Hydrogel network design using multifunctional macromers to coordinate tissue maturation in ovarian follicle culture.
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.
Department of Chemical and Biological Engineering, Northwestern University, 2170 Campus Dr, 3619 Silverman Hall, Evanston, IL 60208, USA.
Ariella
A
Shikanov
Rachel M
RM
Smith
Min
M
Xu
Teresa K
TK
Woodruff
Lonnie D
LD
Shea
D000818:Animals; D005260:Female; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000737:chemistry / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009997:Osmotic Pressure / Q000187:drug effects; D006080:Ovarian Follicle / Q000187:drug effects* / Q000254:growth & development*; D046509:Tissue Culture Techniques / Q000379:methods*; D023822:Tissue Engineering / Q000379:methods*; D014022:Tissue Survival / Q000187:drug effects
D020136:Hydrogel, Polyethylene Glycol Dimethacrylate
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