Top

Cellulose

Published in:

24-01-2022 | Original Research

Thermo-responsive hydrogels based on methylcellulose/Persian gum loaded with taxifolin enhance bone regeneration: an in vitro/in vivo study

Authors: Zahra Sadat Sajadi-Javan, Jaleh Varshosaz, Mina Mirian, Maziar Manshaei, Atousa Aminzadeh

Published in: Cellulose | Issue 4/2022

Activate our intelligent search to find suitable subject content or patents.

search-config

AI-assisted search

Off

Abstract

In-situ forming hydrogels have gained noticeable attention to encapsulate osteogenic agents and regenerate irregular-shape bone defects. In this study, a novel thermosensitive hydrogel based on blended methylcellulose (MC) with Persian gum (PG) was fabricated and enriched with taxifolin (TAX) loaded halloysite nanotubes (HNTs) to enhance mechanical and biological characteristics of the hydrogel in bone tissue engineering. The injectability, mechanical and rheological tests were performed for different hydrogel formulations containing 0.25–1.5 w/v% PG and 1–7 w/v% HNTs. Also, to evaluate the impact of PG and HNTs on hydrogel behavior, the degradation rate and swelling degree of hydrogels were assessed. The optimized MC/PG/HNTs hydrogel containing 1% PG and 3% HNTs (MC/PG-1/HNTs 3%) was easily injectable and gelled rapidly at physiological temperature, while it had the highest mechanical strength due to the existence of PG and HNTs. In vitro release study of TAX from this system also revealed more sustained release compared to HNTs-TAX nanoparticles. Furthermore, the interaction of cells with hydrogel and osteo-conductivity was studied using osteoblast-like cells (MG-63). Results showed higher cell adhesion, proliferation, and gene expression for MC/PG-1/HNTs-TAX hydrogel compared to MC/PG-1 and MC/PG-1/HNTs 3% possibly due to the synergic effect of HNTs and TAX. In addition, Alizarin Red S staining and alkaline phosphatase measurements indicated that the existence of HNTs-TAX promoted osteogenic differentiation. Eventually, animal studies on the femoral defects indicated improved remedy when using the MC/PG-1/HNTs-TAX hydrogel carrying MG-63 cells.

Graphical abstract

previous article Development of chitosan, graphene oxide, and cerium oxide composite blended films: structural, physical, and functional properties

next article Synthesis and surface modification of cellulose cryogels from coconut peat for oil adsorption

Dont have a licence yet? Then find out more about our products and how to get one now:

Springer Professional "Technik"

Online-Abonnement

Mit Springer Professional "Technik" erhalten Sie Zugriff auf:

über 67.000 Bücher
über 390 Zeitschriften

aus folgenden Fachgebieten:

Automobil + Motoren
Bauwesen + Immobilien
Business IT + Informatik
Elektrotechnik + Elektronik
Energie + Nachhaltigkeit
Maschinenbau + Werkstoffe

Jetzt Wissensvorsprung sichern!

inform now

Springer Professional "Wirtschaft+Technik"

Online-Abonnement

Mit Springer Professional "Wirtschaft+Technik" erhalten Sie Zugriff auf:

über 102.000 Bücher
über 537 Zeitschriften

aus folgenden Fachgebieten:

Automobil + Motoren
Bauwesen + Immobilien
Business IT + Informatik
Elektrotechnik + Elektronik
Energie + Nachhaltigkeit
Finance + Banking
Management + Führung
Marketing + Vertrieb
Maschinenbau + Werkstoffe
Versicherung + Risiko

Jetzt Wissensvorsprung sichern!

inform now

Abbasi S (2019) Persian gum (Amygdalus scoparia Spach). In: Razavi SMA (ed) Emerging natural hydrocolloids: rheology and functions. John Wiley & Sons Ltd, Hoboken, pp 273–298CrossRef

Abbasi S (2017) Challenges towards characterization and applications of a novel hydrocolloid: Persian gum. Curr Opin Colloid Interface Sci 28:37–45. https://doi.org/10.1016/j.cocis.2017.03.001CrossRef

Abbasi S, Mohammadi S, Rahimi S (2011) Partial substitution of gelatin with Persian gum and use of Olibanum in production of functional pastille. Biosyst Eng 42:121–131

Agarwal R, García AJ (2015) Biomaterial strategies for engineering implants for enhanced osseointegration and bone repair. Adv Drug Deliv Rev 94:53–62. https://doi.org/10.1016/j.addr.2015.03.013CrossRefPubMedPubMedCentral

