Solar-driven catalysis provides an environmentally benign and energy-sustainable pathway to address pressing global energy and environmental challenges. However, its practical application remains hindered by the suboptimal performance of available photocatalysts. Herein, we report a novel organic/inorganic heterojunction photocatalyst, 5,10,15,20-Tetrakis(4-sulfophenyl)porphyrin (TPPS)/Bi2WO6 (BWO), fabricated by anchoring TPPS onto BWO microspheres. This unique architecture substantially amplifies the internal electric field (IEF) at the heterointerface, thereby promoting efficient charge carrier migration between the two components. Notably, photogenerated holes with strong oxidizing ability accumulate on the BWO surface and participate in hydroxyl radical (•OH) generation. Concurrently, the highly reductive electrons separated on the TPPS component are rapidly captured by molecular oxygen, reducing it to superoxide radicals (•O2–). This synergistic charge partitioning accelerates both the separation and the functional utilization of the strongest reducing and oxidizing species within the system. The resultant reactive radicals, together with the surface-accumulated holes, serve as the primary active species, driving an exceptional degradation efficiency of 90.2%. Consequently, the TPPS/BWO heterojunction achieves a tetracycline abatement rate constant approximately 3.2 folds greater than that of pristine BWO. Mechanistic investigations, integrating experimental characterization with density functional theory (DFT) calculations, reveal that the elevated activity stems from the formation of an organic/inorganic S-scheme heterojunction between TPPS and BWO. This configuration effectively preserves the superior redox capability of the heterojunction system. Overall, this work offers fresh insights into the rational design of organic/inorganic heterointerfaces for photocatalytic environmental remediation.

Tooth-on-Chip platforms recapitulate dental epithelial–mesenchymal (DE-DM) interactions, offering physiologically relevant in vitro models for tooth regeneration. However, broader adoption requires chip-scale analytical methods capable of resolving cell-type-specific transcriptional programs and characterizing mineral formation. Here, we present a multi-modal workflow adapting five established approaches to fibrin hydrogel-based Tooth-on-Chip constructs. Whole-construct RNA extraction yielded high-integrity RNA suitable for bulk RNA sequencing, enabling pooled transcriptional comparisons between dental epithelium and mesenchyme. Magnetic-activated cell sorting achieved efficient recovery and enrichment from chip-relevant cell inputs, while translating this approach to intact constructs revealed a platform-level incompatibility between fibrin dissolution and downstream sorting. Fixation strategies preserved tissue morphology for spatial transcriptomics but came at the cost of RNA quality, and Raman spectroscopy combined with transmission electron microscopy enabled ultrastructural assessment of calcium phosphate deposition, though confirming mature hydroxyapatite required further validation. Together, this workflow establishes a practical framework for benchmarking analytical readouts in fibrin-based Tooth-on-Chip and related organ-on-chip co-culture systems.Established whole-construct RNA extraction for bulk transcriptional profiling of DE-DM co-culturesAdapted cell sorting and dissociation strategies for cell-type-specific enrichment, identifying key compatibility constraintsApplied spatial transcriptomics preparation and spectroscopic/ultrastructural imaging to characterize tissue architecture and calcium phosphate deposition

Pharmaceutical contamination of water bodies poses a growing environmental threat, calling for advanced oxidation technologies capable of complete pollutant removal. Photocatalysis offers a sustainable solution, yet its broader application is hindered by inefficient utilization of charge-carrier. Here, we construct an organic–inorganic S-scheme heterojunction, tetrakis(4-carboxyphenyl)porphyrin/Bi4O5Br2 (TCPP/BB), via interfacial grafting of TCPP onto BB nanosheets. The optimized TCPP/BB heterojunction delivers superior photo-oxidative activity, achieving a TC degradation efficiency of 92.7% within 60 min of visible-light illumination and marking a 0.69-fold enhancement over pristine BB (54.8%). Systematic experimental characterizations and density functional theory (DFT) computations reveal that the built-in electric field across the TCPP/BB heterointerface steers a robust S-scheme charge-migration pathway. Crucially, this configuration not only facilitates the spatial isolation of photogenerated carriers but also safeguards their high-energy redox capacities, thereby ensuring efficient surface reactions. Mechanistic studies, including in situ EPR and radical scavenging assays, identify •O2‒ and h+ as the dominant reactive species. These results highlight the transformative potential of organic-inorganic S-scheme heterostructure concept for efficient water cleanup, offering a sustainable solution to water contamination.

