Sustained delivery of the angiogenic QK peptide through the use of polyglutamate domains to control peptide release from bone graft materials.
Sustained delivery of the angiogenic QK peptide through the use of polyglutamate domains to control peptide release from bone graft materials.
复制标题
通过使用聚谷氨酸结构域持续递送血管生成 QK 肽，以控制骨移植材料中的肽释放。
DOI：
10.1002/jbm.a.36779
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Bellis,SusanL
中科院分区：
文献类型：
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作者：
Pensa,NicholasW;Curry,AndrewS;Reddy,MichaelS;Bellis,SusanL
血管生成在骨移植后的组织再生中起着关键作用；然而，非自体移植材料通常缺乏关键的血管生成生长因子。虽然许多研究都集中在用血管生成因子对移植物进行修饰，但这些分子的受控输送仍然是一个挑战。目前的研究描述了一种从羟基磷灰石(HA)中持续输送血管生成肽的方法，羟基磷灰石是一种常见的同种异体材料。具体地说，利用含有不同数量的谷氨酸的多谷氨酸结构域合成了血管内皮生长因子衍生的“QK”多肽。HA释放多肽的速率与谷氨酸数量呈负相关，二谷氨酸-QK(E_2-QK)首先释放，然后是四谷氨酸-QK(E4-QK)，最后是七谷氨酸-QK(E7-QK)。通过将这些多肽的混合物包裹在HA上，称为PGM-QK(聚谷氨酸修饰混合物)，实现了连续的多肽释放，从而实现了QK的梯度递送。为评价生物活性，将羟基磷灰石表面涂覆PGM-QK，放置于新鲜介质中6 天。以不同的时间间隔收集含有释放的多肽的培养液，并将其放置在人脐静脉内皮细胞(HUVECs)上。评估细胞血管生成信号通路(ERK和Akt)的激活和细胞迁移。结果表明，QK多肽在6d内持续释放，并保持其激活HUVECs的能力。这些发现指出了一种梯度输送血管生成刺激的新方法。
Angiogenesis plays a pivotal role in tissue regeneration following bone‐grafting procedures; however, nonautogenous graft materials typically lack critical angiogenic growth factors. While much research has focused on modifying grafts with angiogenic factors, controlled delivery of these molecules remains a challenge. The current study describes a method for sustained delivery of an angiogenic peptide from hydroxyapatite (HA), a common alloplast material. Specifically, VEGF‐derived “QK” peptides were synthesized with polyglutamate domains containing varying numbers of glutamates. The rate of peptide release from HA inversely correlated with glutamate number, with diglutamate‐QK (E2‐QK) released first, followed by tetraglutamate‐QK (E4‐QK), and finally, heptaglutamate‐QK (E7‐QK). By coating HA with a mixture of these peptides, termed, PGM‐QK (polyglutamate‐modified mixture), sequential peptide release was achieved, enabling gradient QK delivery. To evaluate bioactivity, HA disks were coated with PGM‐QK and then placed in fresh media for 6 days. Media containing the released peptides was collected at varying time intervals and placed on human umbilical vein endothelial cells (HUVECs). Cells were evaluated for activation of angiogenic signaling pathways (ERK and Akt) and cell migration. Results showed that QK peptides were continuously released over the 6‐day interval, and maintained their capacity to activate HUVECs. These findings point to a new approach for gradient delivery of an angiogenic stimulus.