National Engineering Research Center for Biomaterials, Sichuan University , Chengdu 610064, Sichuan, China.
College of Materials Science and Engineering, East China Jiaotong University , Nanchang 330013, Jiangxi, China.
ACS Appl Mater Interfaces. 2017 Feb 1;9(4):3524-3534. doi: 10.1021/acsami.6b15697. Epub 2017 Jan 20.
Tissue engineering aims to generate functional tissue constructs in which proper extracellular matrix (ECM) for cell survival and establishment of a vascular network are necessary. A modular approach via the assembly of modules mimicking the complex tissues' microarchitectural features and establishing a vascular network represents a promising strategy for fabricating larger and more complex tissue constructs. Herein, as a model for this modular tissue engineering, engineered bone-like constructs were developed by self-assembly of osteon-like modules and fast degradable gelatin microspheres. The collagen microspheres acting as osteon-like modules were developed by seeding human umbilical vein endothelial cells (HUVECs) onto collagen microspheres laden with human osteoblast-like cells (MG63) and collagenase. Both HUVECs and MG63 cells were well spatially patterned in the modules, and collagen as ECM well supported cell adhesion, spreading, and functional expression due to its native RGD domains and enzymatic degradation activity. The patterned modules facilitated both the cellular function expression of osteogenic MG63 cells and vasculogenic HUVECs; that is, the osteon-like units were successfully achieved. The assembly of the osteon-like modules and fast degradable gelatin microspheres promoted the vascularization, thus facilitating the osteogenic function expression. The study provides a highly efficient approach to engineering complex 3D tissues with micropatterned cell types and interconnected channels.
组织工程旨在生成功能性组织构建体，其中适当的细胞外基质（ECM）对于细胞存活和建立血管网络是必要的。通过组装模拟复杂组织微观结构特征并建立血管网络的模块的模块化方法是制造更大和更复杂的组织构建体的一种很有前途的策略。在此，作为这种模块化组织工程的模型，通过骨单元样模块的自组装和快速可降解明胶微球来开发工程化的类骨构建体。作为骨单元样模块的胶原微球是通过将人脐静脉内皮细胞（HUVEC）接种到负载有人成骨样细胞（MG63）和胶原酶的胶原微球上来开发的。在模块中，HUVEC 和 MG63 细胞都被很好地进行了空间图案化，由于其天然的 RGD 结构域和酶降解活性，胶原作为 ECM 很好地支持了细胞的黏附、铺展和功能表达。图案化的模块促进了成骨样 MG63 细胞和血管生成性 HUVEC 的细胞功能表达；也就是说，成功地实现了骨单元样单元。骨单元样模块和快速可降解明胶微球的组装促进了血管生成，从而促进了成骨功能的表达。该研究提供了一种高效的方法，可用于工程具有微图案化细胞类型和互连通道的复杂 3D 组织。
