Facilitate Angiogenesis and Neurogenesis by Growth Factors Integrated Decellularized Matrix Hydrogel
Facilitate Angiogenesis and Neurogenesis by Growth Factors Integrated Decellularized Matrix Hydrogel
复制标题
通过生长因子集成脱细胞基质水凝胶促进血管生成和神经发生
DOI：
10.1089/ten.tea.2020.0227
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发表时间：
2020-11-20
影响因子：
4.1
通讯作者：
Quan, Daping
中科院分区：
文献类型：
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作者：
Li, Rui;Xu, Jinghui;Quan, Daping
来自神经组织的脱细胞基质水凝胶已证明其在促进神经再生、髓鞘再生和功能化方面的有效性。同时，血管新生是治疗长距离周围神经缺损的理想方法。为此，我们将血管内皮生长因子(VEGF)和神经生长因子(NGF)同时掺入猪去细胞神经基质水凝胶(pDNM-Gel)中，以诱导新生血管和神经再生。在细胞水平上，含有两种生长因子(GFS)的pDNM-Gel显示出显著的促进轴突延长、雪旺细胞增殖和迁移以及血管/神经相互作用的能力。在挤压周围神经损伤(PNI)大鼠模型中，整合的VEGF更有利于血管生成，而NGF主要促进神经再生。然而，两种GFs在pDNM-Gel中的结合高度促进了运动功能的恢复，突出了脱细胞基质水凝胶用于PNI后神经保护和神经再生的治疗前景。神经功能的恢复依赖于周围神经损伤(PNI)后血管生成和神经再生之间的协同作用。脱细胞神经基质水凝胶因其在构建允许生长的微环境、与多种生长因子(GFS)的亲和力强、促进轴突生长等方面的固有优势而备受关注，被认为是潜在的神经血管生物治疗材料。本研究将神经生长因子(NGF)和血管内皮生长因子(VEGF)掺入猪去细胞神经基质水凝胶(pDNM-Gel)中，用于治疗PNI。两者均与pDNM-Gel强烈结合，并以控释方式释放，在体外可促进轴突伸展和血管样管的形成。特别是，当人脐静脉内皮细胞和神经元在含有pDNM-Gel的GFS上共培养时，发现了伴随生长的现象。在挤压的大鼠坐骨神经模型中，NGF和VEGF的掺入似乎对轴突生长和新生血管有相应但不同的促进作用。两种GFs在促进原位给药后神经功能恢复方面同等重要。这些结果表明，pDNM-Gel不仅是一种可以单独使用的生物活性水凝胶材料，而且还可以作为多种GFS的合适载体，以促进PNI的有效修复。
Impact statementDecellularized 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.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.