Magnesium implant degradation provides immunomodulatory and proangiogenic effects and attenuates peri-implant fibrosis in soft tissues

被引:28
作者
Ben Amara, Heithem [1 ]
Martinez, Diana C. [2 ]
Shah, Furqan A. [1 ]
Loo, Anna Johansson [1 ]
Emanuelsson, Lena [1 ]
Norlindh, Birgitta [1 ]
Willumeit-Romer, Regine [3 ]
Plocinski, Tomasz [2 ]
Swieszkowski, Wojciech [2 ]
Palmquist, Anders [1 ]
Omar, Omar [1 ]
Thomsen, Peter [1 ]
机构
[1] Univ Gothenburg, Sahlgrenska Acad, Inst Clin Sci, Dept Biomat, Box 412, SE-40530 Gothenburg, Sweden
[2] Warsaw Univ Technol, Fac Mat Sci & Engn, Mat Design Div, Biomat Grp, Warsaw, Poland
[3] Helmholtz Zentrum Hereon, Inst Met Biomat, Geesthacht, Germany
基金
瑞典研究理事会;
关键词
Magnesium; Biodegradable implants; Inflammation; Foreign -body reaction; Gene expression; Neovascularization; VIVO CELLULAR INTERACTIONS; IN-VIVO; TITANIUM; ACTIVATION; CHEMOTAXIS; SECRETION; SCAFFOLDS; HYDROGEN; CELLS; SCREW;
D O I
10.1016/j.bioactmat.2023.02.014
中图分类号
R318 [生物医学工程];
学科分类号
0831 ;
摘要
Implants made of magnesium (Mg) are increasingly employed in patients to achieve osteosynthesis while degrading in situ. Since Mg implants and Mg2+ 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 Mg2+ 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 Mg2+ 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.
引用
收藏
页码:353 / 369
页数:17
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