Injectable laminin-functionalized hydrogel for nucleus pulposus regeneration.

Injectable laminin-functionalized hydrogel for nucleus pulposus regeneration.
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DOI:
10.1016/j.biomaterials.2013.06.038
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发表时间:
2013-10
期刊:
影响因子:
14
通讯作者:
Setton, Lori A.
Setton, Lori A.
中科院分区:
工程技术1区
文献类型:
--
作者:
Francisco, Aubrey T.;Mancino, Robert J.;Bowles, Robby D.;Brunger, Jonathan M.;Tainter, David M.;Chen, Yi-Te;Richardson, William J.;Guilak, Farshid;Setton, Lori A.

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将细胞递送至病理性椎间盘 (IVD) 具有增强 IVD 再生的显着治疗潜力。开发保留递送细胞、促进细胞存活以及维持或促进体内 NP 细胞表型的可注射生物材料仍然是一个重大挑战。先前的研究已证明 IVD 髓核 (NP) 区域中的 NP 细胞与层粘连蛋白相互作用,可促进细胞附着和生物合成。这些发现表明,将层粘连蛋白配体掺入细胞递送载体可能有利于促进 NP 细胞存活和表型。在此,开发了一种可注射的层粘连蛋白 111 功能化聚乙二醇 (PEG-LM111) 水凝胶,作为将细胞递送至 IVD 的生物材料载体。我们评估了 PEG-LM111 水凝胶的机械性能及其在 IVD 空间中保留递送细胞的能力。在没有引发剂的情况下,凝胶化在大约 20 分钟内发生,动态剪切模量在 0.9 – 1.4 kPa 范围内。当细胞在 PEG-LM111 载体内递送时,与液体悬浮液中的细胞相比,在培养的 IVD 外植体中的原代 NP 细胞保留在 14 天内显着更高。总之,这些结果表明这种可注射的层粘连蛋白功能化生物材料可能是一种易于使用的载体,用于将细胞递送至 IVD。
Cell delivery to the pathological intervertebral disc (IVD) has significant therapeutic potential for enhancing IVD regeneration. The development of injectable biomaterials that retain delivered cells, promote cell survival, and maintain or promote an NP cell phenotype in vivo remains a significant challenge. Previous studies have demonstrated NP cell – laminin interactions in the nucleus pulposus (NP) region of the IVD that promote cell attachment and biosynthesis. These findings suggest that incorporating laminin ligands into carriers for cell delivery may be beneficial for promoting NP cell survival and phenotype. Here, an injectable, laminin-111 functionalized poly(ethylene glycol) (PEG-LM111) hydrogel was developed as a biomaterial carrier for cell delivery to the IVD. We evaluated the mechanical properties of the PEG-LM111 hydrogel, and its ability to retain delivered cells in the IVD space. Gelation occurred in approximately 20 minutes without an initiator, with dynamic shear moduli in the range of 0.9 – 1.4 kPa. Primary NP cell retention in cultured IVD explants was significantly higher over 14 days when cells were delivered within a PEG-LM111 carrier, as compared to cells in liquid suspension. Together, these results suggest this injectable laminin-functionalized biomaterial may be an easy to use carrier for delivering cells to the IVD.
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