Continuously released Zn(2+) in 3D-printed PLGA/β-TCP/Zn scaffolds for bone defect repair by improving osteoinductive and anti-inflammatory properties.
Continuously released Zn(2+) in 3D-printed PLGA/β-TCP/Zn scaffolds for bone defect repair by improving osteoinductive and anti-inflammatory properties.
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DOI：
10.1016/j.bioactmat.2022.12.015
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发表时间：
2023-06
影响因子：
18.9
通讯作者：
Zhao, Yu
中科院分区：
文献类型：
--
作者：
Li, Chunxu;Sun, Fengbo;Tian, Jingjing;Li, Jiahao;Sun, Haidan;Zhang, Yong;Guo, Shigong;Lin, Yuanhua;Sun, Xiaodan;Zhao, Yu
骨缺损长期不愈合一直是骨科治疗中的一大难题。聚乳酸-羟基乙酸共聚物/β-磷酸三钙（PLGA/β-TCP）人工骨支架材料由于其合适的降解速率和良好的骨传导性有望解决这一问题。然而，其力学性能不足、缺乏成骨诱导性以及植入后感染等问题限制了其大规模临床应用。因此，我们采用低温快速成型3D打印技术，在PLGA/β-TCP中添加锌亚微米颗粒，制备了一种新型骨修复生物支架。我们首先筛选出具有良好生物相容性的含1wt% Zn的支架，并且可以在16周内稳定释放安全剂量的锌离子，以确保长期无毒性。该支架具有仿生松质骨的多级多孔结构，其弹性模量（63.41 ± 1.89 MPa）和抗压强度（2.887 ± 0.025 MPa）接近松质骨。此外，经一系列体内外实验证实，该支架材料对BMSCs的活性无不良影响，并能促进BMSCs的黏附和成骨分化，其成骨和抗炎性能均优于不含锌颗粒的PLGA/β-TCP支架材料。我们还发现这种成骨和抗炎作用可能与Wnt/β-catenin、P38 MAPK和NFkB通路有关。本研究为含锌生物材料骨再生机制的后续研究奠定了基础。我们设想这种支架可能成为临床治疗骨缺损的新策略。方案1：实验和潜在分子机制的示意图。采用LT-RP 3D技术制备的含1 wt% Zn-SPs的PLGA/β-TCP/Zn支架在16周内可稳定释放Zn 2+。PLGA/β-TCP/Zn支架具有仿生结构，具有良好的力学性能、骨诱导性能和抗炎性能。Zn-SPs可能通过激活Wnt/β-catenin、P38 MAPK和抑制NF κ B信号通路促进骨修复。
Long-term nonunion of bone defects has always been a major problem in orthopedic treatment. Artificial bone graft materials such as Poly (lactic-co-glycolic acid)/β-tricalcium phosphate (PLGA/β-TCP) scaffolds are expected to solve this problem due to their suitable degradation rate and good osteoconductivity. However, insufficient mechanical properties, lack of osteoinductivity and infections after implanted limit its large-scale clinical application. Hence, we proposed a novel bone repair bioscaffold by adding zinc submicron particles to PLGA/β-TCP using low temperature rapid prototyping 3D printing technology. We first screened the scaffolds with 1 wt% Zn that had good biocompatibility and could stably release a safe dose of zinc ions within 16 weeks to ensure long-term non-toxicity. As designed, the scaffold had a multi-level porous structure of biomimetic cancellous bone, and the Young's modulus (63.41 ± 1.89 MPa) and compressive strength (2.887 ± 0.025 MPa) of the scaffold were close to those of cancellous bone. In addition, after a series of in vitro and in vivo experiments, the scaffolds proved to have no adverse effects on the viability of BMSCs and promoted their adhesion and osteogenic differentiation, as well as exhibiting higher osteogenic and anti-inflammatory properties than PLGA/β-TCP scaffold without zinc particles. We also found that this osteogenic and anti-inflammatory effect might be related to Wnt/β-catenin, P38 MAPK and NFkB pathways. This study lay a foundation for the follow-up study of bone regeneration mechanism of Zn-containing biomaterials. We envision that this scaffold may become a new strategy for clinical treatment of bone defects. Scheme.1: Schematic diagram of the experiments and the underlying molecular mechanism. The PLGA/β-TCP/Zn scaffold with 1 wt% Zn-SPs prepared by LT-RP 3D technology could stably release Zn2+ within 16 weeks. The PLGA/β-TCP/Zn scaffold had biomimetic structure, good mechanical, osteoinductive and anti-inflammatory properties. Zn-SPs might promote bone repair through activating the Wnt/β-catenin, P38 MAPK and inhibiting the NFkB signaling pathways.
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