Injectable hyaluronic acid based microrods provide local micromechanical and biochemical cues to attenuate cardiac fibrosis after myocardial infarction.
Injectable hyaluronic acid based microrods provide local micromechanical and biochemical cues to attenuate cardiac fibrosis after myocardial infarction.
复制标题
DOI：
10.1016/j.biomaterials.2018.03.042
复制
发表时间：
2018-07
期刊：
影响因子：
14
通讯作者：
Desai TA
中科院分区：
文献类型：
--
作者：
Le LV;Mohindra P;Fang Q;Sievers RE;Mkrtschjan MA;Solis C;Safranek CW;Russell B;Lee RJ;Desai TA
心肌梗死（MI）后的心脏组织修复是组织工程最具挑战性的目标之一。缺血性损伤后，显著的基质重塑和无血管瘢痕组织的形成显著损害受损心肌中的细胞植入和存活。这限制了细胞替代疗法的功效，需要减少病理性瘢痕形成的策略，以创造适合健康组织再生的微环境。在这里，我们证明了离散的透明质酸（HA）为基础的微棒的成功制造提供局部生化和生物力学信号，重新编程细胞和减弱心脏纤维化。HA微棒在生理硬度范围内产生，并显示在透明质酸酶存在下降解。此外，我们发现成纤维细胞与这些微棒在体外相互作用，导致增殖，胶原蛋白表达和肌成纤维细胞表型的其他标志物的显着变化。当注射到成年大鼠MI模型的心肌中时，HA微棒在梗死后6周防止左心室壁变薄并改善心脏功能。
Repairing cardiac tissue after myocardial infarction (MI) is one of the most challenging goals in tissue engineering. Following ischemic injury, significant matrix remodeling and the formation of avascular scar tissue significantly impairs cell engraftment and survival in the damaged myocardium. This limits the efficacy of cell replacement therapies, demanding strategies that reduce pathological scarring to create a suitable microenvironment for healthy tissue regeneration. Here, we demonstrate the successful fabrication of discrete hyaluronic acid (HA)-based microrods to provide local biochemical and biomechanical signals to reprogram cells and attenuate cardiac fibrosis. HA microrods were produced in a range of physiological stiffness and shown to degrade in the presence of hyaluronidase. Additionally, we show that fibroblasts interact with these microrods in vitro, leading to significant changes in proliferation, collagen expression and other markers of a myofibroblast phenotype. When injected into the myocardium of an adult rat MI model, HA microrods prevented left ventricular wall thinning and improved cardiac function at 6 weeks post infarct.