Self-healing hydrogels, a novel class of “smart” hydrogels, possess the ability to autonomously restore their network structure and mechanical properties following damage through the reconnection of a fractured three-dimensional network via reversible interactions. This characteristic enhances their safety and durability, exhibiting significant potential in biomedicine. The key determinants of self-healing hydrogels are their mechanical strength and healing efficiency. Ideally, these hydrogels exhibit both high mechanical strength and good healing efficiency. Nevertheless, an inverse relationship between the mechanical strength and self-healing efficiency of self-healing hydrogels typically exists. Thus, research is currently focused on the development of self-healing hydrogels that combine good biocompatibility, high mechanical strength, and good self-healing efficiency. This review focuses on the research progress that is being made regarding the mechanical properties and self-healing capabilities of self-healing hydrogels, where we aim to achieve a balance between self-healing performance and mechanical strength. We outline the evaluation methods for assessing self-healing performance, followed by providing a summary of recent advancements in the mechanical strength and self-healing efficiency of external-stimulus-triggered self-healing hydrogels and autonomous self-healing hydrogels. Finally, we address the challenges and prospects for the future development of self-healing hydrogels.

Developing robust photocatalysts for photocatalytic environment decontamination is significant and challenging. A novel flower-like S-scheme Ag/Ag6Si2O7/Bi12O17Cl2 (AASO/BOC) plasmonic heterojunction is successfully constructed using a facile route, and applied in photocatalytic destruction of tetracycline hydrochloride (TC) and levofloxacin (LEV) under visible-light irradiation. Benefiting from the combination of S-scheme Bi12O17Cl2/Ag6Si2O7 heterojunction and the plasma Ag, the production and separation of photogenerated carriers are dramatically enhanced. Consequently, compared to the pristine Bi12O17Cl2 and Ag6Si2O7, AASO/BOC displays superior photocatalytic degradation performance. Impressively, the photocatalytic TC degradation rate of AASO/BOC-2 reaches 0.0260 min(-1), which is approximately 3.1, 14.4 and 2.0 times those of Bi12O17Cl2, Ag6Si2O7 and Bi12O17Cl2/Ag6Si2O7, respectively. Moreover, the photocatalytic mechanism of TC degradation is studied in depth via various techniques, and the photogenerated OH, O-2(-) and h(+) collectively contribute to the photo-degradation of TC. This research puts forward a neoteric approach to designing plasmonic S-scheme photocatalysts for environmental applications.

Photocatalytic pollutant removal provides a competitive manner for wastewater purification.The exploration of efficient and durable photocatalysts is significant for this technique.Integrating carbon quantum dots and S-scheme junction into one system represents an effective strategy for achieving the outstanding photocatalytic efficacy.In comparison to S-scheme junction,photocatalysts combining carbon quantum dots and S-scheme junction harness the merits of both,thus holding greater potential.Herein,a multicomponent fibrous photocatalyst of carbon quantum dots/CdS/Ta3N5 that incorporates S-scheme heterojunction and carbon quantum dots is developed for high-efficient destruction of levofloxacin antibiotic.The as-prepared carbon quantum dots/CdS/Ta3N5 heterojunction nanofibers manifest a significantly strengthened photocatalytic levofloxacin degradation activity,with the rate constant(0.0404 min-1)exceeding Ta3N5,CdS/Ta3N5,and CdS by 39.4,2.1,and 7.2 folds.Such remarkable photocatalytic performance is credited to the unique 1D/0D/0D core-shell heterostructure with compact-bound hetero-interface,which favors the synergistic effect between carbon quantum dots modification and S-scheme junction.This work offers a new way for developing new Ta3N5-based heterojunctions for environmental remediation.

