Monitoring Oxygen Levels within Large, Tissue-Engineered Constructs Using Porphyin-Hydrogel Microparticles.
Monitoring Oxygen Levels within Large, Tissue-Engineered Constructs Using Porphyin-Hydrogel Microparticles.
复制标题
使用卟啉水凝胶微粒监测大型组织工程结构内的氧气水平。
DOI：
10.1021/acsbiomaterials.9b00257
复制
发表时间：
2019
影响因子：
5.8
通讯作者：
Grande-Allen,KJane
中科院分区：
文献类型：
--
作者：
Wilson,ReidL;Connell,JenniferP;Grande-Allen,KJane
创造工程器官的一个主要障碍是氧气在生物组织中的扩散有限。生物制造的进步使我们越来越接近能够为大型细胞支架提供氧气的复杂血管网络。然而，用于监测工程组织中氧含量的技术无法适应超过几十微米的成像深度。在这里，我们报告了荧光卟啉-水凝胶微粒的创建，该微粒可以在人造组织中 2 毫米的深度使用。通过将氧响应型卟啉染料与参考染料相结合，微粒产生比率信号，该信号是光稳定的，不受生物材料衰减的影响，并且对氧浓度的生理变化作出响应。这些微粒可以测量 3D 细胞结构内的长距离氧梯度，并准确报告细胞耗氧率。此外，它们与许多水凝胶聚合化学和细胞类型相容，包括原代人类细胞。我们相信这项技术将显着推进细胞化结构中氧梯度可视化的工作，并为组织工程实体器官的工作提供信息。
A major barrier to the creation of engineered organs is the limited diffusion of oxygen through biological tissues. Advances in biofabrication bring us increasingly closer to complex vascular networks capable of supplying oxygen to large cellularized scaffolds. However, technologies for monitoring oxygen levels in engineered tissues do not accommodate imaging depths of more than a few dozen micrometers. Here, we report the creation of fluorescent porphyrin-hydrogel microparticles that can be used at depths of 2 mm into artificial tissues. By combining an oxygen-responsive porphyrin dye with a reference dye, the microparticles generate a ratiometric signal that is photostable, unaffected by attenuation from biological material, and responsive to physiological change in oxygen concentration. These microparticles can measure long-distance oxygen gradients within 3D, cellularized constructs and accurately report cellular oxygen consumption rates. Furthermore, they are compatible with a number of hydrogel polymerization chemistries and cell types, including primary human cells. We believe this technology will significantly advance efforts to visualize oxygen gradients in cellularized constructs and inform efforts to tissue engineer solid organs.