Chronic neuropathic pain severely impairs quality of life, with current therapies often causing adverse effects. Our research group identified αO-conotoxin GeXIVA[1,2] as a potent analgesic candidate derived from marine cone snails. However, its clinical application is limited by rapid clearance and complex administration. This study developed a sustained-release hydrogel microneedle patch encapsulating GeXIVA[1,2] to address these challenges. Optimized 4:3 (w/w) polyvinyl alcohol (PVA)–sucrose hydrogel formulation achieved 98.6% structural integrity and controlled swelling (ratio = 1.9 at 48 h). The microneedles demonstrated uniform conical morphology (height: 889 ± 49 µm, base: 381 ± 26 µm) enabling epidermal penetration. In spared nerve injury (SNI) models, a single microneedle patch application increased mechanical paw withdrawal thresholds from 0.056 g to 0.7269 g, maintaining efficacy for 3 days. Chronic constriction injury (CCI) models showed comparable pain relief. Notably, microneedle patch treatment improved locomotor function in SNI mice (total movement: 1518 cm vs. 1126 cm untreated). This hydrogel microneedle patch platform extends GeXIVA[1,2]’s analgesic duration from hours to days through sustained release, while resolving administration challenges through transdermal delivery, expanding the potential applications of GeXIVA[1,2], and demonstrating a promising strategy for the chronic neuropathic pain management.
Fieldwork carries a high risk of irregular, non-compressible traumatic wounds, which often initiate a vicious cycle of “traumatic bleeding-insect bite-secondary infection”. Conventional dressings cannot combine rapid hemostasis with physical protection against venomous insects, creating an urgent demand for multifunctional field trauma dressings. To solve this problem, this study developed a shape-adaptive bilayer hydrogel that concurrently provides rapid hemostasis, promotes wound repair, and acts as a robust physical barrier. The hydrogel adopts a layered design: the bottom layer (PPTY) achieves autogelation within 3 s upon blood contact, while the top armor protective layer (AP) withstands pressures up to 942 kPa. By incorporating chitosan and sodium citrate into the AP precursor solution, the hydrogel achieved in situ formation within 50 s and developed a stable self-renewing armor layer. The tightly bonded bilayer showed complementary functions. In rat models of femoral artery puncture and tail vein bleeding, PPTY-AP hydrogel significantly reduced blood loss and shortened hemostasis time. Moreover, the hydrogel demonstrated excellent tissue adhesion and moisture retention capacity, promoting full-thickness skin wound healing. This multifunctional, rapidly deployable hydrogel presents a promising solution for field trauma management and offers a new design paradigm for advanced wound dressings.
Chronic neuropathic pain, particularly diabetic neuropathic pain and postherpetic neuralgia, severely impairs patients’ quality of life due to their complex mechanisms and recurrent, long-term nature, making treatment challenging. This study aimed to evaluate the analgesic efficacy of α-conotoxin GeXIVA[1,2], a selective antagonist of the α9α10 nicotinic acetylcholine receptor (nAChR), in rat models of diabetic neuropathic pain and postherpetic neuralgia and investigate its associated physiological and pathological effects. GeXIVA[1,2] was administered continuously for three weeks, with mechanical hypersensitivity assessed through pain sensitivity tests, and behavioral assessments conducted to examine motor coordination and gait. Additionally, neural tissue structure and inflammation were analyzed. The results demonstrated that GeXIVA[1,2] significantly alleviated mechanical hypersensitivity in both diabetic neuropathic pain and postherpetic neuralgia models, with greater efficacy than gabapentin and no signs of tolerance. Behavioral tests indicated no significant effects on motor coordination or gait. Further analysis revealed that GeXIVA[1,2] reduced pro-inflammatory cytokine levels, decreased immune cell infiltration, and promoted repair of damaged nerve fibers. Overall, these findings suggest that GeXIVA[1,2] exerts analgesic effects through anti-inflammatory and neuroprotective mechanisms, providing a potential new therapeutic strategy for diabetic neuropathic pain and postherpetic neuralgia.
Effective wound management is crucial for improved outcomes through timely, personalized therapies. Current dressing‐based treatments lack dynamic regulation and microenvironment modulation, leading to suboptimal healing. Integrating electrical stimulation therapy with electro‐controlled drug delivery promotes skin generation, ensures precise dosing, and accelerates healing. Flexible electronic patches are ideal platforms for these synergistic therapies but face challenges: rigid post‐manufacture shapes and sizes limit adaptability to diverse wound geometries, and substrate materials struggle to meet both wound‐healing and electronic requirements. This study develops a tailorable, transferable flexible electronic patch with a hexagonal modular design, enabling shape/size customization while maintaining electrical continuity. The water‐transfer printing (WTP) technique is used to conveniently transfer conductive chondroitin sulfate (CS) hydrogel (as electrodes and drug reservoirs) and silver circuits onto clinical dressings. This method endows clinical dressings with functionality of electro‐controlled drug release and electrical stimulation, simultaneously addressing substrate performance limitations of flexible electronic patches. The patch demonstrates uniform electrical signal transmission, precise electro‐responsive drug control in CS hydrogels, and adaptability to wounds of different geometries. It retains electrostimulation and electro‐controlled drug delivery performance after cutting, significantly promoting wound healing. This study provides a potential approach to support the advancement of flexible electronics research and clinical translation.