Soft tissue integration (STI) around dental implant abutments is a prerequisite to prevent bacterial invasion and achieve successful dental implant rehabilitation. However, peri-implant STI is a major challenge after dental abutment placement due to alterations in the immune microenvironment upon surgical dental implant installation. Based on known immunomodulatory effects of zinc, we herein deposited zinc/chitosan/gelatin (Zn/CS/Gel) coatings onto titanium substrates to study their effect on macrophages. First, we exposed macrophages to cell culture media containing different zinc ion (Zn2+) concentrations. Next, we explored the immunomodulatory effect of Zn/CS/Gel coatings prepared via facile electrophoretic deposition (EPD). We found that Zn2+ effectively altered the secretome by reducing the secretion of pro-inflammatory and enhancing pro-regenerative cytokine secretion, particularly at a Zn2+ supplementation of approximately 37.5 μM. Zn/CS/Gel coatings released Zn2+ in a concentration range which effectively stimulated pro-regenerative macrophage polarization as demonstrated by M2 macrophage polarization. Additionally, the impact of these Zn2+-exposed macrophages on gingival fibroblasts incubated in conditioned medium showed stimulated adhesion, proliferation, and collagen secretion. Our promising results suggest that controlled release of Zn2+ from Zn/CS/Gel coatings could be applied to immunomodulate peri-implant STI, and to enhance dental implant survival.

To date, severe bone defects remain a significant challenge to the quality of life. All clinically used bone grafts have their limitations. Bone tissue engineering offers the promise of novel bone graft substitutes. Various biomaterial scaffolds are fabricated by mimicking the natural bone structure, mechanical properties, and biological properties. Among them, gelatin methacryloyl (GelMA), as a modified natural biomaterial, possesses a controllable chemical network, high cellular stability and viability, good biocompatibility and degradability, and holds the prospect of a wide range of applications. However, because they are hindered by their mechanical properties, degradation rate, and lack of osteogenic activity, GelMA hydrogels need to be combined with other materials to improve the properties of the composites and endow them with the ability for osteogenesis, vascularization, and neurogenesis. In this paper, we systematically review and summarize the research progress of GelMA composite hydrogel scaffolds in the field of bone defect repair, and discuss ways to improve the properties, which will provide ideas for the design and application of bionic bone substitutes.

Hydroxyapatite nanoparticles (nHA) have gained attention as potential intracellular drug delivery vehicles due to their high binding affinity for various biomolecules and pH-dependent solubility. Yet, the dependence of nHA cytocompatibility on their physicochemical properties remains unclear since numerous studies have revealed starkly contrasting results. These discrepancies may be attributed to differences in size, shape, crystallinity, and aggregation state of nHA, which complicates fundamental understanding of the factors driving nHA cytotoxicity. Here, we hypothesize that nHA cytotoxicity is primarily driven by intracellular calcium levels following the internalization of nHA nanoparticles. By investigating the cytotoxicity of spherical nHA with different crystallinity and dispersity, we find that both lower crystallinity and increased agglomeration of nHA raise cytotoxicity, with nanoparticle agglomeration being the more dominant factor. We show that the internalization of nHA enhances intracellular calcium levels and increases the production of reactive oxygen species (ROS). However, only subtle changes in intracellular calcium are observed, and their physiological relevance remains to be confirmed. In conclusion, we show that nHA agglomeration enhances ROS production and the associated cytotoxicity. These findings provide important guidelines for the future design of nHA-containing formulations for biomedical applications, implying that nHA crystallinity and especially agglomeration should be carefully controlled to optimize biocompatibility and therapeutic efficacy.

