Considering the biological activity of osteoblasts is crucial when devising new approaches to enhance the osseointegration of implant surfaces, as their behavior profoundly influences clinical outcomes. An established inverse correlation exists between osteoblast proliferation and their functional differentiation, which constrains the rapid generation of a significant amount of bone. Examining the surface morphology of implants reveals that roughened titanium surfaces facilitate rapid but thin bone formation, whereas smooth, machined surfaces promote greater volumes of bone formation albeit at a slower pace. Consequently, osteoblasts differentiate faster on roughened surfaces but at the expense of proliferation speed. Moreover, the attachment and initial spreading behavior of osteoblasts are notably compromised on microrough surfaces. This review delves into our current understanding and recent advances in nanonodular texturing, meso-scale texturing, and UV photofunctionalization as potential strategies to address the \"biological dilemma\" of osteoblast kinetics, aiming to improve the quality and quantity of osseointegration. We discuss how these topographical and physicochemical strategies effectively mitigate and even overcome the dichotomy of osteoblast behavior and the biological challenges posed by microrough surfaces. Indeed, surfaces modified with these strategies exhibit enhanced recruitment, attachment, spread, and proliferation of osteoblasts compared to smooth surfaces, while maintaining or amplifying the inherent advantage of cell differentiation. These technology platforms suggest promising avenues for the development of future implants.

The three-dimensional-printed Ti6Al4V implant (3DTi) has been widely accepted for the reconstruction of massive bone defects in orthopedics owing to several advantages, such as its tailored shape design, avoiding bone graft and superior bone-implant interlock. However, the osteoinduction activity of 3DTi is inadequate when applied clinically even though it exhibits osteoconduction. This study developes a comprehensive coatless strategy for the surface improvement of 3DTi through copper (Cu) ion implantation and ultraviolet (UV) photofunctionalization to enhance osteoinductivity. The newly constructed functional 3DTi (UV/Ti-Cu) achieved stable and controllable Cu doping, sustained Cu2+ releasing, and increased surface hydrophilicity. By performing cellular experiments, we determined that the safe dose range of Cu ion implantation was less than 5×1016 ions/cm2. The implanted Cu2+ enhanced the ALP activity and the apatite formation ability of bone marrow stromal cells (BMSCs) while slightly decreasing proliferation ability. When combined with UV photofunctionalization, cell adhesion and proliferation were significantly promoted and bone mineralization was further increased. Meanwhile, UV/Ti-Cu was conducive to the migration and angiogenesis of human umbilical vein endothelial cells (HUVECs) in vitro, theoretically facilitating vascular coupling osteogenesis. In conclusion, UV/Ti-Cu is a novel attempt to apply two coatless techniques for the surface modification of 3DTi. In addition, it is considered a potential bone substrate for repairing bone defects.

The exact mechanisms by which implant surface properties govern osseointegration are incompletely understood. To gain insights into this process, we examined alterations in protein and blood recruitment around screw implants with different surface topographies and wettability using a computational fluid dynamics (CFD) model. Compared with a smooth surface, a microrough implant surface reduced protein infiltration from the outer zone to the implant thread and interface zones by over two-fold. However, the microrough implant surface slowed blood flow in the interface zone by four-fold. As a result, compared with the smooth surface, the microrough surface doubled the protein recruitment/retention index, defined as the mass of proteins present in the area per unit time. Converting implant surfaces from hydrophobic to superhydrophilic increased the mass of protein infiltration 2-3 times and slowed down blood flow by up to two-fold in the implant vicinity for both smooth and microrough surfaces. The protein recruitment/retention index was highest at the implant interface when the implant surface was superhydrophilic and microrough. Thus, this study demonstrates distinct control of the mass and speed of protein and blood flow through implant surface topography, wettability, and their combination, significantly altering the efficiency of protein recruitment. Although microrough surfaces showed both positive and negative impacts on protein recruitment over smooth surfaces, superhydrophilicity was consistently positive regardless of surface topography.

