Transdermal regulation of vascular network bioengineering using a photopolymerizable methacrylated gelatin hydrogel.
Transdermal regulation of vascular network bioengineering using a photopolymerizable methacrylated gelatin hydrogel.
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DOI：
10.1016/j.biomaterials.2013.05.060
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发表时间：
2013-09
期刊：
影响因子：
14
通讯作者：
Melero-Martin, Juan M.
中科院分区：
文献类型：
--
作者：
Lin, Ruei-Zeng;Chen, Ying-Chieh;Moreno-Luna, Rafael;Khademhosseini, Ali;Melero-Martin, Juan M.
寻找与血管形态发生相容的水凝胶材料是组织工程研究的一个活跃领域。一种候选材料是甲基丙烯酸明胶（GelMA），这是一种可紫外光交联的水凝胶，通过将甲基丙烯酸基团添加到明胶的含胺侧基上而合成。含有人内皮细胞集落形成细胞（ecfc）和间充质干细胞（MSCs）的GelMA水凝胶可以在体外光聚合，然后在体内手术移植，作为生成血管网络的一种手段。然而，通过实现微创植入和原位聚合，GelMA的全部临床潜力将得到最好的发挥。在这项研究中，我们证明了GelMA构建物内生物工程人类血管网络的可行性，GelMA构建物首先以液体形式皮下注射到免疫缺陷小鼠中，然后通过透皮暴露于紫外线下快速交联。这些生物工程血管网络在7天内发育，与宿主血管系统形成功能性吻合，并均匀分布在整个构建体中。最值得注意的是，我们证明血管形成过程可以通过调整初始暴露于紫外线下的时间（15-45秒范围）直接调节，随着GelMA交联程度的增加，构建物的血管密度逐渐降低，平均流明大小逐渐减小。我们的研究支持使用GelMA的注射形式，然后进行原位透皮光聚合，作为一种更好的方法，在需要在体内形成血管网络的应用中递送细胞。
The search for hydrogel materials compatible with vascular morphogenesis is an active area of investigation in tissue engineering. One candidate material is methacrylated gelatin (GelMA), a UV-photocrosslinkable hydrogel that is synthesized by adding methacrylate groups to the amine-containing side-groups of gelatin. GelMA hydrogels containing human endothelial colony-forming cells (ECFCs) and mesenchymal stem cells (MSCs) can be photopolymerized ex vivo and then surgically transplanted in vivo as a means to generate vascular networks. However, the full clinical potential of GelMA will be best captured by enabling minimally invasive implantation and in situ polymerization. In this study, we demonstrated the feasibility of bioengineering human vascular networks inside GelMA constructs that were first subcutaneously injected into immunodeficient mice while in liquid form, and then rapidly crosslinked via transdermal exposure to UV light. These bioengineered vascular networks developed within 7 days, formed functional anastomoses with the host vasculature, and were uniformly distributed throughout the constructs. Most notably, we demonstrated that the vascularization process can be directly modulated by adjusting the initial exposure time to UV light (15–45 s range), with constructs displaying progressively less vascular density and smaller average lumen size as the degree of GelMA crosslinking was increased. Our studies support the use of GelMA in its injectable form, followed by in situ transdermal photopolymerization, as a preferable means to deliver cells in applications that require the formation of vascular networks in vivo.
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影响因子：
64.8
作者：
Mammoto, Akiko;Connor, Kip M.;Mammoto, Tadanori;Yung, Chong Wing;Huh, Dongeun;Aderman, Christopher M.;Mostoslavsky, Gustavo;Smith, Lois E. H.;Ingber, Donald E.
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14
作者：
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影响因子：
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通讯作者：
Elisseeff JH
影响因子：
14
作者：
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通讯作者：
Saltzman, W. Mark