The peripheral nervous system (PNS) consists of nerves that extend beyond the brain and spinal cord, connecting the body to the central nervous system (CNS). Peripheral nerve injuries, caused by trauma, compression, or disease, often result in sensory and motor deficits. In the current study, a nanofibrous neural conduit was developed by loading Inula helenium extract into electrospun PCL/gelatin scaffolds. Then, the scaffolds were characterized in vitro using different analysis methods. Then, the electrospun sheets were rolled up to produce neural conduits. Finally, the healing efficacy of the developed system was investigated in a rat model of sciatic nerve injury. Results showed that the animals that were treated with both treadmill exercise and the Inula helenium extract-loaded conduits had significantly better functional recovery and histopathological recovery. ELISA assay showed that the hybrid treatment method increased tissue concentrations of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) and decreased tumor necrosis factor- α (TNF- α) tissue levels.
NoceraGJacobC.Mechanisms of Schwann cell plasticity involved in peripheral nerve repair after injury. Cell Mol Life Sci2020; 77(20): 3977–3989.
2.
LiuKYanLLiR, et al. 3D printed personalized nerve guide conduits for precision repair of peripheral nerve defects. Adv Sci2022; 9(12): e2103875.
3.
CarvalhoCROliveiraJMReisRL.Modern trends for peripheral nerve repair and regeneration: beyond the hollow nerve guidance conduit. Front Bioeng Biotechnol2019; 7: 337.
4.
NagarajanARizwanaNAbrahamM, et al. Polycaprolactone/graphene oxide/acellular matrix nanofibrous scaffolds with antioxidant and promyelinating features for the treatment of peripheral demyelinating diseases. J Mater Sci Mater Med2023; 34(10): 49.
5.
GhaneNKhaliliSNouri KhorasaniS, et al. Regeneration of the peripheral nerve via multifunctional electrospun scaffolds. J Biomed Mater Res A2021; 109(4): 437–452.
6.
LeeSPatelMPatelR.Electrospun nanofiber nerve guidance conduits for peripheral nerve regeneration: a review. Eur Polym J2022; 181: 111663.
7.
LeeS-GKangH.Anti-neuroinflammatory effects of ethanol extract of Inula helenium L (Compositae). Trop J Pharm Res2016; 15(3): 521–526.
8.
SowndhararajanKChoHYuB, et al. Effect of inhalation of essential oil from Inula helenium L. root on electroencephalographic (EEG) activity of the human brain. Eur J Integr Med2016; 8(4): 453–457.
9.
FarzamfarSEhteramiASalehiM, et al. Unrestricted somatic stem cells loaded in nanofibrous conduit as potential candidate for sciatic nerve regeneration. J Mol Neurosci2019; 67(1): 48–61.
10.
RizwanaNAgarwalVNuneM.Antioxidant for neurological diseases and neurotrauma and bioengineering approaches. Antioxidants (Basel)2021; 11(1): 72.
11.
ChiaramonteRPavoneVTestaG, et al. The role of physical exercise and rehabilitative implications in the process of nerve repair in peripheral neuropathies: a systematic review. Diagnostics (Basel)2023; 13(3): 364.
12.
NuneMManchineellaSGovindarajuT, et al. Melanin incorporated electroactive and antioxidant silk fibroin nanofibrous scaffolds for nerve tissue engineering. Mater Sci Eng C Mater Biol Appl2019; 94: 17–25.
AbdelbassetWKElkholiSMIsmailKA, et al. Mequinol-loaded carboxymethyl cellulose/chitosan electrospun wound dressing as a potential candidate to treat diabetic wounds. Cellulose2022; 29(14): 7863–7881.
15.
SalehiMNaseri-NosarMEbrahimi-BaroughS, et al. Sciatic nerve regeneration by transplantation of Schwann cells via erythropoietin controlled-releasing polylactic acid/multiwalled carbon nanotubes/gelatin nanofibrils neural guidance conduit. J Biomed Mater Res B Appl Biomater2018; 106(4): 1463–1476.
16.
MaugeriGD’AgataVTrovatoB, et al. The role of exercise on peripheral nerve regeneration: from animal model to clinical application. Heliyon2021; 7(11): e08281.
17.
