An elevated bone microenvironmental reactive oxygen species (ROS) level is a hallmark of osteoporosis that often leads to the dysfunction of bone-related mesenchymal stem cells (MSCs), which would induce MSC senescence and severely undermine their osteoblastic potential. Herein, we report the in situ construction of bone microenvironment-responsive biofunctional metal–organic framework (bio-MOF) coating on the titanium surface through the coordination between p-xylylenebisphosphonate (PXBP) and Ce/Sr ions by a hydrothermal method. Taking advantage of the anchored Ce and Sr ions, the AHT-Ce/SrMOF implants demonstrate on-demand superoxide dismutase and catalase-like catalytic activities to decompose ROS in MSCs and restore their mitochondrial functions. In vitro analysis showed that the AHT-Ce/SrMOF implants substantially activated the AMP-activated protein kinase (AMPK) signaling pathway in MSCs and reduced the ROS levels. Meanwhile, MSCs grown on AHT-Ce/SrMOF implants displayed significantly higher expressions of the mitochondrial fission marker (DRP1), mitochondrial fusion marker (MFN2 and OPA1), and mitophagy marker (PINK1 and LC3) than those of the AHT-CeMOF and AHT-SrMOF groups, which indicated that the bio-MOF could amend mitochondrial function in MSCs to reverse senescence. In vivo evaluations showed that the bio-MOF-coated Ti implants could restore MSC function in the implant site and promote new bone formation, leading to improved osteointegration in osteoporotic rat. This study may improve implant-mediated fracture healing in the clinics.

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Integrated Ocean Drilling Program Expedition 311 is based on extensive site survey data and historic research at the northern Cascadia margin since 1985. This research includes various regional geophysical surveys using a broad spectrum of seismic techniques, coring and logging by the Ocean Drilling Program Leg 146, heat flow measurements, shallow piston coring, and bottom video observations across a cold-vent field, as well as novel controlled-source electromagnetic and seafloor compliance surveying techniques. The wealth of data available allowed construction of structural cross-sections of the margin, development of models for the formation of gas hydrate in an accretionary prism, and estimation of gas hydrate and free gas concentrations. Expedition 311 established for the first time a transect of drill sites across the northern Cascadia margin to study the evolution of gas hydrate formation over the entire gas hydrate stability field of the accretionary complex. This paper reviews the tectonic framework at the northern Cascadia margin and summarizes the scientific studies that led to the drilling objectives of Expedition 311 Cascadia gas hydrate.

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The bottom-simulating reflector (BSR) of gas hydrate is well imaged from two perpendicular seismic grids in the region of a large carbonate mound, informally called Cucumber Ridge off Vancouver Island. We use a new method to calculate 3-D heat flow map from the BSR depths, in which we incorporate 3-D topographic corrections after calibrated by the drilling results from nearby (Integrated) Ocean Drilling Program Site 889 and Site U1327. We then estimate the associated fluid flow by relating it to the topographically corrected heat flux anomalies. In the midslope region, a heat flux anomaly of 1 mW/m 2 can be associated with an approximate focused fluid flow rate of 0.09 mm/yr. Around Cucumber Ridge, high rates of focused fluid flow were observed at steep slopes with values more than double the average regional diffusive fluid discharge rate of 0.56 mm/yr. As well, in some areas of relatively flat seafloor, the focused fluid flow rates still exceeded 0.5 mm/yr. On the seismic lines the regions of focused fluid flow were commonly associated with seismic blanking zones above the BSR and sometimes with strong reflectors below the BSR, indicating that the faults/fractures provide high-permeability pathways for fluids to carry methane from BSR depths to the seafloor. These high fluid flow regions cover mostly the western portion of our area with gas hydrate concentration estimations of~6% based on empirical correlations from Hydrate Ridge in south off Oregon, significantly higher than previously recognized values of 2.5% in the eastern portion determined from Site U1327.