@article{baf28ab533ec447ca464928135f19839,
title = "Self-Oxygenation of Tissues Orchestrates Full-Thickness Vascularization of Living Implants",
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.",
keywords = "angiogenesis, calcium peroxide, cellular metabolism, hydrophobic micromaterials, implant survival, oxygen generation",
author = "Ali Farzin and Shabir Hassan and {Moreira Teixeira}, {Liliana S.} and Melvin Gurian and Crispim, {Jo{\~a}o F.} and Varun Manhas and Aur{\'e}lie Carlier and Hojae Bae and Liesbet Geris and Iman Noshadi and Shin, {Su Ryon} and Jeroen Leijten",
note = "Funding Information: A.F. and S.H. contributed equally to this work. The authors thank Ay{\c c}a Bal {\"O}zt{\"u}rk and Berivan Cecen for excellent technical assistance in cell culture, and Sun Young Shin and Sang Hong Baek for technical assistance in the characterization of in vivo samples. The authors acknowledge funding the National Institutes of Health (R01AR074234). In addition, J.L. acknowledges financial support from an Innovative Research Incentives Scheme Vidi award (17522) from the Dutch Research Council, European Research Council (ERC, Starting Grant, 759425), JDRF, and Health‐Holland (LSHM19074). S.H. and S.S. were funded by AHA Innovative Project Award (19IPLOI34660079). A.C. acknowledges financial support from the Dutch Research Council scheme Veni award (15075). Funding Information: A.F. and S.H. contributed equally to this work. The authors thank Ay{\c c}a Bal {\"O}zt{\"u}rk and Berivan Cecen for excellent technical assistance in cell culture, and Sun Young Shin and Sang Hong Baek for technical assistance in the characterization of in vivo samples. The authors acknowledge funding the National Institutes of Health (R01AR074234). In addition, J.L. acknowledges financial support from an Innovative Research Incentives Scheme Vidi award (17522) from the Dutch Research Council, European Research Council (ERC, Starting Grant, 759425), JDRF, and Health-Holland (LSHM19074). S.H. and S.S. were funded by AHA Innovative Project Award (19IPLOI34660079). A.C. acknowledges financial support from the Dutch Research Council scheme Veni award (15075). Publisher Copyright: {\textcopyright} 2021 The Authors. Advanced Functional Materials published by Wiley-VCH GmbH",
year = "2021",
month = oct,
day = "14",
doi = "10.1002/adfm.202100850",
language = "British English",
volume = "31",
journal = "Advanced Functional Materials",
issn = "1616-301X",
publisher = "Wiley-VCH Verlag",
number = "42",
}