Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, 1760 Haygood Dr, Atlanta, GA, 30322, USA.
Department of Bioengineering and Sanford Consortium for Regenerative Medicine, University of California, San Diego, 2880 Torrey Pines Scenic Dr, La Jolla, CA, 92037, USA.
Biomater Sci. 2022 Jan 18;10(2):444-456. doi: 10.1039/d1bm01539g.
Pediatric patients with congenital heart defects (CHD) often present with heart failure from increased load on the right ventricle (RV) due to both surgical methods to treat CHD and the disease itself. Patients with RV failure often require transplantation, which is limited due to lack of donor availability and rejection. Previous studies investigating the development and assessment of a bioprinted cardiac patch composed of cardiac extracellular matrix (cECM) and human c-kit + progenitor cells (hCPCs) showed that the construct has promise in treating cardiac dysfunction. The current study investigates cardiac outcomes of patch implantation in a rat model of RV failure. Patch parameters including cECM-inclusion and hCPC-inclusion are investigated. Assessments include hCPC retention, RV function, and tissue remodeling (vascularization, hypertrophy, and fibrosis). Animal model evaluation shows that both cell-free and neonatal hCPC-laden cECM-gelatin methacrylate (GelMA) patches improve RV function and tissue remodeling compared to other patch groups and controls. Inclusion of cECM is the most influential parameter driving therapeutic improvements, with or without cell inclusion. This study paves the way for clinical translation in treating pediatric heart failure using bioprinted GelMA-cECM and hCPC-GelMA-cECM patches.
患有先天性心脏病 (CHD) 的儿科患者由于 CHD 的治疗方法和疾病本身,右心室 (RV) 的负荷增加,常出现心力衰竭。RV 衰竭的患者通常需要进行移植,但由于供体不足和排斥反应,移植受到限制。先前的研究调查了由心脏细胞外基质 (cECM) 和人 c-kit +祖细胞 (hCPC) 组成的生物打印心脏补片的开发和评估,表明该构建体在治疗心脏功能障碍方面具有潜力。本研究调查了 RV 衰竭大鼠模型中补片植入的心脏结局。研究了补片参数,包括 cECM 包含和 hCPC 包含。评估包括 hCPC 保留、RV 功能和组织重塑(血管生成、肥大和纤维化)。动物模型评估表明,与其他补片组和对照组相比,无细胞和新生 hCPC 负载的 cECM-明胶甲基丙烯酰胺 (GelMA) 补片均可改善 RV 功能和组织重塑。包含 cECM 是驱动治疗改善的最具影响力的参数,无论是否包含细胞。这项研究为使用生物打印 GelMA-cECM 和 hCPC-GelMA-cECM 补片治疗儿科心力衰竭的临床转化铺平了道路。