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用于骨组织工程的工程化 3D 打印聚(ε-己内酯)/石墨烯支架。

Engineered 3D printed poly(ɛ-caprolactone)/graphene scaffolds for bone tissue engineering.

机构信息

School of Mechanical, Aerospace and Civil Engineering, The University of Manchester, Manchester M13 9PL, UK.

Graduate Program in Biomedical Sciences, Hermínio Ometto University Centre, Araras 13607339, Sao Paulo, Brazil.

出版信息

Mater Sci Eng C Mater Biol Appl. 2019 Jul;100:759-770. doi: 10.1016/j.msec.2019.03.047. Epub 2019 Mar 16.

DOI:10.1016/j.msec.2019.03.047
PMID:30948113
Abstract

Scaffolds are important physical substrates for cell attachment, proliferation and differentiation. Multiple factors could influence the optimal design of scaffolds for a specific tissue, such as the geometry, the materials used to modulate cell proliferation and differentiation, its biodegradability and biocompatibility. The optimal design of a scaffold for a specific tissue strongly depends on both materials and manufacturing processes. Previous studies of human adipose-derived stem cells (hADSCs) seeded on poly(ε-caprolactone) (PCL)/graphene scaffolds have proved that the addition of small concentrations of graphene to PCL scaffolds improves cell proliferation. Based on such results, this paper further investigates, for the first time, both in vitro and in vivo characteristics of 3D printed PCL/graphene scaffolds. Scaffolds were evaluated from morphological, biological and short term immune response points of view. Results show that the produced scaffolds induce an acceptable level of immune response, suggesting high potential for in vivo applications. Finally, the scaffolds were used to treat a rat calvaria critical size defect with and without applying micro electrical stimulation (10 μA). Quantification of connective and new bone tissue formation and the levels of ALP, RANK, RANKL, OPG were considered. Results show that the use of scaffolds containing graphene and electrical stimulation seems to increase cell migration and cell influx, leading to new tissue formation, well-organized tissue deposition and bone remodelling.

摘要

支架是细胞附着、增殖和分化的重要物理基质。多种因素会影响特定组织支架的最佳设计,例如几何形状、用于调节细胞增殖和分化的材料、其可生物降解性和生物相容性。特定组织支架的最佳设计强烈取决于材料和制造工艺。先前关于人脂肪来源干细胞(hADSCs)接种到聚(ε-己内酯)(PCL)/石墨烯支架上的研究已经证明,向 PCL 支架中添加少量石墨烯可以提高细胞增殖。基于这些结果,本文首次进一步研究了 3D 打印的 PCL/石墨烯支架的体外和体内特性。从形态学、生物学和短期免疫反应的角度评估了支架。结果表明,所制备的支架引起可接受水平的免疫反应,表明其在体内应用中有很大的潜力。最后,将支架用于治疗大鼠颅骨临界尺寸缺损,同时施加和不施加微电刺激(10 μA)。考虑了连接组织和新骨组织形成的定量以及碱性磷酸酶(ALP)、核因子-κB 受体激活因子配体(RANKL)、骨保护素(OPG)的水平。结果表明,使用含有石墨烯和电刺激的支架似乎可以增加细胞迁移和细胞浸润,从而导致新组织形成、组织沉积有序和骨重塑。

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