Copper peptide-incorporated 3D-printed silk-based scaffolds promote vascularized bone regeneration

Copper peptide-incorporated 3D-printed silk-based scaffolds promote vascularized bone regeneration
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掺有铜肽的3D打印丝基支架可促进血管化骨再生

DOI:
10.1016/j.cej.2021.130147
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发表时间:
2021-05
影响因子:
15.1
通讯作者:
Jiang Xinquan
Jiang Xinquan
中科院分区:
工程技术1区
文献类型:
--
作者:
Zhou Mingliang;Wu Xiaolin;Luo Jiaxin;Yang Guangzheng;Lu Yuezhi;Lin Sihan;Jiang Fei;Zhang Wenjie;Jiang Xinquan

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生物活性离子是一种很有前途的血管化骨再生材料。然而,铜等微量元素在较小的浓度范围内发挥作用,当过量蓄积时会产生细胞毒性,限制了其在组织工程中的潜在应用。在这方面,自然产生的纳米金属多肽为金属离子的新用途提供了新的见解。在这里,我们制备了具有铜离子特异性结合三肽的铜肽的3D打印丝基支架,其治疗效果与游离铜离子相似,且毒性更低。我们发现铜肽促进了M2巨噬细胞的极化,M2巨噬细胞表现出抗炎表型,并在早期帮助骨组织修复。此外,释放的铜肽提供了刺激移植的骨髓来源干细胞(BMSC)增殖和细胞因子分泌的微环境。分泌的细胞因子进一步促进了体内和体外的血管生成。此外,在活体大小的颅骨缺损再生实验中,进一步证明了构建的支架种植了BMSC,导致了更好的血管化骨修复。综上所述,铜肽复合丝素支架材料是一种很有前途的血管化骨组织再生材料,也为生物活性离子基生物材料的设计提供了新的途径。
Bioactive ions are promising materials for vascularized bone regeneration. However, trace elements, e.g., copper, exert their effects in a narrow concentration range and cause cytotoxicity when over-accumulated, which limits their potential application in tissue engineering. In this regard, naturally occurring nanosized metallopeptides provide new insight into the novel usage of metal ions. Here, 3D-printed silk-based scaffolds with sustained release of copper peptide, a copper ion-specific binding tripeptide, were fabricated and exhibited similar therapeutic effects to free copper ions, with lower toxicity. We found that copper peptide promoted the polarization of M2 macrophages, which exhibited an anti-inflammatory phenotype and assisted in bone tissue repair during early stage. Moreover, the released copper peptide provided a microenvironment to stimulate transplanted bone marrow-derived stem cell (BMSC) proliferation and cytokine secretion. The secreted cytokines further promoted angiogenesisin vitroandin vivo. In addition,in vivocritical-sized calvarial defect regeneration experiments further demonstrated that fabricated scaffolds seeded with BMSC, resulting in better vascularized bone repair. Altogether, the results indicated that copper peptide incorporated silk-based scaffolds are promising materials for vascularized bone tissue regeneration, as well as providing new approaches for bioactive ion-based biomaterial design.
用于促进骨再生的血管化 3D 打印支架。
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