A novel concept for scaffold-free vessel tissue engineering: self-assembly of microtissue building blocks

J Biotechnol. 2010 Jul 1;148(1):46-55. doi: 10.1016/j.jbiotec.2010.03.002. Epub 2010 Mar 17.


Current scientific attempts to generate in vitro tissue-engineered living blood vessels (TEBVs) show substantial limitations, thereby preventing routine clinical use. In the present report, we describe a novel biotechnology concept to create living small diameter TEBV based exclusively on microtissue self-assembly (living cellular re-aggregates). A novel bioreactor was designed to assemble microtissues in a vascular shape and apply pulsatile flow and circumferential mechanical stimulation. Microtissues composed of human artery-derived fibroblasts (HAFs) and endothelial cells (HUVECs) were accumulated and cultured for 7 and 14 days under pulsatile flow/mechanical stimulation or static culture conditions with a diameter of 3mm and a wall thickness of 1mm. The resulting vessels were analyzed by immunohistochemistry for extracellular matrix (ECM) and cell phenotype (von Willebrand factor, alpha-SMA, Ki67, VEGF). Self-assembled microtissues composed of fibroblasts displayed significantly accelerated ECM formation compared to monolayer cell sheets. Accumulation of vessel-like tissue occurred within 14 days under both, static and flow/mechanical stimulation conditions. A layered tissue formation was observed only in the dynamic group, as indicated by luminal aligned alpha-SMA positive fibroblasts. We could demonstrate that self-assembled cell-based microtissues can be used to generate small diameter TEBV. The significant enhancement of ECM expression and maturation, together with the pre-vascularization capacity makes this approach highly attractive in terms of generating functional small diameter TEBV devoid of any foreign material.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism
  • Arteries / cytology*
  • Biomechanical Phenomena
  • Bioreactors*
  • Blood Vessel Prosthesis*
  • Collagen Type IV / metabolism
  • Endothelial Cells / cytology
  • Fibroblasts / cytology
  • Gene Expression Profiling
  • Humans
  • Immunohistochemistry
  • Models, Cardiovascular
  • Tissue Culture Techniques* / instrumentation
  • Tissue Culture Techniques* / methods
  • Tissue Engineering* / instrumentation
  • Tissue Engineering* / methods
  • Vascular Endothelial Growth Factor A / metabolism
  • von Willebrand Factor / metabolism


  • Actins
  • Collagen Type IV
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • von Willebrand Factor