Department of Orthopedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai Jiao Tong University, Shanghai 200233, China.
The Education Ministry Key Lab of Resource Chemistry and Shanghai Key Laboratory of Rare Earth Functional Materials, Shanghai Normal University, Shanghai 200234, China.
J Mater Chem B. 2020 Jun 24;8(24):5280-5292. doi: 10.1039/d0tb00342e.
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.
一般来说,外源性干细胞的添加和宿主-支架免疫反应限制了羟基磷灰石(HA)/壳聚糖(CS)支架在骨再生中的临床应用。为了实现“促进内源性组织工程”,将磁性 M 型六方铁氧体(SrFe12O19)纳米粒子掺入骨支架中以招募内源性干细胞。然后,利用镧掺入来调节宿主-支架免疫反应,并为招募的内源性干细胞提供一个有利于再生的环境。在这里,我们首先制备和表征了磁性镧掺杂的 HA/CS 支架。实验证明,MLaHA/CS 支架能够有效地招募大鼠骨髓间充质干细胞(rBMSCs),并通过促进巨噬细胞向抗炎表型(M2)极化来调节宿主-支架免疫反应。通过进一步研究其潜在机制,我们发现 MLaHA/CS 支架能够通过上调 Smad 1/5/9 通路的磷酸化来促进 rBMSCs 的成骨分化。当将 MLaHA/CS 支架植入大鼠颅骨缺损中时,磁性纳米粒子和镧的掺入显著促进了新骨的再生,这可以通过 micro-CT 检测和组织学染色来证实。我们的研究结果表明,MLaHA/CS 有望成为一种无细胞和生物相容性的骨再生支架。
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