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PMMA bone cement has been clinically used for decades in vertebroplasty due to its high mechanical strength and satisfactory injectability. However, the interface between bone and PMMA is fragile and more prone to refracture

Activation of coagulation cascades, especially FX and prothrombin, prevents blood loss and reduces mortality from hemorrhagic shock. Inorganic salts are effective but cannot stop bleeding completely in large hemorrhagic events, and rebleeding carries a significant mortality risk. The coagulation mechanism of inorganic salts has been oversimplified in the past two decades, limiting the creation of novel hemostats. Here, on the interface the activation of the coagulation, fibrinolysis, and cell activities were monitored at the protein level. The link between the hydrophilic-hydrophobic interface, hydration layer, microenvironmental structure of the crystal and amorphous salt, protease activity, and adsorption was also uncovered. It reveals that strong water binding and fibrinogen adsorption on kaolin's surface causes rebleeding after hemostasis, resulting in a weak thrombus. The kaolin surface inhibited the FIXa and FVIIIa composite assembly, reducing its positive feedback on the extrinsic pathway. Inspiringly, amorphous bioactive glass (BG) with transient-dynamic ions microenvironment interface are designed to bypass the barrier of the crystal structure hydration shell, hence enhancing the continuous activation of the biomaterial surface on coagulation system. Under comparative exploration, the unique coagulation pattern of BG was obtained: upon contact with the hydrophilic BGs, intrinsic and extrinsic coagulation pathways continuously initiated under the dynamic ionic microenvironment, and prothrombin complexes successfully hydrolyzed to thrombin without platelet membrane involvement, speeding the production of high-strength clots. Further evidence proves that BG more than doubled the survival rate of SD rats than kaolin in the lethal femoral artery, vein, and nerve disconnection hemorrhage model. This study investigates how the surface of inorganic salts assists in coagulation cascades that may help elucidate the clinical application of kaolin-gauze and pave the way to new materials for managing hemorrhage.

Injectable bone biomaterials like bone cement should be designed and fabricated with certain biological criteria, which include: 1) recruitment and polarization of the macrophages from M1 (pro-inflammatory) to M2 (anti-inflammatory) phenotype, 2) enhance vascularization, and 3) activate osteogenic differentiation of bone marrow-derived stem cells to promote bone healing. So far, no injectable biomaterials could spontaneously regulate the entire bone healing process that involves inflammation, angiogenesis, and osteogenesis. Therefore, in this study, we designed bone cement comprised of strontium and copper-incorporated borosilicate glass (Sr/Cu-BSG) in the liquid phase of chitosan to modulate bone healing.

Hybrid surfaces with tunable topography, chemistry, and stiffness have potential to rebuild native extracellular matrix (ECM) and manipulate cell behavior in vitro. However, the fabrication of controllable hybrid surfaces is still challenging. In this study, colloidal self-assembly technology was used to program particles into highly ordered structures with hybrid chemistry and stiffness at biointerfaces. These colloidal self-assembled patterns (cSAPs), including unary, binary, and ternary cSAPs, composed of silicon (Si), polystyrene (PS), and/or poly(N-isopropylacrylamide) (pNIPAM) nanogels (PNGs), were fabricated using either coassembly or layer-by-layer (LBL) methods. The selected binary cSAPs (i.e., PS/PNG and PNG/PS) have a tunable surface topography and wettability between 25 and 37 °C; thus, they can be used as dynamic cell culture substrates. Human adipose-derived mesenchymal stem cells (hASCs), bone marrow-derived mesenchymal stem cells (hBMSCs), and macrophages (THP-1) were investigated on these hybrid cSAPs under a static or dynamic system. The results showed that hybrid cSAPs significantly influenced the focal adhesions, cell morphology, cell migration, and gene expressions of stem cells. In general, stem cells had more vinculin puncta, smaller spreading size, and faster migration speed than the TCPS control. Hybrid cSAPs up-regulated gene expressions of focal adhesion kinase (FAK) and chondrocytes (AGG and SOX9) under static culture, while they also up-regulated osteocytes (COL1 and RUNX2) under dynamic culture. THP-1 macrophages were at M0 state on all cSAPs under static culture. However, cells became sensitive under dynamic culture. For example, some M1 genes (i.e., IL6, CD68, and TNFα) and M2 genes (i.e., IL10 and CD206) were down-regulated, while other M1 genes (i.e., IL1β) and M2 genes (i.e., TGF-β and IL1ra) were up-regulated, depending on the particle combinations. In conclusion, new hybrid cSAPs with thermoresponsive surface properties are versatile materials for stem cells and macrophages manipulation.

