Injectable anti-inflammatory, antioxidant supramolecular nanofiber hydrogel for peripheral nerve injury repair and neuropathic pain relief

TL;DR

A new injectable hydrogel combining anti-inflammatory and antioxidant properties helps repair nerve injuries and reduce neuropathic pain by reducing inflammation and oxidative stress.

Contribution

A novel injectable supramolecular hydrogel (Cur/Betp@Gel) is developed for sustained drug release and effective nerve repair.

Findings

Cur/Betp@Gel shows superior sustained-release and therapeutic effectiveness compared to individual components.

The hydrogel promotes nerve repair and reduces neuropathic pain by inhibiting inflammation and scavenging ROS.

It mitigates spinal inflammation by reducing GFAP and Iba-1 expression in the spinal cord.

Abstract

Patients with peripheral nerve injury (PNI) often experience neuropathic pain (NP), which is difficult to treat effectively due to ongoing inflammation and oxidative stress that impede nerve repair. Traditional anti-inflammatory antioxidants are limited by short half-lives and significant side effects. This study introduces a supramolecular hydrogel formed by combining anti-inflammatory betamethasone phosphate (Betp) with calcium chloride to create betamethasone phosphate hydrogel (Betp@Gel). The antioxidant curcumin (Cur) was incorporated into this gel to form Cur/Betp@Gel, which can be injected directly at the injury site for sustained Cur release. Cur/Betp@Gel demonstrates superior sustained-release capabilities and therapeutic effectiveness compared to Betp@Gel or Cur alone. It enhances pain relief, supports functional recovery after nerve damage, and promotes nerve repair and regeneration. This is achieved by Betp@Gel's anti-inflammatory effects, which inhibit TNF-α, IL-1β, and IL-6, combined with Cur's continuous slow release, which scavenges reactive oxygen species (ROS). Additionally, Cur/Betp@Gel mitigates PNI-induced spinal inflammation by reducing GFAP and Iba-1 expression in the spinal cord. Overall, in-situ injection of Cur/Betp@Gel is a promising strategy for aiding nerve repair and alleviating neuropathic pain.

Anti-inflammatory and antioxidant drugs can effectively alleviate the inflammation and oxidative stress responses caused by peripheral nerve injury. Therefore, in this study, we designed a supramolecular hydrogel with betamethasone phosphate (Betp) as the hydrogelator and loaded the antioxidant curcumin (Cur) to assemble an injectable Cur/Betp@Gel for in situ injection. Cur/Betp@Gel demonstrates superior sustained-release capabilities and therapeutic effectiveness compared to Betp@Gel or Cur alone. It enhances pain relief, supports functional recovery after nerve damage, and promotes nerve repair and regeneration. This is achieved by Betp@Gel's anti-inflammatory effects, which inhibit TNF-α, IL-1β, and IL-6, combined with Cur's continuous slow release, which scavenges reactive oxygen species (ROS). Additionally, Cur/Betp@Gel mitigates PNI-induced spinal inflammation by reducing GFAP and Iba-1 expression in the spinal cord. Overall, in-situ injection of Cur/Betp@Gel is a promising strategy for aiding nerve repair and alleviating neuropathic pain.Image 1

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