Orthopedic implants containing biodegradable magnesium have been used for fracture repair with considerable efficacy; however, the underlying mechanisms by which these implants improve fracture healing remain elusive. Here we show the formation of abundant new bone at peripheral cortical sites after intramedullary implantation of a pin containing ultrapure magnesium into the intact distal femur in rats. This response was accompanied by substantial increases of neuronal calcitonin gene-related polypeptide-α (CGRP) in both the peripheral cortex of the femur and the ipsilateral dorsal root ganglia (DRG). Surgical removal of the periosteum, capsaicin denervation of sensory nerves or knockdown in vivo of the CGRP-receptor-encoding genes Calcrl or Ramp1 substantially reversed the magnesium-induced osteogenesis that we observed in this model. Overexpression of these genes, however, enhanced magnesium-induced osteogenesis. We further found that an elevation of extracellular magnesium induces magnesium transporter 1 (MAGT1)-dependent and transient receptor potential cation channel, subfamily M, member 7 (TRPM7)-dependent magnesium entry, as well as an increase in intracellular adenosine triphosphate (ATP) and the accumulation of terminal synaptic vesicles in isolated rat DRG neurons. In isolated rat periosteum-derived stem cells, CGRP induces CALCRL-and RAMP1-dependent activation of cAMP-responsive element binding protein 1 (CREB1) and SP7 (also known as osterix), and thus enhances osteogenic differentiation of these stem cells. Furthermore, we have developed an innovative, magnesium-containing intramedullary nail that facilitates femur fracture repair in rats with ovariectomy-induced osteoporosis. Taken together, these findings reveal a previously undefined role of magnesium in promoting CGRP-mediated osteogenic differentiation, which suggests the therapeutic potential of this ion in orthopedics.
Relying on the theory of representative bureaucracy-specifically, the notion of symbolic representation-this article examines whether varying the number of female public officials overseeing a local recycling program influences citizens' (especially women's) willingness to cooperate with the government by recycling, thus coproducing important policy outcomes. Using a survey experiment in which the first names of public officials are manipulated, the authors find a clear pattern of increasing willingness on the part of women to coproduce when female names are more represented in the agency responsible for recycling, particularly with respect to the more difficult task of composting food waste. Overall, men in the experiment were less willing to coproduce across all measures and less responsive to the gender balance of names. These findings have important implications for the theory of representative bureaucracy and for efforts to promote the coproduction of public services.
Biodegradable metals (BMs) are metals and alloys expected to corrode gradually in vivo, with an appropriate host response elicited by released corrosion products, then dissolve completely upon fulfilling the mission to assist with tissue healing with no implant residues. In the present review article, three classes of BMs have been systematically reviewed, including Mg-based, Fe-based and Zn-based BMs. Among the three BM systems, Mg-based BMs, which now have several systems reported the successful of clinical trial results, are considered the vanguards and main force. Fe-based BMs, with pure iron and Fe-Mn based alloys as the most promising, are still on the animal test stage. Zn-based BMs, supposed to have the degradation rate between the fast Mg-based BMs and the slow Fe-based BMs, are a rising star with only several reports and need much further research. The future research and development direction for the BMs are proposed, based on the clinical requirements on controllable degradation rate, prolonged mechanical stability and excellent biocompatibility, by optimization of alloy composition design, regulation on microstructure and mechanical properties, and following surface modification.
Hydroxyapatite (HA) is an attractive bioceramic for hard tissue repair and regeneration due to its physicochemical similarities to natural apatite. However, its low fracture toughness, poor tensile strength and weak wear resistance become major obstacles for potential clinical applications. One promising method to tackle with these problems is exploiting graphene and its derivatives (graphene oxide and reduced graphene oxide) as nanoscale reinforcement fillers to fabricate graphene-based hydroxyapatite composites in the form of powders, coatings and scaffolds. The last few years witnessed increasing numbers of studies on the preparation, mechanical and biological evaluations of these novel materials. Herein, various preparation techniques, mechanical behaviors and toughen mechanism, the in vitro/in vivo biocompatible analysis, antibacterial properties of the graphene-based HA composites are presented in this review.
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