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通过分层制造工艺制备的新型纳米羟基磷灰石/聚(ε-己内酯)复合支架的体外和动物研究

In vitro and animal study of novel nano-hydroxyapatite/poly(epsilon-caprolactone) composite scaffolds fabricated by layer manufacturing process.

作者信息

Heo Su-Jin, Kim Seung-Eon, Wei Jie, Kim Dong Hwa, Hyun Young-Taek, Yun Hui-Suk, Kim Hyung Keun, Yoon Taek Rim, Kim Su-Hyang, Park Su-A, Shin Ji Won, Shin Jung-Woog

机构信息

Team of BK21, First Project Team, Department of Biomedical Engineering, Inje University, Gimhae, Gyeongnam, Republic of Korea.

出版信息

Tissue Eng Part A. 2009 May;15(5):977-89. doi: 10.1089/ten.tea.2008.0190.

DOI:10.1089/ten.tea.2008.0190
PMID:18803480
Abstract

The purpose of this study was to propose a computer-controllable scaffold structure made by a layer manufacturing process (LMP) with addition of nano- or micro-sized particles and to investigate the effects of particle size in vitro. In addition, the superiority of this LMP method over the conventional scaffolds made by salt leaching and gas forming process was investigated through animal study. Using the LMP, we have created a new nano-sized hydroxyapatite/poly(epsilon-caprolactone) composite (n-HPC) scaffold and a micro-sized hydroxyapatite/poly(epsilon-caprolactone) composite (m-HPC) scaffold for bone tissue engineering applications. The scaffold macropores were well interconnected, with a porosity of 73% and a pore size of 500 microm. The compressive modulus of the n-HPC and m-HPC scaffolds was 6.76 and 3.18 MPa, respectively. We compared the cellular responses to the two kinds of scaffolds. Both n-HPC and m-HPC exhibited good in vitro biocompatibility. Attachment and proliferation of mesenchymal stem cells were better on the n-HPC than on the m-HPC scaffold. Moreover, significantly higher alkaline phosphatase activity and calcium content were observed on the n-HPC than on the m-HPC scaffold. In an animal study, the LMP scaffolds enhanced bone formation, owing to their well-interconnected pores. Radiological and histological examinations confirmed that the new bony tissue had grown easily into the entire n-HPC scaffold fabricated by LMP. We suggest that the well-interconnected pores in the LMP scaffolds might encourage cell attachment, proliferation, and migration to stimulate cell functions, thus enhancing bone formation in the LMP scaffolds. This study shows that bioactive and biocompatible n-HPC composite scaffolds prepared using an LMP have potential applications in bone tissue engineering.

摘要

本研究的目的是提出一种通过层制造工艺(LMP)制备的、添加了纳米或微米级颗粒的计算机可控支架结构,并在体外研究颗粒尺寸的影响。此外,通过动物研究考察了这种LMP方法相对于传统的盐浸出法和气体成型法制备的支架的优越性。利用LMP,我们制备了用于骨组织工程应用的新型纳米级羟基磷灰石/聚(ε-己内酯)复合材料(n-HPC)支架和微米级羟基磷灰石/聚(ε-己内酯)复合材料(m-HPC)支架。支架的大孔相互连通良好,孔隙率为73%,孔径为500微米。n-HPC和m-HPC支架的压缩模量分别为6.76和3.18 MPa。我们比较了两种支架的细胞反应。n-HPC和m-HPC在体外均表现出良好的生物相容性。间充质干细胞在n-HPC支架上的附着和增殖比在m-HPC支架上更好。此外,在n-HPC支架上观察到的碱性磷酸酶活性和钙含量显著高于m-HPC支架。在动物研究中,LMP支架因其相互连通良好的孔隙而促进了骨形成。放射学和组织学检查证实,新的骨组织很容易长入由LMP制备的整个n-HPC支架中。我们认为,LMP支架中相互连通良好的孔隙可能会促进细胞附着、增殖和迁移,从而刺激细胞功能,进而增强LMP支架中的骨形成。本研究表明,使用LMP制备的具有生物活性和生物相容性的n-HPC复合支架在骨组织工程中具有潜在的应用价值。

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