Orthopedic device-related infections (ODRIs) are difficult to control due to microbial biofilm formation and associated with high-level resistance to conventional antibiotics. In many cases, the only treatment option for ODRI is explantation. Previous studies have shown that application of cathodic potentials at the metal surface can eradicate biofilms, and Mg and Mg-Ti particles have the same effect as cathodic potentials. This study investigated the effects of Mg and Mg-Ti particles on established biofilms and planktonic cells E. coli. Bacterial cultures with developed biofilms or planktonic cells were treated with Mg or Mg-Ti particles, and the viability were assessed using flow cytometry or visual assessment methods (i.e., observation from SEM images and opacity of the solution). It was found that viability of biofilms treated with 16.67 mg/ml of Mg was 2.8 ± 0.96% at the end of 6-hr killing compared to untreated controls. This extent of killing was more significant compared to 24-hr grown biofilms treated with ofloxacin, an antibiotic known to be effective against these bacteria. Biofilms treated with 50 and 100 μg/ml of ofloxacin had 62 ± 4.6% and 52 ± 19.3% survival, respectively, where ofloxacin at these concentrations is known to kill planktonic counterparts very effectively. Inhibition zone tests revealed that biofilms within 2 mm of Mg or Mg-Ti particle clusters were effectively killed. These results demonstrated the potential of Mg or Mg-Ti particles in killing microbial biofilms and potential for controlling ODRI.

Magnesium (Mg) and galvanically coupled magnesium-titanium (Mg-Ti) particles in vitro have been reported previously to kill cells in a dosage-dependent manner. Mg-Ti particles kill cells more effectively than Mg alone, due to the galvanic effect of Mg and Ti. This study further investigated the in vitro cytotoxicity of Mg and Mg-Ti in terms of particle concentration, cell density, time, and proximity. Cell density has an effect on cell viability only at low particle concentrations (below 250 µg/mL), where cell viability dropped only for lower cell densities (5000-10,000 cells/cm2 ) and not for higher cell densities (20,000-30,000 cells/cm2 ), showing that the particles cannot kill if there are more cells present. Cytotoxicity of Mg and Mg-Ti particles is quick and temporary, where the particles kill cells only during particle corrosion (first 24 h). Depending on the percentage of surviving cells, particle concentrations, and ongoing corrosion activity, the remaining live cells either proliferated and recovered, or just remained viable and quiescent. The particle killing is also proximity-dependent, where cell viability was significantly higher for cells far away from the particles (greater than ∼1 mm) compared to those close to the particles (less than ∼1 mm). Although the increase of pH does affect cell viability negatively, it is not the sole killing factor since cell viability is significantly dependent on particle type and proximity but not pH. Mg and Mg-Ti particles used in this study are large enough to prevent direct cell phagocytosis so that the cell killing effect may be attributed to solely electrochemical reactions. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1428-1439, 2018.

The short-term corrosion and micromechanical behavior of 32 unique head-neck taper design/material/assembly conditions was tested using an incremental cyclic fretting corrosion (ICFC) test method previously developed.Seven materials, design, and simulated surgical parameters were evaluated, each being assigned 2 conditions for testing, using a 2Low seating load and high head offset correlated with increased fretting corrosion (P.05). High head offset also contributed to a lower onset load for fretting current and higher micromotion (P.05). Head subsidence measured over the ICFC test for samples seated at 100 N was significantly higher than samples seated at 4000 N. Micromotion for 12-mm head offsets was statistically higher than samples with a 1.5-mm head offset. A number of interactive effects were observed. For example, samples seated at 4000 N were less sensitive to head offset than samples seated at 100 N in terms of the resulting fretting current.Taper locking position, material combination, taper engagement length, taper roughness, and taper dimensions all had weak or no correlation with fretting current and taper micromotion. This test method and experimental design is a versatile means of assessing potential new taper designs in the future.

