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 ...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.展开更多
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)+1 种基金supported by the National Science Foundation Graduate Research Fellowship Program under Grant No.DGE 1841052funding from the Rackham Graduate School Predoctoral fellowship.All schematics were created using BioRender.com.
文摘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.
