Bensiamar Fátima, Olalde Beatriz, Cifuentes Sandra C, Argarate Nerea, Atorrasagasti Garbiñe, González-Carrasco José L, García-Rey Eduardo, Vilaboa Nuria, Saldaña Laura
Hospital Universitario La Paz-IdiPAZ, Paseo de la Castellana 261, 28046 Madrid, Spain. CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Madrid, Spain. These authors contributed equally to this study.
Biomed Mater. 2016 Oct 7;11(5):055011. doi: 10.1088/1748-6041/11/5/055011.
We developed biodegradable polymeric coatings loaded with increasing amounts of dexamethasone on composites based on polylactic acid and Mg particles for bone repair. Incorporation of Mg particles into the polymeric matrix improves the compressive behaviour of the polymer. Mg-containing composites release Mg ions into the culture medium and improve mesenchymal stem cell (MSC) viability, enhance their osteogenic potential and promote the release of angiogenic factors. Dexamethasone-loaded coatings deposited on composites delay Mg ion dissolution while releasing controlled amounts of the drug, which are highly dependent on initial payload. Release kinetic of dexamethasone from the coatings exhibits a fast initial release of the drug followed by a slower secondary release. Bioactivity of the released dexamethasone was explored by monitoring dose-dependent responses of MSCs and macrophages. Biological effects exerted by the released drug are similar to those observed in cells treated with solutions of the glucocorticoid, indicating that the method employed for inclusion of dexamethasone into the coatings does not impair its bioactive behaviour. Culturing MSCs on dexamethasone-releasing coatings enhances extracellular matrix production and initial induction to osteogenic commitment as a function of drug payload. Dexamethasone incorporated into the coatings presents anti-inflammatory activity, as shown by the decrease in the production of cytokines and angiogenic factors by macrophages and MSCs. Deposition of dexamethasone-releasing coatings on polymer/Mg composites appears to be a promising approach to delay composite degradation at the early stage of implantation and may be useful to attenuate inflammation and adverse foreign body reactions.
我们在基于聚乳酸和镁颗粒的复合材料上制备了负载量不断增加的地塞米松的可生物降解聚合物涂层，用于骨修复。将镁颗粒掺入聚合物基体中可改善聚合物的压缩性能。含镁复合材料将镁离子释放到培养基中，提高间充质干细胞（MSC）的活力，增强其成骨潜力并促进血管生成因子的释放。沉积在复合材料上的载地塞米松涂层在释放可控量药物的同时延迟了镁离子的溶解，这高度依赖于初始载药量。地塞米松从涂层中的释放动力学表现出药物的快速初始释放，随后是较慢的二次释放。通过监测MSC和巨噬细胞的剂量依赖性反应来探索释放的地塞米松的生物活性。释放的药物所发挥的生物学效应与用糖皮质激素溶液处理的细胞中观察到的效应相似，这表明将地塞米松纳入涂层所采用的方法不会损害其生物活性行为。在释放地塞米松的涂层上培养MSC可增强细胞外基质的产生，并根据药物载量对成骨定向进行初始诱导。掺入涂层中的地塞米松具有抗炎活性，巨噬细胞和MSC产生的细胞因子和血管生成因子减少即表明了这一点。在聚合物/镁复合材料上沉积释放地塞米松的涂层似乎是一种在植入早期延迟复合材料降解的有前途的方法，并且可能有助于减轻炎症和不良异物反应。
