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3D 生物打印聚乳酸/中孔生物活性玻璃仿生支架具有快速矿化和体外细胞相容性,用于骨组织工程。

3D bioprinted poly(lactic acid)/mesoporous bioactive glass based biomimetic scaffold with rapid apatite crystallization and in-vitro Cytocompatability for bone tissue engineering.

机构信息

Electrochemical Process Engineering Division, CSIR-Central Electrochemical Research Institute (CECRI), Karaikudi 630003, Tamil Nadu, India; Academy of Scientific and Innovative Research (AcSIR) - CSIR, Ghaziabad 201002, Uttar Pradesh, India.

School of Chemical Sciences, Mahatma Gandhi University, Kottayam, Kerala 686560, India; International and Inter University Centre for Nanoscience and Nanotechnology, Mahatma Gandhi University, Kottayam, Kerala 686560, India; School of Energy Materials, Mahatma Gandhi University, Kottayam, Kerala 686560, India; Department of Chemical Sciences, University of Johannesburg, P.O. Box 17011, Doornfontein 2028, Johannesburg, South Africa.

出版信息

Int J Biol Macromol. 2022 Sep 30;217:979-997. doi: 10.1016/j.ijbiomac.2022.07.202. Epub 2022 Jul 29.

DOI:10.1016/j.ijbiomac.2022.07.202
PMID:35908677
Abstract

In the recent years, bone tissue engineering is regarded as the promising solution for treatment of bone defects which arises due to trauma, infection and surgical intervention. In view of this, several polymer or ceramic based constructs are envisaged for bone tissue engineering potential. However, scaffolds based on pure polymeric materials suffer from slow bioactivity characteristics. On the other hand, scaffolds based on ceramic materials do not offer sufficient strength for load bearing applications. In order to overcome these drawbacks, the current work aims to develop mixed matrix scaffolds based on poly (L-lactic acid)/mesoporous bioactive glass composite with the formulation of 30:70 weight ratio, which mimics the natural bone composition. In the current work, PLA/MBG (30:70) composite based bioink suitable for 3D bioprinting is indigenously developed and its rheological characteristics are evaluated. The 3D architecture for PLA/MBG composite scaffold is designed using Solidworks CAD 2015 and the scaffolds are fabricated using pneumatic based 3D bioprinting technology, which has not been documented earlier for this formulation in view of bone tissue engineering in the best of our knowledge. Followed by this, optimization of printing parameters in order to develop 3D PLA/MBG composite constructs with hierarchical pore architecture suitable for bone tissue engineering is performed. The SEM analysis confirmed that the pore size of the 3D printed PLA/MBG composite scaffolds falls in the range of 500-700 μm, which corresponds to the macroporous nature of the scaffolds useful for bone cell growth. The mechanical analysis confirmed the superior compressive modulus and yield strength for PLA/MBG composite scaffold in comparison with neat PLA. The in-vitro bioactivity assessment showed rapid apatite crystallization by attaining Ca/P ratio of 1.66 equivalent to natural bone mineral within 3rd day of SBF treatment for PLA/MBG composite scaffold, thus indicating the excellent bioactivity behaviour. The 3D bioprinted PLA/MBG composite scaffold showed promising response in terms of cell attachment and proliferation, mineralization as well as gene expression characteristics while assessed through of in-vitro biological assessment using MG-63 osteosarcoma cells. In this regard, the 3D bioprinted PLA/MBG scaffold could be applied as potential implant for bone tissue engineering application.

摘要

近年来,骨组织工程被认为是治疗创伤、感染和手术干预引起的骨缺损的有前途的方法。有鉴于此,人们设想了几种基于聚合物或陶瓷的构建体用于骨组织工程。然而,基于纯聚合物材料的支架具有生物活性缓慢的特点。另一方面,基于陶瓷材料的支架不能提供足够的强度用于承重应用。为了克服这些缺点,目前的工作旨在开发基于聚(L-乳酸)/介孔生物活性玻璃的混合基质支架,其配方为 30:70 重量比,模拟天然骨成分。在目前的工作中,开发了适合 3D 生物打印的基于 PLA/MBG(30:70)复合材料的生物墨水,并对其流变特性进行了评估。使用 Solidworks CAD 2015 设计 PLA/MBG 复合材料支架的 3D 结构,并使用基于气动的 3D 生物打印技术制造支架,就我们所知,这在该配方用于骨组织工程方面尚属首次。在此之后,为了开发具有适合骨组织工程的分级孔结构的 3D PLA/MBG 复合结构,对打印参数进行了优化。SEM 分析证实,3D 打印 PLA/MBG 复合支架的孔径范围为 500-700μm,对应于支架的大孔性质,有利于骨细胞生长。力学分析证实 PLA/MBG 复合材料支架的压缩模量和屈服强度优于纯 PLA。体外生物活性评估表明,PLA/MBG 复合材料支架在 SBF 处理第 3 天即可快速形成磷灰石结晶,达到 Ca/P 比为 1.66,相当于天然骨矿物质,表明其具有优异的生物活性。通过体外生物学评估,使用 MG-63 骨肉瘤细胞评估,3D 生物打印的 PLA/MBG 复合材料支架在细胞附着和增殖、矿化以及基因表达特性方面表现出良好的反应。在这方面,3D 生物打印的 PLA/MBG 支架可作为骨组织工程应用的潜在植入物。

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