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化学进展 2021, Vol. 33 Issue (4): 533-542 DOI: 10.7536/PC200537 前一篇   后一篇

• 综述 •

微量元素锶掺杂生物材料在骨修复领域的应用

赵睿1, 杨晓1,*(), 朱向东1, 张兴栋1   

  1. 1 四川大学 国家生物医学材料工程技术研究中心 成都 610064
  • 收稿日期:2020-05-15 修回日期:2020-07-20 出版日期:2021-04-20 发布日期:2020-12-28
  • 通讯作者: 杨晓
  • 基金资助:
    国家自然科学基金面上项目(8197155)
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Application of Trace Element Strontium-Doped Biomaterials in the Field of Bone Regeneration

Rui Zhao1, Xiao Yang1(), Xiangdong Zhu1, Xingdong Zhang1   

  1. 1 National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610064, China
  • Received:2020-05-15 Revised:2020-07-20 Online:2021-04-20 Published:2020-12-28
  • Contact: Xiao Yang
  • Supported by:
    the National Natural Science Foundation of China(8197155)

临床研究证实雷奈酸锶可以通过改善骨形成同时减少骨吸收以抑制骨质疏松症。这些作用部分是通过锶对骨代谢的影响来介导的,微量元素锶能够促进成骨和血管生成。目前,在骨科相关领域对掺锶复合材料的研究日益增多。本文主要综述了锶对骨组织的主要作用机制,以及与骨之间的相互作用,亦着重介绍了不同锶掺杂生物材料在局部骨组织修复中的应用,尤其是在骨质疏松性骨再生中的应用,以期为锶在骨修复中的进一步应用提供理论依据。

关键词： 锶, 骨再生, 雷奈酸锶, 骨质疏松, 生物材料

Clinical studies have confirmed that strontium ranelate can inhibit osteoporosis by improving bone formation and reducing bone resorption. These effects are partly mediated by the effect of strontium on bone metabolism. Trace element strontium can promote osteogenesis as well as angiogenesis. To date, the research on strontium-doped composites is increasing in orthopaedic related field. The current article mainly reviews the main action mechanisms of strontium on bone tissue, including the validated and potential mechanisms, as well as the detailed biological interaction between strontium and bone. This article also focuses on different strontium-doped biomaterials applied in the local bone tissue repair, especially for the osteoporotic bone regeneration. We hope that this review would shed light on the rationale for further application of strontium in bone repair.

Contents:

