Microchannel network hydrogel induced ischemic blood perfusion connection

Nat Commun. 2020 Jan 30;11(1):615. doi: 10.1038/s41467-020-14480-0.

Abstract

Angiogenesis induction into damaged sites has long been an unresolved issue. Local treatment with pro-angiogenic molecules has been the most common approach. However, this approach has critical side effects including inflammatory coupling, tumorous vascular activation, and off-target circulation. Here, the concept that a structure can guide desirable biological function is applied to physically engineer three-dimensional channel networks in implant sites, without any therapeutic treatment. Microchannel networks are generated in a gelatin hydrogel to overcome the diffusion limit of nutrients and oxygen three-dimensionally. Hydrogel implantation in mouse and porcine models of hindlimb ischemia rescues severely damaged tissues by the ingrowth of neighboring host vessels with microchannel perfusion. This effect is guided by microchannel size-specific regenerative macrophage polarization with the consequent functional recovery of endothelial cells. Multiple-site implantation reveals hypoxia and neighboring vessels as major causative factors of the beneficial function. This technique may contribute to the development of therapeutics for hypoxia/inflammatory-related diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenesis Inducing Agents / adverse effects*
  • Animals
  • Disease Models, Animal
  • Endothelial Cells / pathology
  • Equipment Design
  • Female
  • Gelatin / chemistry*
  • Gelatin / pharmacology*
  • Hindlimb / blood supply
  • Hindlimb / diagnostic imaging
  • Hindlimb / pathology
  • Hydrogels / chemistry*
  • Hydrogels / pharmacology*
  • Hydrogels / therapeutic use
  • Hypoxia
  • Ischemia / diagnostic imaging
  • Ischemia / pathology
  • Ischemia / therapy*
  • Macrophages
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Neovascularization, Physiologic / physiology
  • Peripheral Vascular Diseases / pathology
  • Peripheral Vascular Diseases / therapy
  • Prostheses and Implants
  • Swine
  • Wound Healing

Substances

  • Angiogenesis Inducing Agents
  • Hydrogels
  • Gelatin