YongHYRawjiKSGhorbaniS, et al. The benefits of neuroinflammation for the repair of the injured central nervous system. Cell Mol Immunol2019; 16(6): 540–546.
18.
DuBYinHChenY, et al. A waterborne polyurethane 3D scaffold containing PLGA with a controllable degradation rate and an anti-inflammatory effect for potential applications in neural tissue repair. J Mater Chem B2020; 8(20): 4434–4446.
19.
GierlikowskaBGierlikowskiWBekierK, et al. Inula helenium and Grindelia squarrosa as a source of compounds with anti-inflammatory activity in human neutrophils and cultured human respiratory epithelium. J Ethnopharmacol2020; 249: 112311.
20.
ParkEJKimYMParkSW, et al. Induction of HO-1 through p38 MAPK/Nrf2 signaling pathway by ethanol extract of Inula helenium L. reduces inflammation in LPS-activated RAW 264.7 cells and CLP-induced septic mice. Food Chem Toxicol2013; 55: 386–395.
21.
FallahzadehAMohammadiS.An investigation of the antinociceptive and anti-inflammatory effects of hydroalcoholic extract of Inula helenium on male rats. J Babol Univ Med Sci2016; 18(12): 57–63.
22.
VijayavenkataramanS.Nerve guide conduits for peripheral nerve injury repair: a review on design, materials and fabrication methods. Acta Biomater2020; 106: 54–69.
23.
YuXZhangTLiY.3D printing and bioprinting nerve conduits for neural tissue engineering. Polymers (Basel)2020; 12(8): 1637.
24.
SiddiquiNAsawaSBirruB, et al. PCL-based composite scaffold matrices for tissue engineering applications. Mol Biotechnol2018; 60: 506–532.
25.
JiaoZLuoBXiangS, et al. 3D printing of HA/PCL composite tissue engineering scaffolds. Adv Ind Eng Polym Res2019; 2(4): 196–202.
26.
ZlatićNJakovljevićDStankovićM.Temporal, plant part, and interpopulation variability of secondary metabolites and antioxidant activity of Inula helenium L. Plants (Basel)2019; 8(6): 179.
27.
SpiridonINechitaCBNiculauaM, et al. Antioxidant and chemical properties of Inula helenium root extracts. Cent Eur J Chem2013; 11: 1699–1709.
28.
AybastıerÖ. Efficacy of methanol-water extract of Inula helenium root against oxidative DNA damage. J Tradit Chin Med2021; 41(2): 293–300.
29.
QuHFuHHanZ, et al. Biomaterials for bone tissue engineering scaffolds: a review. RSC Adv2019; 9(45): 26252–26262.
30.
LiCOuyangLArmstrongJP, et al. Advances in the fabrication of biomaterials for gradient tissue engineering. Trends Biotechnol2021; 39(2): 150–164.
31.
LiuWXuBZhaoS, et al. Spinal cord tissue engineering via covalent interaction between biomaterials and cells. Sci Adv2023; 9(6): eade8829.
32.
NectowARMarraKGKaplanDL.Biomaterials for the development of peripheral nerve guidance conduits. Tissue Eng Part B Rev2012; 18(1): 40–50.
33.
CaloriIRBragaGde JesusPdCC, et al. Polymer scaffolds as drug delivery systems. Eur Polym J2020; 129: 109621.
34.
RegenhardtRWTakaseHLoEH, et al. Translating concepts of neural repair after stroke: structural and functional targets for recovery. Restor Neurol Neurosci2020; 38(1): 67–92.
35.
KramerSFHungSHBrodtmannA.The impact of physical activity before and after stroke on stroke risk and recovery: a narrative review. Curr Neurol Neurosci Rep2019; 19(6): 28.
36.
GustafssonDKlangAThamsS, et al. The role of BDNF in experimental and clinical traumatic brain injury. Int J Mol Sci2021; 22(7): 3582.
37.
ZhaKYangYTianG, et al. Nerve growth factor (NGF) and NGF receptors in mesenchymal stem/stromal cells: impact on potential therapies. Stem Cells Transl Med2021; 10(7): 1008–1020.
TalebiMKhoramjouyMFeiziA, et al. Novel multi-target therapeutic potential of the genus Inula: advances and opportunities for neuroprotection. Pharmacol Res Mod Chin Med2023; 7(6): 100263.
