Biomedical Microdevices

, Volume 13, Issue 4, pp 717–723 | Cite as

Microfluidic assay of endothelial cell migration in 3D interpenetrating polymer semi-network HA-Collagen hydrogel

  • Gi Seok Jeong
  • Gu Han Kwon
  • Ah Ran Kang
  • Bo Young Jung
  • Yongdoo Park
  • Seok ChungEmail author
  • Sang-Hoon LeeEmail author


Cell migration through the extracellular matrix (ECM) is one of the key features for physiological and pathological processes such as angiogenesis, cancer metastasis, and wound healing. In particular, the quantitative assay of endothelial cell migration under the well-defined three dimensional (3D) microenvironment is important to analyze the angiogenesis mechanism. In this study, we report a microfluidic assay of endothelial cell sprouting and migration into an interpenetrating polymer semi-network HA-Collagen (SIPNs CH) hydrogel as ECM providing an enhanced in vivo mimicking 3D microenvironment to cells. The microfluidic chip could provide a well-controlled gradient of growth factor to cells, whereas the hydrogel could mimic a well-defined 3D microenvironment in vivo. (In addition/Furthermore, the microfluidic chip gives a well-controlled gradient of growth factor to cells) For this reason, three types of hydrogel, composed of semi-interpenetrating networks of collagen and hyaluronic acid were prepared, and firstly we proved the role of the hydrogel in endothelial cell migration. The diffusion property and swelling ratio of the hydrogel were characterized. It modulated the migration of endothelial cells in quantified manner, also being influenced by additional synthesis of Matrix metalloproteinase(MMP)-sensitive remodeling peptides and Arginine–glycine–lycinee (RGD) cell adhesion peptides. We successfully established a novel cell migration platform by changing major determinants such as ECM material under biochemical synthesis and under growth factor gradients in a microfluidic manner.


Cell migration 3D matrix Collagen Hyaluronic acid Semi-interpenetrating networks MMP 



This research was supported by the Converging Research Center Program funded by the Ministry of Education, Science and Technology (2010K001179). Seok Chung was supported by the International Research & Development Program of the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (MEST) of Korea (Grant number:2009-00631).

Supplementary material

10544_2011_9541_MOESM1_ESM.docx (921 kb)
Supplementary Figure 1 Anti-adhesion effect of HMW-HA scaffold. On day 0 (seeding day) HUVECs detached near of HA only, but in 1 day after cell seeding, HUVECs on the channel not directly contact the HA also detached, indirectly shows the role of anti-adhesion effective molecules diffused into the media from the HA. (DOCX 920 kb)
10544_2011_9541_MOESM2_ESM.docx (3.5 mb)
Supplementary Figure 2 Migration and proliferation of HUVECs into HMW-HA(a), SIPNs CH (b-d), and SIPNs CH 21 insensitive(e) hydrogel. Black arrowheads indicate position of scaffold wall, and white arrowheads indicate HUVECs migrate into the scaffold. HUVECs migration into SIPNs CH hydrogel is dependent on the mixing ratio of collagen and HA and MMP sensitiveness. On a HMW-HA(a) and SIPNs CH12(b) hydrogel, HUVEC monolayer was disrupted and detached from their initial position. HUVECs also disappeared on the channel surface. On the SIPNs CH11(c), CH21(d) and CH21-insensitive(e) hydrogel, HUVECs migrated into the scaffold and proliferated on the microfluidic channel under every condition. (DOCX 3572 kb)
10544_2011_9541_MOESM3_ESM.docx (1.1 mb)
Supporting Figure 3 3D initial sprouting of HUVECs into various types of hydrogel; HMW HA(a), CH11(b), CH21(c) and CH21-insensitive(d). Pictures were taken at 4 hours after cell seeding to investigate initial sprouting (white arrowheads) into the hydrogel. All scale bars indicate 200 microns. In the developed SIPN CH hydrogel, the initial sprouting and following endothelial cell migration (Fig. 3) were successfully induced, but perfect tube-like structures could not be found yet. (DOCX 1132 kb)


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Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Gi Seok Jeong
    • 1
  • Gu Han Kwon
    • 1
  • Ah Ran Kang
    • 1
  • Bo Young Jung
    • 2
  • Yongdoo Park
    • 2
  • Seok Chung
    • 3
    Email author
  • Sang-Hoon Lee
    • 1
    Email author
  1. 1.Department of Biomedical Engineering, College of Health ScienceKorea UniversitySeoulKorea
  2. 2.Biomedical Engineering, Brain Korea 21 Project for Biomedical ScienceKorea University Medical CollegeSeoulKorea
  3. 3.School of Mechanical EngineeringKorea UniversitySeoulKorea

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