Painful Terminal Neuroma Prevention by Capping PRGD/PDLLA Conduit in Rat Sciatic Nerves

Abstract

Neuroma formation after amputation as a long‐term deficiency leads to spontaneous neuropathic pain that reduces quality of life of patients. To prevent neuroma formation, capping techniques are implemented as effective treatments. However, an ideal, biocompatible material covering the nerves is an unmet clinical need. In this study, biocompatible characteristics presented by the poly(D,L‐lactic acid)/arginylglycylaspartic acid (RGD peptide) modification of poly{(lactic acid)‐co‐ [(glycolic acid)‐alt‐(L‐lysine)]} (PRGD/PDLLA) are evaluated as a nerve conduit. After being capped on the rat sciatic nerve stump in vivo, rodent behaviors and tissue structures are compared via autotomy scoring and histological analyses. The PRGD/PDLLA capped group gains lower autotomy score and improves the recovery, where inflammatory infiltrations and excessive collagen deposition are defeated. Transmission electron microscopy images of the regeneration of myelin sheath in both groups show that abnormal myelination is only present in the uncapped rats. Changes in related genes (MPZ, MBP, MAG, and Krox20) are monitored quantitative real‐time polymerase chain reaction (qRT‐PCR) for mechanism investigation. The PRGD/PDLLA capping conduits not only act as physical barriers to inhibit the invasion of inflammatory infiltration in the scar tissue but also provide a suitable microenvironment for promoting nerve repairing and avoiding neuroma formation during nerve recovery.

Analysis of an End Neuroma 6 Months after Capping with a Bioresorbable Polycaprolactone Cap (NEUROCAP®) in a Human Model

“…As technology improves, our understanding of the relationship between nerve regeneration and clinically symptomatic neuromas will guide treatment into the near future. The latest technologies include electrospun aligned nanofiber conduits modified with biocompatible peptides to provide a suitable microenvironment to prevent neuroma formation [15]. Our analysis of a bioresorbable polycaprolactone cap is the first in a human model.…”

Covering the proximal nerve stump with chondroitin sulfate proteoglycans prevents traumatic painful neuroma formation by blocking axon regeneration after neurotomy in Sprague Dawley rats

“…Studies have shown that silicone tubes, collagen tubes, microcrystalline chitosan, and PRGD/PDLLA conduits can achieve satisfactory effects in preventing traumatic neuroma formation. [22][23][24][25][26][27][28] Hong et al 29 found that acellular nerve allografts (ANAs) attached to the proximal end of an injured nerve can limit axon growth in a controlled manner, indicating that the use of ANAs as a tool to control neuroma formation may be a viable clinical option. In addition, Zhou et al 11 found that the application of a nanofibrous scaffold consisting of aligned silk fibroin blended with poly(l-lactic acid-co-caprolactone) activated the RhoA/ROCK signaling pathway, which contributed to the prevention of traumatic painful neuroma formation because of its suppressive effect on axon regeneration.…”

Recent Advances on Magnetic Sensitive Hydrogels in Tissue Engineering

“…Neural tissue damages caused by either neurodegenerative diseases or high-energy trauma greatly affect the patients' quality of life worldwide. The mammalian neuronal cells show the limitation of regrowth performance and functional recovery, presenting a critical clinical challenge for surgeons (Yi et al, 2018;Zhang P.-X. et al, 2019).…”