Academy of Medical Engineering and Translational Medicine, Tianjin University, Tianjin, 300072, China.
Department of Neurosurgery, West China Hospital, West China Medical School, Sichuan University, Chengdu, 610041, Sichuan, China.
Stem Cell Res Ther. 2022 Dec 19;13(1):525. doi: 10.1186/s13287-022-03208-0.
The effects of traumatic brain injury (TBI) can include physical disability and even death. The development of effective therapies to promote neurological recovery is still a challenging problem. 3D-printed biomaterials are considered to have a promising future in TBI repair. The injury-preconditioned secretome derived from human umbilical cord blood mesenchymal stem cells showed better stability in neurological recovery after TBI. Therefore, it is reasonable to assume that a biological scaffold loaded with an injury-preconditioned secretome could facilitate neural network reconstruction after TBI.
In this study, we fabricated injury-preconditioned secretome/collagen/heparan sulfate scaffolds by 3D printing. The scaffold structure and porosity were examined by scanning electron microscopy and HE staining. The cytocompatibility of the scaffolds was characterized by MTT analysis, HE staining and electron microscopy. The modified Neurological Severity Score (mNSS), Morris water maze (MWM), and motor evoked potential (MEP) were used to examine the recovery of cognitive and locomotor function after TBI in rats. HE staining, silver staining, Nissl staining, immunofluorescence, and transmission electron microscopy were used to detect the reconstruction of neural structures and pathophysiological processes. The biocompatibility of the scaffolds in vivo was characterized by tolerance exposure and liver/kidney function assays.
The excellent mechanical and porosity characteristics of the composite scaffold allowed it to efficiently regulate the secretome release rate. MTT and cell adhesion assays demonstrated that the scaffold loaded with the injury-preconditioned secretome (3D-CH-IB-ST) had better cytocompatibility than that loaded with the normal secretome (3D-CH-ST). In the rat TBI model, cognitive and locomotor function including mNSS, MWM, and MEP clearly improved when the scaffold was transplanted into the damage site. There is a significant improvement in nerve tissue at the site of lesion. More abundant endogenous neurons with nerve fibers, synaptic structures, and myelin sheaths were observed in the 3D-CH-IB-ST group. Furthermore, the apoptotic response and neuroinflammation were significantly reduced and functional vessels were observed at the injury site. Good exposure tolerance in vivo demonstrated favorable biocompatibility of the scaffold.
Our results demonstrated that injury-preconditioned secretome/collagen/heparan sulfate scaffolds fabricated by 3D printing promoted neurological recovery after TBI by reconstructing neural networks, suggesting that the implantation of the scaffolds could be a novel way to alleviate brain damage following TBI.
创伤性脑损伤 (TBI) 的影响可能包括身体残疾甚至死亡。开发有效的治疗方法以促进神经恢复仍然是一个具有挑战性的问题。3D 打印生物材料被认为在 TBI 修复方面具有广阔的前景。从人脐带血间充质干细胞衍生的损伤预处理分泌组在 TBI 后神经恢复方面表现出更好的稳定性。因此，可以合理地假设负载损伤预处理分泌组的生物支架可以促进 TBI 后的神经网络重建。
在这项研究中，我们通过 3D 打印制造了损伤预处理分泌组/胶原/硫酸乙酰肝素支架。通过扫描电子显微镜和 HE 染色检查支架结构和孔隙率。通过 MTT 分析、HE 染色和电子显微镜检查支架的细胞相容性。改良的神经损伤严重程度评分（mNSS）、Morris 水迷宫（MWM）和运动诱发电位（MEP）用于检测 TBI 后大鼠认知和运动功能的恢复情况。HE 染色、银染色、尼氏染色、免疫荧光和透射电镜用于检测神经结构和病理生理过程的重建。通过耐受力暴露和肝/肾功能检测来评估支架在体内的生物相容性。
复合支架具有优异的机械性能和孔隙率特性，可有效调节分泌组的释放速率。MTT 和细胞黏附试验表明，负载损伤预处理分泌组（3D-CH-IB-ST）的支架比负载正常分泌组（3D-CH-ST）的支架具有更好的细胞相容性。在大鼠 TBI 模型中，当支架移植到损伤部位时，认知和运动功能（包括 mNSS、MWM 和 MEP）明显改善。损伤部位的神经组织明显改善。在 3D-CH-IB-ST 组中观察到更多具有神经纤维、突触结构和髓鞘的内源性神经元。此外，在损伤部位观察到凋亡反应和神经炎症明显减轻，功能性血管增多。体内良好的耐受力证明了支架的良好生物相容性。
我们的结果表明，通过重建神经网络，3D 打印制造的损伤预处理分泌组/胶原/硫酸乙酰肝素支架促进了 TBI 后的神经恢复，提示植入支架可能是减轻 TBI 后脑损伤的一种新方法。
Zotero 插件
