<p>Cerebral hemorrhage is an acute type of stroke with a high mortality rate and very limited options for treatment because of extensive damage to the neurons and the inability of neurons to repair themselves. In this study, we developed a new injectable hydrogel using sericin and gelatin for controlled release of brain-derived neurotrophic factor (BDNF), and we assessed how the hydrogel can provide neuroprotection and promote neuroregeneration after a brain hemorrhage. The hydrogel was made using a self-assembly method with no chemical crosslinking agents, which makes the hydrogel very compatible with tissue and capable of being injected. Characterization of the physicochemical properties of the hydrogel revealed that adding the sericin improved hydrogel stability, decreased pore size, allowing for better BDNF encapsulation, and significantly controlled the release of BDNF for at least 7&#xa0;days. A SH-SY5Y cell injury model using hemin-induced cell death showed BDNF loaded inside the hydrogel improved cell viability, increased cell colony formation and migration, decreased oxidative stress, and decreased apoptosis compared to both free BDNF and blank hydrogel. Additionally, the hydrogel-treated cells had significantly greater outgrowth of neuronal processes and greater expression of neuronal markers such as βIII-tubulin and GAP43 compared to the other treatment groups. The mechanism by which the hydrogel treated the cells was through activation of TrkB signaling and downstream signaling through both the PI3K/Akt and MAPK/ERK pathways as demonstrated by Western blotting and pharmacological inhibition. BDNF released from the hydrogel maintained its biological activity and produced long-lasting therapeutic effect(s). The BDNF delivery and repair of neural tissue for the treatment of cerebrovascular diseases using injectable sericin/gelatin hydrogels are successfully accomplished by this study.</p>

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Injectable sericin/gelatin hydrogel enables sustained BDNF delivery and promotes neural repair under hemorrhagic injury conditions

  • Zhiwei Gu,
  • Jiajie Xia,
  • Zhihao Yang,
  • Dagang Song,
  • Jingjing Guo,
  • Yongde Chen,
  • Chuanjian Tu

摘要

Cerebral hemorrhage is an acute type of stroke with a high mortality rate and very limited options for treatment because of extensive damage to the neurons and the inability of neurons to repair themselves. In this study, we developed a new injectable hydrogel using sericin and gelatin for controlled release of brain-derived neurotrophic factor (BDNF), and we assessed how the hydrogel can provide neuroprotection and promote neuroregeneration after a brain hemorrhage. The hydrogel was made using a self-assembly method with no chemical crosslinking agents, which makes the hydrogel very compatible with tissue and capable of being injected. Characterization of the physicochemical properties of the hydrogel revealed that adding the sericin improved hydrogel stability, decreased pore size, allowing for better BDNF encapsulation, and significantly controlled the release of BDNF for at least 7 days. A SH-SY5Y cell injury model using hemin-induced cell death showed BDNF loaded inside the hydrogel improved cell viability, increased cell colony formation and migration, decreased oxidative stress, and decreased apoptosis compared to both free BDNF and blank hydrogel. Additionally, the hydrogel-treated cells had significantly greater outgrowth of neuronal processes and greater expression of neuronal markers such as βIII-tubulin and GAP43 compared to the other treatment groups. The mechanism by which the hydrogel treated the cells was through activation of TrkB signaling and downstream signaling through both the PI3K/Akt and MAPK/ERK pathways as demonstrated by Western blotting and pharmacological inhibition. BDNF released from the hydrogel maintained its biological activity and produced long-lasting therapeutic effect(s). The BDNF delivery and repair of neural tissue for the treatment of cerebrovascular diseases using injectable sericin/gelatin hydrogels are successfully accomplished by this study.