Extracellular matrix-templating fibrous hydrogels promote ovarian tissue remodeling and oocyte growth.
Extracellular matrix-templating fibrous hydrogels promote ovarian tissue remodeling and oocyte growth.
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DOI：
10.1016/j.bioactmat.2023.10.001
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发表时间：
2024-02
影响因子：
18.9
通讯作者：
中科院分区：
文献类型：
--
作者：
模拟天然组织细胞外成分的合成基质为研究发育和疾病创建了一个综合模型。在这里，我们设计了一种复合材料，通过在 PEG 水凝胶中嵌入用基底膜结合 (BMB) 肽功能化的电纺葡聚糖纤维，保留细胞分泌的 ECM 用于卵巢卵泡培养。在 ECM 隔离纤维存在的情况下，封装的未成熟原始卵泡和卵巢基质细胞聚集成大的类器官样结构，其中层粘连蛋白、基底膜蛋白和 I 型胶原蛋白密集沉积，导致类固醇生成和卵母细胞存活和生长率显着提高。我们确定细胞聚集恢复了对卵母细胞存活至关重要的关键细胞间相互作用，而卵母细胞生长依赖于 BMB 存在下实现的细胞间相互作用。在这里，我们证明了细胞分泌的 ECM 沿着合成纤维的隔离和保留模拟了纤维 ECM 结构，并恢复了对于工程人造卵巢至关重要的细胞-细胞和细胞-基质相互作用。通过将 ECM 隔离纤维嵌入可降解水凝胶中来制备复合水凝胶。封装的细胞重塑了周围的基质，模仿天然 ECM。用 ECM 螯合肽修饰电纺纤维可增加细胞分泌的 ECM 的保留。 ECM 在纤维上的沉积促进细胞聚集成组织样结构。具有 ECM 隔离纤维的复合水凝胶可改善小鼠卵母细胞的存活和生长。
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. Composite hydrogels were fabricated by embedding ECM-sequestering fibers within a degradable hydrogel. Encapsulated cells remodeled the surrounding matrix mimicking native ECM. Decoration of electrospun fibers with ECM-sequestering peptides increased retention of cell-secreted ECM. ECM deposition on fibers facilitated cell aggregation into tissue-like structures. Composite hydrogels with ECM-sequestering fibers improved murine oocyte survival and growth.
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DOI：
10.1038/s41578-021-00279-y
发表时间：
2021
期刊：
Nature reviews. Materials
影响因子：
--
作者：
Hofer M;Lutolf MP
通讯作者：
Lutolf MP
影响因子：
4.6
作者：
Jones A;Bernabé BP;Padmanabhan V;Li J;Shikanov A
通讯作者：
Shikanov A
影响因子：
5.8
作者：
Matera, Daniel L.;Wang, William Y.;Baker, Brendon M.
通讯作者：
Baker, Brendon M.
DOI：
10.1093/humrep/dead008
发表时间：
2023-03-01
期刊：
Human reproduction (Oxford, England)
影响因子：
--
作者：
通讯作者：
--
影响因子：
14
作者：
Hopkins, Thomas I. R.;Bemmer, Victoria L.;Dunlop, Iain E.
通讯作者：
Dunlop, Iain E.