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Functional Human Vascular Network Generated in Photocrosslinkable Gelatin Methacrylate Hydrogels

机译：在光交联的明胶甲基丙烯酸酯水凝胶中产生的功能性人体血管网络。

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The generation of functional, 3D vascular networks is a fundamental prerequisite for the development of many future tissue engineering-based therapies. Current approaches in vascular network bioengineering are largely carried out using natural hydrogels as embedding scaffolds. However, most natural hydrogels present a poor mechanical stability and a suboptimal durability, which are critical limitations that hamper their widespread applicability. The search for improved hydrogels has become a priority in tissue engineering research. Here, the suitability of a photopolymerizable gelatin methacrylate (CelMA) hydrogel to support human progenitor cell-based formation of vascular networks is demonstrated. Using GelMA as the embedding scaffold, it is shown that 3D constructs containing human blood-derived endothelial colony-forming cells (ECFCs) and bone marrow-derived mesenchymal stem cells (MSCs) generate extensive capillary-like networks in vitro. These vascular structures contain distinct lumens that are formed by the fusion of ECFC intracellular vacuoles in a process of vascular morphogenesis. The process of vascular network formation is dependent on the presence of MSCs, which differentiate into perivascular cells occupying abluminal positions within the network. Importantly, it is shown that implantation of cell-laden CelMA hydrogels into immunodeficient mice results in a rapid formation of functional anastomoses between the bioengineered human vascular network and the mouse vasculature. Furthermore, it is shown that the degree of methacrylation of the CelMA can be used to modulate the cellular behavior and the extent of vascular network formation both in vitro and in vivo. These data suggest that CelMA hydrogels can be used for biomedical applications that require the formation of microvascular networks, including the development of complex engineered tissues.
机译：功能性3D血管网络的生成是许多未来基于组织工程的疗法发展的基本前提。血管网络生物工程中的当前方法主要是使用天然水凝胶作为包埋支架来进行的。然而，大多数天然水凝胶表现出较差的机械稳定性和次优的耐久性，这是妨碍其广泛应用的关键限制。在组织工程研究中，寻求改进的水凝胶已成为当务之急。在此，证明了可光聚合的甲基丙烯酸明胶（CelMA）水凝胶适用于支持基于人类祖细胞的血管网络形成。使用GelMA作为嵌入支架，已显示包含人血源性内皮集落形成细胞（ECFC）和骨髓源性间充质干细胞（MSC）的3D构建体在体外可产生广泛的毛细管样网络。这些血管结构包含不同的管腔，这些管腔是在血管形态发生过程中由ECFC细胞内液泡融合形成的。血管网络形成的过程取决于MSC的存在，而MSC分化为占据血管内腺管位置的血管周细胞。重要的是，已证明将载有细胞的CelMA水凝胶植入免疫缺陷小鼠会导致生物工程化的人类血管网络与小鼠脉管系统之间功能性吻合的快速形成。此外，显示了CelMA的甲基丙烯酸化程度可用于在体外和体内调节细胞行为和血管网络形成的程度。这些数据表明，CelMA水凝胶可用于需要形成微血管网络的生物医学应用，包括复杂工程组织的发展。

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  • 来源
    《Advanced Functional Materials》 |2012年第10期|p.2027-2039|共13页
  • 作者

    Ying-Chieh Chen; Ruei-Zeng Lin; Hao Qi; Yunzhi Yang; Hojae Bae; Juan M. Melero-Martin; AH Khademhosseini;

  • 作者单位

    Department of Medicine Center for Biomedical Engineering Brigham and Women's Hospital Harvard Medical School, Boston, MA 02115, USA Wyss Institute for Biologically Inspired Engineering Harvard Medical School Boston, MA 02155, USA Department of Applied Science National Hsinchu University of Education Hsinchu 300, Taiwan;

    Department of Cardiac Surgery Children's Hospital Boston Boston, MA 02115, USA;

    Department of Medicine Center for Biomedical Engineering Brigham and Women's Hospital Harvard Medical School, Boston, MA 02115, USA Wyss Institute for Biologically Inspired Engineering Harvard Medical School Boston, MA 02155, USA;

    Department of Orthopedic Surgery Stanford University 300 Pasteur Drive, Edwards, R155, Stanford, CA 94305, USA Houston Biomaterials Research Center Department of Restorative Dentistry and Biomaterials University of Texas Health Science Center at Houston Houston, TX 77030, USA;

    Department of Medicine Center for Biomedical Engineering Brigham and Women's Hospital Harvard Medical School, Boston, MA 02115, USA Harvard-MIT Division of Health Sciences and Technology Massachusetts Institute ofTechnology Cambridge, MA 02139, USA;

    Department of Cardiac Surgery Children's Hospital Boston Boston, MA 02115, USA Department of Surgery Harvard Medical School Boston, MA 02115, USA;

    Department of Medicine Center for Biomedical Engineering Brigham and Women's Hospital Harvard Medical School, Boston, MA 02115, USA Wyss Institute for Biologically Inspired Engineering Harvard Medical School Boston, MA 02155, USA Harvard-MIT Division of Health Sciences and Technology Massachusetts Institute ofTechnology Cambridge, MA 02139, USA;

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