Damage associated molecular patterns within xenogeneic biologic scaffolds and their effects on host remodeling
Damage associated molecular patterns within xenogeneic biologic scaffolds and their effects on host remodeling
复制标题
DOI：
10.1016/j.biomaterials.2011.09.040
复制
发表时间：
2012-01-01
期刊：
影响因子：
14
通讯作者：
Badylak, S. F.
中科院分区：
文献类型：
--
作者：
Daly, K. A.;Liu, S.;Badylak, S. F.
免疫应答是异种生物支架在体内下游重构的重要决定因素。促炎反应与包囊形成和异物反应相关，而抗炎反应与结构性重塑相关。然而，诱导这种极化的细胞外基质（ECM）内的生物活性和生物诱导分子尚不清楚，尽管可能是细胞残余物，如保留在支架内的损伤相关分子模式（DAMP）可能发挥作用。本研究探讨了常见ECM支架的免疫调节作用。结果显示，组织来源、脱细胞方法和化学交联修饰影响良好表征的DAMP-HMGB 1的存在。此外，这些因素与细胞增殖、死亡、趋化因子CCL 2和CCL 4的分泌以及促炎信号受体toll样受体4（TLR 4）的上调的差异相关。HMGB 1与Escherin的抑制增加了促炎反应，增加了细胞死亡，上调了趋化因子和TLR 4 mRNA的表达。本研究表明HMGB 1和其他DAMPS作为ECM支架内的生物诱导分子的重要性。其他ECM生物活性分子的鉴定和评价将是新生物材料开发的未来关注领域。(C)2011爱思唯尔有限公司保留所有权利。
The immune response is an important determinant of the downstream remodeling of xenogeneic biologic scaffolds in vivo. Pro-inflammatory responses have been correlated with encapsulation and a foreign body reaction, while anti-inflammatory reactions are associated with constructive remodeling. However, the bioactive and bioinductive molecules within the extracellular matrix (ECM) that induce this polarization are unclear, although it is likely that cellular remnants such as damage associated molecular patterns (DAMPs) retained within the scaffold may play a role. The present study investigated the immunomodulatory effects of common ECM scaffolds. Results showed that tissue source, decellularization method and chemical crosslinking modifications affect the presence of the well characterized DAMP - HMGB1. In addition, these factors were correlated with differences in cell proliferation, death, secretion of the chemokines CCL2 and CCL4, and up regulation of the pro-inflammatory signaling receptor toll-like receptor 4 (TLR4). Inhibition of HMGB1 with glycyrrhizin increased the pro-inflammatory response, increasing cell death and up regulating chemokine and TLR4 mRNA expression. The present study suggests the importance of HMGB1 and other DAMPS as bioinductive molecules within the ECM scaffold. Identification and evaluation of other ECM bioactive molecules will be an area of future interest for new biomaterial development. (C) 2011 Elsevier Ltd. All rights reserved.