Graduate Program in Bioengineering, NUS Tissue Engineering Program, DSO Kent Ridge Building Level 4, 117510 Singapore.
Biomaterials. 2011 Nov;32(32):8108-17. doi: 10.1016/j.biomaterials.2011.07.022. Epub 2011 Jul 31.
A significant stumbling block in the creation of functional three-dimensional (3D) engineered tissues is the proper vascularization of the constructs. Furthermore, in the context of electrospinning, the development of 3D constructs using this technique has been hindered by the limited infiltration of cells into their structure. In an attempt to address these issues, a hybrid mesh of poly (ɛ-caprolactone)-collagen blend (PCL/Col) and hyaluronic acid (HA) hydrogel, Heprasil™ was created via a dual electrodeposition system. Simultaneous deposition of HA and PCL/Col allowed the dual loading and controlled release of two potent angiogenic growth factors VEGF(165) and PDGF-BB over a period of five weeks in vitro. Furthermore, this manner of loading sustained the bioactivity of the two growth factors. Utilizing an in-house developed 3D co-culture assay model of human umbilical vein endothelial cells and lung fibroblasts, the growth factor-loaded hybrid meshes was shown to not only support cellular attachment, but also their infiltration and the recapitulation of primitive capillary network in the scaffold's architecture. Thus, the creation of a PCL/Col-Heprasil hybrid scaffold is a step forward toward the attainment of a 3D bio-functionalized, vascularized tissue engineering construct.
在功能性三维(3D)工程组织的构建中,一个显著的障碍是构建体的适当血管化。此外,在静电纺丝的背景下,使用该技术开发 3D 构建体受到细胞有限渗透到其结构中的限制。为了解决这些问题,通过双电沉积系统创建了聚(己内酯)-胶原蛋白共混物(PCL/Col)和透明质酸(HA)水凝胶的混合网格 Heprasil™。HA 和 PCL/Col 的同时沉积允许两种有效的血管生成生长因子 VEGF(165)和 PDGF-BB 在体外五周内进行双重负载和控制释放。此外,这种加载方式维持了两种生长因子的生物活性。利用内部开发的人脐静脉内皮细胞和肺成纤维细胞的 3D 共培养分析模型,负载生长因子的混合网格不仅支持细胞附着,还支持它们的渗透以及支架结构中原始毛细血管网络的再现。因此,PCL/Col-Heprasil 混合支架的创建是朝着获得 3D 生物功能化、血管化组织工程构建体迈出的一步。