Type 2 diabetes (T2D) is on a notable rise worldwide, which leads to unfavorable outcomes during implant treatments. Surface modification of implants and exosome treatment have been utilized to enhance osseointegration. However, there has been insufficient approach to improve adverse osseointegration in T2D conditions. In this study, we successfully loaded TNF-α-treated mesenchymal stem cell (MSC)-derived exosomes onto micro/nano-network titanium (Ti) surfaces. TNF-α-licensed exosome-integrated titanium (TNF-exo-Ti) effectively enhanced M2 macrophage polarization in hyperglycemic conditions, with increased secretion of anti-inflammatory cytokines and decreased secretion of pro-inflammatory cytokines. In addition, TNF-exo-Ti pretreated macrophage further enhanced angiogenesis and osteogenesis of endothelial cells and bone marrow MSCs. More importantly, TNF-exo-Ti markedly promoted osseointegration in T2D mice. Mechanistically, TNF-exo-Ti activated macrophage autophagy to promote M2 polarization through inhibition of the PI3K/AKT/mTOR pathway, which could be abolished by PI3K agonist. Thus, this study established TNF-α-licensed exosome-immobilized titanium surfaces that could rectify macrophage immune states and accelerate osseointegration in T2D conditions.

The surface morphology of titanium metal is an important factor affecting its hydrophilicity and biocompatibility, and exploring the surface treatment strategy of titanium metal is an important way to improve its biocompatibility . In this study , titanium (TA4) was firstly treated by large particle sand blasting and acid etching (SLA) technology, and then the obtained SLA-TA4 was treated by single surface treatments such as alkali-heat, ultraviolet light and plasma bombardment. According to the experimental results, alkali-heat treatment is the best treatment method to improve and maintain surface hydrophilicity of titanium. Then, the nanowire network morphology of titanium surface and its biological property, formed by further surface treatments on the basis of alkali-heat treatment, were investigated. Through the cell adhesion experiment of mouse embryonic osteoblast cells (MC3T3-E1), the ability of titanium material to support cell adhesion and cell spreading was investigated after different surface treatments. The mechanism of biological activity difference of titanium surface formed by different surface treatments was investigated according to the contact angle, pit depth and roughness of the titanium sheet surface. The results showed that the SLA-TA4 titanium sheet after a treatment of alkali heat for 10 h and ultraviolet irradiation for 1 h has the best biological activity and stability. From the perspective of improving surface bioactivity of medical devices, this study has important reference value for relevant researches on surface treatment of titanium implantable medical devices.
钛金属的表面形貌是影响其亲水性及生物相容性的重要因素，探究钛金属表面处理策略是提高其生物相容性的重要途径。本文先采用大颗粒喷砂酸蚀技术（SLA）处理钛金属A4（TA4），对得到的SLA-TA4进行碱热、紫外光照及等离子体轰击等单一方式表面处理。根据实验结果得出，碱热处理是提高并保持钛金属SLA-TA4亲水性的最佳单一处理方法。随后，在碱热处理的基础上，继续研究多种表面处理方式形成的钛金属表面纳米线网络结构及其生物性能。通过小鼠胚胎成骨前体细胞MC3T3-E1黏附实验，比较了不同方式表面处理后，钛金属材料支持细胞黏附、细胞铺展的能力，并根据不同表面处理方式形成的材料表面接触角、微坑深度及粗糙度等参数，分析探讨多种表面处理方式造成的生物活性差异的机制。结果表明，经碱热处理10 h及紫外照射1 h处理后的SLA-TA4 表现出最佳的生物活性及稳定性。从提高医疗器械表面生物活性的角度考虑，本文研究结果或对钛金属植入性器械的表面处理相关研究提供有价值的参考。.

BACKGROUND: Osteoblastic responses play a crucial role in the success of oral implants. Enhanced proliferation of osteoblast cells is associated with reduced cell mortality and an increase in bone regeneration. This study aims to evaluate the osteoblastic responses following oral implantation.
METHODS: Osteoblast stem cells were harvested and subsequently cultivated using cell culture techniques. The osteoblastic phenotype of the extracted cells was confirmed by examining the extracellular matrix. Cell morphogenesis on functionalized biomaterial surfaces was assessed through indirect immunofluorescence staining. The cellular response was investigated in the presence of two types of implant materials: titanium (Ti) and alumina-toughened zirconia (ATZ). Cell viability and apoptosis were quantitatively assessed using MTT assays and flow cytometry, respectively.
RESULTS: The survival of osteoblastic lineage cells was moderately reduced post-implantation. Viability in the Ti implant group remained at approximately 86%, while in the ATZ group, it was observed at 75%, which is considered acceptable. Moreover, there was a significant disparity in cell survival between the two implant groups (p < 0.05). Analysis of apoptosis levels at various concentrations revealed that the rate of apoptosis was 3.6% in the control group and 18.5% in the ATZ group, indicating that apoptosis or programmed cell death in the ATZ-treated group had increased nearly four-fold (p < 0.05).
CONCLUSIONS: The findings of this study indicate a reduction in osteoblastic cell line survival following implant treatment, with titanium implants exhibiting superior performance in terms of cell survival. However, it was also noted that the incidence of apoptosis in osteoblast cells was significantly higher in the presence of zirconium-based implants.

