Treatment of large bone defects (LBDs) is technically demanding. Tissue engineering is an option. A bioactive graft may be produced by combining tissue scaffolds and healing promotive factors in order to accelerate bone repair. We investigated the role of Simvastatin (Sim)-embedded porous Gelapin (Gel) scaffold on experimental bone healing. At first, the effectiveness of different concentrations of Gel and Sim powders was investigated in an experimentally induced femoral hole model in rabbits (n = 6) for 30 days. Then bone bioactive grafts were produced by combination of the effective concentrations of Gel, Sim, and Genipin. The bioimplants were subcutaneously tested in a rabbit model (n = 9) to determine their biocompatibility and biodegradability for 10-30 days. Finally, a large radial bone defect model was produced in rabbits (n = 20), and the bioimplants were inserted in the defects. The untreated and autograft-treated bone defects were served as controls. The animals were euthanized after 30 and 60 days of bone injury. The bone samples were evaluated by radiography, three-dimensional CT scan, bone densitometry, histopathology, and nano-indentation. At a concentration of 5 mg/hole, Sim closed the femoral bone holes after 30 days, while in the defect, autograft, and Gel groups, the holes were open. Both the Gel and Gel-Sim scaffolds were biocompatible and biodegradable. Subcutaneously, the Gel-Sim scaffold was replaced with the newly regenerated ectopic bone after 30 days. After implantation of the Gel-Sim scaffold in the radial bone defects, the scaffold was completely replaced with new woven bone after 30 days which was then matured and remodeled into a cortical bone after 60 days. Sixty days after bone injury, the Gel-Sim-treated defects had significantly higher bone volume, matrix mineralization, elastic modulus, and contact hardness when compared to the controls. The Gel-Sim scaffold may be a suitable option in managing LBDs.

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Several strategies have been used to promote bone repair, with many failing due to the lack of osteoinduction. This report describes an approach for promoting bone healing that attempts to overcome prior shortcomings. First, the role was compared of different concentrations of gelatine (Gel), nanostructured-hydroxyapatite (nHA), simvastatin (Sim) and nHA-Sim particles on healing of small femoral bone defects in rabbits. The effective concentration of each was studied, and then a three-dimensional porous scaffold was designed using Gel, nHA and Sim, which was then cross-linked with genipin. Morphology, degradation profile and Sim delivery properties of the scaffolds were evaluated in vitro. Then, the scaffolds were subcutaneously tested in vivo to determine their biocompatibility, biodegradability and osteogenic properties. Finally, the scaffolds were implanted in a large radial bone defect model in rabbits and their effect on bone regeneration was investigated. The Gel, nHA and Sim with concentrations of 1, 1 and 5 mg/femoral hole were effective during bone healing respectively, and the Sim showed the most osteoinduction and osteoconduction when compared to controls. The Gel-Sim and Gel-nHA-Sim scaffolds continuously and homogenously released Sim into the simulated body fluid in vitro. Subcutaneously, the scaffolds were biocompatible, biodegradable and able to produce ectopic bone after 30 days. Thirty and 60 days after implantation of the scaffolds in radial bone defects, they were completely degraded and replaced with the new bone that had significantly superior morphology, mineral density, bioelectrical, biophysical and micromechanical properties compared with controls. Such bioactive grafts may be a suitable option for bone reconstruction, healing and repair.

frequencies of genotypes and alleles of the two T-786C and G894T polymorphisms when patients with ED and normal controls were compared.• In a multiple logistic regression analysis, the odds ratio (OR) of increased ED was strongly associated with the -786C allele [adjusted OR = 3.12, 95% confidence interval (CI) = 2.28-4.25; P = 0.001] and the 894T allele (adjusted OR = 3.87, 95% CI = 2.53-4.87; P = 0.001).• The data showed a higher prevalence of the T-786C CC genotype (adjusted OR = 2.72, 95% CI = 1.88-3.65; P = 0.006), and the G894T GT (adjusted OR = 1.72, 95% CI 1.24-2.83; P = 0.037) and G894T TT genotypes (adjusted OR = 3.42, 95% CI 2.42-4.26; P = 0.001) in patients with ED than in the controls. CONCLUSIONS• The findings of the present study suggest that the eNOS T-786C and G894T polymorphisms are strong predictors of the predisposition to ED in addition to traditional risk factors, signifying a genetic influence for this multifactorial disease.• Further studies in different ethnic populations are needed to better elucidate the role of eNOS gene polymorphism in the pathogenesis of ED.

The current study aimed to develop a potential wound dressing using vitamin B12-loaded polycaprolacton/gelatin nanofibrous scaffold. In order to produce wound dressings, 1000 mcg of vitamin B12 was added to polycaprolacton/gelatin solution and the nanofibrous scaffolds were fabricated through electrospinning method. The obtained scaffolds were studied regarding their hydrophobicity, microstructure, amount of water absorption, water vapor permeability, tensile strength, release test, and cellular proliferation assay. In vitro studies revealed that the incorporation of vitamin b12 into polycaprolacton/gelatin scaffolds could significantly augment L929 cells proliferation at 1 and 3 days post-seeding. However, there was not statistically significant difference between Vitamin B12-containing and polymer-only scaffolds in tensile strength study, surface wettability measurement, water vapor transmission test, the capacity for water absorption, and nanofiber's diameter. Both vitamin containing and free dressings were applied on the full-thickness excisional wound in rat model to compare their healing potential. Our results showed that after 14 days, vitamin B12 containing dressing could significantly enhance wound closure compared to vitamin B12 free scaffolds (92.27 ± 6.84% vs. 64.62 ± 2.96%). Furthermore, histopathological examinations showed significantly greater epithelial thickness in polycaprolacton/gelatin/vitamin B12 group compared to other experimental groups. This preliminary study suggest potential applicability of the proposed dressing to treat skin wounds in clinic.