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 (β) phase microstructure in both Ga-containing alloys, where Ti-33Nb-5Ga was also dominated by dendritic alpha (α) phase grains in a β-phase matrix. EDS analysis indicated that the α-phase dendrites in Ti-33Nb-5Ga were enriched with titanium, while the β-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.

In the present work, we explored Lewis acid catalysis, via FeCl3, for the heterogeneous surface functionalization of cellulose nanofibrils (CNFs). This approach, characterized by its simplicity and efficiency, facilitates the amidation of nonactivated carboxylic acids in carboxymethylated cellulose nanofibrils (c-CNF). Following the optimization of reaction conditions, we successfully introduced amine-containing polymers, such as polyethylenimine and Jeffamine, onto nanofibers. This introduction significantly enhanced the physicochemical properties of the CNF-based materials, resulting in improved characteristics such as adhesiveness and thermal stability. Reaction mechanistic investigations suggested that endocyclic oxygen of cellulose finely stabilizes the transition state required for further functionalization. Notably, a nanocomposite, containing CNF and a branched low molecular weight polyethylenimine (CNF-PEI 800), was synthesized using the catalytic reaction. The composite CNF-PEI 800 was thoroughly characterized having in mind its potential application as coating biomaterial for medical implants. The resulting CNF-PEI 800 hydrogel exhibits adhesive properties, which complement the established antibacterial qualities of polyethylenimine. Furthermore, CNF-PEI 800 demonstrates its ability to support the proliferation and differentiation of primary human osteoblasts over a period of 7 days.

Medical implant-associated infections (IAI) is a growing threat to patients undergoing implantation surgery. IAI prevention typically relies on medical implants endowed with bactericidal properties achieved through surface modifications with antibiotics. However, the clinical efficacy of this traditional paradigm remains suboptimal, often necessitating revision surgery and posing potentially lethal consequences for patients. To bolster the existing anti-IAI arsenal, we propose herein a chitosan-based bioactive coating, i.e., ChitoAntibac, which exerts bacteria-inhibitory effects either through immune modulation or phage-directed microbial clearance, without relying on conventional antibiotics. The immuno-stimulating effects and phage-induced bactericidal properties can be tailored by engineering the loading dynamic of macrophage migration inhibitory factor (MIF), which polarizes macrophages towards the proinflammatory subtype (M1) with enhanced bacterial phagocytosis, and Staphylococcal Phage K, resulting in rapid and targeted pathogenic clearance (>99.99%) in less than 8 h. Our innovative antibacterial coating opens a new avenue in the pursuit of effective IAI prevention through immuno-stimulation and phage therapeutics.

SUMMARYImplant-associated infections (IAIs) pose serious threats to patients and can be associated with significant morbidity and mortality. These infections may be difficult to diagnose due, in part, to biofilm formation on device surfaces, and because even when microbes are found, their clinical significance may be unclear. Despite recent advances in laboratory testing, IAIs remain a diagnostic challenge. From a therapeutic standpoint, many IAIs currently require device removal and prolonged courses of antimicrobial therapy to effect a cure. Therefore, making an accurate diagnosis, defining both the presence of infection and the involved microorganisms, is paramount. The sensitivity of standard microbial culture for IAI diagnosis varies depending on the type of IAI, the specimen analyzed, and the culture technique(s) used. Although IAI-specific culture-based diagnostics have been described, the challenge of culture-negative IAIs remains. Given this, molecular assays, including both nucleic acid amplification tests and next-generation sequencing-based assays, have been used. In this review, an overview of these challenging infections is presented, as well as an approach to their diagnosis from a microbiologic perspective.

The present study investigated the influence of pore size of strut-based Diamond and surface-based Gyroid structures for their suitability as medical implants. Samples were made additively from laser powder bed fusion process with a relative density of 0.3 and pore sizes ranging from 300 to 1300 μm. They were subsequently examined for their manufacturability and mechanical properties. In addition, non-Newtonian computational fluid dynamics and discrete phase models were conducted to assess pressure drop and cell seeding efficiency. The results showed that both Diamond and Gyroid had higher as-built densities with smaller pore sizes. However, Gyroid demonstrated better manufacturability as its relative density was closer to the as-designed one. In addition, based on mechanical testing, the elastic modulus was largely unaffected by pore size, but post-yielding behaviors differed, especially in Diamond. High mechanical sensitivity in Diamond could be explained partly by Finite Element simulations, which revealed stress localization in Diamond and more uniform stress distribution in Gyroid. Furthermore, we defined the product of the normalized specific surface, normalized pressure drop, and cell seeding efficiency as the indicator of an optimal pore size, in which this factor identified an optimal pore size of approximately 500 μm for both Diamond and Gyroid. Besides, based on such criterion, Gyroid exhibited greater applicability as bone scaffolds. In summary, this study provides comprehensive assessment of the effect of pore size and demonstrates the efficient estimation of an in-silico framework for evaluating lattice structures as medical implants, which could be applied to other lattice architectures.

