Mohindra Priya, Zhong Justin X, Fang Qizhi, Cuylear Darnell L, Huynh Cindy, Qiu Huiliang, Gao Dongwei, Kharbikar Bhushan N, Huang Xiao, Springer Matthew L, Lee Randall J, Desai Tejal A
UC Berkeley-UCSF Graduate Program in Bioengineering, San Francisco, CA, USA.
Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA, USA.
NPJ Regen Med. 2023 Oct 23;8(1):60. doi: 10.1038/s41536-023-00336-w.
Heart failure (HF) remains a global public health burden and often results following myocardial infarction (MI). Following injury, cardiac fibrosis forms in the myocardium which greatly hinders cellular function, survival, and recruitment, thus severely limits tissue regeneration. Here, we leverage biophysical microstructural cues made of hyaluronic acid (HA) loaded with the anti-fibrotic proteoglycan decorin to more robustly attenuate cardiac fibrosis after acute myocardial injury. Microrods showed decorin incorporation throughout the entirety of the hydrogel structures and exhibited first-order release kinetics in vitro. Intramyocardial injections of saline (n = 5), microrods (n = 7), decorin microrods (n = 10), and free decorin (n = 4) were performed in male rat models of ischemia-reperfusion MI to evaluate therapeutic effects on cardiac remodeling and function. Echocardiographic analysis demonstrated that rats treated with decorin microrods (5.21% ± 4.29%) exhibited significantly increased change in ejection fraction (EF) at 8 weeks post-MI compared to rats treated with saline (-4.18% ± 2.78%, p < 0.001) and free decorin (-3.42% ± 1.86%, p < 0.01). Trends in reduced end diastolic volume were also identified in decorin microrod-treated groups compared to those treated with saline, microrods, and free decorin, indicating favorable ventricular remodeling. Quantitative analysis of histology and immunofluorescence staining showed that treatment with decorin microrods reduced cardiac fibrosis (p < 0.05) and cardiomyocyte hypertrophy (p < 0.05) at 8 weeks post-MI compared to saline control. Together, this work aims to contribute important knowledge to guide rationally designed biomaterial development that may be used to successfully treat cardiovascular diseases.
心力衰竭（HF）仍然是一个全球性的公共卫生负担，且常常在心肌梗死（MI）后发生。损伤后，心肌中会形成心脏纤维化，这极大地阻碍了细胞功能、存活和募集，从而严重限制了组织再生。在此，我们利用由负载抗纤维化蛋白聚糖核心蛋白聚糖的透明质酸（HA）制成的生物物理微观结构线索，以更有效地减轻急性心肌损伤后的心脏纤维化。微棒显示核心蛋白聚糖在整个水凝胶结构中均有掺入，并在体外呈现一级释放动力学。在雄性缺血再灌注心肌梗死大鼠模型中进行心肌内注射生理盐水（n = 5）、微棒（n = 7）、核心蛋白聚糖微棒（n = 10）和游离核心蛋白聚糖（n = 4），以评估对心脏重塑和功能的治疗效果。超声心动图分析表明，与注射生理盐水（-4.18% ± 2.78%，p < 0.001）和游离核心蛋白聚糖（-3.42% ± 1.86%，p < 0.01）的大鼠相比，接受核心蛋白聚糖微棒治疗的大鼠在心肌梗死后8周时射血分数（EF）的变化显著增加（5.21% ± 4.29%）。与注射生理盐水、微棒和游离核心蛋白聚糖的组相比，核心蛋白聚糖微棒治疗组的舒张末期容积也有降低趋势，表明心室重塑良好。组织学和免疫荧光染色的定量分析表明，与生理盐水对照组相比，核心蛋白聚糖微棒治疗在心肌梗死后8周时可减少心脏纤维化（p < 0.05）和心肌细胞肥大（p < 0.05）。总之，这项工作旨在提供重要知识，以指导合理设计可用于成功治疗心血管疾病的生物材料的开发。
