Implant-associated infections (IAIs) are the main cause of prosthetic implant failure. Bacterial biofilms prevent antibiotic penetration, and the unique metabolic conditions in hypoxic biofilm microenvironment may limit the efficacy of conventional antibiotic treatment. Escaping survival bacteria may not be continually eradicated, resulting in the recurrence of IAIs. Herein, a sonosensitive metal-organic framework of Cu-TCPP (tetrakis(4-carboxyphenyl) porphyrin) nanosheets and tinidazole doped probiotic-derived membrane vesicles (OMVs) with high-penetration sonodynamic therapy (SDT), bacterial metabolic state interference, and bacterial cuproptosis-like death to eradicate IAIs is proposed. The Cu-TCPP can convert O2 to toxic 1O2 through SDT in the normoxic conditions, enhancing the hypoxic microenvironment and activating the antibacterial activity of tinidazole. The released Cu(II) under ultrasound can be converted to Cu(I) by exogenous poly(tannic acid) (pTA) and endogenous glutathione. The disruption of the bacterial membrane by SDT can enhance the Cu(I) transporter activity. Transcriptomics indicate that the SDT-enhanced Cu(I) overload and hypoxia-activated therapy hinder the tricarboxylic acid cycle (TCA), leading to bacterial cuproptosis-like death. Moreover, the OMVs-activated therapy can polarize macrophages to a M2-like phenotype and facilitate bone repair. The sonodynamic biofilm microenvironment modulation strategy, whereby the hypoxia-enhanced microenvironment is potentiated to synergize SDT with OMVs-activated therapy, provides an effective strategy for antibacterial and osteogenesis performance.

The integration of titanium (Ti)-based implants with bone is limited, resulting in implant failure. This lack of osteointegration is due to the foreign body response (FBR) that occurs after the implantation of biodevices. The process begins with protein adsorption, which is governed by implant surface properties, e.g., chemistry, charge, wettability, and/or topography. The distribution and composition of the protein layer in turn influence the recruitment, differentiation, and modulation of immune and bone cells. The subsequent events that occur at the bone-material interface will ultimately determine whether the implant is encapsulated or will integrate with bone. Despite the numerous studies evaluating the influence of surface properties in the various stages of the FBR, the factors that affect tissue-material interactions are often studied in isolation or in small correlations due to the technical challenges involved in assessing them in vitro or in vivo. Consequently, the influence of protein conformation on the Ti bone implant surface design remains an unresolved research question. The objective of this review is to comprehensively evaluate the existing literature on the effect of surface parameters of Ti and its alloys in the stages of FBR, with a particular focus on protein adsorption and osteoimmunomodulation. This evaluation aims to systematically describe these effects on bone formation.

Implant surface nanofiber (NF) coatings represent an alternative way to prevent/treat periprosthetic joint infection (PJI) via local drug release. We developed and characterized a coaxial erythromycin (EM)-doped PLGA/PCL-PVA NF coating. The purpose of this study was to determine the efficacy of EM-NF coatings (EM0, no EM, EM100 (100 mg/mL), and EM1000 (1000 mg/mL) wt/wt) in a rat PJI model. A strong bond of the EM-NF coating to the surface of titanium (Ti) pins was confirmed by in vitro mechanical testing. Micro-computed tomography (mCT) analysis showed that both EM100 and EM1000 NF effectively reduced periprosthetic osteolysis compared to EM0 at 8 and 16 weeks after implantation. Histology showed that EM100 and EM1000 coatings effectively controlled infection and enhanced periprosthetic new bone formation. The bone implant contact (BIC) of EM100 (35.08%) was higher than negative controls and EM0 (3.43% and 0%, respectively). The bone area fraction occupancy (BAFO) of EM100 (0.63 mm2) was greater than controls and EM0 (0.390 mm2 and 0.0 mm2, respectively). The BAFO of EM100 was higher than that of EM1000 (0.3 mm2). These findings may provide a basis for a new implant surface fabrication strategy aimed at reducing the risks of defective osseointegration and PJI.

The high rate of rejection and failure of orthopedic implants is primarily attributed to incomplete osseointegration and stress at the implant-to-bone interface due to significant differences in the mechanical properties of the implant and the surrounding bone. Various surface treatments have been developed to enhance the osteoconductive properties of implants. The aim of this work was the in vitro characterization of titanium alloy modified with a nanocrystalline hydroxyapatite surface layer in relative comparison to unmodified controls. This investigation focused on the behavior of the surface treatment in relation to the physiological environment. Moreover, the osteogenic response of human osteoblasts and adipose stem cells was assessed. Qualitative characterization of cellular interaction was performed via confocal laser scanning microscopy focusing on the cell nuclei and cytoskeletons. Filipodia were assessed using scanning electron microscopy. The results highlight that the HA treatment promotes protein adhesion as well as gene expression of osteoblasts and stem cells, which is relevant for the inorganic and organic components of the extracellular matrix and bone. In particular, cells grown onto HA-modified titanium alloy are able to promote ECM production, leading to a high expression of collagen I and non-collagenous proteins, which are crucial for regulating mineral matrix formation. Moreover, they present an impressive amount of filipodia having long extensions all over the test surface. These findings suggest that the HA surface treatment under investigation effectively enhances the osteoconductive properties of Ti6Al4V ELI.