Hydrophilicity/hydrophobicity-or wettability-is a key surface characterization metric for titanium used in dental and orthopedic implants. However, the effects of hydrophilicity/hydrophobicity on biological capability remain uncertain, and the relationships between surface wettability and other surface parameters, such as topography and chemistry, are poorly understood. The objective of this study was to identify determinants of surface wettability of titanium and establish the reliability and validity of the assessment. Wettability was evaluated as the contact angle of ddH2O. The age of titanium specimens significantly affected the contact angle, with acid-etched, microrough titanium surfaces becoming superhydrophilic immediately after surface processing, hydrophobic after 7 days, and hydrorepellent after 90 days. Similar age-related loss of hydrophilicity was also confirmed on sandblasted supra-micron rough surfaces so, regardless of surface topography, titanium surfaces eventually become hydrophobic or hydrorepellent with time. On age-standardized titanium, surface roughness increased the contact angle and hydrophobicity. UV treatment of titanium regenerated the superhydrophilicity regardless of age or surface roughness, with rougher surfaces becoming more superhydrophilic than machined surfaces after UV treatment. Conditioning titanium surfaces by autoclaving increased the hydrophobicity of already-hydrophobic surfaces, whereas conditioning with 70% alcohol and hydrating with water or saline attenuated pre-existing hydrophobicity. Conversely, when titanium surfaces were superhydrophilic like UV-treated ones, autoclaving and alcohol cleaning turned the surfaces hydrorepellent and hydrophobic, respectively. UV treatment recovered hydrophilicity without exception. In conclusion, surface roughness accentuates existing wettability and can either increase or decrease the contact angle. Titanium must be age-standardized when evaluating surface wettability. Surface conditioning techniques significantly but unpredictably affect existing wettability. These implied that titanium wettability is significantly influenced by the hydrocarbon pellicle and other contaminants inevitably accumulated. UV treatment may be an effective strategy to standardize wettability by making all titanium surfaces superhydrophilic, thereby allowing the characterization of individual surface topography and chemistry parameters in future studies.

BACKGROUND: Diabetes mellitus affects many organ systems, including bone tissue.In diabetic patients, the activity of osteoblasts is suppressed and the activity of osteoclasts in the bone matrix increases, bone formation decreases, which can disrupt the process of osseointegration and ultimately lead to disintegration and failed implants. Based on the foregoing, with diabetes, it is very important to study bone metabolism to predict and dynamically control dental implants.
OBJECTIVE: To assess the indicators of bone metabolism markers Osteocalcin and β-Cross-Laps in blood serum in patients with type 2 diabetes mellitus with intraosseous dental implants.
METHODS: The study included 86 patients, diagnosed type 2 diabetes mellitus in period 2018 - 2023 with partially or complete edentulous. Implant surgery was performed after periodontal therapy using 367 UV functionalized dental implants in patients 1 group. Patients 2 group was performed implant surgery using 54 dental implants that were not UV functionalization. Final dental prosthetics was performed 4-5 months. UV functionalization of the implant surface was carried out using a UV Activator YWJ-QSY001 (Foshan, Wenjian Medikal Enstriman) for 20 s. The content biochemical markers of bone Osteocalcin and β-Cross-Laps serum was determined by enzyme-linked immunosorbent assay ELISA (ELISA, IFA Roche Diagnostics, Basel, Switzerland) before and after dental implantation according to the manufacturers\' protocols. Outcomes assessed included; implant survival, men MBL, PPD, BOP, RFA, prosthetic success.
RESULTS: There were no clinical examinations of serious biological or prosthetic complications. There is a correlation between different concentrations of Osteocalcin or β-Cross- Laps and the success rate of implants. Implants were shown to be unsuccessful low concentrations of Osteocalcin and high concentrations β-Cross- Laps in serum compared with average mean biochemical markers of bone in 2 group patients. In patients of the 2nd group, the indicators of biochemical bone markers were within the normal range; no correlation was found between osseointegration failers and the complication of peri-implatitis. Short implants success rate was 96,7 %, standart implants success rate was after 97,5 after 5 years.
CONCLUSIONS: Implant therapy can be successfully used in diabetic patients with UV photofunctionalized implants, blood glucose levels should be constantly maintained at a normal level. Monitoring of bone metabolism markers in patients with type 2 diabetes mellitus may have prognostic value for implants and will encourage the practitioner to apply corrective drug therapy in case of violation of markers.

