Protease-Sensitive, VEGF-Mimetic Peptide, and IKVAV Laminin-Derived Peptide Sequences within Elastin-Like Recombinamer Scaffolds Provide Spatiotemporally Synchronized Guidance of Angiogenesis and Neurogenesis
Protease-Sensitive, VEGF-Mimetic Peptide, and IKVAV Laminin-Derived Peptide Sequences within Elastin-Like Recombinamer Scaffolds Provide Spatiotemporally Synchronized Guidance of Angiogenesis and Neurogenesis
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DOI：
10.1002/adhm.202201646
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发表时间：
2022-09-30
影响因子：
10
通讯作者：
Carlos Rodriguez-Cabello, Jose
中科院分区：
文献类型：
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作者：
Gonzalez-Perez, Fernando;Alonso, Matilde;Carlos Rodriguez-Cabello, Jose
血管化和神经支配的时空控制是高级组织再生的一个理想标志。为此，我们设计了一个基于类弹性蛋白重组体 (ELR) 水凝胶的 3D 模型支架。它包含两个内部和明确定义的区域，即小圆柱体，相对于体积具有不同的生物活性。两者均构建在具有快速蛋白水解结构域的蛋白酶敏感 ELR 上，但其中一个具有 VEGF 模拟肽 (QK)，另一个具有层粘连蛋白衍生五肽 (IKVAV)，分别促进血管生成和神经发生。外部部分基于缓慢的蛋白水解序列和 RGD 细胞粘附结构域。体外研究表明 QK 和 IKVAV 肽分别对促进内皮细胞和轴突扩散有作用。最终 3D 支架的皮下植入证明了体内时空控制血管生成和神经发生的能力。具体来说，含有 QK 肽的内部小圆柱体促进快速内皮化，而含有 IKVAV 肽的小圆柱体促进快速神经发生。血管化和神经支配都发生在大块支架渗透之前。该支架表明，有可能在大量渗透之前在支架的预定区域诱导血管化和神经支配。这显着提高了再生活动的效率。
Spatiotemporal control of vascularization and innervation is a desired hallmark in advanced tissue regeneration. For this purpose, we design a 3D model scaffold, based on elastin-like recombinamer (ELR) hydrogels. This contains two interior and well-defined areas, small cylinders, with differentiated bioactivities with respect to the bulk. Both are constructed on a protease sensitive ELR with a fast-proteolyzed domain, but one bears a VEGF-mimetic peptide (QK) and the other a laminin-derived pentapeptide (IKVAV), to promote angiogenesis and neurogenesis, respectively. The outer bulk is based on a slow proteolytic sequence and RGD cell adhesion domains. In vitro studies show the effect of QK and IKVAV peptides on the promotion of endothelial cell and axon spreading, respectively. The subcutaneous implantation of the final 3D scaffold demonstrates the ability to spatiotemporally control angiogenesis and neurogenesis in vivo. Specifically, the inner small cylinder containing the QK peptide promotes fast endothelialization, whereas the one with IKVAV peptide promotes fast neurogenesis. Both, vascularization and innervation take place in advance of the bulk scaffold infiltration. This scaffold shows that it is possible to induce vascularization and innervation in predetermined areas of the scaffold well ahead to the bulk infiltration. That significantly increases the efficiency of the regenerative activity.