Department of Biomedical Engineering, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, 110 8th St, Troy, NY, 12180, USA.
Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, 1623 15th St., Troy, NY, 12180, USA.
Adv Biol (Weinh). 2024 Oct;8(10):e2300531. doi: 10.1002/adbi.202300531. Epub 2024 Jun 27.
A spinal cord injury (SCI) compresses the spinal cord, killing neurons and glia at the injury site and resulting in prolonged inflammation and scarring that prevents regeneration. Astrocytes, the main glia in the spinal cord, become reactive following SCI and contribute to adverse outcomes. The anti-inflammatory cytokine transforming growth factor beta 3 (TGFβ3) has been shown to mitigate astrocyte reactivity; however, the effects of prolonged TGFβ3 exposure on reactive astrocyte phenotype have not yet been explored. This study investigates whether magnetic core-shell electrospun fibers can be used to alter the release rate of TGFβ3 using externally applied magnetic fields, with the eventual application of tailored drug delivery based on SCI severity. Magnetic core-shell fibers are fabricated by incorporating superparamagnetic iron oxide nanoparticles (SPIONs) into the shell and TGFβ3 into the core solution for coaxial electrospinning. Magnetic field stimulation increased the release rate of TGFβ3 from the fibers by 25% over 7 days and released TGFβ3 reduced gene expression of key astrocyte reactivity markers by at least twofold. This is the first study to magnetically deliver bioactive proteins from magnetic fibers and to assess the effect of sustained release of TGFβ3 on reactive astrocyte phenotype.
脊髓损伤 (SCI) 会压迫脊髓,导致损伤部位的神经元和神经胶质细胞死亡,并引发长期的炎症和瘢痕形成,从而阻止再生。星形胶质细胞是脊髓中的主要神经胶质细胞,在 SCI 后会发生反应,并导致不良后果。抗炎细胞因子转化生长因子β 3 (TGFβ3) 已被证明能减轻星形胶质细胞的反应性;然而,TGFβ3 长时间暴露对反应性星形胶质细胞表型的影响尚未得到探索。本研究探讨了是否可以使用外加磁场来改变磁芯壳电纺纤维中 TGFβ3 的释放速率,最终根据 SCI 的严重程度应用定制的药物输送。通过将超顺磁性氧化铁纳米粒子 (SPIONs) 掺入壳层和 TGFβ3 掺入芯溶液中,进行同轴电纺来制备磁性核壳纤维。磁场刺激使纤维中 TGFβ3 的释放速率在 7 天内增加了 25%,释放的 TGFβ3 使关键星形胶质细胞反应性标志物的基因表达至少降低了两倍。这是首次从磁性纤维中磁控输送生物活性蛋白,并评估 TGFβ3 持续释放对反应性星形胶质细胞表型的影响的研究。