The study evaluates the osteointegration of hydroxyapatite (HAp) and hydroxyapatite-titanium (HApTi) biocomposites implanted in the femurs of rabbits. The biocomposites were fabricated using powder metallurgy and subjected to a two-step sintering process. Scanning electron microscopy (SEM) was employed to analyze the morphology, while mesenchymal stem cells were cultured to assess cytotoxicity and proliferation. In vivo experiments involved the implantation of HAp in the left femur and HApTi in the right femur of twenty New Zealand white rabbits. Computed tomography (CT) scans, histological, immunohistochemical, and histomorphometric analyses were performed to assess bone density and osteoblast activity. Results demonstrated that HApTi implants showed superior osteointegration, with higher peri-implant bone density and increased osteoblast count compared to HAp implants. This study concluded that HApTi biocomposites have potential for enhanced bone healing and stability in orthopedic applications.

Introduction: The development of reliable treatments for infected or potentially infected bone loss resulting from open fractures and non-unions is extremely urgent, especially to reduce the prolonged courses of antimicrobial therapy to which affected patients are subjected. Numerous bone graft substitutes have been used over the years, but there are currently no effective solutions to treat critical bone loss, especially in the presence of infection. The present study evaluated the use of the biomorphic calcium phosphate bone scaffold b. Bone™, based on a next-generation resorbable biomimetic biomaterial, in bone reconstruction surgery in cases of infection. Methods: Using an \"in vitro 3D bone fracture model\" to predict the behavior of this drug delivery system during critical bone loss at an infected (or potentially infected) site, the effects of scaffolds loaded with gentamicin or vancomycin on the viability and differentiation capacity of human mesenchymal stem cells (hMSCs) were evaluated. Results: This scaffold, when loaded with gentamicin or vancomycin, exhibits a typical drug release curve that determines the inhibitory effects on the growth of Staphylococcus aureus, Enterococcus faecalis, and Escherichia coli, as well as relative biofilm formation. Discussion: The study demonstrates that b.bone scaffolds can effectively address key challenges in orthopedic surgery and patient care by inhibiting bacterial growth and biofilm formation through rapid, potent antibiotic release, reducing the risk of treatment failure due to resistance, and providing a promising solution for bone infections and improved patient outcomes. Future studies could explore the combination of different antibiotics on these scaffolds for more tailored and effective treatments against post-traumatic osteomyelitis pathogens.

BACKGROUND: This study evaluated the osseointegration potential of functionalised high-performance oxide ceramics (HPOC) in isolation or coated with BMP-2 or RGD peptides in 36 New Zeeland female rabbits using micro-computed tomography (micro CT). The primary outcomes of interest were to assess the amount of ossification evaluating the improvement in the bone volume/ total volume (BV/TV) ratio and trabecular thickness at 6 and 12 weeks. The second outcome of interest was to investigate possible differences in osteointegration between the functionalised silanised HPOC in isolation or coated with Bone Morphogenetic Protein 2 (BMP-2) or RGD peptides.
METHODS: 36 adult female New Zealand white rabbits with a minimum weight of three kg were used. One-third of HPOCs were functionalised with silicon suboxide (SiOx), a third with BMP-2 (sHPOC-BMP2), and another third with RGD (sHPOC-RGD). All samples were scanned with a high-resolution micro CT (U-CTHR, MILabs B.V., Houten, The Netherlands) with a reconstructed voxel resolution of 10 µm. MicroCT scans were reconstructed in three planes and processed using Imalytics Preclinical version 2.1 (Gremse-IT GmbH, Aachen, Germany) software. The total volume (TV), bone volume (BV) and ratio BV/TV were calculated within the coating area.
RESULTS: BV/TV increased significantly from 6 to 12 weeks in all HPOCs: silanised (P = 0.01), BMP-2 (P < 0.0001), and RGD (P < 0.0001) groups. At 12 weeks, the BMP-2 groups demonstrated greater ossification in the RGD (P < 0.0001) and silanised (P = 0.008) groups. Trabecular thickness increased significantly from 6 to 12 weeks (P < 0.0001). At 12 weeks, BMP-2 promoted greater trabecular thickness compared to the silanised group (P = 0.07), although no difference was found with the RGD (P = 0.1) group.
CONCLUSIONS: Sinalised HPOC in isolation or functionalised with BMP-2 or RGD promotes in vivo osteointegration. The sinalised HOPC functionalised with BMP-2 demonstrated the greatest osseointegration.