Ultraviolet (UV) photofunctionalization counteracts the biological aging of titanium to increase the bioactivity and osseointegration of titanium implants. However, UV photofunctionalization currently requires long treatment times of between 12 min and 48 h, precluding routine clinical use. Here, we tested the ability of a novel, xenon excimer lamp emitting 172 nm vacuum UV (VUV) to decompose organic molecules coated on titanium as a surrogate of photofunctionalization. Methylene blue as a model organic molecule was coated on grade 4 commercially pure titanium and treated with four UV light sources: (i) ultraviolet C (UVC), (ii) high-energy UVC (HUVC), (iii) proprietary UV (PUV), and (iv) VUV. After one minute of treatment, VUV decomposed 57% of methylene blue compared with 2%, 36%, and 42% for UVC, HUVC, and PUV, respectively. UV dose-dependency testing revealed maximal methylene blue decomposition with VUV within one minute. Equivalent decomposition was observed on grade 5 titanium alloy specimens, and placing titanium specimens in quartz ampoules did not compromise efficacy. Methylene blue was decomposed even on polymethyl methacrylate acrylic specimens at 20-25% lower efficiency than on titanium specimens, indicating a relatively small contribution of titanium dioxide-mediated photocatalytic decomposition to the total decomposition. Load-testing revealed that VUV maintained high efficacy of methylene blue decomposition regardless of the coating density, whereas other UV light sources showed low efficacy with thin coatings and plateauing efficacy with thicker coatings. This study provides foundational data on rapid and efficient VUV-mediated organic decomposition on titanium. In synergy with quartz ampoules used as containers, VUV has the potential to overcome current technical challenges hampering the clinical application of UV photofunctionalization.

Vertical bone augmentation to create host bone prior to implant placement is one of the most challenging regenerative procedures. The objective of this study is to evaluate the capacity of a UV-photofunctionalized titanium microfiber scaffold to recruit osteoblasts, generate intra-scaffold bone, and integrate with host bone in a vertical augmentation model with unidirectional, limited blood supply. Scaffolds were fabricated by molding and sintering grade 1 commercially pure titanium microfibers (20 μm diameter) and treated with UVC light (200-280 nm wavelength) emitted from a low-pressure mercury lamp for 20 min immediately before experiments. The scaffolds had an even and dense fiber network with 87% porosity and 20-50 mm inter-fiber distance. Surface carbon reduced from 30% on untreated scaffold to 10% after UV treatment, which corresponded to hydro-repellent to superhydrophilic conversion. Vertical infiltration testing revealed that UV-treated scaffolds absorbed 4-, 14-, and 15-times more blood, water, and glycerol than untreated scaffolds, respectively. In vitro, four-times more osteoblasts attached to UV-treated scaffolds than untreated scaffolds three hours after seeding. On day 2, there were 70% more osteoblasts on UV-treated scaffolds. Fluorescent microscopy visualized confluent osteoblasts on UV-treated microfibers two days after seeding but sparse and separated cells on untreated microfibers. Alkaline phosphatase activity and osteocalcin gene expression were significantly greater in osteoblasts grown on UV-treated microfiber scaffolds. In an in vivo model of vertical augmentation on rat femoral cortical bone, the interfacial strength between innate cortical bone and UV-treated microfiber scaffold after two weeks of healing was double that observed between bone and untreated scaffold. Morphological and chemical analysis confirmed seamless integration of the innate cortical and regenerated bone within microfiber networks for UV-treated scaffolds. These results indicate synergy between titanium microfiber scaffolds and UV photofunctionalization to provide a novel and effective strategy for vertical bone augmentation.

