Development and initial characterization of a chemically stabilized elastin-glycosaminoglycan-collagen composite shape-memory hydrogel for nucleus pulposus regeneration.
Development and initial characterization of a chemically stabilized elastin-glycosaminoglycan-collagen composite shape-memory hydrogel for nucleus pulposus regeneration.
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DOI：
10.1002/jbm.a.35104
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发表时间：
2014-12
期刊：
影响因子：
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通讯作者：
J. Mercuri;Caroline P. Addington;Richard Pascal;S. Gill;D. Simionescu
中科院分区：
文献类型：
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作者：
J. Mercuri;Caroline P. Addington;Richard Pascal;S. Gill;D. Simionescu
髓核（NP）是一种具有弹性的亲水性组织，在椎间盘（IVD）的生物力学功能中起重要作用。在IVD退变的早期阶段观察到NP细胞外基质（ECM）的破坏。在此，我们描述了一种新型生物材料的开发和初步表征，该材料试图通过构建化学稳定的弹性-糖胺聚糖-胶原（EGC）复合水凝胶来重建NP的弹性和亲水性质。结果表明，将可溶性弹性蛋白聚集体、6-硫酸软骨素、透明质酸和胶原蛋白混合，经过冷冻干燥、碳二亚胺和五没食酰基葡萄糖固定剂稳定，然后用糖胺聚糖降解酶部分降解，可以形成一种具有独特“形状记忆”海绵特性的弹性亲水性水凝胶。所得到的材料在多次机械压缩后显示出恢复其原始尺寸和含水量的能力，并显示出对加速酶降解的抵抗力。利用人脂肪干细胞（hADSCs）进行的初步体外研究表明，该材料具有细胞相容性，并支持向NP细胞样表型分化。体内生物相容性研究表明，植入4周后，宿主细胞浸润和活性重塑的证据。可行性研究表明，EGC水凝胶可以通过微创方法输送。
Nucleus pulposus (NP) is a resilient and hydrophilic tissue which plays a significant role in the biomechanical function of the intervertebral disc (IVD). Destruction of the NP extracellular matrix (ECM) is observed during the early stages of IVD degeneration. Herein, we describe the development and initial characterization of a novel biomaterial which attempts to recreate the resilient and hydrophilic nature of the NP via the construction of a chemically stabilized elastin-glycosaminoglycan-collagen (EGC) composite hydrogel. Results demonstrated that a resilient, hydrophilic hydrogel which displays a unique "shape-memory" sponge characteristic could be formed from a blend of soluble elastin aggregates, chondroitin-6-sulfate, hyaluronic acid and collagen following freeze-drying, stabilization with a carbodiimide and penta-galloyl glucose-based fixative, and subsequent partial degradation with glycosaminoglycan degrading enzymes. The resultant material exhibited the ability to restore its original dimensions and water content following multi-cycle mechanical compression and illustrated resistance to accelerated enzymatic degradation. Preliminary in vitro studies utilizing human adipose derived stem cells (hADSCs) demonstrated that the material was cytocompatible and supported differentiation towards an NP cell-like phenotype. In vivo biocompatibility studies illustrated host cell infiltration and evidence of active remodeling following 4 weeks of implantation. Feasibility studies demonstrated that the EGC hydrogel could be delivered via minimally invasive methods.