Wallace H. Coulter Department of Biomedical Engineering, Emory University School of Medicine & Georgia Institute of Technology, Atlanta, GA, 30322, USA.
Division of Cardiology, Department of Medicine, Emory University, Atlanta, GA, 30322, USA.
Adv Healthc Mater. 2024 Sep;13(23):e2303972. doi: 10.1002/adhm.202303972. Epub 2024 May 12.
Heart valve disease poses a significant clinical challenge, especially in pediatric populations, due to the inability of existing valve replacements to grow or respond biologically to their microenvironment. Tissue-engineered heart valves (TEHVs) provide a solution by facilitating patient-specific models for self-repair and remodeling. In this study, a 3D-bioprinted TEHV is designed to emulate the trilayer leaflet structure of an aortic valve. A cell-laden hydrogel scaffold made from gelatin methacrylate and polyethylene glycol diacrylate (GelMA/PEGDA) incorporates valvular interstitial-like (VIC-like) cells, being reinforced with a layer of polycaprolactone (PCL). The composition of the hydrogel scaffold remains stable over 7 days, having increased mechanical strength compared to pure GelMA. The scaffold maintains VIC-like cell function and promotes extracellular matrix (ECM) protein expression up to 14 days under two dynamic culture conditions: shear stress and stretching; replicating heart valve behavior within a more physiological-like setting and suggesting remodeling potential via ECM synthesis. This TEHV offers a promising avenue for valve replacements, closely replicating the structural and functional attributes of a native aortic valve, leading to mechanical and biological integration through biomaterial-cellular interactions.
心脏瓣膜疾病构成了重大的临床挑战,尤其是在儿科人群中,因为现有的瓣膜置换物无法生长或对其微环境产生生物响应。组织工程心脏瓣膜 (TEHV) 通过促进患者特异性的自我修复和重塑模型提供了解决方案。在这项研究中,设计了一种 3D 生物打印的 TEHV,以模拟主动脉瓣的三层瓣叶结构。由甲基丙烯酸明胶和聚乙二醇二丙烯酸酯 (GelMA/PEGDA) 制成的细胞负载水凝胶支架包含类似于瓣膜间质细胞 (VIC-like) 的细胞,并通过一层聚己内酯 (PCL) 进行加固。水凝胶支架的组成在 7 天内保持稳定,与纯 GelMA 相比,其机械强度有所增加。该支架在两种动态培养条件下(切应力和拉伸)维持了 VIC-like 细胞的功能,并促进了细胞外基质 (ECM) 蛋白的表达,持续时间长达 14 天;在更接近生理的环境中复制心脏瓣膜的行为,并通过 ECM 合成提示潜在的重塑能力。这种 TEHV 为瓣膜置换提供了一个有前途的途径,它可以紧密复制天然主动脉瓣的结构和功能属性,通过生物材料-细胞相互作用实现机械和生物学的整合。