Construction and Biological Evaluation of Biomimetic Coatings on Titanium Surfaces Using Naringin-7-O-Neohesperidoside at Different Concentrations.

Objective: The biomimetic coating on titanium surface affects the adhesion, proliferation, and differentiation of bone cells on the surface of implants. Naringin-7-O-Neohesperidoside (NRG) positively affects the proliferation and differentiation of bone cells, while inhibiting the formation of osteoclasts, thereby affecting the osteogenic effect. This study aimed to construct biomimetic coatings on pure titanium surfaces using layer by layer (LBL) self-assembly of NRGat different concentrations. The effects of the assembled NRG biomimetic coatings on the proliferation and differentiation of mouse preosteoblast cells (MC3T3-E1) in vitro were investigated. The influence of NRG concentration and culture time on MC3T3-E1 cells was also explored. Methods: LBL is a technology that allows for the creation of thin membranes made of polyelectrolytes through electrostatic attraction between polyanions and polycations, which effectively incorporates charged polyelectrolytes onto solid surfaces while preserving their biological activity. Alkaline phosphatase (ALP) plays a crucial role in biomineralization, and its activity is considered as a marker for osteoblast differentiation. Real-time quantitative PCR accurately and quantitatively measures gene expression levels, which reflect the transcriptional activity of genes and thus reflect the proliferation and differentiation of osteoblasts. The research different concentrations of NRG biomimetic coatings (1×10-4 mol/L, 1×10-5 mol/L, 1×10-6 mol/L, and 1×10-7 mol/L) were constructed on titanium surfaces using the LBL self-assembly technique. The control groups included the blank group and the group without drugs. The effects of the coatings on the proliferation of MC3T3-E1 cells were evaluated by ALP activity assay. The differentiation of MC3T3-E1 cells was evaluated by ALP activity assay. Real-time quantitative PCR was performed to detect the gene expressions of OC mRNA, Runx2 mRNA, and Col1a1 mRNA in MC3T3-E1 cells grown on the titanium samples of different experimental groups. Results: The proliferation indices of all NRG concentration groups were higher than those of the groups without drug and blank groups. The highest ALP value was detected at a concentration of 10-4 mol/L. All NRG concentrations upregulated the expression of Col1al mRNA compared to the group without the drug, and the concentrations of 10-5 mol/L and 10-6 mol/L showed statistically significant differences (P < .01). NRG at a concentration of 10-6 mol/L significantly upregulated the expression of Runx2 mRNA (P < .05), while all NRG concentration groups upregulated the expression of OC mRNA. NRG at a concentration of 10-6 mol/L demonstrated a 4 times increase in Runx2 mRNA expression, indicating a significant impact on osteogenic differentiation. Conclusions: NRG biomimetic coatings on titanium surfaces were successfully constructed using the LBL technique. NRG at different concentrations had stronger effects on the proliferation and differentiation of MC3T3-E1 cells compared to the groups without drug and blank groups, with the concentration of 10-6 mol/L demonstrating the best effect. These findings suggest that NRG-loaded biomimetic coatings may enhance the osseointegration of titanium implants, offering promising prospects for dental and orthopedic applications.

Biomaterials with Antibacterial and Osteoinductive Properties to Repair Infected Bone Defects.

The repair of infected bone defects is still challenging in the fields of orthopedics, oral implantology and maxillofacial surgery. In these cases, the self-healing capacity of bone tissue can be significantly compromised by the large size of bone defects and the potential/active bacterial activity. Infected bone defects are conventionally treated by a systemic/local administration of antibiotics to control infection and a subsequent implantation of bone grafts, such as autografts and allografts. However, these treatment options are time-consuming and usually yield less optimal efficacy. To approach these problems, novel biomaterials with both antibacterial and osteoinductive properties have been developed. The antibacterial property can be conferred by antibiotics and other novel antibacterial biomaterials, such as silver nanoparticles. Bone morphogenetic proteins are used to functionalize the biomaterials with a potent osteoinductive property. By manipulating the carrying modes and release kinetics, these biomaterials are optimized to maximize their antibacterial and osteoinductive functions with minimized cytotoxicity. The findings, in the past decade, have shown a very promising application potential of the novel biomaterials with the dual functions in treating infected bone defects. In this review, we will summarize the current knowledge of novel biomaterials with both antibacterial and osteoinductive properties.

