Arterial vasospasm after microsurgery can cause severe obstruction of blood flow manifested as low tissue temperature,leading to tissue necrosis.The timely discovery and synchronized treatment become pivotal.In this s...Arterial vasospasm after microsurgery can cause severe obstruction of blood flow manifested as low tissue temperature,leading to tissue necrosis.The timely discovery and synchronized treatment become pivotal.In this study,a reversible,intelligent,responsive thermosensitive hydrogel system is constructed employing both the gel–sol transition and the sol–gel transition.The“reversible thermosensitive(RTS)”hydrogel loaded with verapamil hydrochloride is designed to dynamically and continuously regulate the extravascular microenvi-ronment by inhibiting extracellular calcium influx.After accurate implantation and following in situ gelation,the RTS hydrogel reverses to the sol state causing massive drug release to inhibit vasospasm when the tissue tem-perature drops to the predetermined transition temperature.Subsequent restoration of the blood supply allevi-ates further tissue injury.Before the temperature drops,the RTS hydrogel maintains the gel state as a sustained-release reservoir to prevent vasospasm.The inhibition of calcium influx and vasospasm in vitro and in vivo is demonstrated using vascular smooth muscle cells,mice mesenteric arterial rings,and vascular ultrasonic Doppler detection.Subsequent animal experiments demonstrate that RTS hydrogel can promote tissue survival and alleviate tissue injury responding to temperature change.Therefore,this RTS hydrogel holds therapeutic po-tential for diseases requiring timely detection of temperature change.展开更多
基金National Key Research and Development Program of China(2020YFA0908200)National Natural Science Foundation of China(81772099,81801928 and 52103173)+3 种基金China Postdoctoral Science Foundation(2021M692105)Shanghai Municipal Health Commission(20204Y0354)Shanghai Municipal Key Clinical Specialty(shslczdzk00901)Young Physicians Innovation Team Project of the Ninth People’s Hospital of Shanghai Jiao Tong University School of Medicine(QC201902).
文摘Arterial vasospasm after microsurgery can cause severe obstruction of blood flow manifested as low tissue temperature,leading to tissue necrosis.The timely discovery and synchronized treatment become pivotal.In this study,a reversible,intelligent,responsive thermosensitive hydrogel system is constructed employing both the gel–sol transition and the sol–gel transition.The“reversible thermosensitive(RTS)”hydrogel loaded with verapamil hydrochloride is designed to dynamically and continuously regulate the extravascular microenvi-ronment by inhibiting extracellular calcium influx.After accurate implantation and following in situ gelation,the RTS hydrogel reverses to the sol state causing massive drug release to inhibit vasospasm when the tissue tem-perature drops to the predetermined transition temperature.Subsequent restoration of the blood supply allevi-ates further tissue injury.Before the temperature drops,the RTS hydrogel maintains the gel state as a sustained-release reservoir to prevent vasospasm.The inhibition of calcium influx and vasospasm in vitro and in vivo is demonstrated using vascular smooth muscle cells,mice mesenteric arterial rings,and vascular ultrasonic Doppler detection.Subsequent animal experiments demonstrate that RTS hydrogel can promote tissue survival and alleviate tissue injury responding to temperature change.Therefore,this RTS hydrogel holds therapeutic po-tential for diseases requiring timely detection of temperature change.
基金supported by the National Key Research and Development Program of China(2020YFA0908200)the National Natural Science Foundation of China(82272263,82002053,and 82202467)+2 种基金Shanghai Municipal Health Commission(20204Y0354)Shanghai Science and Technology Development Funds(22YF1421400)Shanghai Clinical Research Center of Plastic and Reconstructive Surgery supported by Science and Technology Commission of Shanghai Municipality(22MC1940300)。