Osteosarcoma is a malignant bone cancer that occurs mostly in children and young adults. This study investigated the cytotoxicity of Mg and Mg-Ti microparticles to human osteosarcoma cells. Osteosarcoma cells were killed in a dosage-dependent manner when cells, with a cell seeding density of 30,000 cells/cm2 , were cultured with 0 to 2500 µg/mL of Mg or Mg-Ti in cell culture media for 24-72 h. Mg-Ti killed cells more effectively, where 1250 µg/mL of Mg-Ti killed cells completely by 24 h, while 2500 µg/mL of Mg killed nearly all cells, but not all. Killing due to particle corrosion occurred mostly during the first 24 h, and so the percent cell viability between 24 and 72 h showed not much variability. However, the measurement of live and dead cell numbers, over the timeframe of 24-72 h, showed more insight, such as cell recovery. If particle concentrations were low, the number of live cells increased after 24 h, indicating cell proliferation. If particle concentrations were high, the number of live cells either remained steady or decreased, indicating cell quiescence or continued killing, respectively. Increase in the number of dead cells also indicated killing, while plateau meant discontinued killing. In addition, repeated killing of recovered cells exhibited the same dose-dependent killing profile as the initial experiment, implying little development of cell resistance to treatment. These results, together, show that osteosarcoma cells are susceptible to killing by way of exposure to corroding particles, showing highly effective killing using the galvanic couple of Mg-Ti. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 107B: 178-189, 2019.

Magnesium (Mg) and galvanically coupled magnesium-titanium (Mg-Ti) particles in vitro have been reported previously to kill cells in a dosage-dependent manner. Mg-Ti particles kill cells more effectively than Mg alone, due to the galvanic effect of Mg and Ti. This study further investigated the in vitro cytotoxicity of Mg and Mg-Ti in terms of particle concentration, cell density, time, and proximity. Cell density has an effect on cell viability only at low particle concentrations (below 250 µg/mL), where cell viability dropped only for lower cell densities (5000-10,000 cells/cm

Recent work has shown that reduction reactions at metallic biomaterial surfaces can induce significant killing of cells in proximity to the surface. To exploit this phenomenon for therapeutic purposes, for example, for cancer tumor killing or antibacterial effects (amongst other applications), magnesium metal particles, galvanically coupled to titanium by sputtering, have been evaluated for their cell-killing capability (i.e. cytotoxicity). Magnesium (Mg) particles large enough to prevent particle phagocytosis were investigated, so that only electrochemical reactions, and not particle toxicity per se, caused cytotoxic effects. Titanium (Ti) coated magnesium particles, as well as magnesium-only particles were introduced into MC3T3-E1 mouse pre-osteoblast cell cultures over a range of particle concentrations, and cells were observed to die in a dosage-dependent manner. Ti-coated magnesium particles killed more cells at lower particle concentration than magnesium alone (P0.05), although the pH measured for magnesium and magnesium-titanium had no significant difference at similar particle concentrations. Complete cell killing occurred at 750μg/ml and 1500μg/ml for Mg-Ti and Mg, respectively. Thus, this work demonstrates that galvanically coupled Mg-Ti particles have a significant cell killing capability greater than Mg alone. In addition, when the pH associated with complete killing with particles was created using NaOH only (no particles), then the percentage of cells killed was significantly less (P0.05). Together, these findings show that pH is not the sole factor associated with cell killing and that the electrochemical reactions, including the reduction reactions, play an important role. Reduction reactions on galvanically coupled Mg-Ti and Mg particles may generate reactive oxygen intermediates that are able to kill cells in close proximity to the particles and this approach may lead to potential therapies for infection and cancer.This paper demonstrates that during active corrosion of both Mg and Mg-Ti particles cells cultured with the particles are killed in a dose-dependent particle concentration fashion. Additionally, galvanically-coupled magnesium-titanium microparticles kill cells more effectively than magnesium particles alone. The killing effect was shown to not be due to pH shifts since no differences were seen for different particle types and pH adjusted medium without particles did not exhibit the same level of killing. The significance of this work is the recognition of this killing effect with Mg particles and the potential therapeutic applications in infection control and cancer treatment that this process may provide.