Degradable hydrogels for spatiotemporal control of mesenchymal stem cells localized at decellularized bone allografts.
Degradable hydrogels for spatiotemporal control of mesenchymal stem cells localized at decellularized bone allografts.
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DOI：
10.1016/j.actbio.2014.04.012
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发表时间：
2014-08
影响因子：
9.7
通讯作者：
Benoit, Danielle S. W.
中科院分区：
文献类型：
--
作者：
Hoffman, Michael D.;Van Hove, Amy H.;Benoit, Danielle S. W.
细胞（例如间充质干细胞（MSC））的移植在再生医学领域中具有许多应用。为了使细胞移植策略在治疗上取得成功，必须控制细胞定位和持久性，以最大限度地发挥细胞介导的愈合作用。在此，我们证明了聚（乙二醇）（PEG）水凝胶的水解降解可用于时空控制封装MSC定位到脱细胞骨同种异体移植物在体外和体内。通过改变PEG-d，l-丙交酯-甲基丙烯酸酯大分子单体内可水解降解的丙交酯重复单元的数量，合成了一系列在约1、2和3周内降解的水凝胶。将MSC封装在这些脱细胞骨同种异体移植物周围形成的水凝胶内，并使用非侵入性纵向荧光成像来跟踪体外和体内细胞的持久性。尽管在整个降解过程中，水凝胶网格尺寸比MSC尺寸小约2-3个数量级，但MSC在骨同种异体移植物表面外部的时空定位与体外水凝胶降解动力学相似。因此，怀疑局部的细胞介导的降解和MSC从水凝胶中迁移，特别是因为在水凝胶完全降解后7周，约10%的总移植MSC群体显示出与移植物紧密接近（约650 μm内）。这项工作证明了基于PEG的水凝胶用于控制时空细胞移植用于无数再生医学策略的治疗效用。
Transplantation of cells, such as mesenchymal stem cells (MSCs), has numerous applications in the field of regenerative medicine. For cell transplantation strategies to be successful therapeutically, cellular localization and persistence must be controlled to maximize cell-mediated contributions to healing. Herein, we demonstrate that hydrolytic degradation of poly(ethylene glycol) (PEG) hydrogels can be used to spatiotemporally control encapsulated MSC localization to decellularized bone allografts both in vitro and in vivo. By altering the number of hydrolytically degradable lactide repeat units within PEG-d,l-lactide-methacrylate macromers, a series of hydrogels were synthesized that degraded over ~ 1, 2, and 3 weeks. MSCs were encapsulated within these hydrogels formed around decellularized bone allografts, and non-invasive, longitudinal fluorescence imaging was used to track cell persistence both in vitro and in vivo. Spatiotemporal localization of MSCs to the exterior of bone allograft surfaces was similar to in vitro hydrogel degradation kinetics despite hydrogel mesh sizes being ~ 2–3 orders of magnitude smaller than MSC size throughout the degradation process. Thus, localized, cell-mediated degradation and MSC migration from the hydrogels is suspected particularly as ~ 10 % of the total transplanted MSC population was shown to persist in close proximity (within ~ 650 μm) to grafts 7 weeks after complete hydrogel degradation. This work demonstrates the therapeutic utility of PEG-based hydrogels for controlling spatiotemporal cell transplantation for a myriad of regenerative medicine strategies.
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