TY - JOUR
T1 - Nano oxygen chamber by cascade reaction for hypoxia mitigation and reactive oxygen species scavenging in wound healing
AU - Han, Xiaoxue
AU - Ju, Leah
AU - Saengow, Chai
AU - Ren, Wen
AU - Ewoldt, Randy
AU - Fan, Timothy
AU - Irudayaraj, Joseph
N1 - The authors graciously acknowledge support from the Cancer Scholars Program for XH, a Carle Foundation Hospital and Cancer Center at Illinois initiative. Partial funding from the Health Maker Lab of the Carle Illinois College of Medicine and the Mikashi Award from the Institute of Genomic Biology, University of Illinois at Urbana-Champaign is greatly appreciated. Thanks to Dr. Harley for providing us with the HUVEC cell line. We thank the TEP at Cancer Center at Illinois (UIUC) for assistance in biological evaluation. Our sincere thanks to Karen Doty at the Histology facility in the Department of Comparative Biosciences for the assistance in tissue processing and immunofluorescent staining. We thank Zunaira Shoaib for assistance in tissue analysis. Thanks to Dr. Tor Jensen for assistance in the animal studies.
PY - 2024/5
Y1 - 2024/5
N2 - Hypoxia, excessive reactive oxygen species (ROS), and impaired angiogenesis are prominent obstacles to wound healing following trauma and surgical procedures, often leading to the development of keloids and hypertrophic scars. To address these challenges, a novel approach has been proposed, involving the development of a cascade enzymatic reaction-based nanocarriers-laden wound dressing. This advanced technology incorporates superoxide dismutase modified oxygen nanobubbles and catalase modified oxygen nanobubbles within an alginate hydrogel matrix. The oxygen nano chamber functions through a cascade reaction between superoxide dismutase and catalase, wherein excessive superoxide in the wound environment is enzymatically decomposed into hydrogen peroxide, and this hydrogen peroxide is subsequently converted into oxygen by catalase. This enzymatic cascade effectively controls wound inflammation and hypoxia, mitigating the risk of keloid formation. Concurrently, the oxygen nanobubbles release oxygen continuously, thus providing a sustained supply of oxygen to the wound site. The oxygen release from this dynamic system stimulates fibroblast proliferation, fosters the formation of new blood vessels, and contributes to the overall wound healing process. In the rat full-thickness wound model, the cascade reaction-based nano oxygen chamber displayed a notable capacity to expedite wound healing without scarring. Furthermore, in the pilot study of porcine full-thickness wound healing, a notable acceleration of tissue repair was observed in the conceived cascade reaction-based gel treated group within the 3 days post-surgery, which represents the proliferation stage of healing process. These achievements hold significant importance in ensuring the complete functional recovery of tissues, thereby highlighting its potential as a promising approach for enhancing wound healing outcomes.
AB - Hypoxia, excessive reactive oxygen species (ROS), and impaired angiogenesis are prominent obstacles to wound healing following trauma and surgical procedures, often leading to the development of keloids and hypertrophic scars. To address these challenges, a novel approach has been proposed, involving the development of a cascade enzymatic reaction-based nanocarriers-laden wound dressing. This advanced technology incorporates superoxide dismutase modified oxygen nanobubbles and catalase modified oxygen nanobubbles within an alginate hydrogel matrix. The oxygen nano chamber functions through a cascade reaction between superoxide dismutase and catalase, wherein excessive superoxide in the wound environment is enzymatically decomposed into hydrogen peroxide, and this hydrogen peroxide is subsequently converted into oxygen by catalase. This enzymatic cascade effectively controls wound inflammation and hypoxia, mitigating the risk of keloid formation. Concurrently, the oxygen nanobubbles release oxygen continuously, thus providing a sustained supply of oxygen to the wound site. The oxygen release from this dynamic system stimulates fibroblast proliferation, fosters the formation of new blood vessels, and contributes to the overall wound healing process. In the rat full-thickness wound model, the cascade reaction-based nano oxygen chamber displayed a notable capacity to expedite wound healing without scarring. Furthermore, in the pilot study of porcine full-thickness wound healing, a notable acceleration of tissue repair was observed in the conceived cascade reaction-based gel treated group within the 3 days post-surgery, which represents the proliferation stage of healing process. These achievements hold significant importance in ensuring the complete functional recovery of tissues, thereby highlighting its potential as a promising approach for enhancing wound healing outcomes.
KW - Anti-inflammation
KW - Hypoxia
KW - Oxygen nanobubble
KW - ROS scavenging
KW - Scarless wound healing
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U2 - 10.1016/j.bioactmat.2024.01.010
DO - 10.1016/j.bioactmat.2024.01.010
M3 - Article
C2 - 38312517
AN - SCOPUS:85185160108
SN - 2452-199X
VL - 35
SP - 67
EP - 81
JO - Bioactive Materials
JF - Bioactive Materials
ER -