Implants made of magnesium(Mg)are increasingly employed in patients to achieve osteosynthesis while degrading in situ.Since Mg implants and Mg^(2+)have been suggested to possess anti-inflammatory properties,the clinic...Implants made of magnesium(Mg)are increasingly employed in patients to achieve osteosynthesis while degrading in situ.Since Mg implants and Mg^(2+)have been suggested to possess anti-inflammatory properties,the clinically observed soft tissue inflammation around Mg implants is enigmatic.Here,using a rat soft tissue model and a 1-28 d observation period,we determined the temporo-spatial cell distribution and behavior in relation to sequential changes of pure Mg implant surface properties and Mg^(2+)release.Compared to nondegradable titanium(Ti)implants,Mg degradation exacerbated initial inflammation.Release of Mg degradation products at the tissue-implant interface,culminating at 3 d,actively initiated chemotaxis and upregulated mRNA and protein immunomodulatory markers,particularly inducible nitric oxide synthase and toll-like receptor-4 up to 6 d,yet without a cytotoxic effect.Increased vascularization was demonstrated morphologically,preceded by high expression of vascular endothelial growth factor.The transition to appropriate tissue repair coincided with implant surface enrichment of Ca and P and reduced peri-implant Mg^(2+)concentration.Mg implants revealed a thinner fibrous encapsulation compared with Ti.The detailed understanding of the relationship between Mg material properties and the spatial and time-resolved cellular processes provides a basis for the interpretation of clinical observations and future tailoring of Mg implants.展开更多
文摘Implants made of magnesium(Mg)are increasingly employed in patients to achieve osteosynthesis while degrading in situ.Since Mg implants and Mg^(2+)have been suggested to possess anti-inflammatory properties,the clinically observed soft tissue inflammation around Mg implants is enigmatic.Here,using a rat soft tissue model and a 1-28 d observation period,we determined the temporo-spatial cell distribution and behavior in relation to sequential changes of pure Mg implant surface properties and Mg^(2+)release.Compared to nondegradable titanium(Ti)implants,Mg degradation exacerbated initial inflammation.Release of Mg degradation products at the tissue-implant interface,culminating at 3 d,actively initiated chemotaxis and upregulated mRNA and protein immunomodulatory markers,particularly inducible nitric oxide synthase and toll-like receptor-4 up to 6 d,yet without a cytotoxic effect.Increased vascularization was demonstrated morphologically,preceded by high expression of vascular endothelial growth factor.The transition to appropriate tissue repair coincided with implant surface enrichment of Ca and P and reduced peri-implant Mg^(2+)concentration.Mg implants revealed a thinner fibrous encapsulation compared with Ti.The detailed understanding of the relationship between Mg material properties and the spatial and time-resolved cellular processes provides a basis for the interpretation of clinical observations and future tailoring of Mg implants.
