In the current research, the nanofibrous neural channels were produced by electrospinning of PCL/Gelatin solution loaded with Calendula officinalis extract. The produced scaffolds properties were studied using various in vitro characterization methods. Then, the conduits’ healing potential was investigated in a rat model of PNS injury. In vitro results showed that scaffolds were not toxic and quenched DPPH free radicals. In addition, the extract-loaded conduits exhibited significant anti-inflammatory activity. In vivo study showed that the regular treadmill exercise significantly improved the healing efficacy of the Calendula officinalis-delivering conduits by upregulating BDNF and GFAP proteins.
SalehiMBagherZKamravaSK, et al. Alginate/chitosan hydrogel containing olfactory ectomesenchymal stem cells for sciatic nerve tissue engineering. J Cell Physiol2019; 234(9): 15357–15368.
2.
JabbariFBabaeipourVBakhtiariS.Bacterial cellulose-based composites for nerve tissue engineering. Int J Biol Macromol2022; 217: 120–130.
3.
ZolfagharzadehVAiJSoltaniH, et al. Sustain release of loaded insulin within biomimetic hydrogel microsphere for sciatic tissue engineering in vivo. Int J Biol Macromol2023; 225: 687–700.
4.
GivolOKornhaberRVisentinD, et al. A systematic review of Calendula officinalis extract for wound healing. Wound Repair Regen2019; 27(5): 548–561.
5.
NicolausCJunghannsSHartmannA, et al. In vitro studies to evaluate the wound healing properties of Calendula officinalis extracts. J Ethnopharmacol2017; 196: 94–103.
6.
IonescuOMMignonAIacobAT, et al. New hyaluronic acid/polyethylene oxide-based electrospun nanofibers: design, characterization and in vitro biological evaluation. Polymers2021; 13(8): 1291.
7.
IonescuOMIacobATMignonA, et al. Design, preparation and in vitro characterization of biomimetic and bioactive chitosan/polyethylene oxide based nanofibers as wound dressings. Int J Biol Macromol2021; 193: 996–1008.
8.
SousaIMendesABártoloPJ.PCL scaffolds with collagen bioactivator for applications in tissue engineering. Procedia Eng2013; 59: 279–284.
9.
SiddiquiNAsawaSBirruB, et al. PCL-based composite scaffold matrices for tissue engineering applications. Mol Biotechnol2018; 60: 506–532.
10.
Perez-PuyanaVWieringaPYusteY, et al. Fabrication of hybrid scaffolds obtained from combinations of PCL with gelatin or collagen via electrospinning for skeletal muscle tissue engineering. J Biomed Mater Res A2021; 109(9): 1600–1612.
11.
MaugeriGD’AgataVTrovatoB, et al. The role of exercise on peripheral nerve regeneration: from animal model to clinical application. Heliyon2021; 7(11): e08281.
12.
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.
13.
LanzaRLangerRVacantiJP. Principles of tissue engineering. Academic Press, 2020.
14.
HeidariMBahramiSHRanjbar-MohammadiM, et al. Smart electrospun nanofibers containing PCL/gelatin/graphene oxide for application in nerve tissue engineering. Mater Sci Eng C2019; 103: 109768.
15.
VijayavenkataramanS.Nerve guide conduits for peripheral nerve injury repair: a review on design, materials and fabrication methods. Acta Biomater2020; 106: 54–69.
16.
MuYWuFLuY, et al. Progress of electrospun fibers as nerve conduits for neural tissue repair. Nanomedicine2014; 9(12): 1869–1883.
17.
PreethiKKuttanGKuttanR.Antioxidant potential of an extract of calendula officinalis. Flowers in vitro. and in vivo. Pharm Biol2006; 44(9): 691–697.
18.
JanNWaniUMAndrabiK, et al. Cold stress modulates osmolytes and antioxidant system in Calendula officinalis. Acta Physiol Plant2018; 40: 1–16.
19.
BragaPCDal SassoMCuliciM, et al. Antioxidant activity of Calendula officinalis extract: inhibitory effects on chemiluminescence of human neutrophil bursts and electron paramagnetic resonance spectroscopy. Pharmacology2009; 83(6): 348–355.
20.
HamzawyMAEl-DensharyESHassanNS, et al. Dietary supplementation of Calendula officinalis counteracts the oxidative stress and liver damage resulted from aflatoxin. ISRN Nutr2013; 2013: 538427.
21.
BabaeeNMoslemiDKhalilpourM, et al. Antioxidant capacity of calendula officinalis flowers extract and prevention of radiation induced oropharyngeal mucositis in patients with head and neck cancers: a randomized controlled clinical study. DARU J Pharm Sci2013; 21: 1–7.
