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Induction of Four‐Dimensional Spatiotemporal Geometric Transformations in High Cell Density Tissues via Shape‐Changing Hydrogels
Author(s) -
Lee Yu Bin,
Jeon Oju,
Lee Sang Jin,
Ding Aixiang,
Wells Derrick,
Alsberg Eben
Publication year - 2021
Publication title -
advanced functional materials
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.069
H-Index - 322
eISSN - 1616-3028
pISSN - 1616-301X
DOI - 10.1002/adfm.202010104
Subject(s) - self healing hydrogels , regenerative medicine , tissue engineering , materials science , extracellular matrix , gelatin , regeneration (biology) , biocompatible material , chondrogenesis , biomedical engineering , limiting , nanotechnology , biophysics , stem cell , microbiology and biotechnology , chemistry , biology , polymer chemistry , mechanical engineering , biochemistry , medicine , engineering
Developing and healing tissues begin as cellular condensations. Spatiotemporal changes in tissue geometry, transformations in the spatial distribution of the cells, and extracellular matrix are essential for its evolution into a functional tissue. 4D materials, 3D materials capable of geometric changes, may have the potential to recreate the aforementioned biological phenomenon. However, most reported 4D materials are non‐degradable and/or not biocompatible, limiting their application in regenerative medicine, and to date, there are no systems controlling the geometry of high density cellular condensations and differentiation. Here, 4D high cell density tissues based on shape‐changing hydrogels are described. By sequential photocrosslinking of oxidized and methacrylated alginate (OMA) and methacrylated gelatin (GelMA), bilayered hydrogels presenting controllable geometric changes without any external stimuli are fabricated. Fibroblasts and human adipose‐derived stem cells (ASCs) are encapsulated at concentrations up to 1.0 × 10 8 cells mL –1 in the 4D constructs, and controllable shape changes are achieved in concert with ASCs differentiated down chondrogenic and osteogenic lineages. Bioprinting of the high density cell‐laden OMA and GelMA permits the formation of more complex constructs with defined 4D geometric changes, which may further expand the promise of this approach in regenerative medicine applications.