Beyond microroughness: novel approaches to navigate osteoblast activity on implant surfaces.

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.

Nanofeatured surfaces in dental implants: contemporary insights and impending challenges.

Dental implant therapy, established as standard-of-care nearly three decades ago with the advent of microrough titanium surfaces, revolutionized clinical outcomes through enhanced osseointegration. However, despite this pivotal advancement, challenges persist, including prolonged healing times, restricted clinical indications, plateauing success rates, and a notable incidence of peri-implantitis. This review explores the biological merits and constraints of microrough surfaces and evaluates the current landscape of nanofeatured dental implant surfaces, aiming to illuminate strategies for addressing existing impediments in implant therapy. Currently available nanofeatured dental implants incorporated nano-structures onto their predecessor microrough surfaces. While nanofeature integration into microrough surfaces demonstrates potential for enhancing early-stage osseointegration, it falls short of surpassing its predecessors in terms of osseointegration capacity. This discrepancy may be attributed, in part, to the inherent "dichotomy kinetics" of osteoblasts, wherein increased surface roughness by nanofeatures enhances osteoblast differentiation but concomitantly impedes cell attachment and proliferation. We also showcase a controllable, hybrid micro-nano titanium model surface and contrast it with commercially-available nanofeatured surfaces. Unlike the commercial nanofeatured surfaces, the controllable micro-nano hybrid surface exhibits superior potential for enhancing both cell differentiation and proliferation. Hence, present nanofeatured dental implants represent an evolutionary step from conventional microrough implants, yet they presently lack transformative capacity to surmount existing limitations. Further research and development endeavors are imperative to devise optimized surfaces rooted in fundamental science, thereby propelling technological progress in the field.

Optimizing implant osseointegration, soft tissue responses, and bacterial inhibition: A comprehensive narrative review on the multifaceted approach of the UV photofunctionalization of titanium.

Titanium implants have revolutionized restorative and reconstructive therapy, yet achieving optimal osseointegration and ensuring long-term implant success remain persistent challenges. In this review, we explore a cutting-edge approach to enhancing implant properties: ultraviolet (UV) photofunctionalization. By harnessing UV energy, photofunctionalization rejuvenates aging implants, leveraging and often surpassing the intrinsic potential of titanium materials. The primary aim of this narrative review is to offer an updated perspective on the advancements made in the field, providing a comprehensive overview of recent findings and exploring the relationship between UV-induced physicochemical alterations and cellular responses. There is now compelling evidence of significant transformations in titanium surface chemistry induced by photofunctionalization, transitioning from hydrocarbon-rich to carbon pellicle-free surfaces, generating superhydrophilic surfaces, and modulating the electrostatic properties. These changes are closely associated with improved cellular attachment, spreading, proliferation, differentiation, and, ultimately, osseointegration. Additionally, we discuss clinical studies demonstrating the efficacy of UV photofunctionalization in accelerating and enhancing the osseointegration of dental implants. Furthermore, we delve into recent advancements, including the development of one-minute vacuum UV (VUV) photofunctionalization, which addresses the limitations of conventional UV methods as well as the newly discovered functions of photofunctionalization in modulating soft tissue and bacterial interfaces. By elucidating the intricate relationship between surface science and biology, this body of research lays the groundwork for innovative strategies aimed at enhancing the clinical performance of titanium implants, marking a new era in implantology.

Diagnostic guide for immune checkpoint inhibitor-induced liver injury.

With the widespread use of immune checkpoint inhibitors (ICIs), liver injury (ICI-induced liver injury) as an immune-related adverse event has become a major concern in clinical practice. Because severe cases of liver injury require administration of corticosteroids, a comprehensive evaluation is crucial, including clinical course, blood and imaging tests, and if necessary, pathological examination through liver biopsy. As with liver injury induced by other drugs, classification of injury type by R-value is useful in deciding treatment strategies for ICI-induced liver injury. Histologically, the most representative feature is an acute hepatitis-like hepatocellular injury, characterized by diffuse lobular inflammation accompanied by CD8-positive T lymphocytes. Another condition that can cause liver injury during ICI treatment is cholangitis accompanied by non-obstructive bile duct dilatation and bile duct wall thickening. Many cases of ICI-induced cholangitis are classified as non-hepatocellular injury type, and they have been reported to respond poorly to corticosteroids. It is essential that gastroenterologists/hepatologists and doctors in various departments work in cooperation to develop a system that achieves early diagnosis and appropriate treatment of ICI-induced liver injury.

Risk Factors for Immune Checkpoint Inhibitor-Induced Liver Injury and the Significance of Liver Biopsy.

