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用于制备用于骨组织工程的具有分级多孔结构且负载重组人骨形态发生蛋白-2的钙磷/聚乳酸纳米复合支架的低温3D打印技术

Cryogenic 3D printing for producing hierarchical porous and rhBMP-2-loaded Ca-P/PLLA nanocomposite scaffolds for bone tissue engineering.

作者信息

Wang Chong, Zhao Qilong, Wang Min

机构信息

Department of Mechanical Engineering, Faculty of Engineering, The University of Hong Kong, Pokfulam Road, Hong Kong. School of Mechanical Engineering, Dongguan University of Technology, 1 Daxue Road, Songshanhu, Dongguan, Guangdong, People's Republic of China.

出版信息

Biofabrication. 2017 Jun 7;9(2):025031. doi: 10.1088/1758-5090/aa71c9.

DOI:10.1088/1758-5090/aa71c9
PMID:28589918
Abstract

The performance of bone tissue engineering scaffolds can be assessed through cell responses to scaffolds, including cell attachment, infiltration, morphogenesis, proliferation, differentiation, etc, which are determined or heavily influenced by the composition, structure, mechanical properties, and biological properties (e.g. osteoconductivity and osteoinductivity) of scaffolds. Although some promising 3D printing techniques such as fused deposition modeling and selective laser sintering could be employed to produce biodegradable bone tissue engineering scaffolds with customized shapes and tailored interconnected pores, effective methods for fabricating scaffolds with well-designed hierarchical porous structure (both interconnected macropores and surface micropores) and tunable osteoconductivity/osteoinductivity still need to be developed. In this investigation, a novel cryogenic 3D printing technique was investigated and developed for producing hierarchical porous and recombinant human bone morphogenetic protein-2 (rhBMP-2)-loaded calcium phosphate (Ca-P) nanoparticle/poly(L-lactic acid) nanocomposite scaffolds, in which the Ca-P nanoparticle-incorporated scaffold layer and rhBMP-2-encapsulated scaffold layer were deposited alternatingly using different types of emulsions as printing inks. The mechanical properties of the as-printed scaffolds were comparable to those of human cancellous bone. Sustained releases of Ca ions and rhBMP-2 were achieved and the biological activity of rhBMP-2 was well-preserved. Scaffolds with a desirable hierarchical porous structure and dual delivery of Ca ions and rhBMP-2 exhibited superior performance in directing the behaviors of human bone marrow-derived mesenchymal stem cells and caused improved cell viability, attachment, proliferation, and osteogenic differentiation, which has suggested their great potential for bone tissue engineering.

摘要

骨组织工程支架的性能可通过细胞对支架的反应来评估,包括细胞附着、浸润、形态发生、增殖、分化等,这些反应由支架的组成、结构、力学性能和生物学性能(如骨传导性和骨诱导性)决定或受到其严重影响。尽管一些有前景的3D打印技术,如熔融沉积建模和选择性激光烧结,可用于制造具有定制形状和定制互连孔的可生物降解骨组织工程支架,但仍需要开发有效的方法来制造具有精心设计的分级多孔结构(互连大孔和表面微孔)和可调骨传导性/骨诱导性的支架。在本研究中,研究并开发了一种新型低温3D打印技术,用于制造具有分级多孔结构且负载重组人骨形态发生蛋白-2(rhBMP-2)的磷酸钙(Ca-P)纳米颗粒/聚(L-乳酸)纳米复合支架,其中包含Ca-P纳米颗粒的支架层和封装rhBMP-2的支架层使用不同类型的乳液作为打印墨水交替沉积。打印后的支架力学性能与人松质骨相当。实现了Ca离子和rhBMP-2的持续释放,且rhBMP-2的生物活性得到了良好保留。具有理想分级多孔结构以及Ca离子和rhBMP-2双重递送功能的支架在引导人骨髓间充质干细胞行为方面表现出卓越性能,并提高了细胞活力、附着、增殖和成骨分化能力,这表明它们在骨组织工程中具有巨大潜力。

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