School of Biomedical Engineering, Science and Health Systems, Drexel University, Philadelphia, PA, 19104, USA.
Drug Deliv Transl Res. 2023 Jul;13(7):1983-2014. doi: 10.1007/s13346-023-01290-2. Epub 2023 Feb 10.
Ischemic heart failure (IHF) is a leading cause of morbidity and mortality worldwide, for which heart transplantation remains the only definitive treatment. IHF manifests from myocardial infarction (MI) that initiates tissue remodeling processes, mediated by mechanical changes in the tissue (loss of contractility, softening of the myocardium) that are interdependent with cellular mechanisms (cardiomyocyte death, inflammatory response). The early remodeling phase is characterized by robust inflammation that is necessary for tissue debridement and the initiation of repair processes. While later transition toward an immunoregenerative function is desirable, functional reorientation from an inflammatory to reparatory environment is often lacking, trapping the heart in a chronically inflamed state that perpetuates cardiomyocyte death, ventricular dilatation, excess fibrosis, and progressive IHF. Therapies can redirect the immune microenvironment, including biotherapeutic and biomaterial-based approaches. In this review, we outline these existing approaches, with a particular focus on the immunomodulatory effects of therapeutics (small molecule drugs, biomolecules, and cell or cell-derived products). Cardioprotective strategies, often focusing on immunosuppression, have shown promise in pre-clinical and clinical trials. However, immunoregenerative therapies are emerging that often benefit from exacerbating early inflammation. Biomaterials can be used to enhance these therapies as a result of their intrinsic immunomodulatory properties, parallel mechanisms of action (e.g., mechanical restraint), or by enabling cell or tissue-targeted delivery. We further discuss translatability and the continued progress of technologies and procedures that contribute to the bench-to-bedside development of these critically needed treatments.
缺血性心力衰竭（IHF）是全球发病率和死亡率的主要原因，心脏移植仍然是唯一的根治方法。IHF 源自心肌梗死（MI），引发组织重塑过程，这一过程受到组织力学变化（收缩力丧失、心肌软化）和细胞机制（心肌细胞死亡、炎症反应）的相互影响。早期重塑阶段的特征是强烈的炎症，这对于组织清创和修复过程的启动是必要的。虽然后来向免疫再生功能的转变是理想的，但从炎症到修复环境的功能重新定向往往缺乏，使心脏长期处于慢性炎症状态，从而导致心肌细胞死亡、心室扩张、过度纤维化和进行性 IHF。治疗方法可以重新定向免疫微环境，包括生物治疗和基于生物材料的方法。在这篇综述中，我们概述了这些现有的方法，特别关注治疗方法的免疫调节作用（小分子药物、生物分子和细胞或细胞衍生产品）。心脏保护策略，通常侧重于免疫抑制，在临床前和临床试验中显示出了希望。然而，正在出现免疫再生疗法，它们通常受益于早期炎症的加剧。生物材料由于其固有免疫调节特性、平行作用机制（例如机械约束）或通过实现细胞或组织靶向递送来增强这些疗法。我们进一步讨论了这些急需治疗方法从实验室到临床发展的可转化性和技术与程序的持续进展。
