Tooth infections or injuries involving dental pulp are treated routinely by root canal therapy. Endodontically treated teeth are devitalized, susceptible to re-infections, fractures, and subsequent tooth loss. Here, we report regeneration of dental-pulp-like tissue by cell homing and without cell transplantation. Upon in vivo implantation of endodontically treated real-size, native human teeth in mouse dorsum for the tested 3 weeks, delivery of basic fibroblast growth factor and/or vascular endothelial growth factor (bFGF and/or VEGF) yielded re-cellularized and revascularized connective tissue that integrated to native dentinal wall in root canals. Further, combined delivery of bFGF, VEGF, or platelet-derived growth factor (PDGF) with a basal set of nerve growth factor (NGF) and bone morphogenetic protein-7 (BMP7) generated cellularized and vascularized tissues positive of VEGF antibody staining and apparent neo-dentin formation over the surface of native dentinal wall in some, but not all, endodontically treated teeth. Newly formed dental pulp tissue appeared dense with disconnected cells surrounded by extracellular matrix. Erythrocyte-filled blood vessels were present with endothelial-like cell lining. Reconstructed, multiple microscopic images showed complete fill of dental-pulp-like tissue in the entire root canal from root apex to pulp chamber with tissue integration to dentinal wall upon delivery of bFGF, VEGF, or PDGF with a basal set of NGF and BMP7. Quantitative ELISA showed that combinatory delivery of bFGF, VEGF, or PDGF with basal NGF and BMP7 elaborated von Willerbrand factor, dentin sialoprotein, and NGF. These findings represent the first demonstration of regenerated dental-pulp-like tissue in endodontically treated root canals of real-size, native human teeth. The present chemotaxis-based approach has potent cell homing effects for re-cellularization and revascularization in endodontically treated root canals in vivo, although in an ectopic model. Regeneration of dental pulp by cell homing, rather than cell delivery, may accelerate clinical translation.
In this work, the parameters influencing the degradation of a Na-NiCl 2 (ZEBRA) battery were investigated.Planar Na-NiCl 2 cells using the b 00 -alumina solid electrolyte (BASE) were tested with different C-rates, Ni/NaCl ratios, and capacity windows, in order to identify the key parameters for the degradation of the Na-NiCl 2 battery. The morphology of NaCl and Ni particles was extensively investigated after 60 cycles under various test conditions using a scanning electron microscope. A strong correlation between the particle size (NaCl and Ni) and battery degradation was observed in this work. Even though the growth of both Ni and NaCl can influence the cell degradation, our results indicate that the growth of NaCl is a dominant factor in cell degradation. The use of excess Ni seems to play a role in tolerating the negative effects of particle growth on degradation since the available active surface area of Ni particles can still be sufficient even after particle growth. For NaCl, a large cycling window was the most significant factor, of which effects were amplified with decrease in the Ni/NaCl ratio.
development efforts are still required for reducing the cost and improving the cycle life needed before further penetration of ZEBRA batteries into the stationary energy-storage market.The important effort would be adopting a low-cost cathode chemistry that would replace the Ni cathode with low-cost cathode materials. Among various cathode chemistries that have been considered, [12][13][14][15] the Na-FeCl 2 redox couple could be a promising candidate for a lowcost ZEBRA battery. The overall reaction of Na-FeCl 2 redox couple and battery schematics are described in Figure 1 . [ 16,17 ] The theoretical specifi c capacity and energy density of the Na-FeCl 2 redox reaction are 310 mAh g −1 and 729 Wh kg −1 (without considering melts), which are quite comparable to the values from the Na-NiCl 2 redox couple. Na-FeCl 2 battery technologies have potential advantages over the current state-of-the-art Na-NiCl 2 ZEBRA battery technologies: (1) lower cathode material cost, where the price of Fe (LME price $0.48 kg −1 ) is much lower than Ni (LME price $14.5 kg −1 ) [ 18 ] and (2) more economical material choices (stainless steels could be used for cell components including cathode current collectors and cell cases). Based on the cost model of Na-NiCl 2 ZEBRA battery reported before, [ 19 ] it can easily be estimated that replacing Ni with Fe in Na-NiCl 2 battery could result up to 61% reduction in cell materials cost ($38 kWh −1 for Na-FeCl 2 ) shown in Figures S1 and S2 (Supporting Information). The real cost reduction from replacing Ni powder with Fe powders may not be as signifi cant as the LME price (additional costs for processes to obtain certain purity and particle size of metal powders); however, the advantages of utilizing earth abundance and low-cost Fe cathode in ZEBRA batteries are not diffi cult to foresee. Another effort is to operate a ZEBRA battery at an intermediate temperature (<200 °C), which could substantially lower capital, manufacturing, and maintenance costs by implementing a cost-effective, high-throughput manufacturing process such as compressive polymer seals rather than high-temperature batch processes such as glass sealing, thermal compression bonding, etc. Our recent studies on intermediate-temperature (IT) Na-NiCl 2 batteries reported that the lower operation temperature signifi cantly improves the cycle life by suppressing degradation mechanisms such as particle growth in the cathode materials of ZEBRA batteries. [ 20 ] Therefore, developing IT Na-FeCl 2 ZEBRA batteries is one of the most attractive approaches toward commercializing ZEBRA Sodium-metal chloride batteries, ZEBRA, are considered one of the most important electrochemical devices for stationary energy storage applications because of its advantages of good cycle life, safety, and reliability. However, sodium-nickel chloride (Na-NiCl 2 ) batteries, the most promising redox chemistry in ZEBRA batteries, still face great challenges for the practical application due to its inevitable feature of using Ni cathode (high materials cost). ...
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