Facilitate Angiogenesis and Neurogenesis by Growth Factors Integrated Decellularized Matrix Hydrogel

去细胞化 血管生成 血管内皮生长因子 神经导管 神经生长因子 细胞生物学 化学 脐静脉 自愈水凝胶 神经发生 神经突 新生血管 生物医学工程 细胞外基质 医学 再生(生物学) 癌症研究 生物 体外 生物化学 血管内皮生长因子受体 有机化学 受体
作者
Rui Li,Jinghui Xu,Zilong Rao,Rongli Deng,Yiwei Xu,Shuai Qiu,Houqing Long,Qingtang Zhu,Xiaolin Liu,Ying Bai,Daping Quan
出处
期刊:Tissue Engineering Part A [Mary Ann Liebert]
卷期号:27 (11-12): 771-787 被引量:30
标识
DOI:10.1089/ten.tea.2020.0227
摘要

Neurological functional recovery depends on the synergistic interaction between angiogenesis and neurogenesis after peripheral nerve injury (PNI). Decellularized nerve matrix hydrogels have drawn much attention and been considered as potential therapeutic biomaterials for neurovascularization, due to their intrinsic advantages in construction of a growth-permissive microenvironment, strong affinity to multiple growth factors (GFs), and promotion of neurite outgrowth. In the present study, nerve growth factor (NGF) and vascular endothelial growth factor (VEGF) were incorporated into porcine decellularized nerve matrix hydrogel (pDNM-gel) for PNI treatment. Both GFs bound strongly to pDNM-gel and underwent a controlled release manner, which showed facilitated axonal extension and vascular-like tube formation in vitro. Especially, a companion growth was identified when human umbilical vein endothelial cells and neurons were cocultured on the GFs containing pDNM-gel. In a crushed rat sciatic nerve model, the incorporated NGF and VEGF appeared to contribute for axonal growth and neovascularization correspondingly but separately. Both GFs were equally important in improving nerve functional recovery after in situ administration. These findings indicate that pDNM-gel is not only a bioactive hydrogel-based material that can be used alone, but also serves as suitable carrier of multiple GFs for promoting an effective PNI repair. Impact statement Decellularized matrix hydrogel derived from nerve tissue has demonstrated its effectiveness in promoting nerve reinnervation, remyelination, and functionalization. Meanwhile, angiogenesis is highly desirable for treatment of long-distance peripheral nerve defects. To this end, we incorporated both vascular endothelial growth factor (VEGF) and nerve growth factor (NGF) into porcine decellularized nerve matrix hydrogel (pDNM-gel) to induce neovascularization and neuroregeneration. At the cellular level, the pDNM-gel with both growth factors (GFs) exhibited significant capability in promoting axonal elongation, Schwann cell proliferation and migration, as well as vessel/nerve interaction. In crushed peripheral nerve injury (PNI) rat model, the integrated VEGF was more favorable for angiogenesis, whereas NGF mainly contributed to neurogenesis. However, the combination of both GFs in pDNM-gel highly facilitated motor functional recovery, highlighting the therapeutic promise of decellularized matrix hydrogel for growth factor delivery toward neuroprotection and neuroregeneration after PNI.
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