Solar-powered photocatalysis for treating pharmaceutical wastewater is a promising approach for tackling environmental issues and energy crisis. However, its efficiency is hindered by unsatisfactory light-absorption efficiency, rapid charge recombination, and weak photo-redox potential. Here, an organic/inorganic ternary S-scheme system of carbon quantum dots (CDs)/tetra (4-carboxyphenyl) porphyrin/BiOBr (TCPP/CDs/BOB) was ingeniously built by depositing CDs and TCPP onto BOB microspheres for effective purification of tetracycline hydrochloride (TC) under visible light. The Fermi level difference triggers electron delivery from TCPP to BOB upon hybridization, thereby creating an internal electric field (IEF) at the interface. This impels the effective separation of powerful photo-induced carriers. Moreover, CDs perform as electron reservoirs to further promote S-scheme carrier separation. Thus, more powerful photoelectrons in the CDs and holes in the BOB valence band are reserved for participation in photocatalytic reactions. The optimized TCPP/CDs/BOB-2 heterostructure exhibits an enhanced TC degradation capacity of 83.6% within 40 min and the rate constant of TCPP/CDs/BOB-2 is roughly 2.3, 1.8 and 2.0 times that of BOB, CDs/BOB, and TCPP/BOB, respectively. This work provides a new perspective for exploring organic/inorganic ternary S-scheme photocatalysts for water purification.

Local delivery of messenger ribonucleic acid (mRNA) is increasingly being advocated as a promising new strategy to enhance the performance of biomaterials. While extensive research has been dedicated to the complexation of these oligonucleotides into nanoparticles to facilitate systemic delivery, research on developing suitable biomaterial carriers for the local delivery of mRNA is still scarce. So far, mRNA-nanoparticles (mRNA-NPs) are mainly loaded into traditional polymeric hydrogels. Here, we show that calcium phosphate nanoparticles can be used for both reinforcement of nanoparticle-based hydrogels and the complexation of mRNA. mRNA was incorporated into lipid-coated calcium phosphate nanoparticles (LCPs) formulated with a fusogenic ionizable lipid in the outer layer of the lipid coat. Nanocomposites of gelatin and hydroxyapatite nanoparticles were prepared at various ratios. Higher hydroxyapatite nanoparticle content increased the viscoelastic properties of the nanocomposite but did not affect its self-healing ability. Combination of these nanocomposites with peptide, lipid, and the LCP mRNA formulations achieved local mRNA release as demonstrated by protein expression in cells in contact with the biomaterials. The LCP-based formulation was superior to the other formulations by showing less sensitivity to hydroxyapatite and the highest cytocompatibility.

Peri-implant gingival tissue integration (GTI) is pivotal in determining the long-term success and functionality of dental implants. To enhance GTI, researchers have increasingly focused during the past decade on unraveling the response of gingival tissues to implant surfaces. This increased focus on soft instead of hard tissue integration has led to the development of various models, including in vitro cell culture systems and in vivo animal models, designed to predict and assess GTI around dental implants. However, inconsistent study outcomes between the different models have created confusion, highlighting the need for a comprehensive review. Therefore, the main objective of this review is to present a comprehensive overview of existing in vitro models, ranging from 2D to 3D, specifically designed to investigate cellular behavior relevant to peri-implant GTI. To facilitate a better comprehension of the utility of these models, the review initiates an elucidation of the histological characteristics of gingival tissues surrounding natural dentition, offering insights into the healing dynamics and histological adaptation processes occurring in gingival tissues adjacent to dental implants. In addition, through a critical evaluation of the strengths and limitations inherent in each model, our aim is to contribute to a more profound understanding of their applicability and effectiveness in GTI research.

