Coating Bioactive Microcapsules with Tannic Acid Enhances the Phenotype of the Encapsulated Pluripotent Stem Cells

Abstract

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.

Function of hepatocyte spheroids in bioactive microcapsules is enhanced by endogenous and exogenous hepatocyte growth factor

“…Then total RNA was extracted and purified by using a RNeasy Plant Mini Kit (Qiagen, Valencia, CA, USA) following manufacturer's instructions. cDNA was synthesized with a QuantiTect Reverse Transcription Kit (Roche, Basel, Switzerland), and quantitative real-time RT-PCR was performed with the QuantStudio™ 5 System (Thermo Scientific Inc.) using universal SYBR Green Master (Roche) [ 34 , 44 ]. Relative gene expression was calculated using the comparative threshold cycle (ΔΔCT) method and normalized with glyceraldehyde 3-phophate dehydrogenase (GAPDH) as a housekeeping gene.…”

In Situ Preparation of Tannic Acid-Modified Poly(N-isopropylacrylamide) Hydrogel Coatings for Boosting Cell Response

“…In addition, fewer TAs were chemically bonded on PNIPAAm 2000 -APTES-TA and PNIPAAm 1300 -APTES-TA, which caused easy TA release. Overall, the TA-modified hydrogel coatings on PNIPAAm 860 -APTES-TA and PNIPAAm 500 -APTES-TAare relatively stable in the long term, which may be better suitable for maintaining the protein on coatings [25,34]. tween TAs may be so large that it is difficult to form mutual overlaps of TAs and the stable cross-linking networks of TA may not be created.…”

“…For example, Revzin et al reported that ultrathin TA-coated heparin microgels were able to capture about two times the basic fibroblast growth factor (BFGF) compared to bare heparin microgels. The BFGF release was prolonged by 1–2 d, inducing human pluripotent stem cells to express a higher level of pluripotency [ 25 ]. Therefore, TA was incorporated into PNIPAAm coatings, potentially endowing the coating with the ability to mediate protein behaviors and elevate cell adhesion without the need for rigorous tailoring of coating thickness.…”