Nitric oxide (NO) has been shown to promote revascularization and nerve regeneration after peripheral nerve injury.However,in vivo application of NO remains challenging due to the lack of stable carrier materials capable of storing large amounts of NO molecules and releasing them on a clinically meaningful time scale.Recently,a silica nanoparticle system capable of reversible NO storage and release at a controlled and sustained rate was introduced.In this study,NO-releasing silica nanoparticles (NO-SNs) were delivered to the peripheral nerves in rats after acute crush injury,mixed with natural hydrogel,to ensure the effective application of NO to the lesion.Microangiography using a polymer dye and immunohistochemical staining for the detection of CD34 (a marker for revascularization) results showed that NO-releasing silica nanoparticles increased revascularization at the crush site of the sciatic nerve.The sciatic functional index revealed that there was a significant improvement in sciatic nerve function in NO-treated animals.Histological and anatomical analyses showed that the number of myelinated axons in the crushed sciatic nerve and wet muscle weight excised from NO-treated rats were increased.Moreover,muscle function recovery was improved in rats treated with NO-SNs.Taken together,our results suggest that NO delivered to the injured sciatic nerve triggers enhanced revascularization at the lesion in the early phase after crushing injury,thereby promoting axonal regeneration and improving functional recovery.

Jung II Lee;Ji Hun Park;Yeong-Rim Kim;Kihak Gwon;Hae Won Hwang;Gayoung Jung;Joo-Yup Lee;Jeong-Yun Sun;Jong Woong Park;Jae Ho Shin;Myoung-Ryul Ok

Department of Orthopedic Surgery,College of Medicine,Korea University,Seoul,Republic of Korea;Medical Sensor Biomaterial Research Institute,Kwangwoon University,Seoul,Republic of Korea;Center for Biomaterials,Korea Institute of Science & Technology,Seoul,Republic of Korea;Department of Materials Science and Engineering,Seoul National University,Seoul,Republic of Korea;Department of Orthopedic Surgery,College of Medicine,Catholic University,Seoul,Republic of Korea;Department of Chemistry,Kwangwoon University,Seoul,Republic of Korea

中国神经再生研究（英文版）

[1]Jung II Lee;Ji Hun Park;Yeong-Rim Kim;Kihak Gwon;Hae Won Hwang;Gayoung Jung;Joo-Yup Lee;Jeong-Yun Sun;Jong Woong Park;Jae Ho Shin;Myoung-Ryul Ok-.Delivery of nitric oxide-releasing silica nanoparticles for in vivo revascularization and functional recovery after acute peripheral nerve crush injury)[J].中国神经再生研究（英文版）,2022(09):2043-2049

Microangiography,myelinated

Delivery,nitric,oxide,releasing,silica,nanoparticles,vivo,revascularization,functional,recovery,after,acute,peripheral,injury,Nitric,been,shown,promote,regeneration,However,application,remains,challenging,due,lack,stable,carrier,materials,capable,storing,large,amounts,molecules,them,clinically,meaningful,scale,Recently,system,reversible,storage,release,controlled,sustained,rate,was,introduced,In,this,study,SNs,were,delivered,nerves,rats,mixed,natural,hydrogel,ensure,effective,lesion,using,polymer,dye,immunohistochemical,staining,detection,CD34,marker,results,showed,that,increased,site,sciatic,revealed,significant,improvement,treated,animals,Histological,anatomical,analyses,number,axons,crushed,wet,muscle,weight,excised,from,Moreover,improved,Taken,together,our,suggest,injured,triggers,enhanced,early,phase,crushing,thereby,promoting,axonal,improving

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