Self-Oxygenation of Tissues Orchestrates Full-Thickness Vascularization of Living Implants

Ali Farzin, Shabir Hassan, Liliana S. Moreira Teixeira, Melvin Gurian, João F. Crispim, Varun Manhas, Aurélie Carlier, Hojae Bae, Liesbet Geris, Iman Noshadi, Su Ryon Shin, Jeroen Leijten*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

Bioengineering of tissues and organs has the potential to generate functional replacement organs. However, achieving the full-thickness vascularization that is required for long-term survival of living implants has remained a grand challenge, especially for clinically sized implants. During the pre-vascular phase, implanted engineered tissues are forced to metabolically rely on the diffusion of nutrients from adjacent host-tissue, which for larger living implants results in anoxia, cell death, and ultimately implant failure. Here it is reported that this challenge can be addressed by engineering self-oxygenating tissues, which is achieved via the incorporation of hydrophobic oxygen-generating micromaterials into engineered tissues. Self-oxygenation of tissues transforms anoxic stresses into hypoxic stimulation in a homogenous and tissue size-independent manner. The in situ elevation of oxygen tension enables the sustained production of high quantities of angiogenic factors by implanted cells, which are offered a metabolically protected pro-angiogenic microenvironment. Numerical simulations predict that self-oxygenation of living tissues will effectively orchestrate rapid full-thickness vascularization of implanted tissues, which is empirically confirmed via in vivo experimentation. Self-oxygenation of tissues thus represents a novel, effective, and widely applicable strategy to enable the vascularization living implants, which is expected to advance organ transplantation and regenerative medicine applications.

Original languageEnglish
Article number2100850
JournalAdvanced functional materials
DOIs
Publication statusE-pub ahead of print/First online - 6 Jul 2021

Keywords

  • angiogenesis
  • calcium peroxide
  • cellular metabolism
  • hydrophobic micromaterials
  • implant survival
  • oxygen generation
  • UT-Hybrid-D

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