Vasculogenesis is an important morphogenetic event for vascular tissue engineering and ischemic disease treatment. Stem and progenitor cells can contribute to vasculogenesis via endothelial differentiation and direct participation in blood vessel formation. In this study, we developed an implantable microfluidic device to facilitate formation of three-dimensional (3D) vascular structures by human endothelial progenitor cells (hEPCs). The microfluidic device was made of biodegradable poly(lactic-co-glycolic acid) (PLGA) using a microchannel patterned silicon wafer made by soft lithography. A collagen type I (Col I) hydrogel containing hEPCs filled the microfluidic channels to reconstitute a 3D microenvironment for facilitating vascular structure formation by hEPCs. The device seeded with hEPCs was implanted into the subcutaneous space of athymic mice and retrieved one and four weeks after implantation. Histology and immunohistochemistry revealed that hEPCs formed a 3D capillary network expressing endothelial cell-specific proteins in the channel of the PLGA microfluidic device. This result indicates that a 3D microscale extracellular matrix reconstituted in the microchannel can promote the endothelial differentiation of hEPCs and in turn hEPC-mediated vasculogenesis. The PLGA microfluidic device reported herein may be useful as an implantable tissue-engineering scaffold for vascularized tissue reconstruction and therapeutic angiogenesis.
Bibliographical noteFunding Information:
This work was supported by grants (S. -W. Cho; NRF-2013R1A1A2A10061422 and NRF-2010-0020409) from the National Research Foundation of Korea (NRF). This work was also supported by grants (S. Chung; NRF-2012-022481 from the NRF and 20124010203250 from the Human Resources Program in Energy Technology of the Korea Institute of Energy Technology Evaluation and Planning [KETEP]). Jin Kim was supported by the NRF-2013-Global Ph. D. Fellowship Program. Human cord blood-derived EPCs were kindly provided from Prof. Hyung-Min Chung and Prof. Sung-Hwan Moon of the Konkuk University School of Medicine.
All Science Journal Classification (ASJC) codes
- Applied Microbiology and Biotechnology
- Biomedical Engineering