TY - JOUR
T1 - Self-Oxygenation of Tissues Orchestrates Full-Thickness Vascularization of Living Implants
AU - Farzin, Ali
AU - Hassan, Shabir
AU - Moreira Teixeira, Liliana S.
AU - Gurian, Melvin
AU - Crispim, João F.
AU - Manhas, Varun
AU - Carlier, Aurélie
AU - Bae, Hojae
AU - Geris, Liesbet
AU - Noshadi, Iman
AU - Shin, Su Ryon
AU - Leijten, Jeroen
N1 - Publisher Copyright:
© 2021 The Authors. Advanced Functional Materials published by Wiley-VCH GmbH
PY - 2021/10/14
Y1 - 2021/10/14
N2 - 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.
AB - 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.
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U2 - 10.1002/adfm.202100850
DO - 10.1002/adfm.202100850
M3 - Article
AN - SCOPUS:85109078222
SN - 1616-301X
VL - 31
JO - Advanced Functional Materials
JF - Advanced Functional Materials
IS - 42
M1 - 2100850
ER -