Magnetic lanthanum-doped hydroxyapatite/chitosan scaffolds with endogenous stem cell-recruiting and immunomodulatory properties for bone regeneration
Magnetic lanthanum-doped hydroxyapatite/chitosan scaffolds with endogenous stem cell-recruiting and immunomodulatory properties for bone regeneration
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具有内源干细胞募集和免疫调节特性的磁性掺镧羟基磷灰石/壳聚糖支架，用于骨再生
DOI：
10.1039/d0tb00342e
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发表时间：
2020
影响因子：
7
通讯作者：
Guan Junjie
中科院分区：
文献类型：
--
作者：
Wang Qiyang;Tang Yaqi;Ke Qinfei;Yin Wenjing;Zhang Changqing;Guo Yaping;Guan Junjie
通常，外源性干细胞的加入和宿主对支架的免疫反应限制了羟基磷灰石（HA）/壳聚糖（CS）支架用于骨再生的临床应用。为了实现“促进内源性组织工程”，磁性M型六方晶系铁氧体（SrFe 12 O 19）纳米粒子被纳入骨支架招募内源性干细胞。然后，镧掺入用于调节宿主-支架免疫应答，并为募集的内源性干细胞提供促再生环境。在这里，我们首先制备和表征磁性镧掺杂HA/CS支架。MLaHA/CS支架被证明是有效的招募大鼠骨髓间充质干细胞（rBMSC）和调节主机到支架的免疫反应，通过促进巨噬细胞极化成抗炎表型（M2）在体外。通过进一步研究其潜在机制，我们发现MLaHA/CS支架可以通过上调Smad 1/5/9通路的磷酸化来促进rBMSCs的成骨分化。当MLaHA/CS支架植入大鼠颅骨缺损时，磁性纳米颗粒和镧的掺入显着促进了新骨再生，正如微型CT测定和组织学染色所揭示的那样。我们的研究结果表明，MLaHA/CS显示出巨大的潜力，作为一个无细胞和生物相容性的骨再生支架。
Generally, the addition of exogenous stem cells and host-to-scaffold immune responses restricts the clinical applications of hydroxyapatite (HA)/chitosan (CS) scaffolds for bone regeneration. To achieve “facilitated endogenous tissue engineering”, magnetic M-type hexagonal ferrite (SrFe12O19) nanoparticles were incorporated into bone scaffolds to recruit endogenous stem cells. Then, lanthanum incorporation was utilized to regulate host-to-scaffold immune responses and to provide a pro-regenerative environment for recruited endogenous stem cells. Here, we first fabricated and characterized magnetic lanthanum-doped HA/CS scaffolds. The MLaHA/CS scaffolds were demonstrated to be effective at recruiting rat bone marrow mesenchymal stem cells (rBMSCs) and modulating host-to-scaffold immune responses by promoting macrophage polarization into the anti-inflammatory phenotype (M2) in vitro. By further examining the underlying mechanism, we found that MLaHA/CS scaffolds could promote the osteogenic differentiation of rBMSCs by upregulating the phosphorylation of the Smad 1/5/9 pathway. When MLaHA/CS scaffolds were implanted into rat calvarial defects, the incorporation of magnetic nanoparticles and lanthanum significantly promoted the new bone regeneration, as revealed by micro-CT assays and histological staining. Our findings suggest that MLaHA/CS shows great potential for use as a cell-free and biocompatible scaffold for bone regeneration.