UNASSIGNED: The revolution of orthopedic implant manufacturing is being driven by 3D printing of titanium implants for large bony defects such as those caused by diabetic Charcot arthropathy. Unlike traditional subtractive manufacturing of orthopedic implants, 3D printing fuses titanium powder layer-by-layer, creating a unique surface roughness that could potentially enhance osseointegration. However, the metabolic impairments caused by diabetes, including negative alterations of bone metabolism, can lead to nonunion and decreased osseointegration with traditionally manufactured orthopedic implants. This study aimed to characterize the response of both healthy and diabetic primary human osteoblasts cultured on a medical-grade 3D-printed titanium surface under high and low glucose conditions.
UNASSIGNED: Bone samples were obtained from six patients, three with Type 2 Diabetes Mellitus and three without. Primary osteoblasts were isolated and cultured on 3D-printed titanium discs in high (4.5 g/L D-glucose) and low glucose (1 g/L D-Glucose) media. Cellular morphology, matrix deposition, and mineralization were assessed using scanning electron microscopy and alizarin red staining. Alkaline phosphatase activity and L-lactate concentration was measured in vitro to assess functional osteoblastic activity and cellular metabolism. Osteogenic gene expression of BGLAP, COL1A1, and BMP7 was analyzed using reverse-transcription quantitative polymerase chain reaction.
UNASSIGNED: Diabetic osteoblasts were nonresponsive to variations in glucose levels compared to their healthy counterparts. Alkaline phosphatase activity, L-lactate production, mineral deposition, and osteogenic gene expression remained unchanged in diabetic osteoblasts under both glucose conditions. In contrast, healthy osteoblasts exhibited enhanced functional responsiveness in a high glucose environment and showed a significant increase in osteogenic gene expression of BGLAP, COL1A1, and BMP7 (p<.05).
UNASSIGNED: Our findings suggest that diabetic osteoblasts exhibit impaired responsiveness to variations in glucose concentrations, emphasizing potential osteoblast dysfunction in diabetes. This could have implications for post-surgery glucose management strategies in patients with diabetes. Despite the potential benefits of 3D printing for orthopedic implants, particularly for diabetic Charcot collapse, our results call for further research to optimize these interventions for improved patient outcomes.

The complex biological process of osseointegration and the bio-inertness of bone implants are the major reasons for the high failure rate of long-term implants, and have also promoted the rapid development of multifunctional implant coatings in recent years. Herein, through the special design of peptides, we use layer-by-layer assembly technology to simultaneously display two peptides with different biological functions on the implant surface to address this issue. A variety of surface characterization techniques (ellipsometry, atomic force microscopy, photoelectron spectroscopy, dissipation-quartz crystal microbalance) were used to study in detail the preparation process of the dual peptide functional coating and the physical and chemical properties, such as the composition, mechanical modulus, stability, and roughness of the coating. Compared with single peptide functional coatings, dual-peptide functionalized coatings had much better performances on antioxidant, cellular adhesion in early stage, proliferation and osteogenic differentiation in long term, as well as in vivo osteogenesis and osseointegration capabilities. These findings will promote the development of multifunctional designs in bone implant coatings, as a coping strategy for the complexity of biological process during osteointegration.

The aging population and increasing incidence of trauma among younger age groups have heightened the increasing demand for reliable implant materials. Effective implant materials must demonstrate rapid osseointegration and strong antibacterial properties to ensure optimal patient outcomes and decrease the chance of implant rejection. This study aims to enhance the bone-implant interface by utilizing 45S5 bioglass modified with various concentrations of Fe3O4 as a coating material. The effect of the insertion of Fe3O4 into the bioglass structure was studied using Raman spectroscopy which shows that with the increase in Fe3O4 concentration, new vibration bands associated with Fe-related structural units appeared within the sample. The bioactivity of the prepared glasses was evaluated using immersion tests in simulated body fluid, revealing the formation of a calcium phosphate-rich layer within 24 h on the samples, indicating their potential for enhanced tissue integration. However, the sample modified with 8 mol% of Fe3O4 showed low reactivity, developing a calcium phosphate-rich layer within 96 h. All the bioglasses showed antibacterial activity against the Gram-positive and Gram-negative bacteria. The modified bioglass did not present significant antibacterial properties compared to the bioglass base.