1 Introduction

2 Action mechanism of strontium

2.1 Effect of strontium on osteogenesis

2.2 Effects of strontium on osteoclastogenesis

2.3 Effects of strontium on angiogenesis

3 Strontium doped bone repair materials

3.1 Strontium-doped bone cement

3.2 Strontium-doped calcium phosphate bioceramic

3.3 Strontium-doped bioactive glass

3.4 Bioactive coating of strontium-doped composite

3.5 Other strontium-doped multiphase composites

4 Conclusion and outlook

Key words: strontium, bone regeneration, strontium ranelate, osteoporosis, biomaterials
()
图1 锶(Sr)掺杂材料影响骨重建过程的示意图[25???~29]
Fig.1 Schematic diagram of the effect of strontium-doped materials on the process of bone remodeling[25???~29]
图2 锶(Sr)促进血管生成的机制示意图[38??~41]
Fig.2 Schematic diagram of the mechanism of strontium promoting angiogenesis[38??~41]
图3 Micro-CT显示骨形成的图像和数据。(A)1、8和12周重建股骨冠状切面的Micro-CT图像。右图:种植体与宿主骨间隙(100 μm)内新生骨的重建图像,比例尺=2 mm。(B)Micro-CT定量分析:骨长入率(nBV/nTV)、骨整合率(cBV/cTV)和骨取代率(nBV/DV)( *P<0.05,**P<0.01)[38]
Fig.3 Micro-CT rendered images and data of the bone formation.(A) Reconstructed micro-CT images of coronal sections from the femur at week 1, 8 and 12. Right: 3D reconstructed images of the newly formed bone inside the gap(100 μm) between the implants and host bone(scale bar = 2 mm).(B) Quantitative analysis of micro-CT data: Bone ingrowth rate(nBV/nTV), bone-implant osseointegration rate(cBV/cTV) and bone substitution rate(nBV/DV) were then obtained( *P<0.05,**P<0.01)[38]. Copyright 2020, Elsevier
表1 掺锶材料用于成骨研究的结果总结
Table 1 Summary of previous work on bone formation in the strontium-doped materials
Article material Strontium content Synthesis method In vitro results Animal model Bone formation
Ma et al.
(2019)[47] 		Composite hydrogel 17.91 wt% Physical mixing Good cytocompatibility Rabbit joint Increased
Zhao et al.
(2020)[38] 		Calcium phosphate bioceramic 10 mol% Chemical precipitation method Good cytocompatibility Rat femur Increased
Wang et al.
(2018)[61] 		Compound PEEK 1.03%, 14.27% Hydrothermal method Promote the proliferation and differentiation of MC3T3-E1 - -
Liu et al.
(2019)[66] 		Tricalcium silicate bone
cement. 		0~2 mol% Sol-gel method Good cytocompatibility - -
Nguyen et al.
(2019)[67] 		Strontium-doped calcium
phosphate coated
titanium film 		Sr/Ca=0.129 Cyclic precalcification High expression of osteogenesis-related genes Rat calvarial defect Increased
Thormann et al.
(2013)[9] 		Strontium calcium
phosphate cement 		Sr/Ca=0.123 - High expression of osteogenesis-related genes Metaphyseal fracture of femur
in rats 		Increased
Zhang et al.
(2015)[8] 		Strontium borate
bone cement 		- Physical mixing Promote the proliferation and osteogenic differentiation of human MSCs Rabbit femur Increased
Gao et al.
(2017)[55] 		Si, Sr and F multi-
doped hydroxyapatite 		- One pot
hydrothermal method 		Promote the adhesion and
proliferation of MG63 		- -
Zhao et al.
(2018)[55] 		Strontium doped bioglass/
gelatin scaffold 		- Freeze drying method Promote the polarization of macrophages from M1 to M2 Rat calvarial defect Increased
Boda et al.
(2017)[64] 		Strontium hexaferrite
nanoparticles composite hydroxyapatite 		- Plasma sintering Up-regulate the expression of osteogenesis-related genes - -
Makkar et al.
(2020)[68] 		Strontium doped calcium phosphate coating on
magnesium alloy 		Sr/(Ca+Sr)=0.1 Chemical impregnation method Promote MC3T3-E1 adhesion, proliferation and expression of osteogenic markers Rabbit femur Increased
Yuan et al.
(2018)[69] 		SrHA/phosphoserine-tethered poly(epsilon-
lysine) dendrons 		15 mol% Sol-gel method Down-regulate the expression of inflammatory factors and up-regulate the expression of osteogenesis-related genes Rat femur No change
Zhao et al.
(2018)[70] 		Titanium dioxide
microporous coating doped with Zn/Sr 		3.8 atom%, 4.9 atom% Micro-arc oxidation method Promote cell adhesion,
proliferation, differentiation and mineralization; bacteriostatic 		Rabbit femur Promote osseointe-
gration
Wang et al.
(2019)[71] 		SrHA/silk fibroin
composite nanospheres 		0.1 mol%,
0.5 mol%,
1.0 mol% 		Ultrasonic coprecipitation method Promote the adhesion, growth, proliferation and osteogenic differentiation of MSCs - -
Han et al.
(2019)[72] 		Strontium-doped mineralized PLLA nanofibrous membranes 5%,10%,
15% 		Electrodeposition method Promote the proliferation and osteogenic differentiation
of MSCs 		Rat calvarial defect Increased
Shaltooki et al.
(2019) [73] 		Polycaprolactone/strontium doped bioglass
composite scaffold 		0~15 wt% Solvent method Promote MC3T3-E1 adhesion and osteogenic differentiation - -
Chen et al.
(2019)[74] 		Strontium oxide
graphene nanocomposites 		0.25 wt%,
0.5 wt%,
1.25 wt% 		Covalent cross-linking Promote cell adhesion and
osteogenic differentiation;
secrete angiogenic factors 		Rat calvarial defect Increased
Denry et al.
(2018)[75] 		Strontium-doped fluorapatite glass-ceramics 0~24 mol% Foam impregnation - Rat calvarial defect Increased
图4 从2010至2020年间的锶掺杂生物材料用于成骨研究的文章数量分布(数据来源:google scholar,检索词:strontium、doped、material、bone,检索时间:2020.05)
Fig.4 Distribution of articles on Strontium-doped Biomaterials for Osteogenesis Research from 2010 to 2020(Data Source: google scholar, Key Words: strontium, doped, material, bone,Retrieval time: 2020.05)
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