its potential operation as a biomaterial were also addressed. This was demonstrated by using the AFM cantilever to apply various forces and break the bonds between the polymer film and gold nanoparticles. The AFM instrument offers an insight to the behaviour of low-modulus surface against a higher-modulus nanoparticle. This paper details the bonding and reaction limitations between these materials on the application of an externally applied force. The application of this interaction is highly scrutinised to highlight the potential limitations of a functionalised surface. These findings highlight the importance of conducting comprehensive nanomechanical testing to address concerns related to fabricating intricate biomaterial surfaces featuring nanostructures.

Hydrophobic Coatings with Charge Permeability via Plasma Deposition of Long-Chain Perfluorocarbons.

Hydrophobization of nanotextured catalyst materials is a promising route to enhance the yield of N2 and CO2 conversion into green fuels. However, these applications require a hydrophobic coating to not only promote air trapping but also allow charge transfer at the electrode-electrolyte interface. In this work, nano thin films with thicknesses as low as 7 nm were deposited from the plasma phase of perfluorohexene, perfluorodecene, and perfluorooctane (PFO) precursors using a mild vacuum and gentle powers. Atomic force microscopy (AFM) and X-ray photoelectron spectroscopy (XPS) characterization reveal that the resulting films are conformal and hydrophobic thanks to a good retention of CF2 and CF3 moieties. The PFO films exhibited the highest water contact angle and achieved superhydrophobic states when deposited on top of re-entrant nano features, an indication of successful air trapping. Electrochemical studies further demonstrated that the plasma-deposited PFO films allow charge transfer but could only sustain repeated cyclic voltammetry cycles without losing their hydrophobicity when deposited under optimal conditions. This result indicates that plasma deposition could become a viable route for the hydrophobization of electrocatalysts required to enhance the yield of poorly soluble gas reduction reactions.

Development of Novel Antibacterial Ti-Nb-Ga Alloys with Low Stiffness for Medical Implant Applications.

With the rising demand for medical implants and the dominance of implant-associated failures including infections, extensive research has been prompted into the development of novel biomaterials that can offer desirable characteristics. This study develops and evaluates new titanium-based alloys containing gallium additions with the aim of offering beneficial antibacterial properties while having a reduced stiffness level to minimise the effect of stress shielding when in contact with bone. The focus is on the microstructure, mechanical properties, antimicrobial activity, and cytocompatibility to inform the suitability of the designed alloys as biometals. Novel Ti-33Nb-xGa alloys (x = 3, 5 wt%) were produced via casting followed by homogenisation treatment, where all results were compared to the currently employed alloy Ti-6Al-4V. Optical microscopy, scanning electron microscopy (SEM), and energy dispersive spectroscopy (EDS) results depicted a single beta (ß) phase microstructure in both Ga-containing alloys, where Ti-33Nb-5Ga was also dominated by dendritic alpha (α) phase grains in a ß-phase matrix. EDS analysis indicated that the α-phase dendrites in Ti-33Nb-5Ga were enriched with titanium, while the ß-phase was richer in niobium and gallium elements. Mechanical properties were measured using nanoindentation and microhardness methods, where the Young's modulus for Ti-33Nb-3Ga and Ti-33Nb-5Ga was found to be 75.4 ± 2.4 and 67.2 ± 1.6 GPa, respectively, a significant reduction of 37% and 44% with respect to Ti-6Al-4V. This reduction helps address the disproportionate Young's modulus between titanium implant components and cortical bone. Importantly, both alloys successfully achieved superior antimicrobial properties against Gram-negative P. aeruginosa and Gram-positive S. aureus bacteria. Antibacterial efficacy was noted at up to 90 ± 5% for the 3 wt% alloy and 95 ± 3% for the 5 wt% alloy. These findings signify a substantial enhancement of the antimicrobial performance when compared to Ti-6Al-4V which exhibited very small rates (up to 6.3 ± 1.5%). No cytotoxicity was observed in hGF cell lines over 24 h. Cell morphology and cytoskeleton distribution appeared to depict typical morphology with a prominent nucleus, elongated fibroblastic spindle-shaped morphology, and F-actin filamentous stress fibres in a well-defined structure of parallel bundles along the cellular axis. The developed alloys in this work have shown very promising results and are suggested to be further examined towards the use of orthopaedic implant components.

Development of "Intelligent particles" for the treatment of dental caries.