Hexavalent chromium (Cr(VI)) may be a hazardous and nonbiodegradable waste matter which will cause substantial environmental damage. Fabricating powerful photosystems to achieve efficacious elimination of Cr(VI) holds eminent promise in solving environmental issues. Thanks to their outstanding photo/electrical properties, large surface area, and customizable structure, metal -organic framework (MOF) catalysts have attracted widespread attention within the field of pollutant degradation and reduction. Nevertheless, due to the recombination of photo -generated charge carriers, pristine semiconductor MOFs' photocatalytic performance is inadequate. To overcome this challenge, one of the most typical and effective strategies is to create heterojunctions by combining MOFs with another semiconductor. Among these strategies, the innovative step -scheme (S -scheme) heterojunction has gained increasing prominence. Unlike traditional type II and Z -scheme heterojunctions, the built-in electric field at the S -scheme heterojunction boundary enhances spatial charge separation and boosts redox capacity, thereby improving photocatalytic performance. In this study, a creative MOF-based S -scheme architecture with oxygen vacancies (OV) was built via in situ growth of MIL-101(Fe) crystals on the surface of OV-rich BiOCl microspheres. The optimized MIL-101(Fe)/BiOCl heterojunction exhibited exceptional photocatalytic performance in photo -reducing high concentrations of Cr(VI) and 88.5% of Cr(VI) solution (10 mg center dot L -1 , 100 mL) can be removed within 60 min, which is about 4.4 and 9.0 times that of BiOCl and MIL-101(Fe). Besides, the MIL-101(Fe)/BiOCl manifests impressive practical implementation prospect due to its high antiinterference property, robustness and reusability. Photoelectron spectroscopy results validated that built-in electric field, bending band, and Coulomb attraction facilitated the transition of photoelectrons from the conduction band (CB) of BiOCl to the valence band (VB) of MIL-101(Fe), where they recombined with the photo -created holes. This suggests an S -scheme interfacial photo -carrier detachment mechanism at the MIL-101(Fe)/BiOCl interface. In addition, BET measurements indicated a notable increase in surface area with the introduction of MIL-101(Fe). The OV-rich S -scheme MIL101(Fe)/BiOCl heterostructure boasts more reactive sites, enhanced interfacial charge separation, and optimal redox ability of photo -carriers, leading to enhanced photocatalytic properties. Measurements of active radical scavenging and electron spin resonance (ESR) confirm that e - and center dot O 2 - are the primary active species during photocatalysis. These discoveries would open up new avenues for developing defective semiconductor/MOF S -scheme photocatalyst for environmental purification.

Tightly sealed peri-implant gingival tissue provides a barrier against oral bacterial invasion, protecting the alveolar bone and maintaining long-term implant survival. To investigate if zinc can enhance the integration between peri-implant gingival tissue and abutment surface, we herein present novel zinc/chitosan/gelatin (Zn/CS/Gel) coatings prepared using the electrophoretic deposition (EPD) technique. The effect of these coatings on human gingival fibroblasts (hGFs) was investigated by culturing these cells on top of the EPD coatings. Surface characterization demonstrated that Zn2+ were released in a sustained and pH-responsive manner. The preclinical cell culture evaluation of these coatings indicated that the zinc-containing coatings enhanced cell migration, adhesion and collagen secretion of hGFs. Moreover, the zinc-containing coatings exhibited antibacterial efficacy by inhibiting the growth of Porphyromonas gingivalis and reducing attachment of Staphylococcus aureus. Notably, zinc-free CS/Gel coatings prevented attachment of P. gingivalis as well. The coatings were also shown to be cytocompatible with epithelial cells and osteoblasts, which are other relevant cell types which surround dental implants after clinical placement. Based on our findings, it can be concluded that Zn-containing coatings hold promise to enhance the adhesion of gingival tissue to the implant surface, which may potentially contribute to the formation of a robust peri-implant soft sealing counteracting bacterial invasion.

Treating bone infections with common antibiotics is challenging, since pathogens like Staphylococcus aureus can reside inside macrophages. To target these intracellular bacteria, we have proposed nanoparticles (NPs) as drug carriers. This study aims to investigate the efficacy of hydroxyapatite and gelatin NPs, selected in view of their bone mimicry and potential for targeted delivery, as carriers for the antibacterial agents zinc and vancomycin. Therefore, two distinct NPs are fabricated: zinc-doped hydroxyapatite (ZnHA) and vancomycin-loaded gelatin (VGel) NPs. The NPs are characterized based on morphology, size, chemical composition, cellular internalization, and intracellular bactericidal efficacy. Specifically, the intracellular bactericidal efficacy is tested using a validated coculture model of human THP-1 derived macrophages and phagocytosed S. aureus bacteria. Scanning electron microscopy (SEM) and Fourier transform-infrared spectroscopy (FTIR) results show that the spherical NPs are synthesized successfully. These NPs are internalized by THP-1 cells and show >75% colocalization with lysosomes without compromising the viability of the THP-1 cells. Both ZnHA and VGel NPs substantially reduce the intracellular survival of S. aureus compared to the direct addition of dissolved zinc and vancomycin. Concluding, our NPs are highly effective drug delivery vehicles to kill intracellular S. aureus, which stress the potential of these NPs for future clinical translation.

