TY - JOUR
T1 - Bacteria-Activated Dual pH-and Temperature-Responsive Hydrogel for Targeted Elimination of Infection and Improved Wound Healing
AU - Haidari, Hanif
AU - Vasilev, Krasimir
AU - Cowin, Allison J.
AU - Kopecki, Zlatko
PY - 2022/11/23
Y1 - 2022/11/23
N2 - Antibacterial treatment that provides on-demand release of therapeutics that can kill a broad spectrum of pathogens while maintaining long-Term efficacy and without developing resistance or causing side effects is urgently required in clinical practice. Here, we demonstrate the development of a multistimuli-responsive hydrogel, prepared by cross-linking N-isopropylacrylamide with acrylic acid and loaded with ultrasmall silver nanoparticles (AgNPs), offering the on-demand release of Ag+ ions triggered by changes in the wound microenvironment. We demonstrate that this dual-responsive hydrogel is highly sensitive to a typical wound pH and temperature change, evidenced by the restricted release of Ag+ ions at acidic pH (<5.5) while significantly promoting the release in alkaline pH (>7.4) (>90% release). The pH-dependent release and antibacterial effect show minimal killing at pH 4 or 5.5 but dramatically activated at pH 7.4 and 10, eliminating >95% of the pathogens. The in vivo antibacterial efficacy and safety showed a high potency to clear Staphylococcus aureus wound infection while significantly accelerating the wound healing rate. This multifunctional hydrogel presents a promising bacteria-responsive delivery platform that serves as an on-demand carrier to not only reduce side effects but also significantly boost the antibacterial efficiency based on physiological needs. It offers great potential to improve the way wound infections are treated with direct clinical implications, providing a single platform for long-lasting application in wound management.
AB - Antibacterial treatment that provides on-demand release of therapeutics that can kill a broad spectrum of pathogens while maintaining long-Term efficacy and without developing resistance or causing side effects is urgently required in clinical practice. Here, we demonstrate the development of a multistimuli-responsive hydrogel, prepared by cross-linking N-isopropylacrylamide with acrylic acid and loaded with ultrasmall silver nanoparticles (AgNPs), offering the on-demand release of Ag+ ions triggered by changes in the wound microenvironment. We demonstrate that this dual-responsive hydrogel is highly sensitive to a typical wound pH and temperature change, evidenced by the restricted release of Ag+ ions at acidic pH (<5.5) while significantly promoting the release in alkaline pH (>7.4) (>90% release). The pH-dependent release and antibacterial effect show minimal killing at pH 4 or 5.5 but dramatically activated at pH 7.4 and 10, eliminating >95% of the pathogens. The in vivo antibacterial efficacy and safety showed a high potency to clear Staphylococcus aureus wound infection while significantly accelerating the wound healing rate. This multifunctional hydrogel presents a promising bacteria-responsive delivery platform that serves as an on-demand carrier to not only reduce side effects but also significantly boost the antibacterial efficiency based on physiological needs. It offers great potential to improve the way wound infections are treated with direct clinical implications, providing a single platform for long-lasting application in wound management.
KW - bacteria-responsive
KW - dual-responsive release
KW - multifunctional hydrogel
KW - on-demand release
KW - pH-responsive
KW - pH-responsive silver release
KW - triggered release
KW - wound healing
UR - http://www.scopus.com/inward/record.url?scp=85141951329&partnerID=8YFLogxK
UR - http://purl.org/au-research/grants/NHMRC/1194466
UR - http://purl.org/au-research/grants/ARC/DP180101254
U2 - 10.1021/acsami.2c15659
DO - 10.1021/acsami.2c15659
M3 - Article
AN - SCOPUS:85141951329
SN - 1944-8244
VL - 14
SP - 51744
EP - 51762
JO - ACS Applied Materials and Interfaces
JF - ACS Applied Materials and Interfaces
IS - 46
ER -