Masoumi Nafiseh, Annabi Nasim, Assmann Alexander, Larson Benjamin L, Hjortnaes Jesper, Alemdar Neslihan, Kharaziha Mahshid, Manning Keefe B, Mayer John E, Khademhosseini Ali
Biomaterials Innovation Research Center, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, 65 Landsdowne Street, Cambridge, MA 02139, USA; Department of Cardiac Surgery, Boston Children's Hospital and Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA; Department of Bioengineering, The Pennsylvania State University, 205 Hallowell Building, State College, PA 16802, USA; Harvard-MIT Division of Health Sciences and Technology and The David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 500 Main Street, Cambridge, MA 02139, USA.
Biomaterials Innovation Research Center, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, 65 Landsdowne Street, Cambridge, MA 02139, USA; Wyss Institute for Biologically Inspired Engineering, Harvard University, 3 Blackfan Circle, Boston, MA 02115, USA.
Biomaterials. 2014 Sep;35(27):7774-85. doi: 10.1016/j.biomaterials.2014.04.039. Epub 2014 Jun 16.
Tissue engineered heart valves (TEHVs) that can grow and remodel have the potential to serve as permanent replacements of the current non-viable prosthetic valves particularly for pediatric patients. A major challenge in designing functional TEHVs is to mimic both structural and anisotropic mechanical characteristics of the native valve leaflets. To establish a more biomimetic model of TEHV, we fabricated tri-layered scaffolds by combining electrospinning and microfabrication techniques. These constructs were fabricated by assembling microfabricated poly(glycerol sebacate) (PGS) and fibrous PGS/poly(caprolactone) (PCL) electrospun sheets to develop elastic scaffolds with tunable anisotropic mechanical properties similar to the mechanical characteristics of the native heart valves. The engineered scaffolds supported the growth of valvular interstitial cells (VICs) and mesenchymal stem cells (MSCs) within the 3D structure and promoted the deposition of heart valve extracellular matrix (ECM). MSCs were also organized and aligned along the anisotropic axes of the engineered tri-layered scaffolds. In addition, the fabricated constructs opened and closed properly in an ex vivo model of porcine heart valve leaflet tissue replacement. The engineered tri-layered scaffolds have the potential for successful translation towards TEHV replacements.
能够生长和重塑的组织工程心脏瓣膜(TEHV)有潜力作为当前不可存活的人工瓣膜的永久性替代品,特别是对于儿科患者。设计功能性TEHV的一个主要挑战是模拟天然瓣膜小叶的结构和各向异性机械特性。为了建立一个更具仿生学的TEHV模型,我们通过结合静电纺丝和微加工技术制造了三层支架。这些构建体是通过组装微加工的聚癸二酸甘油酯(PGS)和纤维状PGS/聚己内酯(PCL)静电纺丝片材制成的,以开发具有可调各向异性机械性能的弹性支架,类似于天然心脏瓣膜的机械特性。工程化支架支持瓣膜间质细胞(VIC)和间充质干细胞(MSC)在三维结构内生长,并促进心脏瓣膜细胞外基质(ECM)的沉积。MSC也沿着工程化三层支架的各向异性轴排列。此外,在猪心脏瓣膜小叶组织置换的体外模型中,制造的构建体能够正确地打开和关闭。工程化三层支架有成功转化为TEHV替代品的潜力。