Delivery of nitric oxide-releasing silica nanoparticles for in vivo revascularization and functional recovery after acute peripheral nerve crush injury

Jung Il 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

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)2043-2049
Number of pages7
JournalNeural Regeneration Research
Volume17
Issue number9
DOIs
Publication statusPublished - 2022 Sep

Keywords

  • crush injury
  • nerve injury, nerve regeneration
  • nitric oxide
  • peripheral nerve
  • revascularization
  • silica nanoparticles

ASJC Scopus subject areas

  • Developmental Neuroscience

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