Ropivacaine microsphere-loaded electroconductive nerve dressings for long-acting analgesia and functional recovery following diabetic peripheral nerve injury

Fangguo Liang; Yusheng Yang; Yuyong Chen; Jiajun Xie; Shencai Liu; Zilin Tan; Liangjie Tian; Zhiqiang Yu; Zhanjun Shi; Peigen Xie; Hong Ding; Qinfeng Yang

doi:10.1016/j.mtbio.2023.100712

Ropivacaine microsphere-loaded electroconductive nerve dressings for long-acting analgesia and functional recovery following diabetic peripheral nerve injury

Mater Today Bio. 2023 Jun 23:21:100712. doi: 10.1016/j.mtbio.2023.100712. eCollection 2023 Aug.

Authors

Fangguo Liang¹, Yusheng Yang², Yuyong Chen³, Jiajun Xie⁴, Shencai Liu⁴, Zilin Tan⁵, Liangjie Tian², Zhiqiang Yu⁶, Zhanjun Shi⁴, Peigen Xie⁷, Hong Ding⁸, Qinfeng Yang⁴

Affiliations

¹ Department of Plastic and Cosmetic Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, 510515, China.
² Division of Orthopaedics and Traumatology, Department of Orthopaedics, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, 510515, China.
³ Department of Orthopedics, Southern University of Science and Technology Hospital, Shenzhen, Guangdong Province, 510800, China.
⁴ Division of Orthopaedic Surgery, Department of Orthopaedics, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, 510515, China.
⁵ Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, 510515, China.
⁶ Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, Guangdong, 510515, China.
⁷ Department of Spine Surgery, The Third Affiliated Hospital of Sun Yat-sen, University, Guangzhou, Guangdong Province, 510600, China.
⁸ Department of Anesthesiology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, 510515, China.

Abstract

In recent years, electroconductive hydrogels (ECHs) have shown great potential in promoting nerve regeneration and motor function recovery following diabetic peripheral nerve injury (PNI), attributed to their similar electrical and mechanical characteristics to innate nervous tissue. It is well-established that PNI causes motor deficits and pain, especially in diabetics. Current evidence suggests that ropivacaine (ROP) encapsulated in poly lactic-co-glycolic acid (PLGA) microspheres (MSs) yield a sustained analgesic effect. In this study, an ECH electroconductive network loaded with MS/ROP (ECH-MS/ROP) was designed as a promising therapeutic approach for diabetic PNI to exert lasting analgesia and functional recovery. This dual delivery system allowed ROP's slow and sequential release, achieving sustained analgesia as demonstrated by our in vivo experiments. Meanwhile, this system was designed like a lamellar dressing, with desirable adhesive and self-curling properties, convenient for treating injured nerve tissues via automatically wrapping tube-like structures, facilitating the process of implantation. Our in vitro assays verified that ECH-MS/ROP was able to enhance the adhesion and motility of Schwann cells. Besides, both in vitro and in vivo studies substantiated that ECH-MS/ROP stimulated myelinated axon regeneration through the MEK/ERK signaling pathway, thereby improving muscular denervation atrophy and facilitating functional recovery. Therefore, this study suggests that the ECH-MS/ROP dressing provides a promising strategy for treating diabetic PNI to facilitate nerve regeneration, functional recovery and pain relief.

Keywords: Analgesia; Diabetic peripheral nerve injury; Electroconductive hydrogel; Nerve regeneration; Ropivacaine microspheres.