Vastly extended drug release from poly(pro-17β-estradiol) materials facilitates in vitro neurotrophism and neuroprotection
Vastly extended drug release from poly(pro-17β-estradiol) materials facilitates in vitro neurotrophism and neuroprotection
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DOI：
10.1038/s41467-019-12835-w
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发表时间：
2019-10-23
影响因子：
16.6
通讯作者：
Palermo, Edmund F.
中科院分区：
文献类型：
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作者：
D'Amato, Anthony R.;Puhl, Devan L.;Palermo, Edmund F.
中枢神经系统（CNS）损伤持续多年，目前没有治疗方法可以解决在这一时间尺度上发展的复杂损伤级联。17 β -雌二醇（E2）在中枢神经系统内具有广泛的趋向性，靶向并诱导损伤后无数细胞的有益表型变化。为了解决大量延长E2释放的未满足需求，我们报道了第一代聚（pro-E2）生物材料支架，该支架通过体外缓慢水解在1-10年内释放纳米摩尔浓度的E2。由于其精细调节的特性，这些支架在体外证明了促进和引导神经突延伸的能力，并在体外保护神经元免受氧化应激的影响。本文报道的这些材料的设计和测试表明了下一代可植入生物材料的第一步，这些材料具有长时间释放和良好的再生潜力。
Central nervous system (CNS) injuries persist for years, and currently there are no therapeutics that can address the complex injury cascade that develops over this time-scale. 17 beta-estradiol (E2) has broad tropism within the CNS, targeting and inducing beneficial phenotypic changes in myriad cells following injury. To address the unmet need for vastly prolonged E2 release, we report first-generation poly(pro-E2) biomaterial scaffolds that release E2 at nanomolar concentrations over the course of 1-10 years via slow hydrolysis in vitro. As a result of their finely tuned properties, these scaffolds demonstrate the ability to promote and guide neurite extension ex vivo and protect neurons from oxidative stress in vitro. The design and testing of these materials reported herein demonstrate the first step towards next-generation implantable biomaterials with prolonged release and excellent regenerative potential.