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

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.