Low-dose rhBMP2/7 heterodimer to reconstruct peri-implant bone defects: a micro-CT evaluation.

OBJECTIVES: To delineate the dynamic micro-architectures of bone induced by low-dose bone morphogenetic protein (BMP)-2/7 heterodimer in peri-implant bone defects compared to BMP2 and BMP7 homodimer. MATERIAL AND METHODS: Peri-implant bone defects (8 mm in diameter, 4 mm in depth) were created surrounding SLA-treated titanium implants (3.1 mm in diameter, 10 mm in length) in minipig's calvaria. We administrated collagen sponges with adsorbed low-dose (30 ng/mm(3) ) BMP2/7 to treat the defects using BMP2, BMP7 or no BMP as controls.2, 3 and 6 weeks after implantation, we adopted micro-computer tomography to evaluate the micro-architectures of new bone using the following parameters: relative bone volume (BV/TV), trabecular number (Tb.N), trabecular thickness (Tb.Th), trabecular separation (Tb.Sp), connectivity density, and structure mode index (SMI). Bone implant contact (BIC) was also revealed histologically. RESULTS: Consistent with 2 and 3 weeks, after 6 weeks post-operation, BMP2/7 resulted in significantly higher BV/TV (63.033 ± 2.055%) and significantly lower SMI (-4.405 ± 0.500) than BMP2 (BV/TV: 43.133 ± 2.001%; SMI: -0.086 ± 0.041) and BMP7 (BV/TV: 41.467 ± 1.850%; SMI: -0.044 ± 0.016) respectively. Significant differences were also found in Tb.N, Tb.Th and Tb.Sp at all time points. At 2 weeks, BMP2/7 resulted in significantly higher BIC than the controls. CONCLUSIONS: Low-dose BMP2/7 heterodimer facilitated more rapid bone regeneration in better quality in peri-implant bone defects than BMP2 and BMP7 homodimers.

All-trans retinoic acid can antagonize osteoblastogenesis induced by different BMPs irrespective of their dimerization types and dose-efficiencies.

INTRODUCTION: Alcoholism can lead to low mineral density, compromised regenerative bone capacity and delayed osteointegration of dental implants. This may be partially attributed to the inhibitive effect of all-trans retinoic acid (ATRA), a metabolite of alcohol, on osteoblastogenesis. Our previous studies demonstrated that heterodimeric bone morphogenetic protein 2/7 (BMP2/7) was a more potent BMP than homodimeric BMP2 or BMP7, and could antagonize the inhibitive effect of ATRA to rescue osteoblastogenesis. MATERIALS AND METHODS: In this study, we compared the effectiveness of BMP2/7, BMP2 and BMP7 in restoring osteoblastogenesis of murine preosteoblasts upon inhibition with 1 µM ATRA, and we further analyzed the potential mechanisms. We measured the following parameters: cell viability, ALP, OCN, mineralization, the expression of osteogenic differentiation marker genes (Collagen I, ALP and OCN) and the expression of BMP signaling key genes (Dlx5, Runx2, Osterix and Smad1). RESULTS: BMP2/7 treatment alone induced significantly higher osteoblastogenesis compared to BMP2 and BMP7. When cells were treated by ATRA, BMP2/7 was superior only in rescuing cell viability and ALP activity, compared to BMP2 or BMP7. However, BMP2/7 was not superior to BMP2 or BMP7 in restoring OCN expression and extracellular mineralized nodules, or in rescuing expression of two key osteogenic genes, Dlx5 and Runx2. Irrespective of their dimeric types or potency, the selected BMPs could antagonize the inhibitory effect of ATRA on osteoblastogenesis. CONCLUSION: The presence of ATRA, BMP2/7 still induced significantly higher cell viability and early differentiation than the homodimers. However, ATRA significantly attenuated the advantages of BMP2/7 in inducing late and final osteoblastogenic differentiation over the homodimers.

