Developing hyaluronic acid microgels for sustained delivery of platelet lysate for tissue engineering applications

Developing hyaluronic acid microgels for sustained delivery of platelet lysate for tissue engineering applications
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DOI:
10.1016/j.ijbiomac.2019.10.036
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发表时间:
2020-02-01
影响因子:
8.2
通讯作者:
Dijkstra, Pieter J.
Dijkstra, Pieter J.
中科院分区:
化学1区
文献类型:
--
作者:
Jooybar, Elaheh;Abdekhodaie, Mohammad J.;Dijkstra, Pieter J.

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血小板裂解物 (PL) 是一种含有高浓度生长因子 (GF) 的血液制品,可被认为是一种经济有效的多种 GF 来源。在这项研究中,开发了基于透明质酸 (HA) 的微凝胶用于递送 PL 蛋白。采用油包水乳液法制备球形微凝胶。首先,将透明质酸接枝酪胺基团,然后在过氧化氢和辣根过氧化物酶存在下通过酶促反应使制备的微滴交联。由于静电相互作用,这些微凝胶像大多数 GF 一样,是有前途的带正电蛋白质捕获载体。当微凝胶在 PL 溶液中孵育时,会发生蛋白质负载,这主要由血浆蛋白质的非特异性吸附控制。尽管这阻碍了装载效率,但可以通过重复洗涤和孵育步骤来增加装载量。负载的微凝胶可以持续释放 PL 生长因子两周。当将富含 PL 的微凝胶嵌入 HA 本体水凝胶中时,与不含微凝胶的构建体相比,细胞增殖更高。这些发现表明,所开发的微凝胶是持续递送 PL 生长因子的潜在候选者,并为其体内半衰期短的问题提供了解决方案。 (C) 2019 年作者。由 Elsevier B.V. 出版
Platelet lysate (PL), a blood product that contains high concentrations of growth factors (GFs), can be considered as a cost-effective source of multiple GFs. In this study, hyaluronic acid (HA) based microgels were developed for delivery of PL proteins. Spherical microgel were prepared using a water in oil emulsion method. First, hyaluronic acid was grafted with tyramine groups, after which prepared microdroplets were crosslinked via an enzymatic reaction in the presence of hydrogen peroxide and horseradish peroxidase. Because of electrostatic interactions, these microgels are promising carriers for positively charged proteins entrapment like most of the GFs. When microgels are incubated in PL solution, protein loading takes place which is mainly governed by nonspecific adsorption of plasma proteins. Although this hampered loading efficiency, loading could be increased by repeated washing and incubation steps. The loaded microgels presented a sustained release of PL growth factors for a period of two weeks. When PL enriched microgels were embedded in a HA bulk hydrogel, cell proliferation was higher compared to constructs without microgels. These findings suggest that the developed microgels are a potential candidate for sustained delivery of PL growth factors and present a solution to the issue of their short half-lives in vivo. (C) 2019 The Authors. Published by Elsevier B.V.