Physicochemical Properties in 3D Hydrogel Modulate Cellular Reprogramming into Induced Pluripotent Stem Cells

Abstract

Understanding the biophysical relationships between stem cells and applied biomaterials can facilitate the ability to control the functions and behaviors of stem cells. However, the role of 3D microenvironment in stem cell biology remains largely unexplored, compared with that of 2D cell‐culture environment. Here, a new strategy that improves the efficacy of Yamanaka's four‐factor‐induced cellular reprogramming into induced pluripotent stem cells (iPSCs) by incorporating cues derived from the 3D microenvironment and biophysical ligands is reported. Among the various 3D hydrogel systems tested, methacrylated hyaluronic acid (HA) hydrogel significantly improves cellular reprogramming into iPSCs. Additionally, the initial upregulation of CD44 in encapsulated cells in low‐level methacrylated soft HA hydrogel accelerates the reprogramming. In conclusion, the reported HA hydrogel with low modulus accelerates reprogramming into iPSCs and thus offers potential advantages for translational applications.

Core–Shell Spheroid‐Laden Microgels Crosslinked under Biocompatible Conditions for Probing Cancer‐Stromal Communication

“…These values are in the same order of magnitude as those found for bulk measurement of MCS hydrogels. [ 20,44 ]…”

“…These values are in the same order of magnitude as those found for bulk measurement of MCS hydrogels. [20,44] Together with the microscopic evolution of MCSs, in a relatively stiff environment (756 Pa), the size of MCSs was markedly decreased and the contour of was more spheroidal. While in the soft environment (45 Pa), the MCSs seemed to be larger in size and were less likely to be arrested.…”

“…[18,19] Among these, encapsulating cells into microscale-hydrogels (microgels) using a microfluidic device to generate MCSs is an effective and highthroughput strategy. [20][21][22] Recent advances in the development of microfluidic platform for MCS growth, release, and drug screening have been demonstrated by many groups. [23][24][25][26] Given the microscale of MCSs-laden microgels, the biophysical techniques for the artificial cancer niche characterization are largely unexplored.…”

Heparinized Gelatin-Based Hydrogels for Differentiation of Induced Pluripotent Stem Cells

“…Specifically, norbornene-functionalized gelatin (GelNB) served as the backbone of the cross-linked hydrogels. While proteolytically labile and cell adhesive gelatin has been widely used as a substrate for the 2D cell culture, − its use for the 3D culture of hiPSCs is limited. Via thiol-norbornene photocross-linking, GelNB was used to cross-link thiolated cross-linkers, including multi-arm PEG-thiol (e.g., PEG-tetra-thiol or PEG4SH) or thiolated HA (THA) .…”

3D Printed Biocatalytic Living Materials with Dual‐Network Reinforced Bioinks

“…[ 30–32 ] As the primary choice for bioink material, hydrogel offers a high‐water biofriendly condition for embedded cells and allows for the exchange of nutrients and wastes with microenvironments through porous structures, opening a new avenue for microbial cell immobilization. [ 33,34 ] Coupled with additive manufacturing, hydrogel‐based living materials are capable of controlling the spatial distribution of cellular and chemical compositions, [ 35–37 ] giving rise to unprecedented chances to boost the overall biocatalytic performance even in comparison with conventional liquid culture and to create a new paradigm for studying bacterial consortia. [ 28 ] Nonetheless, the development of living materials by 3D printing has been greatly hampered by the limited availability of reinforced hydrogels that are able to balance printability and cell function.…”