Emerson Amy E, Sugamura Yuka, Mazboudi Jad, Abdallah Tuhfah M, Seaton Charmayne D, Ghasemi Azin, Kodibagkar Vikram D, Weaver Jessica D
School of Biological and Health Systems Engineering, Arizona State University, Tempe, Arizona, USA.
J Biomed Mater Res A. 2024 Sep;112(9):1506-1517. doi: 10.1002/jbm.a.37707. Epub 2024 Mar 15.
Hydrogel cell encapsulation devices are a common approach to reduce the need for chronic systemic immunosuppression in allogeneic cell product transplantation. Macroencapsulation approaches are an appealing strategy, as they maximize graft retrievability and cell dosage within a single device; however, macroencapsulation devices face oxygen transport challenges as geometries increase from preclinical to clinical scales. Device design guided by computational approaches can facilitate graft oxygen availability to encapsulated cells in vivo but is limited without accurate measurement of oxygen levels within the transplant site and graft. In this study, we engineer pO reporter composite hydrogels (PORCH) to enable spatiotemporal measurement of oxygen tension within macroencapsulation devices using the proton Imaging of siloxanes to map tissue oxygenation levels (PISTOL) magnetic resonance imaging approach. We engineer two methods of incorporating siloxane oximetry reporters within hydrogel devices, an emulsion and microbead-based approach, and evaluate PORCH cytotoxicity on co-encapsulated cells and accuracy in quantifying oxygen tension in vitro. We find that both emulsion and microbead PORCH approaches enable accurate in situ oxygen quantification using PISTOL magnetic resonance oximetry, and that the emulsion-based PORCH approach results in higher spatial resolution.
水凝胶细胞封装装置是减少同种异体细胞产品移植中对慢性全身免疫抑制需求的常用方法。大封装方法是一种有吸引力的策略,因为它们在单个装置内使移植物可回收性和细胞剂量最大化;然而,随着几何尺寸从临床前规模增加到临床规模,大封装装置面临氧气传输挑战。由计算方法指导的装置设计可以促进体内封装细胞的移植物氧气供应,但在没有准确测量移植部位和移植物内氧气水平的情况下是有限的。在本研究中,我们设计了pO报告复合水凝胶(PORCH),以使用硅氧烷质子成像绘制组织氧合水平(PISTOL)磁共振成像方法,实现对大封装装置内氧张力的时空测量。我们设计了两种将硅氧烷血氧测定报告分子纳入水凝胶装置的方法,一种基于乳液和微珠的方法,并评估了PORCH对共封装细胞的细胞毒性以及体外定量氧张力的准确性。我们发现,乳液和微珠PORCH方法都能够使用PISTOL磁共振血氧测定法进行准确的原位氧定量,并且基于乳液的PORCH方法具有更高的空间分辨率。