Immune checkpoint inhibitor (ICI)-induced liver injury (LI) is a common adverse event, but the clinical characteristics based on the classification of hepatocellular injury and cholestatic types are not fully evaluated. This study aims to analyze risk factors and histological findings in relation to the classification of ICI-induced LI. In total, 254 ICI-induced LI patients among 1086 treated with ICIs between September 2014 and March 2022 were classified according to the diagnostic criteria for drug-induced LI (DILI), and their risk factors and outcomes were evaluated. Kaplan-Meier analyses showed that overall survival in patients with hepatocellular-injury-type LI was significantly longer than others (p < 0.05). Regarding pre-treatment factors, the lymphocyte count was significantly higher in patients with ICI-induced LI, especially in hepatocellular-injury-type LI. Gamma glutamyl transferase (γGTP) and alkaline phosphatase (ALP) were also significantly lower in patients with ICI-induced LI (p < 0.05). Multivariate analyses revealed that malignant melanoma, high lymphocyte count, and low ALP levels were extracted as factors contributing to hepatocellular-injury-type LI. The histological findings among 37 patients diagnosed as ICI-induced LI via liver biopsy also revealed that the spotty/focal necrosis was significantly frequent in hepatocellular-injury-type LI, whereas ductular reactions were frequently observed in cholestatic-type LI. It is suggested that the histological inflammation pattern in patients with LI is closely correlated with the type of DILI.

Clinical Significance and Remaining Issues of Anti-HBc Antibody and HBV Core-Related Antigen.

Currently, hepatitis B virus (HBV) core antibody (anti-HBc antibody) and HBV core-related antigen (HBcrAg) are widely used as serum markers for diagnosis based on the HBV core region. This review focused on anti-HBc antibodies and HBcrAg and aimed to summarize the clinical significance of currently used assay systems and the issues involved. While anti-HBc is very significant for clinical diagnosis, the clinical significance of quantitative assay of anti-HBc antibody has been reevaluated with improvements in diagnostic performance, including its association with clinical stage and prediction of carcinogenesis and reactivation. In addition, concerning the new HBcrAg, a high-sensitivity assay method has recently been established, and its diagnostic significance, including the prediction of reactivation, is being reevaluated. On the other hand, the quantitative level of anti-HBc antibody expressed in different units among assay systems complicates the interpretation of the results. However, it is difficult to standardize assay systems as they vary in advantages, and caution is needed in interpreting the assay results. In conclusion, with the development of highly sensitive HBcrAg and anti-HBc antibody, a rapid and sensitive detection assay system has been developed and used in clinical practice. In the future, it is hoped that a global standard will be created based on the many clinical findings.

Achieving Complete Human Gingival Fibroblast Collagen Coverage on Implant Abutments through Vacuum Ultraviolet (VUV) Photofunctionalization.

PURPOSE: The formation of a biological seal between implant abutments and the surrounding soft tissue is a preventive strategy against peri-implantitis. The aim of this study is to test the hypothesis that surfaces of prosthetic implant abutments treated with vacuum ultraviolet (VUV) light enhance the growth and function of human gingival fibroblasts. MATERIALS AND METHODS: Implant abutments were treated with 172 nm VUV light for one minute. Untreated abutments were subjected as controls. Their surface properties were characterized using SEM, contact angle measurements, and chemical composition analysis. Human gingival fibroblasts were cultured on both untreated and VUV-treated abutments to evaluate cell attachment, proliferation, distribution, and collagen production. Cell detachment assays were also performed under various mechanical and chemical stimuli. RESULTS: After VUV treatment, implant abutments demonstrated a notable transition from hydrophobic to hydrophilic wettability. Surface element analysis revealed a considerable reduction in surface carbon and increases in oxygen and titanium elements on the VUV-treated surfaces. On day 1 of culture, 3.9 times more fibroblasts attached on VUV-treated abutments than on untreated control abutments. Fibroblastic proliferation increased 1.9-3.1 times on VUV-treated abutments, along with a significant improvement in the distribution of populating cells. Collagen production on VUV-treated abutments increased by 1.5-1.7 times. While untreated abutment surfaces showed voids and limited spread of collagen deposition, dense and full coverage of collagen was observed on VUV-treated abutments, with a great contrast in the challenging axial surface zone. Cell retention against mechanical and chemical detaching stimuli was increased 11.3 and 4.3 times, respectively, by VUV treatment. CONCLUSION: Treatment of implant abutments with VUV light for one minute resulted in a reduction of surface carbon and a transformation of the surface from hydrophobic to hydrophilic. This led to enhanced attachment, proliferation, and retention of human gingival fibroblasts, along with nearly complete collagen coverage on implant abutments. These in vitro results indicate the promising potential of utilizing VUV photofunctionalized implant abutments to enhance soft tissue reaction and sealing mechanisms.

Octacalcium phosphate collagen composite for periodontal regeneration in a canine one-wall intrabony defect.

