摘要
Synthetic matrices which mimic the extracellular composition of native tissue create a comprehensive model for studying development and disease.Here,we have engineered a composite material which retains cell-secreted ECM for the culture of ovarian follicles by embedding electrospun dextran fibers functionalized with basement membrane binder(BMB)peptide in PEG hydrogels.In the presence of ECM-sequestering fibers,encapsulated immature primordial follicles and ovarian stromal cells aggregated into large organoid-like structures with dense deposition of laminin,perlecan,and collagen I,leading to steroidogenesis and significantly greater rates of oocyte survival and growth.We determined that cell aggregation restored key cell-cell interactions critical for oocyte survival,whereas oocyte growth was dependent on cell-matrix interactions achieved in the presence of BMB.Here we have shown that sequestration and retention of cell-secreted ECM along synthetic fibers mimics fibrous ECM structure and restores the cell-cell and cell-matrix interactions critical for engineering an artificial ovary.
基金
supported by the National Institutes of Health(R01 HD099402 to AS,R01 EB030474 to BMB,F31 HD100069 to CENT)
the Juvenile Diabetes Research Foundation(1-INO-2020-916-A-N to BMB)
supported by the National Science Foundation Graduate Research Fellowship Program under Grant No.DGE 1841052
funding from the Rackham Graduate School Predoctoral fellowship.All schematics were created using BioRender.com.
作者简介
Corresponding author:Ariella Shikanov,Department of Biomedical Engineering,University of Michigan,Ann Arbor,MI 48109,USA.E-mail address:shikanov@umich.edu。
