Choi Daheui, Gwon Kihak, Hong Hye Jin, Baskaran Harihara, Calvo-Lozano Olalla, Gonzalez-Suarez Alan M, Park Kyungtae, de Hoyos-Vega Jose M, Lechuga Laura M, Hong Jinkee, Stybayeva Gulnaz, Revzin Alexander
Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, Minnesota 55905, United States.
Department of Chemical and Biomolecular Engineering, Case Western Reserve University, Cleveland, Ohio 44106, United States.
ACS Appl Mater Interfaces. 2022 Jun 4. doi: 10.1021/acsami.2c06783.
Human pluripotent stem cells (hPSCs) may be differentiated into any adult cell type and therefore hold incredible promise for cell therapeutics and disease modeling. There is increasing interest in three-dimensional (3D) hPSC culture because of improved differentiation outcomes and potential for scale up. Our team has recently described bioactive heparin (Hep)-containing core-shell microcapsules that promote rapid aggregation of stem cells into spheroids and may also be loaded with growth factors for the local and sustained delivery to the encapsulated cells. In this study, we explored the possibility of further modulating bioactivity of microcapsules through the use of an ultrathin coating composed of tannic acid (TA). Deposition of the TA film onto model substrates functionalized with Hep and poly(ethylene glycol) was characterized by ellipsometry and atomic force microscopy. Furthermore, the presence of the TA coating was observed to increase the amount of basic fibroblast growth factor (bFGF) incorporation by up to twofold and to extend its release from 5 to 7 days. Most significantly, TA-microcapsules loaded with bFGF induced higher levels of pluripotency expression compared to uncoated microcapsules containing bFGF. Engineered microcapsules described here represent a new stem cell culture approach that enables 3D cultivation and relies on local delivery of inductive cues.
人多能干细胞（hPSC）可分化为任何成体细胞类型，因此在细胞治疗和疾病建模方面具有巨大潜力。由于分化效果改善且具有扩大培养的潜力，三维（3D）hPSC培养越来越受到关注。我们的团队最近描述了含生物活性肝素（Hep）的核壳微胶囊，它能促进干细胞快速聚集成球体，还可装载生长因子以局部持续递送至包封的细胞。在本研究中，我们探索了通过使用由单宁酸（TA）组成的超薄涂层进一步调节微胶囊生物活性的可能性。通过椭偏仪和原子力显微镜对TA膜沉积到用Hep和聚乙二醇功能化的模型底物上进行了表征。此外，观察到TA涂层的存在使碱性成纤维细胞生长因子（bFGF）的掺入量增加了两倍，并将其释放时间从5天延长至7天。最显著的是，与含有bFGF的未涂层微胶囊相比，装载bFGF的TA微胶囊诱导了更高水平的多能性表达。本文所述的工程化微胶囊代表了一种新的干细胞培养方法，它能够进行3D培养并依赖于诱导信号的局部递送。