Alencastre I, Sousa D, Alves C et al (2016) Delivery of pharmaceutics to bone: nanotechnologies, high-throughput processing and in silico mathematical models. Eur Cell Mater 31:355–381. https://doi.org/10.22203/eCM.v031a23CrossRefPubMed

Alves MC, de Almeida PA, Polonini HC et al (2018) Taxifolin: evaluation through Ex vivo permeations on human skin and porcine vaginal mucosa. Curr Drug Deliv 15:1123–1134. https://doi.org/10.2174/1567201815666180116090258CrossRefPubMed

Amini AR, Laurencin CT, Nukavarapu SP (2012) Bone tissue engineering: recent advances and challenges. Crit Rev Biomed Eng 40:363–408. https://doi.org/10.1615/critrevbiomedeng.v40.i5.10CrossRefPubMedPubMedCentral

Amir Afshar H, Ghaee A (2016) Preparation of aminated chitosan/alginate scaffold containing halloysite nanotubes with improved cell attachment. Carbohydr Polym 151:1120–1131. https://doi.org/10.1016/j.carbpol.2016.06.063CrossRefPubMed

Amiryaghoubi N, Noroozi Pesyan N, Fathi M, Omidi Y (2020) Injectable thermosensitive hybrid hydrogel containing graphene oxide and chitosan as dental pulp stem cells scaffold for bone tissue engineering. Int J Biol Macromol 162:1338–1357. https://doi.org/10.1016/j.ijbiomac.2020.06.138CrossRefPubMed

Azmi S, Razak SIA, Abdul Kadir M et al (2016) Reinforcement of poly(vinyl alcohol) hydrogel with halloysite nanotubes as potential biomedical materials. Soft Mater. https://doi.org/10.1080/1539445X.2016.1242500CrossRef

Bain MK, Bhowmick B, Maity D et al (2012) Synergistic effect of salt mixture on the gelation temperature and morphology of methylcellulose hydrogel. Int J Biol Macromol 51:831–836. https://doi.org/10.1016/j.ijbiomac.2012.07.028CrossRefPubMed

Bavnhøj CG, Knopp MM, Madsen CM, Löbmann K (2019) The role interplay between mesoporous silica pore volume and surface area and their effect on drug loading capacity. Int J Pharm X 1:100008. https://doi.org/10.1016/j.ijpx.2019.100008CrossRefPubMedPubMedCentral

Boraei SBA, Nourmohammadi J, Bakhshandeh B et al (2021) Enhanced osteogenesis of gelatin-halloysite nanocomposite scaffold mediated by loading strontium ranelate. Int J Polym Mater Polym Biomater 70:392–402. https://doi.org/10.1080/00914037.2020.1725754CrossRef

Cai C, Liu C, Zhao L et al (2018) Effects of Taxifolin on Osteoclastogenesis in vitro and in vivo. Front Pharmacol 9:1286. https://doi.org/10.3389/fphar.2018.01286CrossRefPubMedPubMedCentral

Córdoba A, Manzanaro-Moreno N, Colom C et al (2018) Quercitrin nanocoated implant surfaces reduce osteoclast activity in vitro and in vivo. Int J Mol Sci. https://doi.org/10.3390/ijms19113319CrossRefPubMedPubMedCentral

Dabestani M, Kadkhodaee R, Phillips GO, Abbasi S (2018) Persian gum: a comprehensive review on its physicochemical and functional properties. Food Hydrocoll 78:92–99. https://doi.org/10.1016/j.foodhyd.2017.06.006CrossRef

Dalwadi C, Patel G (2018) Thermosensitive nanohydrogel of 5-fluorouracil for head and neck cancer: preparation, characterization and cytotoxicity assay. Int J Nanomedicine 13:31–33. https://doi.org/10.2147/IJN.S124702CrossRefPubMedPubMedCentral

Deng L, Liu Y, Yang L et al (2020) Injectable and bioactive methylcellulose hydrogel carrying bone mesenchymal stem cells as a filler for critical-size defects with enhanced bone regeneration. Colloids Surf B Biointerfaces 194:111159. https://doi.org/10.1016/j.colsurfb.2020.111159CrossRefPubMed

Fadavi G, Mohammadifar MA, Zargarran A et al (2014) Composition and physicochemical properties of Zedo gum exudates from Amygdalus scoparia. Carbohydr Polym 101:1074–1080. https://doi.org/10.1016/j.carbpol.2013.09.095CrossRefPubMed

