A defect-in-continuity in the canine femur: and in-vivo experimental model for the study of bone graft incorporation.

The in-vivo study of bone graft incorporation has traditionally used a segmental diaphyseal bone defect. This model reliably produces a nonunion, but is complicated by graft instability and altered limb loading stresses. The authors discuss the advantages of a defect-in-continuity canine femur model which produces a more consistent union with fewer mechanical complications despite the absence of fixation. This proposed model permits analysis of radiographic, histologic and biomechanical data which are more applicable to the usual clinical setting in which bone graft is required

Age-related changes to macrophages are detrimental to fracture healing in mice.

The elderly population suffers from higher rates of complications during fracture healing that result in increased morbidity and mortality. Inflammatory dysregulation is associated with increased age and is a contributing factor to the myriad of age-related diseases. Therefore, we investigated age-related changes to an important cellular regulator of inflammation, the macrophage, and the impact on fracture healing outcomes. We demonstrated that old mice (24 months) have delayed fracture healing with significantly less bone and more cartilage compared to young mice (3 months). The quantity of infiltrating macrophages into the fracture callus was similar in old and young mice. However, RNA-seq analysis demonstrated distinct differences in the transcriptomes of macrophages derived from the fracture callus of old and young mice, with an up-regulation of M1/pro-inflammatory genes in macrophages from old mice as well as dysregulation of other immune-related genes. Preventing infiltration of the fracture site by macrophages in old mice improved healing outcomes, with significantly more bone in the calluses of treated mice compared to age-matched controls. After preventing infiltration by macrophages, the macrophages remaining within the fracture callus were collected and examined via RNA-seq analysis, and their transcriptome resembled macrophages from young calluses. Taken together, infiltrating macrophages from old mice demonstrate detrimental age-related changes, and depleting infiltrating macrophages can improve fracture healing in old mice

Site Specific Effects of Zoledronic Acid during Tibial and Mandibular Fracture Repair

Numerous factors can affect skeletal regeneration, including the extent of bone injury, mechanical loading, inflammation and exogenous molecules. Bisphosphonates are anticatabolic agents that have been widely used to treat a variety of metabolic bone diseases. Zoledronate (ZA), a nitrogen-containing bisphosphonate (N-BP), is the most potent bisphosphonate among the clinically approved bisphosphonates. Cases of bisphosphonate-induced osteonecrosis of the jaw have been reported in patients receiving long term N-BP treatment. Yet, osteonecrosis does not occur in long bones. The aim of this study was to compare the effects of zoledronate on long bone and cranial bone regeneration using a previously established model of non-stabilized tibial fractures and a new model of mandibular fracture repair. Contrary to tibial fractures, which heal mainly through endochondral ossification, mandibular fractures healed via endochondral and intramembranous ossification with a lesser degree of endochondral ossification compared to tibial fractures. In the tibia, ZA reduced callus and cartilage formation during the early stages of repair. In parallel, we found a delay in cartilage hypertrophy and a decrease in angiogenesis during the soft callus phase of repair. During later stages of repair, ZA delayed callus, cartilage and bone remodeling. In the mandible, ZA delayed callus, cartilage and bone remodeling in correlation with a decrease in osteoclast number during the soft and hard callus phases of repair. These results reveal a more profound impact of ZA on cartilage and bone remodeling in the mandible compared to the tibia. This may predispose mandible bone to adverse effects of ZA in disease conditions. These results also imply that therapeutic effects of ZA may need to be optimized using time and dose-specific treatments in cranial versus long bones

Stimulating Fracture Healing in Ischemic Environments: Does Oxygen Direct Stem Cell Fate during Fracture Healing?

Bone fractures represent an enormous societal and economic burden as one of the most prevalent causes of disability worldwide. Each year, nearly 15 million people are affected by fractures in the United States alone. Data indicate that the blood supply is critical for fracture healing; as data indicate that concomitant bone and vascular injury are major risk factors for non-union. However, the various role(s) that the vasculature plays remains speculative. Fracture stabilization dictates stem cell fate choices during repair. In stabilized fractures stem cells differentiate directly into osteoblasts and heal the injury by intramembranous ossification. In contrast, in non-stable fractures stem cells differentiate into chondrocytes and the bone heals through endochondral ossification, where a cartilage template transforms into bone as the chondrocytes transform into osteoblasts. One suggested role of the vasculature has been to participate in the stem cell fate decisions due to delivery of oxygen. In stable fractures, the blood vessels are thought to remain intact and promote osteogenesis, while in non-stable fractures, continual disruption of the vasculature creates hypoxia that favors formation of cartilage, which is avascular. However, recent data suggests that non-stable fractures are more vascularized than stable fractures, that oxygen does not appear associated with differentiation of stem cells into chondrocytes and osteoblasts, that cartilage is not hypoxic, and that oxygen, not sustained hypoxia, is required for angiogenesis. These unexpected results, which contrast other published studies, are indicative of the need to better understand the complex, spatio-temporal regulation of vascularization and oxygenation in fracture healing. This work has also revealed that oxygen, along with the promotion of angiogenesis, may be novel adjuvants that can stimulate healing in select patient populations

H2TI2O5 H2O nanowire as an intermediary phase of TIO2 anode for dye sensitized solar cell

In the last years, nanostructures have been widely used in energy harvesting devices, such as dye-sensitized solar cells (DSSCs), nanogenerators, and fuel cells, due to their high efficiency and light weight [1-4]. Therefore, nanostructure based DSSCs are likely to be lowcost, high efficiency, and simple in preparation, which is promising as a renewable energy resource for sustainable development of the future. Besides DSSC applications, nanostructures have been used in energy storage fields, such as lithium ion batteries (LIBs), due to their highenergy density and long cycle life [5, 6]. A great challenge is to combine solar energy conversion and storage into one device. Using (Ti) sheet as substrate for TiO2 nanorods grown as intermediary, the integrated power pack can be flexible and directly harvest and store energy by the electron conduction of the substrate. Thereby, using double-sided TiO2 nanorods not only provide larger electrode area for DSSCs and LIBs but also can improve the electron transport properties of DSSCs and avoid irregular expansion when the insertion/removal of lithium along a specific orientation in anode material [7]. Compared with other integrated solar power supplies, double-sided TiO2 nanorods with large area can be prepared by a simple, cost-effective, and controllable electrochemical process. Moreover, such H2Ti2O5 ·H2O material are good precursor of titania and metal titanate, and have well-controlled shapes such as nanotubes and nanosheets [8,9]. H2Ti2O5 are usually synthesized by solvothermal treatment of titania or by ion-exchange of alkaline metal titanates. Until now, the synthesis of H2Ti2O5 have been less frequently reported than those of other hydrogen titanates, such as H2Ti3O7 and H2T4O9, and it is formed as sheet-like particles[10,11]. The structure of H2Ti2O5 has not been well established, it is reported to be a layered compound which is an isostructure to K2Ti2O5 [12]. In this paper, we report the successful hydrothermal synthesis of H2Ti2O5 ·H2O nanowire as an intermediary phase of TiO2 anode for dye sensitized solar cell. The structure of products was determined by powder X-ray diffraction (XRD) PW 3040/60 X’Pert PRO using Cu-Kα radiation with (λ=1.5418Å), in the range 2θ = 10-80°, at room temperature. A Scanning Electron Microscope InspectS (SEM) was used to observe the morphology of synthesized nanocrystals. . The diffuse reflectance spectra (DSR) was obtained using a Lambda 950 UV-Vis-NIR Spectrophotometer with 150 mm integrating sphere in the wavelength range of 300–800 nm