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Poly(ester amide) microspheres are efficient vehicles for long-term intracerebral growth factor delivery and improve functional recovery after stroke
Biomedical Materials ( IF 4 ) Pub Date : 2020-11-21 , DOI: 10.1088/1748-605x/aba4f6
Tamar Memanishvili 1 , Emanuela Monni 1 , Jemal Tatarishivili 1 , Olle Lindvall 1 , Alexander Tsiskaridze 2 , Zaal Kokaia 1 , Daniel Tornero 1
Affiliation  

Growth factors promote plasticity in injured brain and improve impaired functions. For clinical application, efficient approaches for growth factor delivery into the brain are necessary. Poly(ester amide) (PEA)-derived microspheres (MS) could serve as vehicles due to their thermal and mechanical properties, biocompatibility and biodegradability. Vascular endothelial growth factor (VEGF) exerts both vascular and neuronal actions, making it suitable to stimulate post-stroke recovery. Here, PEA (composed of adipic acid, L-phenyl-alanine and 1,4-butanediol) MS were loaded with VEGF and injected intracerebrally in mice subjected to cortical stroke. Loaded MS provided sustained release of VEGF in vitro and, after injection, biologically active VEGF was released long-term, as evidenced by high VEGF immunoreactivity, increased VEGF tissue levels, and higher vessel density and more NG2+ cells in injured hemisphere of animals with VEGF-loaded as compared to non-loaded MS. Loaded MS gave rise to more rapid recovery of neurological score. Both loaded and non-loaded MS induced improvement in neurological score and adhesive removal test, probably due to anti-inflammatory action. In summary, grafted PEA MS can act as efficient vehicles, with anti-inflammatory action, for long-term delivery of growth factors into injured brain. Our data suggest PEA MS as a new tool for neurorestorative approaches with therapeutic potential.



中文翻译:

聚(酯酰胺)微球是长期脑内生长因子输送和改善中风后功能恢复的有效载体

生长因子促进受伤大脑的可塑性并改善受损的功能。对于临床应用,将生长因子输送到大脑的有效方法是必要的。聚(酯酰胺)(PEA)衍生的微球(MS)由于其热和机械性能、生物相容性和生物降解性,可以用作载体。血管内皮生长因子 (VEGF) 发挥血管和神经元作用,使其适合刺激中风后恢复。在这里,PEA(由己二酸、L-苯丙氨酸和 1,4-丁二醇组成)MS 装载 VEGF,并在遭受皮质中风的小鼠脑内注射。加载的 MS 提供了体外VEGF 的持续释放并且,在注射后,具有生物活性的 VEGF 被长期释放,与未加载的 MS 相比,加载 VEGF 的动物的损伤半球中的高 VEGF 免疫反应性、增加的 VEGF 组织水平、更高的血管密度和更多的 NG2+ 细胞证明了这一点. 加载 MS 使神经系统评分恢复得更快。加载和未加载的 MS 均诱导神经评分和粘合剂去除测试的改善,这可能是由于抗炎作用。总之,移植的 PEA MS 可以作为具有抗炎作用的有效载体,将生长因子长期输送到受伤的大脑中。我们的数据表明 PEA MS 是一种具有治疗潜力的神经修复方法的新工具。

更新日期:2020-11-21
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