Self-assembling peptide hydrogel for intervertebral disc tissue engineering
Self-assembling peptide hydrogel for intervertebral disc tissue engineering
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DOI：
10.1016/j.actbio.2016.09.033
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发表时间：
2016-12-01
影响因子：
9.7
通讯作者：
Gough, Julie E.
中科院分区：
文献类型：
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作者：
Wan, Simon;Borland, Samantha;Gough, Julie E.
基于细胞的椎间盘再生疗法被认为有望用于退行性椎间盘疾病的治疗，这种疾病与下背痛密切相关。一个从头自组装肽水凝胶（SAPH），选择其生物相容性，可剪裁的性能和纳米纤维结构，作为细胞载体和支架髓核（NP）组织工程研究。振荡流变学确定该系统可能通过微创手术递送，并且可以优化机械性能以匹配天然人NP的刚度。在SAPH中三维培养NP细胞（NPC）后，NP特异性基因（KRT 8、KRT 18、FOXF1）的上调证实了该系统可以在单层培养期间去分化后恢复NP表型。在整个培养过程中，细胞活力很高，同时与体内NPC相似，活细胞群保持稳定。最后，SAPH刺激聚集蛋白聚糖和II型胶原沉积，两个重要的NP细胞外基质成分的时间依赖性增加。研究结果支持了SAPH可作为细胞输送系统和支架用于治疗退行性椎间盘疾病的假设。重要性声明由于人口老龄化和目前治疗效果有限，下背痛（LBP）的患病率很普遍。由于腰椎间盘突出症与椎间盘退变密切相关，以细胞为基础的治疗方法被认为可以通过修复椎间盘组织来缓解腰椎间盘突出症，各种天然和合成的生物材料已经被研究作为潜在的椎间盘组织工程支架。自组装肽水凝胶（SAPHs）结合了天然和合成生物材料的优点，联合收割机，具有生物相容性和易改性等优点，本研究表明，SAPHs具有与天然组织相当的强度，可注射，恢复了体外诊断细胞表型，并刺激适当基质成分的沉积。结果表明，SAPHs作为IVD组织工程支架的前景。皇冠版权所有（C）2016由爱思唯尔有限公司代表Acta Materialia Inc.
Cell-based therapies for regeneration of intervertebral discs are regarded to hold promise for degenerative disc disease treatment, a condition that is strongly linked to lower back pain. A de novo self-assembling peptide hydrogel (SAPH), chosen for its biocompatibility, tailorable properties and nanofibrous architecture, was investigated as a cell carrier and scaffold for nucleus pulposus (NP) tissue engineering. Oscillatory rheology determined that the system would likely be deliverable via minimally invasive procedure and mechanical properties could be optimised to match the stiffness of the native human NP. After three-dimensional culture of NP cells (NPCs) in the SAPH, upregulation of NP-specific genes (KRT8, KRT18, FOXF1) confirmed that the system could restore the NP phenotype following dedifferentiation during monolayer culture. Cell viability was high throughout culture whilst, similarly to NPCs in vivo, the viable cell population remained stable. Finally, the SAPH stimulated time-dependent increases in aggrecan and type II collagen deposition, two important NP extracellular matrix components. Results supported the hypothesis that the SAPH could be used as a cell delivery system and scaffold for the treatment of degenerative disc disease.Statement of SignificanceLower back pain (LBP) prevalence is widespread due to an aging population and the limited efficacy of current treatments. As LBP is strongly associated with intervertebral disc (IVD) degeneration, it is thought that cell-based therapies could alleviate LBP by repairing IVD tissue.Various natural and synthetic biomaterials have been investigated as potential IVD tissue engineering scaffolds. Self-assembling peptide hydrogels (SAPHs) combine advantages of both natural and synthetic biomaterials; for example they are biocompatible and have easily modifiable properties.The present study demonstrated that a de novo SAPH had comparable strength to the native tissue, was injectable, restored the IVD cell phenotype and stimulated deposition of appropriate matrix components. Results illustrated the promise of SAPHs as scaffolds for IVD tissue engineering. Crown Copyright (C) 2016 Published by Elsevier Ltd on behalf of Acta Materialia Inc.