Dental caries is one of the most prevalent non-communicable diseases worldwide, mediated by a multispecies biofilm that consists of high levels of acidogenic bacteria which ferment sugar to acid and cause teeth demineralization. Current treatment practice remains insufficient in addressing 1) rapid clearance of therapeutic agents from the oral environment 2) destroying bacteria that contribute to the healthy oral microbiome. In addition, increasing concerns over antibiotic resistance calls for innovative alternatives. In this study, we developed a pH responsive nano-carrier for delivery of polycationic silver nanoparticles. Branched-PEI capped silver nanoparticles (BPEI-AgNPs) were encapsulated in a tannic acid - Fe (III) complex-modified poly(D,L-lactic-co-glycolic acid) (PLGA) particle (Fe(III)-TA/PLGA@BPEI-AgNPs) to enhance binding to the plaque biofilm and demonstrate "intelligence" by releasing BPEI-AgNPs under acidic conditions that promote dental caries The constructed Fe(III)-TA/PLGA@BPEI-AgNPs (intelligent particles - IPs) exhibited significant binding to an axenic S. mutans biofilm grown on hydroxyapatite. Ag+ ions were released faster from the IPs at pH 4.0 (cariogenic pH) compared to pH 7.4. The antibiofilm results indicated that IPs can significantly reduce S. mutans biofilm volume and viability under acidic conditions. Cytotoxicity on differentiated Caco-2 cells and human gingival fibroblasts indicated that IPs were not cytotoxic. These findings demonstrate great potential of IPs in the treatment of dental caries.

Engineering antibacterial bioceramics: Design principles and mechanisms of action.

The urgency to address skeletal abnormalities and diseases through innovative approaches has led to a significant interdisciplinary convergence of engineering, 3D printing, and design in developing individualised bioceramic bioscaffolds. This review explores into the recent advancements and future trajectory of non-antibiotic antibacterial bioceramics in bone tissue engineering, an importance given the escalating challenges of orthopaedic infections, antibiotic resistance, and emergent pathogens. Initially, the review provides an in-depth exploration of the complex interactions among bacteria, immune cells, and bioceramics in clinical contexts, highlighting the multifaceted nature of infection dynamics, including protein adsorption, immunological responses, bacterial adherence, and endotoxin release. Then, focus on the next-generation bioceramics designed to offer multifunctionality, especially in delivering antibacterial properties independent of traditional antibiotics. A key highlight of this study is the exploration of smart antibacterial bioceramics, marking a revolutionary stride in medical implant technology. The review also aims to guide the ongoing development and clinical adoption of bioceramic materials, focusing on their dual capabilities in promoting bone regeneration and exhibiting antibacterial properties. These next-generation bioceramics represent a paradigm shift in medical implant technology, offering multifunctional benefits that transcend traditional approaches.

Biomimetic Bacterium-like Particles Loaded with Aggregation-Induced Emission Photosensitizers as Plasma Coatings for Implant-Associated Infections.

Developing novel antibacterial strategies has become an urgent requisite to overcome the increasing pervasiveness of antimicrobial-resistant bacteria and the advent of biofilms. Aggregation-induced emission-based photosensitizers (AIE PSs) are promising candidates due to their unique photodynamic and photothermal properties. Bioengineering structure-inherent AIE PSs for developing thin film coatings is still an unexplored area in the field of nanoscience. We have adopted a synergistic approach combining plasma technology and AIE PS-based photodynamic therapy to develop coatings that can eradicate bacterial infections. Here, we loaded AIE PSs within biomimetic bacterium-like particles derived from a probiotic strain, Lactobacillus fermentum. These hybrid conjugates are then immobilized on polyoxazoline-coated substrates to develop a bioinspired coating to fight against implant-associated infections. These coatings could selectively kill Gram-positive and Gram-negative bacteria, but not damage mammalian cells. The mechanistic studies revealed that the coatings can generate reactive oxygen species that can rupture the bacterial cell membranes. The mRNA gene expression of proinflammatory cytokines confirmed that they can modulate infection-related immune responses. Thus, this nature-inspired design has opened a new avenue for the fabrication of a next-generation antibacterial coating to reduce infections and associated burdens.

Antibacterial Textile Coating Armoured with Aggregation-Induced Emission Photosensitisers to Prevent Healthcare-Associated Infections.

In the quest to curtail the spread of healthcare-associated infections, this work showcases the fabrication of a cutting-edge antibacterial textile coating armoured with aggregation-induced emission photosensitisers (AIE PS) to prevent bacterial colonisation on textiles. The adopted methodology includes a multi-step process using plasma polymerisation and subsequent integration of AIE PS on their surface. The antibacterial effectiveness of the coating was tested against Pseudomonas aeruginosa and Staphylococcus aureus after light irradiation for 1 h. Furthermore, antibacterial mechanistic studies revealed their ability to generate reactive oxygen species that can damage bacterial cell membrane integrity. The results of this investigation can be used to develop ground-breaking explanations for infection deterrence, principally in situations where hospital fabrics play a critical part in the transmission of diseases. The antibacterial coating for textiles developed in this study holds great promise as an efficient strategy to promote public health and reduce the danger of bacterial diseases through regular contact with fabrics.

Damage Behavior with Atomic Force Microscopy on Anti-Bacterial Nanostructure Arrays.

