Exploring the efficacy of catha edulis extract-loaded nanofibrous scaffolds seeded with bone marrow-derived stem cells for diabetic wound healing: A preclinical investigation
Restricted accessResearch articleFirst published online July, 2024
Exploring the efficacy of catha edulis extract-loaded nanofibrous scaffolds seeded with bone marrow-derived stem cells for diabetic wound healing: A preclinical investigation
The aim of this study was to investigate the potential of incorporating catha edulis extract into polycaprolacton/gelatin scaffolds using electrospinning technique for the treatment of diabetic wounds in a rat model.
Methods:
The in vitro characterization of the scaffolds was performed using various assays, including anti-inflammatory assay, microstructure study, DPPH radical scavenging assay, cell viability assay, hemocompatibility assay, and bacterial penetration assays. The scaffolds were then seeded with bone marrow-derived stem cells and cultured before implantation into the rat model.
Results:
The results of the in vitro study showed that the produced scaffolds were nanofibrous, antioxidative, and non-toxic to skin cells. In vivo study demonstrated that the stem cell and catha edulis extract-loaded scaffolds had the highest rate of wound closure and histomorphometric parameters compared to other groups. Moreover, gene expression studies showed that the developed wound dressings increased the expression of VEGF gene and reduced the expression of glutathione peroxidase gene.
Conclusion:
These findings suggest that the catha edulis extract-loaded polycaprolacton/gelatin scaffolds could be a promising therapeutic option for diabetic wounds.
DengLDuCSongP, et al. The role of oxidative stress and antioxidants in diabetic wound healing. Oxid Med Cell Longev2021; 2021: 8852759.
2.
ChenJHeJYangY, et al. Antibacterial adhesive self-healing hydrogels to promote diabetic wound healing. Acta Biomaterial2022; 146: 119–130.
3.
BaiQHanKDongK, et al. Potential applications of nanomaterials and technology for diabetic wound healing. Int J Nanomed2020; 15: 9717–9743.
4.
AnYLinSTanX, et al. Exosomes from adipose-derived stem cells and application to skin wound healing. Cell Prolifer2021; 54: e12993.
5.
MaziniLRochetteLAdmouB, et al. Hopes and limits of adipose-derived stem cells (adscs) and mesenchymal stem cells (mscs) in wound healing. Int J Mol Sci2020; 21: 1306.
MooreKMMurthyABGraham-GuryshEG, et al. Polymeric biomaterial scaffolds for tumoricidal stem cell glioblastoma therapy. ACS Biomat Sci Eng2020; 6: 3762–3777.
8.
RahmaniANadriSKazemiHS, et al. Conductive electrospun scaffolds with electrical stimulation for neural differentiation of conjunctiva mesenchymal stem cells. Artif Org2019; 43: 780–790.
9.
AmbekarRSKandasubramanianB.Progress in the advancement of porous biopolymer scaffold: tissue engineering application. Indus Eng Chem Res2019; 58: 6163–6194.
10.
Echeverria MolinaMIMalollariKGKomvopoulosK.Design challenges in polymeric scaffolds for tissue engineering. Front Bioeng Biotechnol2021; 9: 617141.
11.
CaloriIRBragaGde JesusPCC, et al. Polymer scaffolds as drug delivery systems. Eur Poly J2020; 129: 109621.
12.
BordoneMBettencourtA. Management of bone diseases: looking at scaffold-based strategies for drug delivery. Drug Del Trans Res2023; 13: 79–104.
OyunguEKioyPGPatelNB.Proconvulsant effect of khat (catha edulis) in sprague dawley rats. J Ethnopharmacol2009; 121: 476–478.
15.
FarzamfarSSalehiMTavangarSM, et al. A novel polycaprolactone/carbon nanofiber composite as a conductive neural guidance channel: an in vitro and in vivo study. Prog Biomater2019; 8: 239–248.
16.
SalehiMEhteramiAFarzamfarS, et al. Accelerating healing of excisional wound with alginate hydrogel containing naringenin in rat model. Drug Del Trans Res2021; 11: 142–153.
17.
JintaoY.Idebenone-loaded wound dressings promote diabetic wound healing through downregulation of il1b, nfkb genes and upregulation of fgf2 gene. Res Veter Sci2022; 151: 128–137.
18.
AbbaszadehMMeybodiSMZareiA, et al. Cellulose acetate nanofibrous wound dressings loaded with 1% probucol alleviate oxidative stress and promote diabetic wound healing: an in vitro and in vivo study. Cellulose2022; 29: 5359–5374.
19.
SamadianHZamiriSEhteramiA, et al. Electrospun cellulose acetate/gelatin nanofibrous wound dressing containing berberine for diabetic foot ulcer healing: in vitro and in vivo studies. Scient Rep2020; 10: 8312.
20.
EhteramiASalehiMFarzamfarS, et al. Chitosan/alginate hydrogels containing alpha-tocopherol for wound healing in rat model. J Drug Del Sci Technol2019; 51: 204–213.
21.
FarzamfarSEhteramiASalehiM, et al. Unrestricted somatic stem cells loaded in nanofibrous conduit as potential candidate for sciatic nerve regeneration. J Mol Neurosci2019; 67: 48–61.
22.
DingXZhangLZhouD, et al. The effects of propolis-loaded chitosan nanoparticles and menstrual blood stem cells on lps-induced ovarian inflammation in the murine ovary in vivo: an in vitro and in vivo study. Reprod Toxicol2023;123: 108514.
23.
YeLGaoZRohaniS.Intervertebral disk regeneration in a rat model by allopurinol–loaded chitosan/alginate hydrogel. Biomol Biomed2023; 23: 661–670.
