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3D 打印 Ti-6Al-4V 支架以支持成骨细胞并限制细菌功能而不使用药物:预测方程和实验。

3-D printed Ti-6Al-4V scaffolds for supporting osteoblast and restricting bacterial functions without using drugs: Predictive equations and experiments.

机构信息

Department of Chemical Engineering, Northeastern University, Boston, MA 02115, USA.

HD Lifesciences LLC, Woburn, MA 01801, USA.

出版信息

Acta Biomater. 2019 Sep 15;96:662-673. doi: 10.1016/j.actbio.2019.06.055. Epub 2019 Jul 3.

DOI:10.1016/j.actbio.2019.06.055
PMID:31279162
Abstract

Conditions resulting from musculoskeletal deficiencies (MSDs) are wide-ranging and retain the likelihood for restricting motion or producing pain, especially in the lower back, neck, and upper limbs. Engineered scaffold devices are being produced to replace antiquated modalities that suffer from structural and mechanical deficiencies in the treatment of MSDs. Here, as-fabricated Ti-6Al-4V-based Hive™ interbody fusion scaffolds, commercialized by HD Lifesciences LLC, were assayed for their osteogenicity and antibacterial potential using a series of characterization and in vitro tests, as well as by quantitative analyses. A topographical assessment of the Hive™ meshes indicated that the elementally pure substrates are microscopically porous and rough, in addition to displaying structural heterogeneity. Roughness estimations and static contact angle measurements recommended the use of the as-fabricated Ti-6Al-4V substrates for supporting osteoblast attachment, especially, due to the improved surface roughness and wettability values of these scaffolds relative to the unembellished Ti-6Al-4V surfaces. Quantitative correlations relating the surface properties of roughness and energy were applied to predict cellular behaviors. Cell growth suppositions were experimentally corroborated. Critical in vitro data indicated the competencies of the Hive™ scaffolds for promoting the adhesion and proliferation of human fetal osteoblasts (hFOBs), accumulating substantial calcium deposition from metabolizing hFOBs, and restricting the attachment of bacteria. The model system that investigated the pre-adsorption of casein proteins along the Hive™ test substrates additionally furthered the notion that bacterial attachment may be restricted, with short-scale adhesion dynamics serving as the theoretical basis for this hypothesis. In this manner, this study showed that through predictive models and experiments, these novel 3D printed Ti-based scaffolds can increase bone cell while decreasing bacteria functions without using drugs. STATEMENT OF SIGNIFICANCE: Sintered Ti-6Al-4V spinal fusion devices (Hive™) manufactured and marketed by HD Lifesciences LLC were assessed for their biocompatibility and antibacterial performance. A mixed methods approach was employed, whereby quantitative measures were used to predict the ability for Hive™ substrates to adsorb specialized proteins and to restrict bacterial surface colonization. In vitro tests that evaluated bone cell and bacterial adhesion, calcium deposition, and protein adsorption supported quantitative predictions. The data herein presented demonstrate the following: (1) surface energy is an important predictor of implant-cell interactions, (2) strong correlations exist between surface energy and surface roughness, (3) mathematical models can be used to improve and predict implant device perofrmance, and (4) porous, rough, 3D-printed materials perform well in terms of biocompatibility and antimicrobial efficacy.

摘要

由肌肉骨骼缺陷(MSD)引起的病症范围广泛,并有可能限制运动或产生疼痛,尤其是在背部、颈部和上肢。为了替代在治疗 MSD 方面存在结构和机械缺陷的陈旧模式,正在制造工程支架设备。在这里,由 HD Lifesciences LLC 商业化的 Ti-6Al-4V 基 Hive™椎间融合支架,通过一系列表征和体外测试以及定量分析,对其成骨和抗菌潜力进行了测定。对 Hive™网眼的形貌评估表明,元素纯基底在微观上是多孔和粗糙的,此外还显示出结构异质性。粗糙度估算和静态接触角测量建议使用制造的 Ti-6Al-4V 基底来支持成骨细胞附着,特别是由于这些支架相对于未修饰的 Ti-6Al-4V 表面具有改善的表面粗糙度和润湿性值。与粗糙度和能量表面特性相关的定量相关性可用于预测细胞行为。细胞生长假设得到了实验验证。关键的体外数据表明,Hive™支架具有促进人胎成骨细胞(hFOB)附着和增殖的能力,从代谢 hFOB 中积累大量钙沉积,并限制细菌附着。在研究 Hive™测试基底预吸附酪蛋白蛋白的模型系统中,进一步证实了细菌附着可能受到限制的观点,短期附着动力学为该假设提供了理论依据。通过这种方式,本研究表明,通过预测模型和实验,这些新型 3D 打印 Ti 基支架可以在不使用药物的情况下增加骨细胞,同时减少细菌功能。意义声明:由 HD Lifesciences LLC 制造和销售的烧结 Ti-6Al-4V 脊柱融合装置(Hive™)评估了其生物相容性和抗菌性能。采用混合方法,其中定量测量用于预测 Hive™基底吸附专用蛋白和限制细菌表面定植的能力。评估骨细胞和细菌附着、钙沉积和蛋白质吸附的体外测试支持定量预测。本文介绍的数据表明:(1)表面能是植入细胞相互作用的重要预测指标,(2)表面能与表面粗糙度之间存在很强的相关性,(3)数学模型可用于改善和预测植入设备的性能,(4)多孔、粗糙的 3D 打印材料在生物相容性和抗菌效果方面表现良好。

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