Sliding Hydrogels with Mobile Molecular Ligands and Crosslinks as 3D Stem Cell Niche

The development of a sliding hydrogel with mobile crosslinks and biochemical ligands as a 3D stem cell niche is reported. The molecular mobility of this sliding hydrogel allows stem cells to reorganize the surrounding ligands and change their morphology in 3D. Without changing matrix stiffness, sliding hydrogels support efficient stem cell differentiation toward multiple lineages including adipogenesis, chondrogenesis, and osteogenesis.

[1]  Akira Harada,et al.  The molecular necklace: a rotaxane containing many threaded α-cyclodextrins , 1992, Nature.

[2]  Murat Guvendiren,et al.  Stiffening hydrogels to probe short- and long-term cellular responses to dynamic mechanics , 2012, Nature Communications.

[3]  David J Mooney,et al.  Extracellular matrix stiffness and composition jointly regulate the induction of malignant phenotypes in mammary epithelium. , 2014, Nature materials.

[4]  K. Ito,et al.  Local and network structure of thermoreversible polyrotaxane hydrogels based on poly(ethylene glycol) and methylated alpha-cyclodextrins. , 2006, The journal of physical chemistry. B.

[5]  Kohzo Ito,et al.  Slide-ring materials using topological supramolecular architecture , 2010 .

[6]  J. Hubbell,et al.  SPARC-derived protease substrates to enhance the plasmin sensitivity of molecularly engineered PEG hydrogels. , 2011, Biomaterials.

[7]  Eben Alsberg,et al.  FRET measurements of cell-traction forces and nano-scale clustering of adhesion ligands varied by substrate stiffness. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[8]  Robert Langer,et al.  Materials for stem cell factories of the future. , 2014, Nature materials.

[9]  K. Ito,et al.  The Polyrotaxane Gel: A Topological Gel by Figure‐of‐Eight Cross‐links , 2001 .

[10]  Erkki Ruoslahti,et al.  Cell attachment activity of fibronectin can be duplicated by small synthetic fragments of the molecule , 1984, Nature.

[11]  Christopher S. Chen,et al.  Cell shape, cytoskeletal tension, and RhoA regulate stem cell lineage commitment. , 2004, Developmental cell.

[12]  Kohzo Ito,et al.  Recent advances in the preparation of cyclodextrin-based polyrotaxanes and their applications to soft materials. , 2007, Soft matter.

[13]  S. Sen,et al.  Matrix Elasticity Directs Stem Cell Lineage Specification , 2006, Cell.

[14]  P. Ma,et al.  Ionically crosslinked alginate hydrogels as scaffolds for tissue engineering: part 1. Structure, gelation rate and mechanical properties. , 2001, Biomaterials.

[15]  Wesley R. Legant,et al.  Measurement of mechanical tractions exerted by cells in three-dimensional matrices , 2010, Nature Methods.

[16]  J. Hubbell,et al.  Enhanced proteolytic degradation of molecularly engineered PEG hydrogels in response to MMP-1 and MMP-2. , 2010, Biomaterials.

[17]  Ravi A. Desai,et al.  Mechanical regulation of cell function with geometrically modulated elastomeric substrates , 2010, Nature Methods.

[18]  Yu Suk Choi,et al.  Interplay of Matrix Stiffness and Protein Tethering in Stem Cell Differentiation , 2014, Nature materials.

[19]  Fan Yang,et al.  Engineering interpenetrating network hydrogels as biomimetic cell niche with independently tunable biochemical and mechanical properties. , 2014, Biomaterials.

[20]  Jerry C. Hu,et al.  Unlike Bone, Cartilage Regeneration Remains Elusive , 2012, Science.

[21]  F. Guilak,et al.  Control of stem cell fate by physical interactions with the extracellular matrix. , 2009, Cell stem cell.

[22]  Akira Harada,et al.  Complex formation between poly(ethylene glycol) and α-cyclodextrin , 1990 .

[23]  Liming Bian,et al.  The influence of hyaluronic acid hydrogel crosslinking density and macromolecular diffusivity on human MSC chondrogenesis and hypertrophy. , 2013, Biomaterials.

[24]  James C. Weaver,et al.  Hydrogels with tunable stress relaxation regulate stem cell fate and activity , 2015, Nature materials.

[25]  M. Pittenger,et al.  Multilineage potential of adult human mesenchymal stem cells. , 1999, Science.

[26]  Yoshimi Tanaka,et al.  Novel hydrogels with excellent mechanical performance , 2005 .

[27]  Todd C. McDevitt,et al.  Materials as stem cell regulators. , 2014, Nature materials.

[28]  Kristi S. Anseth,et al.  Photodegradable Hydrogels for Dynamic Tuning of Physical and Chemical Properties , 2009, Science.

[29]  Wesley R. Legant,et al.  Degradation-mediated cellular traction directs stem cell fate in covalently crosslinked three-dimensional hydrogels , 2013, Nature materials.

[30]  Jan C. M. van Hest,et al.  Peptide- and Protein-Based Hydrogels , 2012 .

[31]  K. Anseth,et al.  A Biosynthetic Scaffold that Facilitates Chondrocyte-Mediated Degradation and Promotes Articular Cartilage Extracellular Matrix Deposition , 2015, Regenerative Engineering and Translational Medicine.

[32]  Antonios G Mikos,et al.  Biomimetic materials for tissue engineering. , 2003, Biomaterials.

[33]  David J. Mooney,et al.  Harnessing Traction-Mediated Manipulation of the Cell-Matrix Interface to Control Stem Cell Fate , 2010, Nature materials.

[34]  J. A. Hubbell,et al.  Cell‐Responsive Synthetic Hydrogels , 2003 .