Biomaterials for 4D stem cell culture

Amber M. Hilderbrand, Elisa M. Ovadia, Matthew S. Rehmann, Prathamesh M. Kharkar, Chen Guo, April M. Kloxin

Research output: Contribution to journalReview articlepeer-review

41 Scopus citations


Stem cells reside in complex three-dimensional (3D) environments within the body that change with time, promoting various cellular functions and processes such as migration and differentiation. These complex changes in the surrounding environment dictate cell fate yet, until recently, have been challenging to mimic within cell culture systems. Hydrogel-based biomaterials are well suited to mimic aspects of these in vivo environments, owing to their high water content, soft tissue-like elasticity, and often-tunable biochemical content. Further, hydrogels can be engineered to achieve changes in matrix properties over time to better mimic dynamic native microenvironments for probing and directing stem cell function and fate. This review will focus on techniques to form hydrogel-based biomaterials and modify their properties in time during cell culture using select addition reactions, cleavage reactions, or non-covalent interactions. Recent applications of these techniques for the culture of stem cells in four dimensions (i.e., in three dimensions with changes over time) also will be discussed for studying essential stem cell processes.

Original languageEnglish (US)
Pages (from-to)212-224
Number of pages13
JournalCurrent Opinion in Solid State and Materials Science
Issue number4
StatePublished - Aug 1 2016
Externally publishedYes

Bibliographical note

Funding Information:
The authors would like to acknowledge support, for related work in their laboratories, from the National Science Foundation CAREER Award (DMR-1253906 ), the Delaware COBRE program with a grant from the National Institute of General Medical Sciences ( NIGMS P20GM104316 ) from the NIH, the NIH Chemistry-Biology Interface program at the University of Delaware ( NIH T32GM008550 ), the Burroughs Welcome Fund ( 1006787 ), the Pew Charitable Trusts ( 00026178 ), and the University of Delaware Research Foundation .

Publisher Copyright:
© 2016 Elsevier Ltd


  • 3D cell culture
  • Biomaterials
  • Click chemistry
  • Hydrogels
  • Stem cells


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