Osteoinductive supplements without side effects stand out from the growth factors and drugs widely used in bone tissue engineering. Lithium magnesium sodium silicate hydrate (laponite) nanoflake is a promising bioactive component for bone regeneration, attributed to its inherent biosafety and effective osteoinductivity. Up to now, the in vivo osteogenic potential and mechanisms of laponite-encapsulated fibrous membranes remain largely unexplored. This study presents a unique method for homogeneously integrating high concentrations of laponite RDS into a polycaprolactone (PCL) matrix by dispersing laponite RDS sol into the polymer solution. Subsequently, a core-shell fibrous membrane (10RP-PG), embedding laponite-loaded PCL in its core, was crafted using coaxial electrospinning. The PCL core's slow degradation and the shell's gradient degradation enabled the sustained release of bioactive ions (Si and Mg) from laponite. In vivo studies on a critical-sized calvarial bone defect model demonstrated that the 10RP-PG membrane markedly enhanced bone formation and remodeling by accelerating the process of endochondral ossification. Further transcriptome analysis suggested that osteogenesis in the 10RP-PG membrane is driven by Mg and Si from endocytosed laponite, activating pathways related to ossification and endochondral ossification, including Hippo, Wnt and Notch. The fabricated nanocomposite fibrous membranes hold great promise in the fields of critical-sized bone defect repair.

The Astragalus mongholicus Bunge and Panax notoginseng formula (A&P) has been clinically shown to effectively slow down the progression of chronic kidney disease (CKD) and has demonstrated significant anti-fibrosis effects in experimental CKD model. However, the specific active ingredients and underlying mechanism are still unclear. The active ingredients of A&P were analyzed by Ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-HR-MS). A mouse model of CKD was constructed by 5/6 nephrectomy. Renal function was assessed by creatinine and urea nitrogen. Real-time PCR and Western Blot were performed to detect the mRNA and protein changes in kidney and cells. An in vitro fibrotic cell model was constructed by TGF-β induction in TCMK-1 cells. The results showed that thirteen active ingredients of A&P were identified by UPLC-HR-MS, nine of which were identified by analysis with standards, among which the relative percentage of NOB was high. We found that NOB treatment significantly improved renal function, pathological damage and reduced the expression level of fibrotic factors in CKD mice. The results also demonstrated that Lgals1 was overexpressed in the interstitial kidney of CKD mice, and NOB treatment significantly reduced its expression level, while inhibiting PI3K and AKT phosphorylation. Interestingly, overexpression of Lgals1 significantly increased fibrosis in TCMK1 cells and upregulated the activity of PI3K and AKT, which were strongly inhibited by NOB treatment. NOB is one of the main active components of A&P. The molecular mechanism by which NOB ameliorates renal fibrosis in CKD may be through the inhibition of Lgals1/PI3K/AKT signaling pathway.

