Brazhkina Olga, Park Jeong Hun, Brown Milton, Walcott Jelisha C, Han Jonghyeuk, Turchetti Arianna, Roychowdhury Swarnima, Prasad Ria Soni, Kim Matthew J, Itzhaki Ilanit, De Jesus Morales Kenneth J, Hollister Scott J, Davis Michael E
Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University School of Medicine, Atlanta, GA, 30332, United States.
Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University School of Medicine, Atlanta, GA, 30332, United States; Center for 3D Medical Fabrication, Georgia Institute of Technology and Emory University, 313 Ferst Drive, Atlanta, GA, 30332, United States.
Biomaterials. 2025 Dec;323:123418. doi: 10.1016/j.biomaterials.2025.123418. Epub 2025 May 20.
Novel cardiac patch designs achieved by advanced 3D manufacturing continue to have favorable impacts on the repair and regeneration of the myocardium after injury. Briefly, auxetic units with a negative Poisson's ratio have already shown remarkable promise for serving as a next-generation complex scaffold in left ventricular disease. In this study we biofabricated a 3D printed polycaprolactone (PCL) cardiac auxetic patch loaded with high density contractile induced pluripotent stem cell-derived cardiomyocytes (iCMs) and examined the synergist effect of iCM auxetic patches on a chronic myocardial infarct rodent model compared to a stiffer non-auxetic control patch architecture. A week after the induction of a temporary left anterior descending artery ligation, we administered the treatment groups in the form of patch implantation over the ischemic area after initial acute inflammation was complete and prior to granulation tissue formation following the infarct for clinical relevance. Our findings highlight that auxetic patches can provide additional ventricular support and diminished adverse ventricular remodeling, as seen through ejection fraction outputs and histology, and iCM-laden auxetics show localized regenerative potential through increased vascularization compared to controls with no patch or a non-auxetic patch architecture. Exploration on the impact of a negative Poisson's ratio on both global functional outcomes and local therapeutic benefit highlights that iCM-laden auxetics should be further surveyed for other cardiac pathophysiologic conditions, including more in-depth studies on infarction or right ventricular disease.
通过先进的3D制造实现的新型心脏贴片设计，持续对损伤后心肌的修复和再生产生有利影响。简而言之，具有负泊松比的拉胀单元，已显示出作为下一代左心室疾病复杂支架的巨大潜力。在本研究中，我们生物制造了一种3D打印的聚己内酯（PCL）心脏拉胀贴片，其中加载了高密度收缩性诱导多能干细胞衍生的心肌细胞（iCMs），并研究了与较硬的非拉胀对照贴片结构相比，iCM拉胀贴片对慢性心肌梗死啮齿动物模型的协同作用。在诱导暂时性左前降支动脉结扎一周后，在初始急性炎症完全消退且梗死灶肉芽组织形成之前，我们以贴片植入的形式对治疗组进行给药，以符合临床实际情况。我们的研究结果表明，拉胀贴片可以提供额外的心室支持并减少不良心室重塑，这通过射血分数输出和组织学得以体现，并且与未贴片或非拉胀贴片结构的对照组相比，载有iCM的拉胀贴片通过增加血管生成显示出局部再生潜力。对负泊松比对整体功能结果和局部治疗益处的影响进行探索表明，载有iCM的拉胀贴片应针对其他心脏病理生理状况进行进一步研究，包括对梗死或右心室疾病的更深入研究。
