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应用高分辨率 DLP 立体光固化技术制造用于骨再生的磷酸三钙支架。

Application of high resolution DLP stereolithography for fabrication of tricalcium phosphate scaffolds for bone regeneration.

机构信息

Institute of Musculoskeletal Sciences (IOMS), UCL Division of Surgery and Interventional Science, Royal National Orthopaedic Hospital-NHS Trust. Stanmore, Middlesex, HA7 4LP, United Kingdom.

Department of Chemistry, University College London, London, United Kingdom.

出版信息

Biomed Mater. 2019 Jun 19;14(4):045018. doi: 10.1088/1748-605X/ab279d.

DOI:10.1088/1748-605X/ab279d
PMID:31170697
Abstract

Bone regeneration requires porous and mechanically stable scaffolds to support tissue integration and angiogenesis, which is essential for bone tissue regeneration. With the advent of additive manufacturing processes, production of complex porous architectures has become feasible. However, a balance has to be sorted between the porous architecture and mechanical stability, which facilitates bone regeneration for load bearing applications. The current study evaluates the use of high resolution digital light processing (DLP) -based additive manufacturing to produce complex but mechanical stable scaffolds based on β-tricalcium phosphate (β-TCP) for bone regeneration. Four different geometries: a rectilinear Grid, a hexagonal Kagome, a Schwarz primitive, and a hollow Schwarz architecture are designed with 400 μm pores and 75 or 50 vol% porosity. However, after initial screening for design stability and mechanical properties, only the rectilinear Grid structure, and the hexagonal Kagome structure are found to be reproducible and showed higher mechanical properties. Micro computed tomography (μ-CT) analysis shows <2 vol% error in porosity and <6% relative deviation of average pore sizes for the Grid structures. At 50 vol% porosity, this architecture also has the highest compressive strength of 44.7 MPa (Weibull modulus is 5.28), while bulk specimens reach 235 ± 37 MPa. To evaluate suitability of 3D scaffolds produced by DLP methods for bone regeneration, scaffolds were cultured with murine preosteoblastic MC3T3-E1 cells. Short term study showed cell growth over 14 d, with more than two-fold increase of alkaline phosphatase (ALP) activity compared to cells on 2D tissue culture plastic. Collagen deposition was increased by a factor of 1.5-2 when compared to the 2D controls. This confirms retention of biocompatible and osteo-inductive properties of β-TCP following the DLP process. This study has implications for designing of the high resolution porous scaffolds for bone regenerative applications and contributes to understanding of DLP based additive manufacturing process for medical applications.

摘要

骨再生需要多孔且机械稳定的支架来支持组织整合和血管生成,这对于骨组织再生至关重要。随着增材制造工艺的出现,复杂多孔结构的生产成为可能。然而,必须在多孔结构和机械稳定性之间取得平衡,这有利于承载应用中的骨再生。本研究评估了使用高分辨率数字光处理(DLP)基于添加剂制造生产基于β-磷酸三钙(β-TCP)的用于骨再生的复杂但机械稳定的支架。设计了四种不同的几何形状:直线网格、六方凯格、施瓦茨基元和中空施瓦茨结构,具有 400μm 的孔和 75 或 50vol%的孔隙率。然而,在进行设计稳定性和机械性能的初步筛选后,只有直线网格结构和六方凯格结构被发现是可重复的,并显示出更高的机械性能。微计算机断层扫描(μ-CT)分析表明,网格结构的孔隙率误差<2vol%,平均孔径的相对偏差<6%。在 50vol%的孔隙率下,该结构还具有最高的压缩强度 44.7MPa(威布尔模量为 5.28),而块状标本达到 235±37MPa。为了评估通过 DLP 方法生产的 3D 支架用于骨再生的适宜性,将支架与鼠前成骨细胞 MC3T3-E1 细胞共培养。短期研究表明,细胞在 14 天内生长,碱性磷酸酶(ALP)活性比 2D 组织培养塑料上的细胞增加了两倍多。与 2D 对照相比,胶原蛋白沉积增加了 1.5-2 倍。这证实了β-TCP 在 DLP 工艺后保留了生物相容性和成骨性。本研究对设计用于骨再生应用的高分辨率多孔支架具有重要意义,并有助于理解用于医疗应用的 DLP 基于添加剂制造工艺。

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