A novel hydrogel-based combination therapy for effective neuroregeneration after spinal cord injury
A novel hydrogel-based combination therapy for effective neuroregeneration after spinal cord injury
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DOI：
10.1016/j.cej.2021.128964
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发表时间：
2021-07
影响因子：
15.1
通讯作者：
Qingqing Wang;Xiaoying Dong;Hongyu Zhang;Peifeng Li;Xiaojie Lu;Min Wu;Weiqi Zhang;Xianfeng Lin;Yixin Zheng;Yuqin Mao;Jing Zhang;Yutian Lin;xiangxiang chen;Dingwen Chen;Jian Wang;Jian Xiao
中科院分区：
文献类型：
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作者：
Qingqing Wang;Xiaoying Dong;Hongyu Zhang;Peifeng Li;Xiaojie Lu;Min Wu;Weiqi Zhang;Xianfeng Lin;Yixin Zheng;Yuqin Mao;Jing Zhang;Yutian Lin;xiangxiang chen;Dingwen Chen;Jian Wang;Jian Xiao
脊髓损伤(SCI)在世界范围内仍是一个具有挑战性的临床问题。综合疗法是治疗脊髓损伤的一种有前景的治疗策略。最近的研究报道，多西紫杉醇(DTX)促进内源性轴突再生，碱性成纤维细胞生长因子(BFGF)调节脊髓损伤后神经元的存活、可塑性和细胞外基质(ECM)。我们构建了一种新型的生物相容脂质体(LIP)，它以丝素蛋白(SF)水凝胶为核心(SLIP)，同时传递具有不同物理化学特性的碱性成纤维细胞生长因子和DTX。随后，将SLIP-bFGF/DTX添加到SF水凝胶中，形成三维支架凝胶(SLIP-bFGF/DTX@SF)。我们评估了SLIP@SF的药理学特性，并调查了组织学和功能结果。滑脱-bFGF/DTX@SF治疗能有效延长药物在脊髓损伤部位的半衰期，通过重塑细胞外基质(ECM)桥接囊肿，改善脊髓损伤大鼠的运动功能。此外，这种水凝胶对病变区域丰富的多糖具有很强的亲和力，为脊髓损伤的治疗提供了一种独特的治疗方法。此外，药物抑制微管动力学和细胞外基质重塑的机制也反映了脊髓损伤的病理特征。这种新的多药给药系统实现了显着的功能改进，同时解决了脊髓损伤病理的多个关键方面，表明了良好的临床翻译前景。
Spinal cord injury (SCI) remains a challenging clinical problem worldwide. Combination therapy is a promising therapeutic strategy for SCI. Recent investigations have reported that docetaxel (DTX) facilitates intrinsic axonal regeneration, and basic fibroblast growth factor (bFGF) regulates neuronal survival, plasticity, and extracellular matrix (ECM) after SCI. We constructed a novel biocompatible liposome (LIP) with a silk fibroin (SF) hydrogel core (SLIP) to simultaneously deliver bFGF and DTX, which have different physiochemical characteristics. Subsequently, SLIP-bFGF/DTX was added to the SF hydrogel to form a three-dimensional scaffold gel (SLIP-bFGF/DTX@SF). We evaluated the pharmacological properties of SLIP@SF and investigated histological and functional outcomes. A SLIP-bFGF/DTX@SF treatment effectively prolonged the drug half-life in the injured spinal cord area, bridged cysts by remodeling the extracellular matrix (ECM), and improved the motor function of rats with SCI. Additionally, this hydrogel demonstrated a strong affinity for the polysaccharides enriched in the lesion area providing a unique therapeutic approach for the treatment of SCI. Furthermore, the mechanisms of inhibition of microtubule dynamics and reshaping of the ECM by the drugs were demonstrated to reflected the pathological features of SCI. This novel multidrug delivery system achieves a significant functional improvement a simultaneously addresses multiple key aspects of SCI pathology indicating favorable clinical translational prospects.