The atomic force microscope is a versatile tool for assessing the topography, friction, and roughness of a broad spectrum of surfaces, encompassing anti-bacterial nanostructure arrays. Measuring and comparing all these values with one instrument allows clear comparisons of many nanomechanical reactions and anomalies. Increasing nano-Newton-level forces through the cantilever tip allows for the testing and measuring of failure points, damage behavior, and functionality under unfavorable conditions. Subjecting a grade 5 titanium alloy to hydrothermally etched nanostructures while applying elevated cantilever tip forces resulted in the observation of irreversible damage through atomic force microscopy. Despite the damage, a rough and non-uniform morphology remained that may still allow it to perform in its intended application as an anti-bacterial implant surface. Utilizing an atomic force microscope enables the evaluation of these surfaces before their biomedical application.

Selenium-SelK-GPX4 axis protects nucleus pulposus cells against mechanical overloading-induced ferroptosis and attenuates senescence of intervertebral disc.

Intervertebral disc degeneration (IVDD) is one of the most prevalent spinal degenerative disorders and imposes places heavy medical and economic burdens on individuals and society. Mechanical overloading applied to the intervertebral disc (IVD) has been widely recognized as an important cause of IVDD. Mechanical overloading-induced chondrocyte ferroptosis was reported, but the potential association between ferroptosis and mechanical overloading remains to be illustrated in nucleus pulposus (NP) cells. In this study, we discovered that excessive mechanical loading induced ferroptosis and endoplasmic reticulum (ER) stress, which were detected by mitochondria and associated markers, by increasing the intracellular free Ca2+ level through the Piezo1 ion channel localized on the plasma membrane and ER membrane in NP cells. Besides, we proposed that intracellular free Ca2+ level elevation and the activation of ER stress are positive feedback processes that promote each other, consistent with the results that the level of ER stress in coccygeal discs of aged Piezo1-CKO mice were significantly lower than that of aged WT mice. Then, we confirmed that selenium supplementation decreased intracellular free Ca2+ level by mitigating ER stress through upregulating Selenoprotein K (SelK) expression. Besides, ferroptosis caused by the impaired production and function of Glutathione peroxidase 4 (GPX4) due to mechanical overloading-induced calcium overload could be improved by selenium supplementation through Se-GPX4 axis and Se-SelK axis in vivo and in vitro, eventually presenting the stabilization of the extracellular matrix (ECM). Our findings reveal the important role of ferroptosis in mechanical overloading-induced IVDD, and selenium supplementation promotes significance to attenuate ferroptosis and thus alleviates IVDD, which might provide insights into potential therapeutic interventions for IVDD.

Staphylococcus aureus surface attachment selectively influences tolerance against charged antibiotics.

The threat of infection during implant placement surgery remains a considerable burden for millions of patients worldwide. To combat this threat, clinicians employ a range of anti-infective strategies and practices. One of the most common interventions is the use of prophylactic antibiotic treatment during implant placement surgery. However, these practices can be detrimental by promoting the resilience of biofilm-forming bacteria and enabling them to persist throughout treatment and re-emerge later, causing a life-threatening infection. Thus, it is of the utmost importance to elucidate the events occurring during the initial stages of bacterial surface attachment and determine whether any biological processes may be targeted to improve surgical outcomes. Using gene expression analysis, we identified a cellular mechanism of S. aureus which modifies its cell surface charge following attachment to a medical grade titanium surface. We determined the upregulation of two systems involved in the d-alanylation of teichoic acids and the lysylation of phosphatidylglycerol. We supported these molecular findings by utilizing synchrotron-sourced attenuated total reflection Fourier-transform infrared microspectroscopy to analyze the biomolecular properties of the S. aureus cell surface following attachment. As a direct consequence, S. aureus quickly becomes substantially more tolerant to the positively charged vancomycin, but not the negatively charged cefazolin. The present study can assist clinicians in rationally selecting the most potent antibiotic in prophylaxis treatments. Furthermore, it highlights a cellular process that could potentially be targeted by novel technologies and strategies to improve the outcome of antibiotic prophylaxis during implant placement surgery. STATEMENT OF SIGNIFICANCE: The antibiotic tolerance of bacteria in biofilm is a well-established phenomenon. However, the physiological adaptations employed by Staphylococcus aureus to increase its antibiotic tolerance during the early stages of surface attachment are poorly understood. Using multiple techniques, including gene expression analysis and synchrotron-sourced Fourier-transform infrared microspectroscopy, we generated insights into the physiological response of S. aureus following attachment to a medical grade titanium surface. We showed that this phenotypic transition enables S. aureus to better tolerate the positively charged vancomycin, but not the negatively charged cefazolin. These findings shed light on the antibiotic tolerance mechanisms employed by S. aureus to survive prophylactically administered antibiotics and can help clinicians to protect patients from infections.

