Platelet-like particles improve fibrin network properties in a hemophilic model of provisional matrix structural defects
Platelet-like particles improve fibrin network properties in a hemophilic model of provisional matrix structural defects
复制标题
DOI：
10.1016/j.jcis.2020.05.088
复制
发表时间：
2020-10-01
影响因子：
9.9
通讯作者：
Brown, Ashley C.
中科院分区：
文献类型：
--
作者：
Nandi, Seema;Sommerville, Laura;Brown, Ashley C.
受伤后，会形成富含纤维蛋白的临时基质，以阻止失血，并为浸润细胞提供支架，从而重建受损组织。纤维蛋白网络形成的缺陷会导致愈合结果受损，正如血友病所证明的那样。血小板-纤维蛋白相互作用通过凝块收缩极大地影响纤维蛋白网络结构，从而随着时间的推移增加纤维蛋白密度。先前开发的止血血小板样颗粒（PLP）能够模仿血小板功能，包括与纤维蛋白纤维结合、增强凝血和诱导凝块回缩。在本研究中，我们旨在将 PLP 应用于纤维蛋白网络结构缺陷的体外血浆 B 型血友病模型中，以确定 PLP 在血友病样异常纤维蛋白网络形成中改善纤维蛋白结构和伤口愈合反应的能力。通过共聚焦显微镜、微柱偏转模型、原子力显微镜和临时纤维蛋白基质内早期细胞迁移的体外伤口愈合模型评估了 PLP 对结构缺陷的凝块网络的影响。 PLP 改善了血友病条件下早期伤口愈合的体外模型中的凝块网络密度、力生成和硬度，并促进成纤维细胞迁移，这表明 PLP 可以提供仿生平台，用于改善导致纤维蛋白网络形成缺陷的疾病条件下的伤口愈合事件。 (C) 2020 Elsevier Inc. 保留所有权利。
Following injury, a fibrin-rich provisional matrix is formed to stem blood loss and provide a scaffold for infiltrating cells, which rebuild the damaged tissue. Defects in fibrin network formation contribute to impaired healing outcomes, as evidenced in hemophilia. Platelet-fibrin interactions greatly influence fibrin network structure via clot contraction, which increases fibrin density over time. Previously developed hemostatic platelet-like particles (PLPs) are capable of mimicking platelet functions including binding to fibrin fibers, augmenting clotting, and inducing clot retraction. In this study, we aimed to apply PLPs within a plasma-based in vitro hemophilia B model of deficient fibrin network structure to determine the ability of PLPs to improve fibrin structure and wound healing responses within hemophilia-like abnormal fibrin network formation. PLP impact on structurally deficient clot networks was assessed via confocal microscopy, a micropost deflection model, atomic force microscopy and an in vitro wound healing model of early cell migration within a provisional fibrin matrix. PLPs improved clot network density, force generation, and stiffness, and promoted fibroblast migration within an in vitro model of early wound healing under hemophilic conditions, indicating that PLPs could provide a biomimetic platform for improving wound healing events in disease conditions that cause deficient fibrin network formation. (C) 2020 Elsevier Inc. All rights reserved.