Diabetic patients often struggle with wound healing and are at higher risk of infections, necessitating the development of a stretchable, adhesive hydrogel dressing with antibacterial and angiogenesis-promoting properties. In this study, we synthesized a series of adhesive, antibacterial and anti-inflammatory hydrogels using free radical polymerization with materials including methacrylated hyaluronic acid (HAMA), N-[tris(hydroxymethyl)methyl]acrylamide (THMA), and 3-(bis(pyridin-2-ylmethyl)amino)propyl methacrylate (DPAMA). By leveraging the strong affinity of zinc(II)-dipicolylamine coordination complexes for the phosphorylated groups in dexamethasone sodium phosphate (DMSP), Zn2+ and DMSP were successfully incorporated into the hydrogel. The results demonstrated that the hydrogels possessed excellent adhesiveness and mechanical properties, enabling them to adhere closely to the skin while remaining easily removable without causing trauma. Antibacterial tests demonstrated significant inhibitory effects against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus), attributed to the slow release of Zn2+, which effectively suppressed bacterial growth. Additionally, the slow release of DMSP provided strong anti-inflammatory effects. The DHTDZ2 hydrogel, containing 1.5 mg/mL Zn2+ and 4 mg/mL DMSP, significantly accelerated the healing of full-thickness skin wounds. In vitro angiogenesis, immunofluorescence, and immuno-histochemical results further confirmed that the DHTDZ2 hydrogel promoted angiogenesis and reduced the expression of pro-inflammatory factors. In summary, the hydrogel is an effective wound healing dressing that can reduce wound infections and inflammation.

Successful treatment of infected bone defects caused by multi-drug resistant bacteria (MDR) has become a major clinical challenge, stressing the urgent need for effective antibacterial bone graft substitutes. Mesoporous bioactive glass nanoparticles (MBGNs), a rapidly emerging class of nanoscale biomaterials, offer specific ad-vantages for the development of biomaterials to treat bone infection due to endowed antibacterial features. Herein, we propose a facile post-modification sol-gel strategy to synthesize effective antibacterial MBGNs doped with copper ions (Cu-PMMBGNs). In this strategy, amine functional groups as chelating agents were introduced to premade mesoporous silica nanoparticles (MSNs) which further facilitate the incorporation of high content of calcium (-17 mol%) and copper ions (-8 mol%) without compromising nanoparticle shape, mesoporosity, and homogeneity. The resulting nanoparticles were degradable and showed rapidly induce abundant deposition of apatite crystals on their surface upon soaking in simulated body fluids (SBF) after 3 days. Cu-PMMBGNs exhibited a dose-dependent inhibitory effect on Methicillin-resistant Staphylococcus aureus (MRSA) bacteria, which are common pathogens causing severe bone infections. Most importantly, the nanoparticles containing 5 mol% copper ions at concentrations of 500 and 1000 mu g.mL-1 showed highly effective antibacterial performance as reflected by a 99.9 % reduction of bacterial viability. Nanoparticles at a concentration of 500 mu g.mL-1 showed no significant cytotoxicity toward preosteoblast cells (-85-89 % cell viability) compared to the control group. In addition, the nanoscale properties of synthesized Cu-PMMBGNs (-100 nm in size) facilitated their internali-zation into preosteoblast cells, which highlights their potential as intracellular carriers in combating intracellular bacteria. Therefore, these copper-doped nanoparticles hold strong promise for use as an antibacterial component in antibacterial bone substitutes such as hydrogels, nanocomposites, and coatings.

Electrophoretic deposition (EPD) is an effective technique to construct coatings onto the surface of medical devices. These coatings can act as reservoirs for local delivery of therapeutic agents, including metal ions and metal-free drugs. This manuscript presents a comprehensive overview of the fundamentals and application of EPD coatings for local delivery of therapeutic agents, with a specific focus on the mechanism and control over loading and release of therapeutic agents. After a brief introduction of the EPD coating process, the matrices that are most commonly deposited using EPD for drug delivery purposes are summarized including the mechanism of their deposition without additives and co-deposition with additives. Subsequently, three strategies towards loading therapeutic agents are discussed, including i) co-deposition of therapeutic agents with coating matrices, ii) pre-loading therapeutic agents into microcarriers, and iii) post-loading therapeutic agents into prepared coatings. Furthermore, factors influencing loading (e.g., EPD processing parameters and additives) are identified. Subsequently, the release mechanisms as well as the influence of both intrinsic (e.g., additives, layered structures, building blocks, and microcarrier properties) and extrinsic processing parameters (e.g., pH, electric, magnetic and photothermal stimuli) used to tune the release kinetics are presented. Additionally, the applications of therapeutic agent loaded EPD coatings are summarized. Finally, the remaining challenges and future perspectives related to the use of EPD coatings for drug delivery purposes are reviewed.