Vancomycin tolerance of adherent Staphylococcus aureus is impeded by nanospike-induced physiological changes.

Bacterial colonization of implantable biomaterials is an ever-pervasive threat that causes devastating infections, yet continues to elude resolution. In the present study, we report how a rationally designed antibacterial surface containing sharp nanospikes can enhance the susceptibility of pathogenic bacteria to antibiotics used in prophylactic procedures. We show that Staphylococcus aureus, once adhered to a titanium surface, changes its cell-surface charge to increase its tolerance to vancomycin. However, if the Ti surface is modified to bear sharp nanospikes, the activity of vancomycin is rejuvenated, leading to increased bacterial cell death through synergistic activity. Analysis of differential gene expression provided evidence of a set of genes involved with the modification of cell surface charge. Synchrotron-sourced attenuated Fourier-transform infrared microspectroscopy (ATR-FTIR), together with multivariate analysis, was utilized to further elucidate the biochemical changes of S. aureus adhered to nanospikes. By inhibiting the ability of the pathogen to reduce its net negative charge, the nanoengineered surface renders S. aureus more susceptible to positively charged antimicrobials such as vancomycin. This finding highlights the opportunity to enhance the potency of prophylactic antibiotic treatments during implant placement surgery by employing devices having surfaces modified with spike-like nanostructures.

Novel Antibacterial Materials and Coatings-A Perspective by the Editors.

The fight between humans and bacteria has escalated to a new level.

Transforming Spirulina maxima Biomass into Ultrathin Bioactive Coatings Using an Atmospheric Plasma Jet: A New Approach to Healing of Infected Wounds.

The challenge of wound healing, particularly in patients with comorbidities such as diabetes, is intensified by wound infection and the accelerating problem of bacterial resistance to current remedies such as antibiotics and silver. One promising approach harnesses the bioactive and antibacterial compound C-phycocyanin from the microalga Spirulina maxima. However, the current processes of extracting this compound and developing coatings are unsustainable and difficult to achieve. To circumvent these obstacles, a novel, sustainable argon atmospheric plasma jet (Ar-APJ) technology that transforms S. maxima biomass into bioactive coatings is presented. This Ar-APJ can selectively disrupt the cell walls of S. maxima, converting them into bioactive ultrathin coatings, which are found to be durable under aqueous conditions. The findings demonstrate that Ar-APJ-transformed bioactive coatings show better antibacterial activity against Staphylococcus aureus and Pseudomonas aeruginosa. Moreover, these coatings exhibit compatibility with macrophages, induce an anti-inflammatory response by reducing interleukin 6 production, and promote cell migration in keratinocytes. This study offers an innovative, single-step, sustainable technology for transforming microalgae into bioactive coatings. The approach reported here has immense potential for the generation of bioactive coatings for combating wound infections and may offer a significant advance in wound care research and application.

Noninvasive and Microinvasive Nanoscale Drug Delivery Platforms for Hard Tissue Engineering.

Bone tissue plays a crucial role in protecting internal organs and providing structural support and locomotion of the body. Treatment of hard tissue defects and medical conditions due to physical injuries, genetic disorders, aging, metabolic syndromes, and infections is more often a complex and drawn out process. Presently, dealing with hard-tissue-based clinical problems is still mostly conducted via surgical interventions. However, advances in nanotechnology over the last decades have led to shifting trends in clinical practice toward noninvasive and microinvasive methods. In this review article, recent advances in the development of nanoscale platforms for bone tissue engineering have been reviewed and critically discussed to provide a comprehensive understanding of the advantages and disadvantages of noninvasive and microinvasive methods for treating medical conditions related to hard tissue regeneration and repair.

Gallium Liquid Metal: Nanotoolbox for Antimicrobial Applications.

The proliferation of drug resistance in microbial pathogens poses a significant threat to human health. Hence, treatment measures are essential to surmount this growing problem. In this context, liquid metal nanoparticles are promising. Gallium, a post-transition metal notable for being a liquid at physiological temperature, has drawn attention for its distinctive properties, high antimicrobial efficacy, and low toxicity. Moreover, gallium nanoparticles demonstrate anti-inflammatory properties in immune cells. Gallium can alloy with other metals and be prepared in various composites to modify and tailor its characteristics and functionality. More importantly, the bactericidal mechanism of gallium liquid metal could sidestep the threat of emerging drug resistance mechanisms. Building on this rationale, gallium-based liquid metal nanoparticles can enable impactful and innovative strategic pathways in the battle against antimicrobial resistance. This review outlines the characteristics of gallium-based liquid metals at the nanoscale and their corresponding antimicrobial mechanisms to provide a comprehensive yet succinct overview of their current antimicrobial applications. In addition, challenges and opportunities that require further research efforts have been identified and discussed.