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增材制造的 BaTiO 复合支架:一种用于承重骨组织工程应用的新策略。

Additively manufactured BaTiO composite scaffolds: A novel strategy for load bearing bone tissue engineering applications.

机构信息

Nanotechnology and Integrated Bio-Engineering Centre (NIBEC), Ulster University, Shore Road, BT37 0QB Newtownabbey, United Kingdom.

Division of Pharmacy and Optometry, School of Health Sciences, Faculty of Biology, Medicine and Health (FMBH), University of Manchester, Oxford Road, M13 9PT Manchester, United Kingdom.

出版信息

Mater Sci Eng C Mater Biol Appl. 2021 Jul;126:112192. doi: 10.1016/j.msec.2021.112192. Epub 2021 May 19.

DOI:10.1016/j.msec.2021.112192
PMID:34082989
Abstract

Piezoelectric ceramics, such as BaTiO, have gained considerable attention in bone tissue engineering applications thanks to their biocompatibility, ability to sustain a charged surface as well as improve bone cells' adhesion and proliferation. However, the poor processability and brittleness of these materials hinder the fabrication of three-dimensional scaffolds for load bearing tissue engineering applications. For the first time, this study focused on the fabrication and characterisation of BaTiO composite scaffolds by using a multi-material 3D printing technology. Polycaprolactone (PCL) was selected and used as dispersion phase for its low melting point, easy processability and wide adoption in bone tissue engineering. The proposed single-step extrusion-based strategy enabled a faster and solvent-free process, where raw materials in powder forms were mechanically mixed and subsequently fed into the 3D printing system for further processing. PCL, PCL/hydroxyapatite and PCL/BaTiO composite scaffolds were successfully produced with high level of consistency and an inner architecture made of seamlessly integrated layers. The inclusion of BaTiO ceramic particles (10% wt.) significantly improved the mechanical performance of the scaffolds (54 ± 0.5 MPa) compared to PCL/hydroxyapatite scaffolds (40.4 ± 0.1 MPa); moreover, the presence of BaTiO increased the dielectric permittivity over the entire frequency spectrum and tested temperatures. Human osteoblasts Saos-2 were seeded on scaffolds and cellular adhesion, proliferation, differentiation and deposition of bone-like extracellular matrix were evaluated. All tested scaffolds (PCL, PCL/hydroxyapatite and PCL/BaTiO) supported cell growth and viability, preserving the characteristic cellular osteoblastic phenotype morphology, with PCL/BaTiO composite scaffolds exhibiting higher mineralisation (ALP activity) and deposited bone-like extracellular matrix (osteocalcin and collagen I). The single-step multi-material additive manufacturing technology used for the fabrication of electroactive PCL/BaTiO composite scaffolds holds great promise for sustainability (reduced material waste and manufacturing costs) and it importantly suggests PCL/BaTiO scaffolds as promising candidates for load bearing bone tissue engineering applications to solve unmet clinical needs.

摘要

压电陶瓷,如 BaTiO,由于其生物相容性、维持带电表面的能力以及改善骨细胞的粘附和增殖能力,在骨组织工程应用中引起了相当大的关注。然而,这些材料的加工性能差和脆性阻碍了用于承重组织工程应用的三维支架的制造。本研究首次专注于使用多材料 3D 打印技术制造 BaTiO 复合材料支架并对其进行了表征。选择聚己内酯 (PCL) 作为分散相,因其熔点低、加工性能好且在骨组织工程中广泛应用。所提出的基于单步挤出的策略实现了更快、无溶剂的工艺,其中粉末形式的原材料通过机械混合并随后送入 3D 打印系统进行进一步加工。成功制备了 PCL、PCL/羟基磷灰石和 PCL/BaTiO 复合材料支架,具有高度的一致性和由无缝集成层构成的内部结构。与 PCL/羟基磷灰石支架(40.4 ± 0.1 MPa)相比,添加 10%wt 的 BaTiO 陶瓷颗粒显著提高了支架的机械性能(54 ± 0.5 MPa);此外,BaTiO 的存在增加了整个频谱和测试温度下的介电常数。人成骨肉瘤细胞 Saos-2 接种在支架上,并评估了细胞粘附、增殖、分化和骨样细胞外基质的沉积。所有测试的支架(PCL、PCL/羟基磷灰石和 PCL/BaTiO)均支持细胞生长和活力,保持成骨细胞特征形态,PCL/BaTiO 复合材料支架表现出更高的矿化(碱性磷酸酶活性)和沉积的骨样细胞外基质(骨钙素和 I 型胶原蛋白)。用于制造电活性 PCL/BaTiO 复合材料支架的单步多材料增材制造技术具有可持续性(减少材料浪费和制造成本)的巨大潜力,并且重要的是表明 PCL/BaTiO 支架是满足承重骨组织工程应用需求的有前途的候选材料。

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