Department of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States.
Biomacromolecules. 2011 Nov 14;12(11):4127-35. doi: 10.1021/bm201198x. Epub 2011 Oct 11.
Increased myocardial wall stress after myocardial infarction (MI) initiates the process of adverse left ventricular (LV) remodeling that is manifest as progressive LV dilatation, loss of global contractile function, and symptomatic heart failure, and recent work has shown that reduction in wall stress through injectable bulking agents attenuates these outcomes. In this study, hyaluronic acid (HA) was functionalized to exhibit controlled and tunable mechanics and degradation once cross-linked, in an attempt to assess the temporal dependency of mechanical stabilization in LV remodeling. Specifically, two hydrolytically degrading (low and high HeMA-HA, degrading in ~3 and 10 weeks, respectively) and two stable (low and high MeHA, little mass loss even after 8 weeks) hydrogels with similar initial mechanics (low: ~7 kPa; high: ~35-40 kPa) were evaluated in an ovine model of MI. Generally, the more stable hydrogels maintained myocardial wall thickness in the apical and basilar regions more efficiently (low MeHA: apical: 6.5 mm, basilar: 7 mm, high MeHA: apical: 7.0 mm basilar: 7.2 mm) than the hydrolytically degrading hydrogels (low HeMA-HA: apical: 3.5 mm, basilar: 6.0 mm, high HeMA-HA: apical: 4.1 mm, basilar: 6.1 mm); however, all hydrogel groups were improved compared to infarct controls (IC) (apical: 2.2 mm, basilar: 4.6 mm). Histological analysis at 8 weeks demonstrated that although both degradable hydrogels resulted in increased inflammation, all treatments resulted in increased vessel formation compared to IC. Further evaluation revealed that while high HeMA-HA and high MeHA maintained reduced LV volumes at 2 weeks, high MeHA was more effective at 8 weeks, implying that longer wall stabilization is needed for volume maintenance. All hydrogel groups resulted in better cardiac output (CO) values than IC.
心肌梗死后（MI）心肌壁应力增加会引发不良的左心室（LV）重构过程，表现为 LV 进行性扩张、整体收缩功能丧失和症状性心力衰竭，最近的研究表明，通过注射性填充剂降低壁应力可以减轻这些后果。在这项研究中，透明质酸（HA）经过功能化修饰后表现出可控且可调的机械性能和交联后的降解性能，旨在评估 LV 重构中机械稳定的时间依赖性。具体来说，研究评估了两种具有水解降解性（低和高 HeMA-HA，分别在约 3 周和 10 周内降解）和两种稳定（低和高 MeHA，即使在 8 周后质量损失也很小）的水凝胶，它们具有相似的初始机械性能（低：约 7 kPa；高：约 35-40 kPa），在羊 MI 模型中进行了评估。一般来说，更稳定的水凝胶更有效地维持心尖和基底区域的心肌壁厚度（低 MeHA：心尖：6.5 毫米，基底：7 毫米，高 MeHA：心尖：7.0 毫米基底：7.2 毫米）比水解降解水凝胶（低 HeMA-HA：心尖：3.5 毫米，基底：6.0 毫米，高 HeMA-HA：心尖：4.1 毫米，基底：6.1 毫米）；然而，与梗死对照（IC）相比，所有水凝胶组都有所改善（心尖：2.2 毫米，基底：4.6 毫米）。8 周的组织学分析表明，尽管两种可降解水凝胶都导致炎症增加，但与 IC 相比，所有治疗方法都导致血管形成增加。进一步评估表明，虽然高 HeMA-HA 和高 MeHA 在 2 周时维持 LV 容积减少，但高 MeHA 在 8 周时更有效，这意味着维持容积需要更长时间的壁稳定。与 IC 相比，所有水凝胶组的心脏输出（CO）值都更好。
