A Dose‐Dependent Spatiotemporal Response of Angiogenesis Elicited by Zn Biodegradation during the Initial Stage of Bone Regeneration
Junlong Tan,
Shuang Li,
Chaoyang Sun
et al.
Abstract:The indispensable role of zinc (Zn) in bone metabolism endows biodegradable Zn‐based materials with the bioactivity to facilitate bone regeneration in bone trauma. However, the impact of Zn biodegradation on the progress of bone repair remains to be unfolded, especially the angiogenesis, which plays a vital role in the subsequent bone regeneration. It is found that a consistent dose‐dependent spatiotemporal response of angiogenesis is induced by Zn biodegradation both in vivo and in vitro. In a critical bone d… Show more
“…As an essential trace element, Zn is involved in many metabolic reactions 25 . In particular, Zn has a regulatory effect on the bone immune system 26,27 inhibit polarization towards pro-inflammatory phenotype macrophage (M1) 28 . Meanwhile, Li demonstrates bone immunomodulatory prowess by enhancing anti-inflammatory factors like Arg1, Il-4, and Il-10.…”
Reconciling the dilemma between rapid degradation and overdose toxicity is challenging in biodegradable materials when shifting from bulk to porous materials. Here, we achieve significant bone ingrowth into Zn-based porous scaffolds with 90% porosity via osteoinmunomodulation. At microscale, an alloy incorporating 0.8 wt% Li is employed to create a eutectoid lamellar structure featuring the LiZn4 and Zn phases. This microstructure optimally balances high strength with immunomodulation effects. At mesoscale, surface pattern with nanoscale roughness facilitates filopodia formation and macrophage spreading. At macroscale, the isotropic minimal surface G unit exhibits a proper degradation rate with more uniform feature compared to the anisotropic BCC unit. In vivo, the G scaffold demonstrates a heightened efficiency in promoting macrophage polarization toward an anti-inflammatory phenotype, subsequently leading to significantly elevated osteogenic markers, increased collagen deposition, and enhanced new bone formation. In vitro, transcriptomic analysis reveals the activation of JAK/STAT pathways in macrophages via up regulating the expression of Il-4, Il-10, subsequently promoting osteogenesis.
“…As an essential trace element, Zn is involved in many metabolic reactions 25 . In particular, Zn has a regulatory effect on the bone immune system 26,27 inhibit polarization towards pro-inflammatory phenotype macrophage (M1) 28 . Meanwhile, Li demonstrates bone immunomodulatory prowess by enhancing anti-inflammatory factors like Arg1, Il-4, and Il-10.…”
Reconciling the dilemma between rapid degradation and overdose toxicity is challenging in biodegradable materials when shifting from bulk to porous materials. Here, we achieve significant bone ingrowth into Zn-based porous scaffolds with 90% porosity via osteoinmunomodulation. At microscale, an alloy incorporating 0.8 wt% Li is employed to create a eutectoid lamellar structure featuring the LiZn4 and Zn phases. This microstructure optimally balances high strength with immunomodulation effects. At mesoscale, surface pattern with nanoscale roughness facilitates filopodia formation and macrophage spreading. At macroscale, the isotropic minimal surface G unit exhibits a proper degradation rate with more uniform feature compared to the anisotropic BCC unit. In vivo, the G scaffold demonstrates a heightened efficiency in promoting macrophage polarization toward an anti-inflammatory phenotype, subsequently leading to significantly elevated osteogenic markers, increased collagen deposition, and enhanced new bone formation. In vitro, transcriptomic analysis reveals the activation of JAK/STAT pathways in macrophages via up regulating the expression of Il-4, Il-10, subsequently promoting osteogenesis.
“…Guo et al demonstrated that a pure Zn membrane (30 μm thick) lost less than 30% in thickness and preserved its barrier function after 10 weeks of degradation in a rat calvarial critical-sized bone defect model . Tan et al reported that a compact corrosion product layer was left after complete degradation of the pure Zn foil, which could act as a secondary phase to the barrier functionality of the membrane and provide a barrier effect for a longer period. , Moreover, Si et al fabricated Ca–P-coated Mg-2.0Zn-1.0Gd (wt %) alloys with a degradation rate of 260 μm/yr, and the in vivo results indicated that the alloy can fulfill its task without rupture for 3 months . In this study, the Mg/Cu-MOF-coated samples presented a suitable degradation rate of 65.0–146.1 μm/yr.…”
Recently, zinc (Zn) and its alloys have demonstrated great potential as guided bone regeneration (GBR) membranes to treat the problems of insufficient alveolar bone volume and long-term osseointegration instability during dental implantology. However, bone regeneration is a complex process consisting of osteogenesis, angiogenesis, and antibacterial function. For now, the in vivo osteogenic performance and antibacterial activity of pure Zn are inadequate, and thus fabricating a platform to endow Zn membranes with multifunctions may be essential to address these issues. In this study, various bimetallic magnesium/copper metal−organic framework (Mg/Cu-MOF) coatings were fabricated and immobilized on pure Zn. The results indicated that the degradation rate and water stability of Mg/Cu-MOF coatings could be regulated by controlling the feeding ratio of Cu 2+ . As the coating and Zn substrate degraded, an alkaline microenvironment enriched with Zn 2+ , Mg 2+ , and Cu 2+ was generated. It significantly improved calcium phosphate deposition, differentiation of osteoblasts, and vascularization of endothelial cells in the extracts. Among them, Mg/Cu1 showed the best comprehensive performance. The superior antibacterial activity of Mg/Cu1 was demonstrated in vitro and in vivo, which indicated significantly enhanced bacteriostatic activity against Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli as compared to that of the bare sample. Bimetallic Mg/Cu-MOF coating could properly coordinate the multifunction on a Zn membrane and could be a promising platform for promoting its bone regeneration, which could pave the way for Zn-based materials to be used as barrier membranes in oral clinical trials.
“…2a, the composite hydrogels of Zn 2+ @TA and Fe 2+ -Zn 2+ @TA gave relatively greater OD values than Fe 2+ @TA and pure H, probably because Zn 2+ could enhance cell proliferation. 30,31 In particular, upon NIR irradiation (10 min, 808 nm, 1 W cm −2 ), H-Fe 2+ -Zn 2+ -NIR and H-Fe 2+ -NIR achieved a higher OD than those without NIR irradiation, showcasing mild photothermal stimulation on cell proliferation. 11 Moreover, the hydrogel dressing would directly contact damaged tissues, and the blood compatibility was characterized by an in vitro hemolysis experiment.…”
Section: In Vitro and In Vivo Biocompatibility Of The Pga Composite H...mentioning
Regulating wound microenvironment to promote proliferation, vascularization, and wound healing are challenging for hemostats and wound dressings. Herein, the polypeptide composite hydrogels have been simply fabricated by mixing less amount...
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