Injectable pre-cultured tissue modules catalyze the formation of extensive functional microvasculature in vivo

Sci Rep. 2020 Sep 23;10(1):15562. doi: 10.1038/s41598-020-72576-5.


Revascularization of ischemic tissues is a major barrier to restoring tissue function in many pathologies. Delivery of pro-angiogenic factors has shown some benefit, but it is difficult to recapitulate the complex set of factors required to form stable vasculature. Cell-based therapies and pre-vascularized tissues have shown promise, but the former require time for vascular assembly in situ while the latter require invasive surgery to implant vascularized scaffolds. Here, we developed cell-laden fibrin microbeads that can be pre-cultured to form primitive vascular networks within the modular structures. These microbeads can be delivered in a minimally invasive manner and form functional microvasculature in vivo. Microbeads containing endothelial cells and stromal fibroblasts were pre-cultured for 3 days in vitro and then injected within a fibrin matrix into subcutaneous pockets on the dorsal flanks of SCID mice. Vessels deployed from these pre-cultured microbeads formed functional connections to host vasculature within 3 days and exhibited extensive, mature vessel coverage after 7 days in vivo. Cellular microbeads showed vascularization potential comparable to bulk cellular hydrogels in this pilot study. Furthermore, our findings highlight some potentially advantageous characteristics of pre-cultured microbeads, such as volume preservation and vascular network distribution, which may be beneficial for treating ischemic diseases.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cells, Cultured
  • Fibrin / chemistry
  • Fibrin / pharmacology*
  • Fibroblasts / drug effects
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Hydrogels / chemistry
  • Hydrogels / pharmacology*
  • Mice
  • Microspheres
  • Microvessels / drug effects
  • Microvessels / growth & development
  • Neovascularization, Physiologic*
  • Tissue Engineering*
  • Tissue Scaffolds / chemistry


  • Hydrogels
  • Fibrin