OBJECTIVE: This study aimed to evaluate the regenerative capacities of octacalcium phosphate collagen composite (OCP/Col) in one-wall intrabony defects in dogs. The background data discuss the present state of the field: No study has assessed the efficacy of OCP/Col for periodontal regeneration therapy despite the fact that OCP/Col has proved to be efficient for bone regeneration. METHODS: In six beagle dogs, the mandibular left third premolars were extracted 12 weeks before the experimental surgery. Standardized bone defects (5 mm in height and 4 mm in width) were simulated on the distal surface of the second premolars and mesially on the fourth premolars. The defect was filled with either OCP/Col (experimental group) or left empty (control group). Histological and histomorphometric characteristics were compared 8 weeks after surgery. RESULTS: No infectious or ankylotic complications were detected at any of the tested sites. The experimental group exhibited a significantly greater volume, height, and area of newly formed bone than the control group. The former also showed a greater height of the newly formed cementum than the latter, although the results were not statistically significant. The newly formed periodontal ligaments were inserted into newly formed bone and cementum in the experimental group. CONCLUSION: OCP/Col demonstrated high efficacy for bone and periodontal tissue regeneration that can be successfully applied for one-wall intrabony defects.

Human Gingival Fibroblast Growth and Function in Response to Laser-Induced Meso-and Microscale Hybrid Topography on Dental Implant Healing Abutments.

PURPOSE: Laser-created titanium surface topographies enhance soft tissue attachment and implant stability. However, knowledge about the underlying mechanisms governing the tissue-level reaction is lacking. The objective of this study was to examine the behavior and function of human gingival fibroblasts growing on healing abutments with or without laser-textured topography. MATERIALS AND METHODS: Human primary gingival connective tissue fibroblasts were cultured on healing abutments with machined or laser-textured (Laser-Lok, BioHorizons) surfaces. Cellular and molecular responses were evaluated by cell density assay (WST-1), fluorescence microscopy, qRT-PCR, and detachment test. RESULTS: The machined surface showed mono-directional traces and scratches from milling, whereas the laser-textured surface showed a distinct morphology consisting of mono-directional meso-scale channels (15 µm pitch) and woven, oblique micro-ridges formed within the channel. There were no differences in initial fibroblast attachment, subsequent fibroblast proliferation, nor collagen production between the machined and laser-textured surfaces. Fibroblasts growing on laser-textured surface spread mono-directionally along the meso-channels, while cells growing on machined surfaces spread randomly. Fibroblasts on laser-textured surfaces were 1.8-times more resistant to detachment than those on machined surfaces. An adhesive glycoprotein (fibronectin) and trans-membrane adhesion linker gene (integrin beta-1) were upregulated on laser-textured surfaces. CONCLUSIONS: The increased fibroblast retention, uniform growth, increased transcription of cell adhesion proteins compellingly explain the enhanced tissue-level response to laser-created, hybrid textured titanium surfaces. These results provide a cellular and molecular rationale for the tissue reaction to this unique surface and support its extended use from implant fixtures and healing abutments to diverse prosthetic components where enhanced soft tissue responses would be desirable.

Disparity in the Influence of Implant Provisional Materials on Human Gingival Fibroblasts with Different Phases of Cell Settlement: An In Vitro Study.

The development of healthy peri-implant soft tissues is critical to achieving the esthetic and biological success of implant restorations throughout all stages of healing and tissue maturation, starting with provisionalization. The purpose of this study was to investigate the effects of eight different implant provisional materials on human gingival fibroblasts at various stages of cell settlement by examining initial cell attachment, growth, and function. Eight different specimens-bis-acrylic 1 and 2, flowable and bulk-fill composites, self-curing acrylic 1 and 2, milled acrylic, and titanium (Ti) alloy as a control-were fabricated in rectangular plates (n = 3). The condition of human gingival fibroblasts was divided into two groups: those in direct contact with test materials (contact experiment) and those in close proximity to test materials (proximity experiment). The proximity experiment was further divided into three phases: pre-settlement, early settlement, and late settlement. A cell culture insert containing each test plate was placed into a well where the cells were pre-cultured. The number of attached cells, cell proliferation, resistance to detachment, and collagen production were evaluated. In the contact experiment, bis-acrylics and composites showed detrimental effects on cells. The number of cells attached to milled acrylic and self-curing acrylic was relatively high, being approximately 70% and 20-30%, respectively, of that on Ti alloy. There was a significant difference between self-curing acrylic 1 and 2, even with the same curing modality. The cell retention ability also varied considerably among the materials. Although the detrimental effects were mitigated in the proximity experiment compared to the contact experiment, adverse effects on cell growth and collagen production remained significant during all phases of cell settlement for bis-acrylics and flowable composite. Specifically, the early settlement phase was not sufficient to significantly mitigate the material cytotoxicity. The flowable composite was consistently more cytotoxic than the bulk-fill composite. The harmful effects of the provisional materials on gingival fibroblasts vary considerably depending on the curing modality and compositions. Pre-settlement of cells mitigated the harmful effects, implying the susceptibility to material toxicity varies depending on the progress of wound healing and tissue condition. However, cell pre-settlement was not sufficient to fully restore the fibroblastic function to the normal level. Particularly, the adverse effects of bis-acrylics and flowable composite remained significant. Milled and self-curing acrylic exhibited excellent and acceptable biocompatibility, respectively, compared to other materials.