Farokhi M, Sharifi S, Shafieyan Y et al (2012) Porous crosslinked poly(ε-caprolactone fumarate)/nanohydroxyapatite composites for bone tissue engineering. J Biomed Mater Res A 100:1051–1060. https://doi.org/10.1002/jbm.a.33241CrossRefPubMed

Ghasemzadeh H, Modiri F (2020) Application of novel Persian gum hydrocolloid in soil stabilization. Carbohydr Polym 246:116639. https://doi.org/10.1016/j.carbpol.2020.116639CrossRefPubMed

Hadavi M, Hasannia S, Faghihi S et al (2017) Novel calcified gum Arabic porous nano-composite scaffold for bone tissue regeneration. Biochem Biophys Res Commun 488:671–678. https://doi.org/10.1016/j.bbrc.2017.03.046CrossRefPubMed

Hasan SMK, Zainuddin S, Tanthongsack J et al (2018) A study of poly (3-hydroxybutyrate-co-3-hydroxyvalerate) biofilms’ thermal and biodegradable properties reinforced with halloysite nanotubes. J Compos Mater 52:3199–3207. https://doi.org/10.1177/0021998318763246CrossRef

Hasibi F, Nasirpour A, Varshosaz J et al (2020) Formulation and characterization of taxifolin-loaded lipid nanovesicles (Liposomes, niosomes, and transfersomes) for beverage fortification. Eur J Lipid Sci Technol 122:1900105. https://doi.org/10.1002/ejlt.201900105CrossRef

Hejazi F, Mirzadeh H (2016) Roll-designed 3D nanofibrous scaffold suitable for the regeneration of load bearing bone defects. Prog Biomater 5:199–211. https://doi.org/10.1007/s40204-016-0058-2CrossRefPubMedPubMedCentral

Huang B, Liu M, Long Z et al (2017) Effects of halloysite nanotubes on physical properties and cytocompatibility of alginate composite hydrogels. Mater Sci Eng C 70:303–310. https://doi.org/10.1016/j.msec.2016.09.001CrossRef

Huang B, Liu M, Zhou C (2017) Cellulose–halloysite nanotube composite hydrogels for curcumin delivery. Cellulose 24:2861–2875. https://doi.org/10.1007/s10570-017-1316-8CrossRef

Huang K, Ou Q, Xie Y et al (2019) Halloysite nanotube based scaffold for enhanced bone regeneration. ACS Biomater Sci Eng 5:4037–4047. https://doi.org/10.1021/acsbiomaterials.9b00277CrossRefPubMed

Huang Y, Guo W, Zhang J et al (2020) Thermosensitive hydrogels based on methylcellulose derivatives for prevention of postoperative adhesion. Cellulose 27:1555–1571. https://doi.org/10.1007/s10570-019-02857-4CrossRef

Khodaei D, Oltrogge K, Hamidi-Esfahani Z (2020) Preparation and characterization of blended edible films manufactured using gelatin, tragacanth gum and Persian gum. LWT 117:108617. https://doi.org/10.1016/j.lwt.2019.108617CrossRef

Kim MH, Kim BS, Park H et al (2018) Injectable methylcellulose hydrogel containing calcium phosphate nanoparticles for bone regeneration. Int J Biol Macromol 109:57–64. https://doi.org/10.1016/j.ijbiomac.2017.12.068CrossRefPubMed

Kondiah PJ, Choonara YE, Kondiah PPD et al (2016) A Review of injectable polymeric hydrogel systems for application in bone tissue engineering. Molecules. https://doi.org/10.3390/molecules21111580CrossRefPubMedPubMedCentral

Kouhi M, Varshosaz J, Beni B, Sarmadi A (2020) Injectable gellan gum/lignocellulose nanofibrils hydrogels enriched with melatonin loaded forsterite nanoparticles for cartilage tissue engineering: fabrication, characterization and cell culture studies. Mater Sci Eng C 115:111114. https://doi.org/10.1016/j.msec.2020.111114CrossRef

Kumar A, Matari IAI, Choi H et al (2019) Development of halloysite nanotube/carboxylated-cellulose nanocrystal-reinforced and ionically-crosslinked polysaccharide hydrogels. Mater Sci Eng C Mater Biol Appl 104:109983. https://doi.org/10.1016/j.msec.2019.109983CrossRefPubMed