UV photofunctionalization of Zirconia-based materials for abutment fabrication is a promising approach that might influence the formation of a sound peri-implant seal, thus promoting long-term soft and hard tissue implant integration. This study aimed to evaluate the effect of UV treatment of test specimens made by two different ZnO2-based ceramic materials on the hydrophilicity, cell cytotoxicity, and proliferation of human gingival fibroblasts (HGFs). Two Zirconia-based materials, high-translucent and ultra-translucent multi-layered Zirconia (Katana, Kuraray Noritake, Japan), were used to prepare a total of 40 specimens distributed in two equally sized groups based on the material (n = 20). The same surface finishing protocol was applied for all specimens, as suggested by the manufacturer. Half the specimens from each group were treated with UV-C light for 48 h. Water contact angle (WCA), fibroblast cytotoxicity, and proliferation were investigated. The WCA values for the high-translucent Zirconia ranged from 69.9° ± 6.4° to 73.7° ± 13.9° for the treated/non-treated specimens and from 79.5° ± 12.8° to 83.4° ± 11.4° for the ultra-translucent multi-layered Zirconia, respectively. However, the difference was insignificant (F(16) = 3.50, p = 0.292). No significant difference was observed for the fibroblast cytotoxicity test. The results for proliferation revealed a significant difference, which was material-dependent (F(8) = 9.58, p = 0.005). We found that UV surface photofunctionalization of ZrO2-based materials alters the human gingival fibroblast cell viability, which might produce favourable results for cell proliferation.

Three-dimensional (3D)-printed porous Ti6Al4V implants play an important role in the reconstruction of bone defects. However, its osseointegration capacity needs to be further improved, and related methods are inadequate, especially lacking customized surface treatment technology. Consequently, we aimed to design an omnidirectional radiator based on ultraviolet (UV) photofunctionalization for the surface treatment of 3D-printed porous Ti6Al4V implants, and studied its osseointegration promotion effects in vitro and in vivo, while elucidating related mechanisms. Following UV treatment, the porous Ti6Al4V scaffolds exhibited significantly improved hydrophilicity, cytocompatibility, and alkaline phosphatase activity, while preserving their original mechanical properties. The increased osteointegration strength was further proven using a rabbit condyle defect model in vivo, in which UV treatment exhibited a high efficiency in the osteointegration enhancement of porous Ti6Al4V scaffolds by increasing bone ingrowth (BI), the bone-implant contact ratio (BICR), and the mineralized/osteoid bone ratio. The advantages of UV treatment for 3D-printed porous Ti6Al4V implants using the omnidirectional radiator in the study were as follows: 1) it can significantly improve the osseointegration capacity of porous titanium implants despite the blocking out of UV rays by the porous structure; 2) it can evenly treat the surface of porous implants while preserving their original topography or other morphological features; and 3) it is an easy-to-operate low-cost process, making it worthy of wide clinical application.

BACKGROUND: Ultraviolet (UV) and non-thermal plasma functionalization are surface treatment modalities that seem able to improve osseointegration. The aim of this systematic review and meta-analysis is to assess the effect of the two methods and possible differences.
METHODS: The systematic research of pre-clinical animal studies was conducted up to May 2020 in the databases PubMed/Medline, Scopus and the Cochrane Lybrary. A meta-analysis was performed by using the DerSimonian-Laird estimator in random-effects models.
RESULTS: Through the digital search, 518 articles were identified; after duplicate removal and screening process 10 papers were included. Four studies evaluating UV treatment in rabbits were included in the meta-analysis. The qualitative evaluation of the included studies showed that both UV photofunctionalization and non-thermal plasma argon functionalization of titanium implant surfaces might be effective in vivo to improve the osseointegration. The meta-analysis on four studies evaluating UV treatment in rabbits showed that bone to implant contact values (expressed as standardized mean differences and raw mean differences) were significantly increased in the bio-activated groups when follow-up times were relatively homogeneous, although a high heterogeneity (I2 > 75%) was found in all models.
CONCLUSIONS: The present systematic review and meta-analysis on pre-clinical studies demonstrated that chair-side treatment of implants with UV or non-thermal plasma appear to be effective for improving osseointegration. This systematic review supports further clinical trials on this topic.