Johnson Ian, Wang Sebo Michelle, Silken Christine, Liu Huinan
Department of Bioengineering, University of California at Riverside, 900 University Avenue, Riverside, CA 92521, United States.
Department of Bioengineering, University of California at Riverside, 900 University Avenue, Riverside, CA 92521, United States; Materials Science and Engineering Program, University of California at Riverside, 900 University Avenue, Riverside, CA 92521, United States; The Stem Cell Center, University of California at Riverside, 900 University Avenue, Riverside, CA 92521, United States; Cellular, Molecular, and Developmental Biology (CMDB) Program, University of California at Riverside, 900 University Avenue, Riverside, CA 92521, United States.
Acta Biomater. 2016 May;36:332-49. doi: 10.1016/j.actbio.2016.03.026. Epub 2016 Mar 19.
Nanocomposite coatings offer multiple functions simultaneously to improve the interfacial properties of magnesium (Mg) alloys for skeletal implant applications, e.g., controlling the degradation rate of Mg substrates, improving bone cell functions, and providing drug delivery capability. However, the effective service time of nanocomposite coatings may be limited due to their early delamination from the Mg-based substrates. Therefore, the objective of this study was to address the delamination issue of nanocomposite coatings, improve the coating properties for reducing the degradation of Mg-based substrates, and thus improve their cytocompatibility with bone marrow derived mesenchymal stem cells (BMSCs). The surface conditions of the substrates, polymer component type of the nanocomposite coatings, and post-deposition processing are the key parameters that contribute to the efficacy of the nanocomposite coatings in regulating substrate degradation and bone cell responses. Specifically, the effects of metallic surface versus alkaline heat-treated hydroxide surface of the substrates on coating quality were investigated. For the nanocomposite coatings, nanophase hydroxyapatite (nHA) was dispersed in three types of biodegradable polymers, i.e., poly(lactic-co-glycolic acid) (PLGA), poly(l-lactic acid) (PLLA), or poly(caprolactone) (PCL) to determine which polymer component could provide integrated properties for slowest Mg degradation. The nanocomposite coatings with or without post-deposition processing, i.e., melting, annealing, were compared to determine which processing route improved the properties of the nanocomposite coatings most significantly. The results showed that optimizing the coating processes addressed the delamination issue. The melted then annealed nHA/PCL coating on the metallic Mg substrates showed the slowest degradation and the best coating adhesion, among all the combinations of conditions studied; and, it improved the adhesion density of BMSCs. This study elucidated the key parameters for optimizing nanocomposite coatings on Mg-based substrates for skeletal implant applications, and provided rational design guidelines for the nanocomposite coatings on Mg alloys for potential clinical translation of biodegradable Mg-based implants.
This manuscript describes the systemic optimization of nanocomposite coatings to control the degradation and bioactivity of magnesium for skeletal implant applications. The key parameters influencing the integrity and functions of the nanocomposite coatings on magnesium were identified, guidelines for the optimization of the coatings were established, and the benefits of coating optimization were demonstrated through reduced magnesium degradation and increased bone marrow derived mesenchymal stem cell (BMSC) adhesion in vitro. The guidelines developed in this manuscript are valuable for the biometal field to improve the design of bioresorbable implants and devices, which will advance the clinical translation of magnesium-based implants.
纳米复合涂层可同时提供多种功能，以改善镁（Mg）合金在骨骼植入应用中的界面性能，例如控制镁基体的降解速率、改善骨细胞功能以及提供药物递送能力。然而，纳米复合涂层的有效服役时间可能会受到限制，因为它们会过早地从镁基基体上分层。因此，本研究的目的是解决纳米复合涂层的分层问题，改善涂层性能以减少镁基基体的降解，从而提高其与骨髓间充质干细胞（BMSC）的细胞相容性。基体的表面条件、纳米复合涂层的聚合物成分类型以及沉积后处理是影响纳米复合涂层调节基体降解和骨细胞反应效果的关键参数。具体而言，研究了基体的金属表面与碱热处理氢氧化物表面对涂层质量的影响。对于纳米复合涂层，将纳米相羟基磷灰石（nHA）分散在三种可生物降解聚合物中，即聚（乳酸-共-乙醇酸）（PLGA）、聚（L-乳酸）（PLLA）或聚己内酯（PCL），以确定哪种聚合物成分能够提供使镁降解最慢的综合性能。比较了经过或未经沉积后处理（即熔化、退火）的纳米复合涂层，以确定哪种处理路线能最显著地改善纳米复合涂层的性能。结果表明，优化涂层工艺解决了分层问题。在所有研究的条件组合中，金属镁基体上先熔化然后退火的nHA/PCL涂层降解最慢且涂层附着力最佳；并且，它提高了BMSC的黏附密度。本研究阐明了在镁基基体上优化用于骨骼植入应用的纳米复合涂层的关键参数，并为镁合金上的纳米复合涂层提供了合理的设计指南，以促进可生物降解镁基植入物的潜在临床转化。
本手稿描述了纳米复合涂层的系统优化，以控制镁在骨骼植入应用中的降解和生物活性。确定了影响镁上纳米复合涂层完整性和功能的关键参数，建立了涂层优化指南，并通过降低镁降解和增加体外骨髓间充质干细胞（BMSC）黏附证明了涂层优化的益处。本手稿中制定的指南对于生物金属领域改进可生物吸收植入物和器械的设计具有重要价值，这将推动镁基植入物的临床转化。