Application of MRI in indirect temporomandibular joint injury without condylar fracture.

OBJECTIVE: To discuss the application of MRI in indirect temporomandibular joint injury without condylar fracture. METHODS: MRI examination on temporomandibular joint was conducted in 28 patients with indirect injury to temporomandibular joint without condylar fracture. The scanning sequence included T(1)WI, PDWI on oblique sagittal section at both open and closed mouth positions, and T(1)WI, T(2)WI on oblique coronal section. The MRI appearance was analyzed by 2 senior radiologists. RESULTS: Among the 56 temporomandibular joints of 28 patients, 35 joints exhibited pathological changes on MRI, in which there were 9 bone injuries, 21 articular disc dislocation, 24 intracapsular hematocele and hydrops. CONCLUSIONS: MRI can clearly reveal bone injury, articular disc dislocation as well as articular capsule abnormality in the indirect injury of temporomandibular joint without condylar fracture. It is highly advocated in clinical use.

Multivariate linear regression analysis to identify general factors for quantitative predictions of implant stability quotient values.

OBJECTIVES: This study identified potential general influencing factors for a mathematical prediction of implant stability quotient (ISQ) values in clinical practice. METHODS: We collected the ISQ values of 557 implants from 2 different brands (SICace and Osstem) placed by 2 surgeons in 336 patients. Surgeon 1 placed 329 SICace implants, and surgeon 2 placed 113 SICace implants and 115 Osstem implants. ISQ measurements were taken at T1 (immediately after implant placement) and T2 (before dental restoration). A multivariate linear regression model was used to analyze the influence of the following 11 candidate factors for stability prediction: sex, age, maxillary/mandibular location, bone type, immediate/delayed implantation, bone grafting, insertion torque, I-stage or II-stage healing pattern, implant diameter, implant length and T1-T2 time interval. RESULTS: The need for bone grafting as a predictor significantly influenced ISQ values in all three groups at T1 (weight coefficients ranging from -4 to -5). In contrast, implant diameter consistently influenced the ISQ values in all three groups at T2 (weight coefficients ranging from 3.4 to 4.2). Other factors, such as sex, age, I/II-stage implantation and bone type, did not significantly influence ISQ values at T2, and implant length did not significantly influence ISQ values at T1 or T2. CONCLUSIONS: These findings provide a rational basis for mathematical models to quantitatively predict the ISQ values of implants in clinical practice.

BMP2/7 heterodimer is a stronger inducer of bone regeneration in peri-implant bone defects model than BMP2 or BMP7 homodimer.

This study aimed to compare the effects of bone morphogenetic protein BMP2/7 heterodimer and BMP homodimers on bone regeneration in bone defects model. Identical peri-implant bone defects model were created using proper controls on the frontal skull in 18 minipigs. Collagen sponges with low-dose (30 ng/mL) BMP2/7 heterodimer, BMP2 or BMP7 homodimer were filled in the defects. New bone formation and the expression of type I collagen (Col1), alkaline phosphatase (ALP) and osteocalcin (OCN) were evaluated after 2, 3, and 6 weeks of implantation. BMP2/7 resulted in significantly higher new bone areas percentage in the defect region than BMP2 and BMP7 (p<0.05). Immunohistochemical staining of Col1, ALP and OCN was stronger in BMP2/7 group than BMP2, BMP7 and control group (p<0.05). These results demonstrate that BMP2/7 heterodimer is a stronger inducer of osteoblastogenesis and could be applied at low dose to reduce the cost and side effects of BMP homodimers.