Hydrogel network design using multifunctional macromers to coordinate tissue maturation in ovarian follicle culture

Ariella Shikanov, Rachel M. Smith, Min Xu, Teresa K. Woodruff, Lonnie D. Shea*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

98 Scopus citations

Abstract

Synthetic hydrogels with tunable properties are appealing for regenerative medicine. A critical limitation in hydrogel design at low solids concentration is the formation of defects, which increase gelation times and swelling, and reduce elasticity. Here, we report that trifunctional cross-linking peptides applied to 4-arm poly-(ethylene glycol) (PEG) hydrogels decreased swelling and gelation time relative to bi-functional crosslinkers. In contrast to bi-functional peptides, the third cross-linking site on the peptide created a branch point if an intramolecular cross-link formed, which prevented non-functional " dangling-ends" in the hydrogel network and enhanced the number of elastically active cross-links. The improved network formation enabled mouse ovarian follicle encapsulation and maturation in vitro. Hydrogels with bi-functional crosslinkers resulted in cellular dehydration, likely due to osmosis during the prolonged gelation. For trifunctional crosslinkers, the hydrogels supported a 17-fold volumetric expansion of the tissue during culture, with expansion dependent on the ability of the follicle to rearrange its microenvironment, which is controlled through the sensitivity of the cross-linking peptide to the proteolytic activity of plasmin. The improved network design enabled ovarian follicle culture in a completely synthetic system, and can advance fertility preservation technology for women facing premature infertility from anticancer therapies.

Original languageEnglish (US)
Pages (from-to)2524-2531
Number of pages8
JournalBiomaterials
Volume32
Issue number10
DOIs
StatePublished - Apr 2011

Keywords

  • Hydrogel
  • Michael type addition
  • Ovarian follicle
  • Tunable degradation

ASJC Scopus subject areas

  • Bioengineering
  • Ceramics and Composites
  • Biophysics
  • Biomaterials
  • Mechanics of Materials

Fingerprint

Dive into the research topics of 'Hydrogel network design using multifunctional macromers to coordinate tissue maturation in ovarian follicle culture'. Together they form a unique fingerprint.

Cite this