BACKGROUND: The search for effective antimicrobial agents to mitigate peri-implant infections remains a crucial aspect of implant dentistry. This study aimed to evaluate and compare the antimicrobial efficacy of i-PRF, A-PRF+, and enamel matrix derivative (EMD) on decontaminated rough and smooth titanium (Ti) discs.
METHODS: Rough and smooth Ti discs were coated with multispecies biofilm and thoroughly debrided using a chitosan-bristled brush. Subsequently, i-PRF, A-PRF+, and EMD were applied. Untreated discs served as control. Residual adherent bacteria present on the treated Ti discs were visualized by SEM and quantified using culture technique, and colony-forming units (CFUs) were measured after 48 h and 7 days.
RESULTS: i-PRF demonstrated better antimicrobial effectiveness on both smooth and rough implant surfaces as compared to A-PRF+ and EMD (p < 0.001). In all the experimental groups, smooth Ti discs displayed a greater reduction in microbes compared to rough Ti discs when treated with the biologics. The major reduction in CFU values was determined after seven days.
CONCLUSIONS: i-PRF as a regenerative material may also be suitable for decontaminating implant surfaces, which could influence tissue healing and regenerative outcomes positively.

Titanium and titanium alloys are widely favored materials for orthopedic implants due to their exceptional mechanical properties and biological inertness. The additional benefit of sustained local release of bioactive substances further promotes bone tissue formation, thereby augmenting the osseointegration capacity of titanium implants and attracting increasing attention in bone tissue engineering. Among these bioactive substances, growth factors have shown remarkable osteogenic and angiogenic induction capabilities. Consequently, researchers have developed various physical, chemical, and biological loading techniques to incorporate growth factors into titanium implants, ensuring controlled release kinetics. In contrast to conventional treatment modalities, the localized release of growth factors from functionalized titanium implants not only enhances osseointegration but also reduces the risk of complications. This review provides a comprehensive examination of the types and mechanisms of growth factors, along with a detailed exploration of the methodologies used to load growth factors onto the surface of titanium implants. Moreover, it highlights recent advancements in the application of growth factors to the surface of titanium implants (Scheme 1). Finally, the review discusses current limitations and future prospects for growth factor-functionalized titanium implants. In summary, this paper presents cutting-edge design strategies aimed at enhancing the bone regenerative capacity of growth factor-functionalized titanium implants-a significant advancement in the field of enhanced bone regeneration.

Surface treatment of implants facilitates osseointegration, with nanostructured surfaces exhibiting accelerated peri-implant bone regeneration. This study compared bone-to-implant contact (BIC) in implants with hydroxyapatite (HA), sand-blasted and acid-etched (SLA), and SLA with calcium (Ca)-coated (XPEED®) surfaces. Seventy-five disk-shaped grade 4 Ti specimens divided into three groups were prepared, with 16 implants per group tested in New Zealand white rabbits. Surface characterization was performed using X-ray diffraction (XRD), field emission scanning electron microscopy (FE-SEM), digital microscopy, and a contact angle analyzer. Cell viability, proliferation, and adhesion were assessed using MC3T3-E1 cells. Apatite formation was evaluated using modified simulated body fluid (m-SBF) incubation. After 4 weeks of healing, the outcomes reviewed were BIC, bone area (BA), removal torque tests, and histomorphometric evaluation. A microstructure analysis revealed irregular pores across all groups, with the XPEED group exhibiting a nanostructured Ca-coated surface. Surface characterization showed a crystalline CaTiO3 layer on XPEED surfaces, with evenly distributed Ca penetrating the implants. All surfaces provided excellent environments for cell growth. The XPEED and SLA groups showed significantly higher cell density and viability with superior osseointegration than HA (p < 0.05); XPEED exhibited the highest absorbance values. Thus, XPEED surface treatment improved implant performance, biocompatibility, stability, and osseointegration.

