Safety and efficacy of an injectable extracellular matrix hydrogel for treating myocardial infarction.
Safety and efficacy of an injectable extracellular matrix hydrogel for treating myocardial infarction.
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DOI：
10.1126/scitranslmed.3005503
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发表时间：
2013-02-20
影响因子：
17.1
通讯作者：
Christman KL
中科院分区：
文献类型：
--
作者：
Seif-Naraghi SB;Singelyn JM;Salvatore MA;Osborn KG;Wang JJ;Sampat U;Kwan OL;Strachan GM;Wong J;Schup-Magoffin PJ;Braden RL;Bartels K;DeQuach JA;Preul M;Kinsey AM;DeMaria AN;Dib N;Christman KL
需要新的治疗方法来预防心肌梗死（MI）后心力衰竭。作为心肌梗死方法转化的实验性治疗策略，必须在模拟临床情况的相关动物模型中建立安全性和有效性。我们开发了一种从猪心肌细胞外基质（ECM）中提取的可注射水凝胶，作为心肌梗死后心脏修复的支架。在这项研究中，我们在模拟临床环境的大型和小型动物研究中建立了这种可注射生物材料的安全性和有效性。梗死猪在心肌梗死后两周经皮经心内膜注射心肌基质水凝胶，并在三个月后进行评估。超声心动图显示心功能、心室容积和整体壁运动评分均有改善。此外，与对照组相比，注射基质的猪在心内膜处发现了明显更大的心肌区。在大鼠中，我们建立了这种生物材料的安全性，并通过直接注射到左心室管腔和炎症研究来探索宿主反应，两者都支持这种材料的生物相容性。人体血液的血液相容性研究表明，暴露于相关浓度的材料不影响凝血时间或血小板活化。因此，这项工作为这种心脏特异性生物材料的临床研究提供了一个强大的平台，这种生物材料可以通过导管输送。
New therapies are needed to prevent heart failure after myocardial infarction (MI). As experimental treatment strategies for MI approach translation, safety and efficacy must be established in relevant animal models that mimic the clinical situation. We have developed an injectable hydrogel derived from porcine myocardial extracellular matrix (ECM) as a scaffold for cardiac repair post-MI. In this study, we establish the safety and efficacy of this injectable biomaterial in large-and small-animal studies that simulate the clinical setting. Infarcted pigs were treated with percutaneous transendocardial injections of the myocardial matrix hydrogel two weeks post-MI and evaluated after three months. Echocardiography indicated improvement in cardiac function, ventricular volumes, and global wall motion scores. Furthermore, a significantly larger zone of cardiac muscle was found at the endocardium in matrix-injected pigs compared to controls. In rats, we establish the safety of this biomaterial and explore the host response via direct injection into the left ventricular lumen and in an inflammation study, both of which support the biocompatibility of this material. Hemocompatibility studies with human blood indicate that exposure to the material at relevant concentrations does not affect clotting times or platelet activation. This work therefore provides a strong platform to move forward in clinical studies with this cardiac-specific biomaterial that can be delivered by catheter.
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影响因子：
37.8
作者：
Roger VL;Go AS;Lloyd-Jones DM;Benjamin EJ;Berry JD;Borden WB;Bravata DM;Dai S;Ford ES;Fox CS;Fullerton HJ;Gillespie C;Hailpern SM;Heit JA;Howard VJ;Kissela BM;Kittner SJ;Lackland DT;Lichtman JH;Lisabeth LD;Makuc DM;Marcus GM;Marelli A;Matchar DB;Moy CS;Mozaffarian D;Mussolino ME;Nichol G;Paynter NP;Soliman EZ;Sorlie PD;Sotoodehnia N;Turan TN;Virani SS;Wong ND;Woo D;Turner MB;American Heart Association Statistics Committee and Stroke Statistics Subcommittee
通讯作者：
American Heart Association Statistics Committee and Stroke Statistics Subcommittee
影响因子：
3.1
作者：
DeQuach JA;Lin JE;Cam C;Hu D;Salvatore MA;Sheikh F;Christman KL
通讯作者：
Christman KL
影响因子：
4.6
作者：
Mukherjee, Rupak;Zavadzkas, Juozas A.;Saunders, Stuart M.;McLean, Julie E.;Jeffords, Laura B.;Beck, Christy;Stroud, Robert E.;Leone, Allyson M.;Koval, Christine N.;Rivers, William T.;Basu, Shubhayu;Sheehy, Alexander;Michal, Gene;Spinale, Francis G.
通讯作者：
Spinale, Francis G.
影响因子：
37.8
作者：
Lin, Yi-Dong;Yeh, Ming-Long;Hsieh, Patrick C. H.
通讯作者：
Hsieh, Patrick C. H.
影响因子：
4.6
作者：
Hamamoto, Hirotsugu;Gorman, Joseph H., III;Ryan, Liam P.;Hinmon, Robin;Martens, Timothy P.;Schuster, Michael D.;Plappert, Theodore;Kiupel, Matti;John-Sutton, Martin G. St.;Itescu, Silviu;Gorman, Robert C.
通讯作者：
Gorman, Robert C.