In recent years, antibacterial coatings have become an important approach in the global fight against bacterial pathogens. Developments in materials science, chemistry, and biochemistry have led to a plethora of materials and chemical compounds that have the potential to create antibacterial coatings. However, insufficient attention has been paid to the analysis of the techniques and technologies used to apply these coatings. Among the various inorganic coating techniques, atomic layer deposition (ALD) is worthy of note. It enables the successful synthesis of high-purity inorganic nanocoatings on surfaces of complex shape and topography, while also providing precise control over their thickness and composition. ALD has various industrial applications, but its practical application in medicine is still limited. In recent years, a considerable number of papers have been published on the proposed use of thin films and coatings produced via ALD in medicine, notably those with antibacterial properties. The aim of this paper is to carefully evaluate and analyze the relevant literature on this topic. Simple oxide coatings, including TiO2, ZnO, Fe2O3, MgO, and ZrO2, were examined, as well as coatings containing metal nanoparticles such as Ag, Cu, Pt, and Au, and mixed systems such as TiO2-ZnO, TiO2-ZrO2, ZnO-Al2O3, TiO2-Ag, and ZnO-Ag. Through comparative analysis, we have been able to draw conclusions on the effectiveness of various antibacterial coatings of different compositions, including key characteristics such as thickness, morphology, and crystal structure. The use of ALD in the development of antibacterial coatings for various applications was analyzed. Furthermore, assumptions were made about the most promising areas of development. The final section provides a comparison of different coatings, as well as the advantages, disadvantages, and prospects of using ALD for the industrial production of antibacterial coatings.

With the rising demand for implantable orthopaedic medical devices and the dominance of device-associated infections, extensive research into the development of novel materials has been prompted. Among these, new-generation titanium alloys with biocompatible elements and improved stiffness levels have received much attention. Furthermore, the development of titanium-based materials that can impart antibacterial function has demonstrated promising results, where gallium has exhibited superior antimicrobial action. This has been evidenced by the addition of gallium to various biomaterials including titanium alloys. Therefore, this paper aims to review the antibacterial activity of gallium when incorporated into biomedical materials, with a focus on titanium-based alloys. First, discussion into the development of new-generation Ti alloys that possess biocompatible elements and reduced Young\'s moduli is presented. This includes a brief review of the influence of alloying elements, processing techniques and the resulting biocompatibilities of the materials found in the literature. The antibacterial effect of gallium added to various materials, including bioglasses, liquid metals, and bioceramics, is then reviewed and discussed. Finally, a key focus is given to the incorporation of gallium into titanium systems for which the inherent mechanical, biocompatible, and antibacterial effects are reviewed and discussed in more detail, leading to suggestions and directions for further research in this area.

Biomedical implants have recently shown excellent application potential in tissue repair and replacement. Applying three-dimensional (3D) printing to implant scaffold fabrication can help to address individual needs more precisely. Fourdimensional (4D) printing emerges rapidly based on the development of shape-responsive materials and design methods, which makes the production of dynamic functional implants possible. Smart implants can be pre-designed to respond to endogenous or exogenous stimuli and perform seamless integration with regular/ irregular tissue defects, defect-luminal organs, or curved structures via programmed shape morphing. At the same time, they offer great advantages in minimally invasive surgery due to the small-to-large volume transition. In addition, 4D-printed cellular scaffolds can generate extracellular matrix (ECM)-mimetic structures that interact with the contacting cells, expanding the possible sources of tissue/organ grafts and substitutes. This review summarizes the typical technologies and materials of 4D-printed scaffolds, and the programming designs and applications of these scaffolds are further highlighted. Finally, we propose the prospects and outlook of 4D-printed shape-morphing implants.

UNASSIGNED: To evaluate the effect of bone remodelling around a reduced-diameter dental implant on its fatigue limit using finite element analysis (FEA).
UNASSIGNED: A dental implant assembly, which included a reduced-diameter dental implant (Biomet-3i external hex), an abutment (GingiHue®) and a connector screw (Gold-Tite Square screw), was scanned using micro-computed tomography (Skyscan 1172). Its dimensions were measured using Mimics (Materialise) and an optical microscope (Keyence). The digital replicas of the physical specimens were constructed using SOLIDWORKS (Dassault Systems). A cylindrical bone specimen holder with two layers (cortical and cancellous bone) was designed in SOLIDWORKS. Two assemblies were created: (a) Model 1: Having non-remodelled bone; (b) Model 2: Cancellous bone remodelled at the regions adjacent to the implant screw threads. FEA was performed in ABAQUS (SIMULIA). In Model 1, the Young\'s modulus of cortical and cancellous bone were 20 GPa and 14 GPa, respectively. For Model 2, the region of the cancellous bone adjacent to the implant screw threads was assigned a Young\'s modulus of 20 GPa. fe-safe (SIMULIA) was used to estimate the fatigue limit.
UNASSIGNED: The maximum von Mises stress under 100 N load was 439.9 MPa for both models 1 and 2 and was located at the connector screw. The fatigue limit was 116.4 N for both models 1 and 2.
UNASSIGNED: The results suggest that implant fatigue resistance tested according to ISO 14801 may be accurately predicted without bothering to simulate the non-homogeneous stiffness that occurs at the bone-implant interface in the clinical case.

The deployment of structures that enable localized release of bioactive molecules can result in more efficacious treatment of disease and better integration of implantable bionic devices. The strategic design of a biopolymeric coating can be used to engineer the optimal release profile depending on the task at hand. As illustrative examples, here advances in delivery of drugs from bone, brain, ocular, and cardiovascular implants are reviewed. These areas are focused to highlight that both hard and soft tissue implants can benefit from controlled localized delivery. The composition of biopolymers used to achieve appropriate delivery to the selected tissue types, and their corresponding outcomes are brought to the fore. To conclude, key factors in designing drug-loaded biopolymeric coatings for biomedical implants are highlighted.