UNASSIGNED: Implant success and the state of the surrounding bone require multiple measures, especially in humans, and this study aimed to identify the development of the state of the latter by means of radiographic examination performed during the period of osseointegration as well as investigate the changes in bone density that occur after implant installation and 2 months after functional loading. Implant success rates are affected by bone density at the implant site. Therefore, understanding changes in bone density after dental implant placement is essential, as it correlates with subsequent implant success.
UNASSIGNED: Digital radiographs of 28 implants were taken and evaluated at four intervals: preoperatively, 1 and 3 months postoperatively, and 2 months following placement of the permanent prosthesis. Gray values were measured in different areas around the implants through analyzing X-ray images and measuring bone density around the implants using EzDent - 2D software. The aim of this study was to investigate changes in bone density around implants in three regions: apex, neck, and body, as well as to record average density values during the observation period by measuring digital image gray levels (the gray values of the digital radiographs). This was conducted to determine local bone densities in dental implant recipient sites and to study changes in local bone densities at different intervals, preoperatively and postoperatively and after placement of the prosthesis.
UNASSIGNED: A decrease was observed in gray values proportional to reference values 1-month after implant insertion, but these increased at 3 months after insertion and continued to rise 2 months after placement of the prosthesis in the apical, body, and neck regions of the implant.
UNASSIGNED: Sensor-tuned radiography can be used as an effective method to support clinical follow-ups as well as measure changes in bone densities around implants in critical cases.

Dental Implants are expected to possess both excellent osteointegration and antibacterial activity because poor osseointegration and infection are two major causes of titanium implant failure. In this study, we constructed layer-by-layer self-assembly films consisting of anionic casein phosphopeptides-amorphous calcium phosphate (CPP-ACP) and cationic poly (L-lysine) (PLL) on sandblasted and acid etched (SLA) titanium surfaces and evaluated their osseointegration and antibacterial performance in vitro and in vivo. The surface properties were examined, including microstructure, elemental composition, wettability, and Ca2+ ion release. The impact the surfaces had on the adhesion, proliferation and differentiation abilities of MC3T3-E1 cells were investigated, as well as the material\'s antibacterial performance after exposure to the oral microorganisms such as Porphyromonas gingivalis (P. g) and Actinobacillus actinomycetemcomitans (A. a). For the in vivo studies, SLA and Ti (PLL/CA-3.0)10 implants were inserted into the extraction socket immediately after extracting the rabbit mandibular anterior teeth with or without exposure to mixed bacteria solution (P. g & A. a). Three rabbits in each group were sacrificed to collect samples at 2, 4, and 6 weeks of post-implantation, respectively. Radiographic and histomorphometry examinations were performed to evaluate the implant osseointegration. The modified titanium surfaces were successfully prepared and appeared as a compact nano-structure with high hydrophilicity. In particular, the Ti (PLL/CA-3.0)10 surface was able to continuously release Ca2+ ions. From the in vitro and in vivo studies, the modified titanium surfaces expressed enhanced osteogenic and antibacterial properties. Hence, the PLL/CPP-ACP multilayer coating on titanium surfaces was constructed via a layer-by-layer self-assembly technology, possibly improving the biofunctionalization of Ti-based dental implants.

Objective: Titanium implants are widely used in surgeries for their biocompatibility and mechanical properties. However, excessive titanium particle release can cause implant failure. This study explores Atomic Layer Deposition (ALD) to coat commercially pure titanium (Cp-Ti) with TiO2, aiming to improve its frictional and corrosion resistance while reducing particle release. By comparing TiO2 films with varying ALD cycle numbers, we assess surface properties, particle release, friction, and corrosion performance, providing insights into mitigating particle release from implants. Methods: Cp-Ti surfaces were prepared and coated with TiO2 films of 100, 300, and 500 ALD cycles. Surface characterization involved SEM, EDX, and XRD. Friction was tested using SEM, nanoindentation, and ICP-MS. Corrosion resistance was evaluated through immersion tests and electrochemical analysis. Cytotoxicity was assessed using BMSCs. Results: Surface characterization revealed smoother surfaces with increased ALD cycles, confirming successful TiO2 deposition. Friction testing showed reduced friction coefficients with higher ALD cycles, supported by nanoindentation results. Corrosion resistance improved with increasing ALD cycles, as evidenced by electrochemical tests and reduced titanium release. Cytotoxicity studies showed no significant cytotoxic effects. Conclusion: ALD-coated TiO2 films significantly enhance frictional and corrosion resistance of titanium implants while reducing particle release. The study underscores the importance of ALD cycle numbers in optimizing film performance, offering insights for designing implants with improved properties.

Anodized titania nanotubes have been considered as an effective coating for bone implants due to their ability to induce osteogenesis, whereas the osteogenic mechanism is not fully understood. Our previous study has revealed the potential role of autophagy in osteogenic regulation of nanotubular surface, whereas how the autophagy is activated remains unknown. In this study, we focused on the cell membrane curvature-sensing protein Bif-1 and its effect on the regulation of autophagy. Both autophagosomes formation and autophagic flux were enhanced on the nanotubular surface, as indicated by LC3-II accumulation and p62 degradation. In the meanwhile, the Bif-1 was significantly upregulated, which contributed to autophagy activation and osteogenic differentiation through Beclin-1/PIK3C3 signaling pathway. In conclusion, these findings have bridged the gap between extracellular physical nanotopography and intracellular autophagy activation, which may provide a deeper insight into the signaling transition from mechanical to biological across the cell membrane.