Timing underpins the benefits associated with injectable collagen biomaterial therapy for the treatment of myocardial infarction
Timing underpins the benefits associated with injectable collagen biomaterial therapy for the treatment of myocardial infarction
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DOI：
10.1016/j.biomaterials.2014.11.004
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发表时间：
2015-01-01
期刊：
影响因子：
14
通讯作者：
Suuronen, Erik J.
中科院分区：
文献类型：
--
作者：
Blackburn, Nick J. R.;Sofrenovic, Tanja;Suuronen, Erik J.
可注射水凝胶生物材料是促进心肌梗死后修复和再生的有前途的治疗方法。然而，递送的时间和生物材料治疗赋予其益处的机制仍是有待解决的转化问题。我们在心肌梗死后3个不同的给药时间点评估可注射胶原基质的疗效。梗死小鼠在心肌梗死后3小时、1周或2周接受基质或对照（生理盐水）治疗。较早的治疗可以更好地预防心室负重构和长期心功能恶化（长达3个月），而等待较长时间给予基质（心肌梗死后1周和2周）则降低了治疗效果。胶原基质递送不刺激炎症反应急性和有利调节炎症在心肌长期。我们发现基质与宿主组织相互作用，改变心肌细胞因子谱，促进血管生成，减少纤维化和细胞死亡。这项工作强调了递送时间可以显著影响可注射水凝胶保护心肌梗死后环境的能力，这将是心脏生物材料治疗临床转化中的一个重要考虑因素。(C) 2014 Elsevier Ltd.版权所有。
Injectable hydrogel biomaterials are promising therapies to promote repair and regeneration post-myocardial infarction (MI). However, the timing of delivery and the mechanisms through which biomaterial treatments confer their benefits are translational issues that remain to be addressed. We assessed the efficacy of an injectable collagen matrix at 3 different delivery time points post-MI. Infarcted mice received the matrix or control (saline) treatment at 3 h, 1 week or 2 weeks after MI. The earlier treatment delivery better prevented negative ventricular remodeling and long-term deterioration of cardiac function (up to 3 months), whereas waiting longer to administer the matrix (1 and 2 weeks post-MI) reduced the therapeutic effects. Collagen matrix delivery did not stimulate an inflammatory response acutely and favorably modulated inflammation in the myocardium long-term. We found that the matrix interacts with the host tissue to alter the myocardial cytokine profile, promote angiogenesis, and reduce fibrosis and cell death. This work highlights that the timing of delivery can significantly affect the ability of an injectable hydrogel to protect the post-MI environment, which will be an important consideration in the clinical translation of cardiac biomaterial therapy. (C) 2014 Elsevier Ltd. All rights reserved.