A Unification of Nanotopography and Extracellular Matrix in Electrospun Scaffolds for Bioengineered Hepatic Models.
A Unification of Nanotopography and Extracellular Matrix in Electrospun Scaffolds for Bioengineered Hepatic Models.
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DOI：
10.1021/acsabm.3c00032
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发表时间：
2023-06-19
影响因子：
4.7
通讯作者：
Callanan, Anthony
中科院分区：
文献类型：
--
作者：
Gao, Yunxi;Bate, Thomas S R;Callanan, Anthony
供体肝脏短缺是一个关键的全球公共卫生问题，因为全器官移植是肝脏疾病的唯一确定性治疗方法。肝组织工程旨在通过体外组织构建来复制或恢复功能，这可能导致活动性和慢性肝病的替代治疗。具有模拟复杂细胞外基质（ECM）及其对细胞行为的影响的潜力的多功能支架的配制对于在构建体上培养细胞是必不可少的。在支架上单独使用地形或生物线索都显示出对肝细胞存活和生长的影响。在这项研究中，我们研究了这两种协同效应，并开发了一种新的程序，直接混合全器官血管灌注脱细胞大鼠肝脏ECM（dECM）到静电纺丝纤维定制的表面纳米形貌。通过水接触角、拉伸试验和降解研究分析支架的亲水性、机械性能和稳定性。结果表明，我们的新型杂化支架具有增强的亲水性，并且纳米形貌在水解降解14天后保持其原始形式。接种人肝细胞（HepG 2）以分析支架的生物相容性。细胞活力和DNA定量意味着在培养期间稳定的细胞增殖，在混合支架上观察到最高的白蛋白分泌。扫描电镜显示，与对照组相比，混合支架上的细胞形态明显不同，HepG 2在培养期结束时开始形成单层;同时，典型的肝脏标志物和ECM基因也受到影响，如混合支架上出现白蛋白的增加趋势。总之，我们的研究结果提供了一种可重复的方法和利用动物组织来源的ECM，并强调地形刺激和生化线索的协同作用，在肝组织工程静电纺丝支架。
Donor liver shortage is a crucial global public health problem as whole-organ transplantation is the only definitive cure for liver disease. Liver tissue engineering aims to reproduce or restore function through in vitro tissue constructs, which may lead to alternative treatments for active and chronic liver disease. The formulation of a multifunctional scaffold that has the potential to mimic the complex extracellular matrix (ECM) and their influence on cellular behavior, are essential for culturing cells on a construct. The separate employment of topographic or biological cues on a scaffold has both shown influences on hepatocyte survival and growth. In this study, we investigate both of these synergistic effects and developed a new procedure to directly blend whole-organ vascular perfusion-decellularized rat liver ECM (dECM) into electrospun fibers with tailored surface nanotopography. Water contact angle, tensile test, and degradation studies were conducted to analyze scaffold hydrophilicity, mechanical properties, and stability. The results show that our novel hybrid scaffolds have enhanced hydrophilicity, and the nanotopography retained its original form after hydrolytic degradation for 14 days. Human hepatocytes (HepG2) were seeded to analyze the scaffold biocompatibility. Cell viability and DNA quantification imply steady cell proliferation over the culture period, with the highest albumin secretion observed on the hybrid scaffold. Scanning electron microscopy shows that cell morphology was distinctly different on hybrid scaffolds compared to control groups, where HepG2 began to form a monolayer toward the end of the culture period; meanwhile, typical hepatic markers and ECM genes were also influenced, such as an increasing trend of albumin appearing on the hybrid scaffolds. Taken together, our findings provide a reproducible approach and utilization of animal tissue-derived ECM and emphasize the synergism of topographical stimuli and biochemical cues on electrospun scaffolds in liver tissue engineering.
影响因子：
4.2
作者：
Scheffschick, Andrea;Babel, Jonas;Sperling, Sebastian;Nerusch, Julia;Herzog, Natalie;Seehofer, Daniel;Damm, Georg
通讯作者：
Damm, Georg