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用于骨组织工程的混合 3D 打印载阿司匹林脂质体复合支架

A hybrid 3D-printed aspirin-laden liposome composite scaffold for bone tissue engineering.

机构信息

Laboratory of Biomaterials and Regenerative Medicine, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871, China.

出版信息

J Mater Chem B. 2019 Jan 28;7(4):619-629. doi: 10.1039/c8tb02756k. Epub 2019 Jan 4.

Abstract

Bone defects are some of the most difficult injuries to treat in clinical medicine. Evidence from cellular and animal studies suggests that aspirin exhibits protective effects on bone by promoting both the survival of osteoblast precursor stem cells and osteoblast differentiation. However, acquired resistance to aspirin and its cytotoxicity significantly limit its therapeutic application. Controlled release systems have been confirmed to promote the efficacy of certain drugs for bone regeneration. Additionally, the controlled release of a high dose of drug allows for lower dosing over an extended period. In this way, nano-liposomal encapsulation of aspirin can be used to reduce the cytotoxicity of the overall dose. Using a series of osteogenic experiments, this study found that an aspirin-laden liposome delivery system (Asp@Lipo) obviously promoted osteogenesis and immunomodulation of human mesenchymal stem cells (hMSCs). We also studied the in vitro capacity of polycaprolactone (PCL)-based bioactive composite (PCL-Asp@Lipo) scaffolds to facilitate cell proliferation and osteoblast differentiation. Compared to a common scaffold, ALP assays, immunofluorescence and calcium mineralisation studies revealed that the PCL-Asp@Lipo scaffolds enhanced the osteogenic differentiation of hMSCs. Subsequently, along with the cells, PCL and PCL-Asp@Lipo scaffolds were both implanted subcutaneously into nude mice for estimation of osteo-inductivity after 6 weeks, the PCL-Asp@Lipo composite scaffold exhibited more osteogenic activity than the bare PCL scaffold. This approach has potential applications in bone tissue repair and regenerative medicine.

摘要

骨缺损是临床医学中最难治疗的损伤之一。细胞和动物研究的证据表明,阿司匹林通过促进成骨前体细胞干细胞的存活和成骨分化,对骨骼表现出保护作用。然而,阿司匹林的获得性耐药性及其细胞毒性极大地限制了其治疗应用。已证实控制释放系统可促进某些用于骨再生的药物的疗效。此外,药物的高剂量的控制释放允许在延长的时间内进行较低剂量的给药。通过这种方式,可以使用阿司匹林的纳米脂质体包封来降低总剂量的细胞毒性。通过一系列成骨实验,本研究发现载有阿司匹林的脂质体递药系统(Asp@Lipo)明显促进了人间充质干细胞(hMSCs)的成骨作用和免疫调节作用。我们还研究了基于聚己内酯(PCL)的生物活性复合材料(PCL-Asp@Lipo)支架在体外促进细胞增殖和成骨细胞分化的能力。与普通支架相比,碱性磷酸酶(ALP)测定、免疫荧光和钙矿化研究表明,PCL-Asp@Lipo 支架增强了 hMSCs 的成骨分化。随后,将 PCL 和 PCL-Asp@Lipo 支架与细胞一起植入裸鼠皮下,6 周后评估其成骨诱导性,PCL-Asp@Lipo 复合支架的成骨活性高于裸 PCL 支架。这种方法在骨组织修复和再生医学中有潜在的应用。

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