Injectable and Photocurable Gene Scaffold Facilitates Efficient Repair of Spinal Cord Injury,ACS Applied Materials & Interfaces

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Injectable and Photocurable Gene Scaffold Facilitates Efficient Repair of Spinal Cord Injury
ACS Applied Materials & Interfaces ( IF 8.3 ) Pub Date : 2024-01-07 , DOI: 10.1021/acsami.3c14902
Yan Gao ₁ , Kaiyu Wang ₁ , Shan Wu ₁ , Jieping Wu ₁ , Jin Zhang ₁ , Jingmei Li ₁ , Sibei Lei ₁ , Xingmei Duan ₂ , Ke Men ₁

Affiliation

RNA interference-based gene therapy has led to a strategy for spinal cord injury (SCI) therapy. However, there have been high requirements regarding the optimal gene delivery vector for siRNA-based SCI gene therapy. Here, we developed an injectable and photocurable lipid nanoparticle GelMA (PLNG) hydrogel scaffold for controlled dual siRNA delivery at the SCI wound site. The prepared PLNG scaffold could efficiently protect and retain the bioactivity of the siRNA nanocomplex. It facilitated sustainable siRNA release along with degradation in 7 days. After loading dual siRNA targeting phosphatase and tensin homologue (PTEN) and macrophage migration inhibitory factor (MIF) simultaneously, the locally administered siRNAs/PLNG scaffold efficiently improved the Basso mouse scale (BMS) score and recovered ankle joint movement and plantar stepping after treatment with only three doses. We further proved that the siRNAs/PLNG scaffold successfully regulated the activities of neurons, microglia, and macrophages, thus promoting neuron axon regeneration and remyelination. The protein array results suggested that the siRNAs/PLNG scaffold could increase the expression of growth factors and decrease the expression of inflammatory factors to regulate neuroinflammation in SCI and create a neural repair environment. Our results suggested that the PLNG scaffold siRNA delivery system is a potential candidate for siRNA-based SCI therapy.

中文翻译：

可注射和光固化基因支架促进脊髓损伤的有效修复

基于 RNA 干扰的基因治疗已形成脊髓损伤 (SCI) 治疗策略。然而，对于基于 siRNA 的 SCI 基因治疗的最佳基因递送载体有很高的要求。在这里，我们开发了一种可注射、可光固化的脂质纳米颗粒 GelMA (PLNG) 水凝胶支架，用于在 SCI 伤口部位进行受控的双 siRNA 递送。制备的PLNG支架可以有效保护和保留siRNA纳米复合物的生物活性。它促进了 siRNA 的可持续释放以及 7 天内的降解。同时加载靶向磷酸酶和张力蛋白同源物（PTEN）和巨噬细胞迁移抑制因子（MIF）的双siRNA后，局部施用的siRNA/PLNG支架有效改善了Basso小鼠量表（BMS）评分，并在治疗后恢复了踝关节运动和足底迈步。只有三剂。我们进一步证明，siRNAs/PLNG支架成功调节神经元、小胶质细胞和巨噬细胞的活性，从而促进神经元轴突再生和髓鞘再生。蛋白质阵列结果表明，siRNA/PLNG支架可以增加生长因子的表达并减少炎症因子的表达，从而调节SCI中的神经炎症并创造神经修复环境。我们的结果表明，PLNG 支架 siRNA 递送系统是基于 siRNA 的 SCI 治疗的潜在候选者。

更新日期：2024-01-07

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