Gas-modulating microcapsules for spatiotemporal control of hypoxia.
Gas-modulating microcapsules for spatiotemporal control of hypoxia.
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DOI：
10.1073/pnas.2217557120
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发表时间：
2023-04-18
影响因子：
11.1
通讯作者：
Abh, Kristopher A. Kilian
中科院分区：
文献类型：
--
作者：
Molley, Thomas G.;Jiang, Shouyuan;Ong, Louis;Kopecky, Chantal;Ranaweera, Chavinya D.;Jalandhra, Gagan K.;Milton, Laura;Kardia, Egi;Zhou, Zeheng;Rnjak-Kovacina, Jelena;Waters, Shafagh A.;Toh, Yi-Chin;Abh, Kristopher A. Kilian
体内细胞需要精确的组织特异性氧水平，范围为 1% 至 14%。目前需要专门的培养箱来模拟这些条件，并且与片上人体设备等小型化多组织培养不兼容。本文描述了有助于细胞培养中氧张力时空控制的微型胶囊。这一进步的关键是封装程序，该程序可在微量体积内产生最高的酶稳定性和活性。我们展示了控制氧气如何影响癌细胞生长、类器官发育和新血管的形成。控制胶囊的放置可在单个实验中提供氧介导的组织形态发生的时空梯度。微胶囊的灵活性为基础研究和治疗提供了空间，其中氧压的控制可能具有临床实用性。氧是参与调节发育、体内平衡和疾病的重要分子。组织中的氧含量在 1% 到 14% 之间变化，体内平衡的偏差会影响各种生理过程的调节。在这项工作中，我们开发了一种以高负载能力封装酶的方法，该方法可以精确控制细胞培养物中的氧含量。在这里，单个微胶囊能够局部扰乱氧平衡，并且改变基质嵌入微胶囊的浓度和分布提供时空控制。我们证明了干细胞、癌细胞、内皮细胞、癌球体和肠类器官群体中缺氧信号的减弱。改变胶囊放置、培养基配方和补充时间可产生可调节的氧梯度，并在单孔中同时进行空间生长和形态发生。应用于雏鸡绒毛尿囊膜的含有水凝胶薄膜的胶囊可促进新血管形成，为局部治疗或水凝胶伤口敷料提供范围。该平台可以多种形式使用，包括水凝胶沉积、用于 3D 生物打印的颗粒固体以及可注射生物材料。总体而言，该平台的简单性和灵活性将证明对于几乎任何体外或体内形式的氧介导过程的基础研究都是有用的，并且有可能包含在用于治疗损伤或疾病的生物医学材料中。
Cells in the body require precise tissue-specific oxygen levels varying from 1 to 14%. Specialized incubators are currently required to mimic these conditions and are not compatible with miniaturized multitissue cultures like body-on-a-chip devices. This article describes microscale capsules that facilitate spatiotemporal control of oxygen tension in cell culture. Key to this advance is an encapsulation procedure that yields the highest reported enzyme stability and activity within a microscale volume. We demonstrate how controlling oxygen affects cancer cell growth, organoid development, and formation of new blood vessels. Controlling capsule placement provides spatiotemporal gradients of oxygen-mediated tissue morphogenesis within single experiments. The flexibility of microcapsules provides scope for fundamental research and therapeutics where control of oxygen tension may have clinical utility. Oxygen is a vital molecule involved in regulating development, homeostasis, and disease. The oxygen levels in tissue vary from 1 to 14% with deviations from homeostasis impacting regulation of various physiological processes. In this work, we developed an approach to encapsulate enzymes at high loading capacity, which precisely controls the oxygen content in cell culture. Here, a single microcapsule is able to locally perturb the oxygen balance, and varying the concentration and distribution of matrix-embedded microcapsules provides spatiotemporal control. We demonstrate attenuation of hypoxia signaling in populations of stem cells, cancer cells, endothelial cells, cancer spheroids, and intestinal organoids. Varying capsule placement, media formulation, and timing of replenishment yields tunable oxygen gradients, with concurrent spatial growth and morphogenesis in a single well. Capsule containing hydrogel films applied to chick chorioallantoic membranes encourages neovascularization, providing scope for topical treatments or hydrogel wound dressings. This platform can be used in a variety of formats, including deposition in hydrogels, as granular solids for 3D bioprinting, and as injectable biomaterials. Overall, this platform’s simplicity and flexibility will prove useful for fundamental studies of oxygen-mediated processes in virtually any in vitro or in vivo format, with scope for inclusion in biomedical materials for treating injury or disease.
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影响因子：
3.4
作者：
Baumann RP;Penketh PG;Seow HA;Shyam K;Sartorelli AC
通讯作者：
Sartorelli AC
载有细胞的梯度微凝胶悬浮液，用于生物制作过程中分化的空间控制。
影响因子：
10
作者：
Molley, Thomas G.;Hung, Tzong-tyng;Kilian, Kristopher A.
通讯作者：
Kilian, Kristopher A.
影响因子：
4.1
作者：
Dawes, Camron S.;Konig, Heiko;Lin, Chien-Chi
通讯作者：
Lin, Chien-Chi
影响因子：
56.9
作者：
Lee, Haeshin;Dellatore, Shara M.;Messersmith, Phillip B.
通讯作者：
Messersmith, Phillip B.
影响因子：
--
作者：
LOIKE, JD;CAO, L;STERN, D
通讯作者：
STERN, D