An injectable capillary-like microstructured alginate hydrogel improves left ventricular function after myocardial infarction in rats.
An injectable capillary-like microstructured alginate hydrogel improves left ventricular function after myocardial infarction in rats.
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DOI：
10.1016/j.ijcard.2016.06.158
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发表时间：
2016-10-01
影响因子：
3.5
通讯作者：
Pepine CJ
中科院分区：
文献类型：
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作者：
Rocca DG;Willenberg BJ;Qi Y;Simmons CS;Rubiano A;Ferreira LF;Huo T;Petersen JW;Ruchaya PJ;Wate PS;Wise EA;Handberg EM;Cogle CR;Batich CD;Byrne BJ;Pepine CJ
一种新的心肌梗死（MI）后治疗方法是将高含水量的高分子生物材料凝胶（水凝胶）注射到受损的心肌中，以调节心脏的负性重构和保持心脏功能。我们研究了一种新型凝胶化海藻酸盐水凝胶的治疗潜力，这种水凝胶具有独特的均匀毛细血管样通道的微观结构（称为Capgel）。在诱导前路心肌梗死后不久（48小时），Sprague Dawley大鼠在梗死边界区心肌内直接注射Capgel （n=12）或不注射Capgel （n=10，对照组）。超声心动图在48小时（第0周）和4周（第4周）评估左心室功能。超声心动图显示，注射凝胶后左心室收缩功能改善了27%：分数缩短从第0周的26±3%增加到第4周的33±2% （p=0.001）。4周后注射部位出现了Capgel，但在8周时很少出现。剩余凝胶中大量填充CD68+巨噬细胞和CD206+簇和血管。体外实验评估Capgel释放的血管紧张素-(1-7)。血管紧张素-(1-7)从Capgel中持续释放90天。Capgel是一种可降解的生物活性水凝胶，由凝胶化的毛细血管海藻酸盐凝胶组成，用于心肌内注射似乎是安全的，与心肌梗死后大鼠左心室功能的改善有关，并可能提供血管紧张素的长期供应（1-7）。
A new post–myocardial infarction (MI) therapy is injection of high-water content polymeric biomaterial gels (hydrogels) into damaged myocardium to modulate cardiac negative remodeling and preserve heart function. We investigated the therapeutic potential of a novel gelatinized alginate hydrogel with a unique microstructure of uniform capillary-like channels (termed Capgel). Shortly (48 hours) after induced anterior MI, Sprague Dawley rats received intramyocardial injection of Capgel directly into the antero-septal wall at the infarct border zone (n=12) or no injection (n=10, controls). Echocardiograms were performed at 48h (week 0) and 4 weeks (week 4) to evaluate left ventricular function. Echocardiograms showed 27% improvement of left ventricular systolic function over time with gel injection: fractional shortening increased from 26±3% at week 0 to 33±2% at week 4 (p=0.001). Capgel was present at the injection site after 4 weeks, but was minimal at 8 weeks. The remaining gel was heavily populated by CD68+ macrophages with CD206+ clusters and blood vessels. An in vitro experiment was performed to assess Angiotensin-(1-7) released from Capgel. Angiotensin-(1-7) was released from the Capgel in a sustained manner for 90 days. Use of Capgel, a degradable, bioactive hydrogel composed of gelatinized capillary-alginate gel, appears safe for intramyocardial injection, is associated with improved left ventricular function after MI in rats, and may provide a long-term supply of Angiotensin-(1-7).