期刊
BIOMATERIALS
卷 32, 期 10, 页码 2524-2531出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2010.12.027
关键词
Hydrogel; Tunable degradation; Michael type addition; Ovarian follicle
资金
- U.S. Army Research Office
- U.S. Army Medical Research and Materiel Command
- Northwestern University for peptide synthesis and purification
- NIH [U54HD41857, PL1EB008542]
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. (C) 2010 Elsevier Ltd. All rights reserved.
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