UMMS Affiliation

Department of Orthopedics and Physical Rehabilitation

Publication Date


Document Type



Biochemistry, Biophysics, and Structural Biology | Cell Biology | Cells | Medicinal-Pharmaceutical Chemistry | Molecular, Cellular, and Tissue Engineering


Viscoelasticity, stiffness, and degradation of tissue matrices regulate cell behavior, yet predictive synergistic tuning of these properties in synthetic cellular niches remains elusive. We hypothesize that reversible physical cross-linking can be quantitatively introduced to synthetic hydrogels to accelerate stress relaxation and enhance network stiffness, while strategic placement of isolated labile linkages near cross-linking sites can predict hydrogel degradation, both of which are essential for creating adaptive cellular niches. To test these hypotheses, chondrocytes were encapsulated in hydrogels formed by biorthogonal covalent and noncovalent physical cross-linking of a pair of hydrophilic building blocks. The stiffer and more viscoelastic hydrogels with DBCO-DBCO physical cross-links facilitated proliferation and chondrogenic ECM deposition of encapsulated cells by dissipating stress imposed by expanding cell mass/ECM via dynamic disruption/reformation of physical cross-links. Degradation of labile linkages near covalent cross-linkers further facilitated cell proliferation and timed cell release while maintaining chondrogenic phenotype. This work presents new chemical tools for engineering permissive synthetic niches for cell encapsulation, 3D expansion, and release.

Rights and Permissions

Copyright © 2018 American Chemical Society. This is an open access article published under an ACS AuthorChoice License, which permits copying and redistribution of the article or any adaptations for non-commercial purposes.

DOI of Published Version



ACS Cent Sci. 2018 Aug 22;4(8):971-981. doi: 10.1021/acscentsci.8b00170. Epub 2018 Jul 20. Link to article on publisher's site

Journal/Book/Conference Title

ACS central science

Related Resources

Link to Article in PubMed

PubMed ID