22.
DindaMDasguptaUSinghN, et al. PI3K-mediated proliferation of fibroblasts by Calendula officinalis tincture: implication in wound healing. Phytother Res2015; 29: 607–616.
23.
PatrickKKumarSEdwardsonPA, et al. Induction of vascularisation by an aqueous extract of the flowers of Calendula officinalis L. the European marigold. Phytomedicine1996; 3(1): 11–18.
24.
AbutahaNNasrFAMohammedAZ, et al. Calendula arvensis L. as an anti-cancer agent against breast cancer cell lines. Mol Biol Rep2019; 46: 2187–2196.
25.
FronzaMHeinzmannBHamburgerM, et al. Determination of the wound healing effect of Calendula extracts using the scratch assay with 3T3 fibroblasts. J Ethnopharmacol2009; 126(3): 463–467.
26.
UkiyaMAkihisaTYasukawaK, et al. Anti-inflammatory, anti-tumor-promoting, and cytotoxic activities of constituents of marigold (Calendula officinalis) flowers. J Nat Prod2006; 69(12): 1692–1696.
27.
Della LoggiaRTubaroASosaS, et al. Topical anti-inflammatory activity of Calendula officinalis extracts. Planta Méd1990; 56(6): 658.
28.
SilvaDFerreiraMSSousa-LoboJM, et al. Anti-inflammatory activity of Calendula officinalis L. Flower extract. Cosmetics2021; 8(2): 31.
29.
PreethiKCKuttanGKuttanR.Anti-inflammatory activity of flower extract of Calendula officinalis Linn. and its possible mechanism of action. Indian J Exp Biol2009; 47(2): 113–120.
30.
RahmatiMMillsDKUrbanskaAM, et al. Electrospinning for tissue engineering applications. Prog Mater Sci2021; 117: 100721.
31.
RoccoKAMaxfieldMWBestCA, et al. In vivo applications of electrospun tissue-engineered vascular grafts: a review. Tissue Eng Part B Rev2014; 20(6): 628–640.
32.
Muerza-CascanteMLHaylockDHutmacherDW, et al. Melt electrospinning and its technologization in tissue engineering. Tissue Eng Part B Rev2015; 21(2): 187–202.
33.
KhatiwalaVKShekharNAggarwalS, et al. Biodegradation of poly (ε-caprolactone)(PCL) film by Alcaligenes faecalis. J Polym Environ2008; 16: 61–67.
34.
DulnikJDenisPSajkiewiczP, et al. Biodegradation of bicomponent PCL/gelatin and PCL/collagen nanofibers electrospun from alternative solvent system. Polym Degrad Stab2016; 130: 10–21.
35.
TokiwaYCalabiaBP.Biodegradability and biodegradation of polyesters. J Polym Environ2007; 15: 259–267.
36.
CaloriIRBragaGda Costa Carvalho de JesusP, et al. Polymer scaffolds as drug delivery systems. Eur Polym J2020; 129: 109621.
37.
WillerthSMSakiyama-ElbertSE.Approaches to neural tissue engineering using scaffolds for drug delivery. Adv Drug Delivery Rev2007; 59(4–5): 325–338.
38.
MoioliEKClarkPAXinX, et al. Matrices and scaffolds for drug delivery in dental, oral and craniofacial tissue engineering. Adv Drug Delivery Rev2007; 59(4–5): 308–324.
39.
FregnanFMuratoriLSimõesAR, et al. Role of inflammatory cytokines in peripheral nerve injury. Neural Regen Res2012; 7(29): 2259.
40.
ZhangDLuYZhaoX, et al. Aerobic exercise attenuates neurodegeneration and promotes functional recovery–why it matters for neurorehabilitation & neural repair. Neurochem Int2020; 141: 104862.
41.
QuaneyBMBoydLAMcDowdJM, et al. Aerobic exercise improves cognition and motor function poststroke. Neurorehabil Neural Repair2009; 23(9): 879–885.
42.
DobkinBH.Training and exercise to drive poststroke recovery. Nat Clin Pract Neurol2008; 4(2): 76–85.
43.
WuYRakotoarisoaMAngelovB, et al. Self-assembled nanoscale materials for neuronal regeneration: a focus on BDNF protein and nucleic acid biotherapeutic delivery. Nanomaterials2022; 12(13): 2267.
44.
NicolettiVGPajerKCalcagnoD, et al. The role of metals in the neuroregenerative action of BDNF, GDNF, NGF and other neurotrophic factors. Biomolecules2022; 12(8): 1015.
