Gong Zhe, Lei Dong, Wang Chenggui, Yu Chao, Xia Kaishun, Shu Jiawei, Ying Liwei, Du Jiangnan, Wang Jingkai, Huang Xianpeng, Ni Licheng, Wang Cong, Lin Jingquan, Li Fangcai, You Zhengwei, Liang Chengzhen
Department of Orthopedics, 2nd Affiliated Hospital, School of Medicine, Zhejiang University, #88 Jie Fang Road, Hangzhou, 310009 Zhejiang, PR China.
Orthopedics Research Institute of Zhejiang University, No. 88, Jiefang Road, Hangzhou 310009, China.
ACS Biomater Sci Eng. 2020 Nov 9;6(11):6331-6343. doi: 10.1021/acsbiomaterials.0c01057. Epub 2020 Oct 7.
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 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.
尽管经过了数十年的研究，脊髓损伤（SCI）仍然会对人体造成无法修复的损害。必须克服阻碍脊髓损伤后神经元再生和延伸的关键挑战，包括过度表达的胶质瘢痕形成和损伤组织中的强烈炎症反应。神经干细胞（NSCs）移植因其具有生长因子分泌和抗炎等有益作用，是一种很有前景的治疗方法。然而，神经干细胞通常会分化为星形胶质细胞，这被认为是当前神经干细胞治疗的一个潜在局限性。在此，我们制备了一种弹性聚（癸二酰甘油）（PSeD）支架，以模拟天然脊髓的力学性能。PSeD支架涂覆有聚（癸二酰甘油）-异亮氨酸-赖氨酸-缬氨酸-丙氨酸-缬氨酸-丝氨酸（PSeD-IKVAVS），以创建一个生物活性界面。本课题的核心要点分为两部分。第一，PSeD是一种生物弹性体，其力学性能与天然脊髓相似。这一特性减少了弹性体对脊髓组织的直接刺激，进而降低了宿主脊髓组织引起的免疫反应或抵抗力。第二，IKVAVS肽修饰PSeD以创建一个生物活性界面，以支持神经干细胞的生长和分化。在该研究中，与脊髓损伤组相比，PSeD-IKVAVS/神经干细胞组中CD68阳性巨噬细胞的数量减少（分别为20%和60%）。支架诱导的低炎症对神经干细胞有益，导致运动功能恢复增加，如巴索-贝蒂-布雷斯纳汉评分增加所示（PSeD-IKVAVS/神经干细胞组平均评分为5分，脊髓损伤组平均评分为2分）。基于上述两个特性，制备了一种PSeD-IKVAVS生物弹性体，它为移植后的神经干细胞提供了一个有益的生物活性微环境。