24.
IbaokurgilFYildirimBAYildirimS. Effects of hypericum scabrum l. Essential oil on wound healing in streptozotocin-induced diabetic rats. Cutan Ocular Toxicol2022; 41: 137–144.
25.
Bahremandi-ToloueEMohammadalizadehZMukherjeeS, et al. Incorporation of inorganic bioceramics into electrospun scaffolds for tissue engineering applications: a review. Ceram Int2022; 48: 8803–8837.
KhorshidiSSoloukAMirzadehH, et al. A review of key challenges of electrospun scaffolds for tissue-engineering applications. J Tissue Eng Regenr Med2016; 10: 715–738.
28.
LimSHMaoH-Q.Electrospun scaffolds for stem cell engineering. Adv Drug Del Rev2009; 61: 1084–1096.
29.
DudaiNFischerRSegevD, et al. Antioxidative activity of khat (catha edulis forsk.). Int Sympon Nat Preser Food Feed Cosmet2006; 778: 859.
30.
Al-HaboriM.The potential adverse effects of habitual use of catha edulis (khat). Expert Opn Drug Saf2005; 4: 1145–1154.
31.
HailuYMAtlabachewMChandravanshiBS, et al. Composition of essential oil and antioxidant activity of khat (catha edulis forsk), ethiopia. Chem Int2017; 3: 25.
32.
NajiKMAl-MaqtariMAAl-AsbahiAA, et al. Effect of daily chewing soft buds and leaves of catha edulis (khat) on the antioxidant defense system and oxidative stress markers in blood. Arab J Sci Eng2015; 40: 1–6.
33.
HorakovaJMikesPSamanA, et al. Comprehensive assessment of electrospun scaffolds hemocompatibility. Mater Sci Eng C2018; 82: 330–335.
34.
Naseri-NosarMFarzamfarSSahrapeymaH, et al. Cerium oxide nanoparticle-containing poly (ε-caprolactone)/gelatin electrospun film as a potential wound dressing material: in vitro and in vivo evaluation. Mater Sci Eng C2017; 81: 366–372.
35.
SamadianHSalehiMFarzamfarS, et al. In vitro and in vivo evaluation of electrospun cellulose acetate/gelatin/hydroxyapatite nanocomposite mats for wound dressing applications. Artif Cells Nanomed Biotechnol2018; 46: 964–974.
36.
FarzamfarSNaseri-NosarMSamadianH, et al. Taurine-loaded poly (ε-caprolactone)/gelatin electrospun mat as a potential wound dressing material: in vitro and in vivo evaluation. J Bioact Compat Poly2018; 33: 282–294.
37.
GebremedhnKKahsayMHAkliluM.Green synthesis of cuo nanoparticles using leaf extract of catha edulis and its antibacterial activity. J Pharm Pharmacol2019; 7: 327–342.
38.
AndualemWWSabirFKMohammedET, et al. Synthesis of copper oxide nanoparticles using plant leaf extract of catha edulis and its antibacterial activity. J Nanotechnol2020; 2020: 2932434.
39.
SousaIMendesAPereiraRF, et al. Collagen surface modified poly (ε-caprolactone) scaffolds with improved hydrophilicity and cell adhesion properties. Mater Let2014; 134: 263–27.
40.
SzotCSBuchananCFGatenholmP, et al. Investigation of cancer cell behavior on nanofibrous scaffolds. Mater Sci Eng C2011; 31: 37–42.
41.
LeeSJLiuJOhSH, et al. Development of a composite vascular scaffolding system that withstands physiological vascular conditions. Biomaterials2008; 29: 2891–2898.
42.
Al-MeshalITariqMParmarN, et al. Anti-inflammatory activity of the flavonoid fraction of khat (catha edulis forsk). Agents Actions1986; 17: 379–380.
43.
Al-MamaryMAl-HaboriMAl-AghbariA, et al. Investigation into the toxicological effects of catha edulis leaves: a short term study in animals. Phytother Res2002; 16: 127–132.
44.
Al-ZubairiAIsmailPPeiCP, et al. Genotoxic effect of catha edulis (khat) crude extract after sub-chronic administration in rats. Environ Toxicol Pharmacol2008; 25: 298–303.
45.
Al-MaweriSAWarnakulasuriyaSSamranA.Khat (catha edulis) and its oral health effects: an updated review. J Invest Clin Dent2018; 9: e12288.
46.
Al-HashemFHBin-JaliahIDallakMA, et al. Khat (catha edulis) extract increases oxidative stress parameters and impairs renal and hepatic functions in rats. Bahr Med Bull2011; 33: 1–9.
47.
LauKPausRTiedeS, et al. Exploring the role of stem cells in cutaneous wound healing. Exp Dermatol2009; 18: 921–933.
48.
KucharzewskiMRojczykEWilemska-KucharzewskaK, et al. Novel trends in application of stem cells in skin wound healing. Eur J Pharmacol2019; 843: 307–315.
49.
WuYWangJScottPG, et al. Bone marrow-derived stem cells in wound healing: a review. Wound Repair Regen2007; 15: S18–S26.
50.
NasserMWuYDanaouiY, et al. Engineering microenvironments towards harnessing pro-angiogenic potential of mesenchymal stem cells. Mater Sci Eng C2019; 102: 75–84.
51.
ShewameneZEngidaworkE. Subacute administration of crude khat (catha edulis f.) Extract induces mild to moderate nephrotoxicity in rats. BMC Complement Alter Med2014; 14: 1–8.
