An injectable extracellular matrix for the reconstruction of epidural fat and the prevention of epidural fibrosis
An injectable extracellular matrix for the reconstruction of epidural fat and the prevention of epidural fibrosis
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DOI：
10.1088/1748-6041/11/3/035010
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发表时间：
2016-06-01
影响因子：
4
通讯作者：
Chen, Ming-Hong
中科院分区：
文献类型：
--
作者：
Lin, Cheng-Yi;Liu, Tse-Ying;Chen, Ming-Hong
广泛的硬膜外纤维化是脊柱手术后的常见并发症，可导致疼痛和活动受限。在本研究中，开发了一种新颖的仿生方法来防止硬脑膜术后粘连。我们的目的是通过开发一种可注射的脱细胞脂肪基质（DAM），其中含有透明质酸（HA）水凝胶，并负载脂肪基质细胞（ASC），从而重建硬膜外脂肪，从而防止疤痕组织粘附。可注射的 DAM 由猪脂肪组织通过四个冻融循环以及随后的胃蛋白酶消化来制备。残留分析证实了无去垢剂脱细胞的功效，同时大多数硫酸化糖胺聚糖和胶原蛋白得以保留。 Transwell 迁移实验证明了含有 DAM 的 HA 水凝胶的抗渗透特性。 3D 培养 14 天后，含有 DAM 的 HA 水凝胶在 ASC 的成脂分化中表现出诱导潜力。在体内研究中，将负载 ASC 的含有 DAM 的 HA 水凝胶（DAM/ASC 掺入的 HA 水凝胶）注射到成年椎板切除雄性大鼠中，并通过显微镜组织学检查评估结果。体内数据表明，HA水凝胶、DAM和ASC都是工程化脂肪组织阻止纤维组织侵袭的能力所必需的。我们的结果表明，这种可注射的 DAM/ASC 掺入 HA 水凝胶在软组织重建和硬膜外纤维化预防的微创手术中具有潜在的应用。
Extensive epidural fibrosis is a common complication following spinal surgery and can cause pain and limited mobility. In the present study, a novel biomimetic approach was developed to prevent postsurgical adhesion of the dura. We aimed to reconstruct epidural fat, which prevents scartissue adhesion, through the development of an injectable decellularized adipose matrix (DAM)containing hyaluronic acid (HA) hydrogel loaded with adipose stromal cells (ASCs). Injectable DAM was prepared from porcine adipose tissue by four freeze-thaw cycles with subsequent pepsin digestion. Residual analyses confirmed the efficacy of detergent-free decellularization, while most sulfated glycosaminoglycans and collagen were preserved. The Transwell migration assay demonstrated the anti-infiltrative property of the DAM-containing HA hydrogel. After 14 d of 3D culture, the DAM-containing HA hydrogel showed inductive potential in the adipogenic differentiation of ASCs. For an in vivo study, the ASC-loaded DAM-containing HA hydrogel (DAM/ASC-incorporated HA hydrogel) was injected into adult laminectomized male rats, and the results were assessed by microscopic histological examination. The in vivo data indicated that HA hydrogel, DAM, and ASCs were all required for the ability of the engineered fat tissue to block the invasion of the fibrous tissue. Our results suggested that this injectable DAM/ASC-incorporated HA hydrogel has potential applications in minimally invasive surgery for soft-tissue reconstruction and epidural fibrosis prevention.