Bioactive Elastic Scaffolds Loaded with Neural Stem Cells Promote Rapid Spinal Cord Regeneration,ACS Biomaterials Science & Engineering

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Bioactive Elastic Scaffolds Loaded with Neural Stem Cells Promote Rapid Spinal Cord Regeneration
ACS Biomaterials Science & Engineering ( IF 5.4 ) Pub Date : 2020-09-17 , DOI: 10.1021/acsbiomaterials.0c01057
Zhe Gong _{1,

2} , Dong Lei ₃ , Chenggui Wang _{1,

2} , Chao Yu _{1,

2} , Kaishun Xia _{1,

2} , Jiawei Shu _{1,

2} , Liwei Ying _{1,

2} , Jiangnan Du _{1,

2} , Jingkai Wang _{1,

2} , Xianpeng Huang _{1,

2} , Licheng Ni _{1,

2} , Cong Wang _{1,

2} , Jingquan Lin ₄ , Fangcai Li _{1,

2} , Zhengwei You ₃ , Chengzhen Liang _{1,

2}

Affiliation

Despite decades of research, spinal cord injury (SCI) still causes irreparable damage to the human body. Key challenges that hinder the regeneration and extension of neurons following SCI must be overcome, including the overexpressed glial scar formation and strong inflammatory responses in lesion tissue. Transplantation of neural stem cells (NSCs) represents a promising therapeutic method due to its beneficial roles like growth factor secretion and anti-inflammation. However, NSCs usually differentiate into astrocytes, which is considered as one potential limitation of current NSC therapy. Herein, we fabricate an elastic poly(sebacoyl diglyceride) (PSeD) scaffold to mimic the mechanical properties of the natural spinal cord. The PSeD scaffold is coated with poly(sebacoyl diglyceride)-isoleucine-lysine-valine-alanine-valine-serine (PSeD-IKVAVS) to create a bioactive interface. The core point of this topic is divided into two parts. First, PSeD is a bioelastomer and its mechanical properties are similar to those of the natural spinal cord. This feature reduces the direct stimulation to the spinal cord tissue by the elastomer and then reduces the immune response or resistance caused by the host spinal cord tissue. Second, the IKVAVS peptide modifies PSeD to create a bioactive interface to support NSC growth and differentiation. In the in vivo study, the number of CD68-positive macrophages decreased in the PSeD-IKVAVS/NSC group compared to that in the SCI group (20% vs 60%). The low inflammation induced by the scaffold was beneficial to NSCs, resulting in increased locomotor recovery, as indicated by the increased Basso–Beattie–Bresnahan score (5, the average score in the PSeD-IKVAVS/NSC group, vs 2, the average score in the SCI group). Based on the above two characteristics, a PSeD-IKVAVS bioelastomer is fabricated, which provides a beneficial and bioactive microenvironment for NSCs after transplantation.

中文翻译：

具有神经干细胞的生物活性弹性支架促进脊髓快速再生。

尽管进行了数十年的研究，脊髓损伤（SCI）仍然会对人体造成无法弥补的损害。必须克服阻碍SCI后神经元再生和扩展的关键挑战，包括过表达的神经胶质瘢痕形成和病变组织中强烈的炎症反应。神经干细胞（NSC）的移植由于其有益的作用（如生长因子分泌和抗炎作用）而代表了一种有前途的治疗方法。然而，NSC通常分化为星形胶质细胞，这被认为是当前NSC治疗的一种潜在限制。本文中，我们制造了一种弹性聚（癸二酰基甘油二酸酯）（PSeD）支架，以模仿天然脊髓的机械性能。PSeD支架涂有聚（癸二酰基甘油二酸酯）-异亮氨酸-赖氨酸-缬氨酸-丙氨酸-缬氨酸-丝氨酸（PSeD-IKVAVS），可形成生物活性界面。本主题的核心分为两个部分。首先，PSeD是一种生物弹性体，其机械性能与天然脊髓相似。该特征减少了弹性体对脊髓组织的直接刺激，然后减少了由宿主脊髓组织引起的免疫应答或抵抗力。其次，IKVAVS肽修饰PSeD以创建生物活性界面以支持NSC的生长和分化。在里面该特征减少了弹性体对脊髓组织的直接刺激，然后减少了由宿主脊髓组织引起的免疫应答或抵抗力。其次，IKVAVS肽修饰PSeD以创建生物活性界面来支持NSC的生长和分化。在里面该特征减少了弹性体对脊髓组织的直接刺激，然后减少了由宿主脊髓组织引起的免疫应答或抵抗力。其次，IKVAVS肽修饰PSeD以创建生物活性界面来支持NSC的生长和分化。在里面在体内研究中，与SCI组相比，PSeD-IKVAVS / NSC组的CD68阳性巨噬细胞数量减少了（20％比60％）。Basso-Beattie-Bresnahan评分提高（5，PSeD-IKVAVS / NSC组的平均得分，而平均得分为2）表明，支架引起的低炎症对NSC有益，导致运动恢复增加。在SCI组中）。基于以上两个特征，制备了PSeD-IKVAVS生物弹性体，为NSC移植后提供了有益的生物活性微环境。

更新日期：2020-11-09

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