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一种用于提高骨科植入物使用寿命的多方面仿生界面。

A multifaceted biomimetic interface to improve the longevity of orthopedic implants.

作者信息

Croes Michiel, Akhavan Behnam, Sharifahmadian Omid, Fan Haiyang, Mertens Raya, Tan Richard P, Chunara Aliza, Fadzil Arifah A, Wise Steven G, Kruyt Moyo C, Wijdicks Sebastiaan, Hennink Wim E, Bilek Marcela M M, Amin Yavari Saber

机构信息

Department of Orthopedics, University Medical Center Utrecht, Utrecht 3508GA, the Netherlands.

School of Biomedical Engineering, University of Sydney, Sydney, NSW 2006, Australia; School of Physics, University of Sydney, Sydney, New South Wales 2006, Australia.

出版信息

Acta Biomater. 2020 Jul 1;110:266-279. doi: 10.1016/j.actbio.2020.04.020. Epub 2020 Apr 25.

Abstract

The rise of additive manufacturing has provided a paradigm shift in the fabrication of precise, patient-specific implants that replicate the physical properties of native bone. However, eliciting an optimal biological response from such materials for rapid bone integration remains a challenge. Here we propose for the first time a one-step ion-assisted plasma polymerization process to create bio-functional 3D printed titanium (Ti) implants that offer rapid bone integration. Using selective laser melting, porous Ti implants with enhanced bone-mimicking mechanical properties were fabricated. The implants were functionalized uniformly with a highly reactive, radical-rich polymeric coating generated using a unique combination of plasma polymerization and plasma immersion ion implantation. We demonstrated the performance of such activated Ti implants with a focus on the coating's homogeneity, stability, and biological functionality. It was shown that the optimized coating was highly robust and possessed superb physico-chemical stability in a corrosive physiological solution. The plasma activated coating was cytocompatible and non-immunogenic; and through its high reactivity, it allowed for easy, one-step covalent immobilization of functional biomolecules in the absence of solvents or chemicals. The activated Ti implants bio-functionalized with bone morphogenetic protein 2 (BMP-2) showed a reduced protein desorption and a more sustained osteoblast response both in vitro and in vivo compared to implants modified through conventional physisorption of BMP-2. The versatile new approach presented here will enable the development of bio-functionalized additively manufactured implants that are patient-specific and offer improved integration with host tissue. STATEMENT OF SIGNIFICANCE: Additive manufacturing has revolutionized the fabrication of patient-specific orthopedic implants. Although such 3D printed implants can show desirable mechanical and mass transport properties, they often require surface bio-functionalities to enable control over the biological response. Surface covalent immobilization of bioactive molecules is a viable approach to achieve this. Here we report the development of additively manufactured titanium implants that precisely replicate the physical properties of native bone and are bio-functionalized in a simple, reagent-free step. Our results show that covalent attachment of bone-related growth factors through ion-assisted plasma polymerized interlayers circumvents their desorption in physiological solution and significantly improves the bone induction by the implants both in vitro and in vivo.

摘要

增材制造的兴起为制造精确的、针对患者的植入物带来了范式转变,这种植入物能够复制天然骨骼的物理特性。然而,要使这类材料引发最佳生物反应以实现快速骨整合,仍然是一项挑战。在此,我们首次提出一种一步离子辅助等离子体聚合工艺,以制造具有生物功能的3D打印钛(Ti)植入物,实现快速骨整合。利用选择性激光熔化技术,制造出具有增强的仿骨力学性能的多孔Ti植入物。通过等离子体聚合和等离子体浸没离子注入的独特组合,生成富含高活性自由基的聚合物涂层,使植入物均匀功能化。我们重点研究了这种活化Ti植入物涂层的均匀性、稳定性和生物功能。结果表明,优化后的涂层具有高度稳定性,在腐蚀性生理溶液中具有出色的物理化学稳定性。等离子体活化涂层具有细胞相容性且无免疫原性;通过其高反应活性,在无溶剂或化学物质的情况下,可轻松实现功能生物分子的一步共价固定。与通过传统物理吸附BMP-2修饰的植入物相比,用骨形态发生蛋白2(BMP-2)进行生物功能化的活化Ti植入物在体外和体内均表现出蛋白质解吸减少以及成骨细胞反应更持久。本文介绍的这种通用新方法将推动生物功能化增材制造植入物的开发,这些植入物针对患者定制,与宿主组织的整合性更好。重要性声明:增材制造彻底改变了针对患者的骨科植入物的制造方式。尽管此类3D打印植入物可展现出理想的力学和传质性能,但它们通常需要表面生物功能来控制生物反应。生物活性分子的表面共价固定是实现这一目标的可行方法。在此,我们报告了增材制造钛植入物的开发情况,该植入物精确复制天然骨骼的物理特性,并通过简单的无试剂步骤进行生物功能化。我们的结果表明,通过离子辅助等离子体聚合中间层共价连接骨相关生长因子可避免其在生理溶液中的解吸,并显著提高植入物在体外和体内的骨诱导能力。

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