Kumar A, Rao KM, Han SS (2017) Development of sodium alginate-xanthan gum based nanocomposite scaffolds reinforced with cellulose nanocrystals and halloysite nanotubes. Polym Test 63:214–225CrossRef

Kurczewska J, Pecyna P, Ratajczak M et al (2017) Halloysite nanotubes as carriers of vancomycin in alginate-based wound dressing. Saudi Pharm J SPJ Off Publ Saudi Pharm Soc 25:911–920. https://doi.org/10.1016/j.jsps.2017.02.007CrossRef

Lektemur Alpan A, Kızıldağ A, Özdede M et al (2020) The effects of taxifolin on alveolar bone in experimental periodontitis in rats. Arch Oral Biol 117:104823. https://doi.org/10.1016/j.archoralbio.2020.104823CrossRefPubMed

Li X, Nikiforow I, Pohl K et al (2013) Polyurethane coatings reinforced by halloysite nanotubes. Coatings 3:16–25. https://doi.org/10.3390/coatings3010016CrossRef

Liu M, Wu C, Jiao Y et al (2013) Chitosan-halloysite nanotubes nanocomposite scaffolds for tissue engineering. J Mater Chem B 1:2078–2089. https://doi.org/10.1039/c3tb20084aCrossRefPubMed

Liu Z, Yao P (2015) Injectable thermo-responsive hydrogel composed of xanthan gum and methylcellulose double networks with shear-thinning property. Carbohydr Polym 132:490–498. https://doi.org/10.1016/j.carbpol.2015.06.013CrossRefPubMed

Lun H, Ouyang J, Yang H (2014) Natural halloysite nanotubes modified as an aspirin carrier. RSC Adv 4:44197–44202. https://doi.org/10.1039/C4RA09006CCrossRef

Lvov Y, Wang W, Zhang L, Fakhrullin R (2016) Halloysite clay nanotubes for loading and sustained release of functional compounds. Adv Mater 28:1227–1250. https://doi.org/10.1002/adma.201502341CrossRefPubMed

Moeinpour F, Soofivand F, Mohseni-Shahri FS (2019) Controlled release of losartan from acid- and heat-treated halloysite nanotubes. Med Chem Res 28:160–168. https://doi.org/10.1007/s00044-018-2273-yCrossRef

Mokhtari H, Kharaziha M, Karimzadeh F, Tavakoli S (2019) An injectable mechanically robust hydrogel of Kappa-carrageenan-dopamine functionalized graphene oxide for promoting cell growth. Carbohydr Polym 214:234–249. https://doi.org/10.1016/j.carbpol.2019.03.030CrossRefPubMed

Molaei H, Jahanbin K (2018) Structural features of a new water-soluble polysaccharide from the gum exudates of Amygdalus scoparia Spach (Zedo gum). Carbohydr Polym 182:98–105. https://doi.org/10.1016/j.carbpol.2017.10.099CrossRefPubMed

Morsi NM, Nabil Shamma R, Osama Eladawy N, Abdelkhalek AA (2019) Bioactive injectable triple acting thermosensitive hydrogel enriched with nano-hydroxyapatite for bone regeneration: in-vitro characterization, Saos-2 cell line cell viability and osteogenic markers evaluation. Drug Dev Ind Pharm 45:787–804. https://doi.org/10.1080/03639045.2019.1572184CrossRefPubMed

Naumenko EA, Guryanov ID, Yendluri R et al (2016) Clay nanotube-biopolymer composite scaffolds for tissue engineering. Nanoscale 8:7257–7271. https://doi.org/10.1039/c6nr00641hCrossRefPubMed

Pan Q, Li N, Hong Y et al (2017) Halloysite clay nanotubes as effective nanocarriers for the adsorption and loading of vancomycin for sustained release. RSC Adv 7:21352–21359. https://doi.org/10.1039/C7RA00376ECrossRef

Pietraszek A, Karewicz A, Widnic M et al (2019) Halloysite-alkaline phosphatase system-A potential bioactive component of scaffold for bone tissue engineering. Colloids Surf B Biointerfaces 173:1–8. https://doi.org/10.1016/j.colsurfb.2018.09.040CrossRefPubMed

Rangabhatla ASL, Tantishaiyakul V, Oungbho K, Boonrat O (2016) Fabrication of pluronic and methylcellulose for etidronate delivery and their application for osteogenesis. Int J Pharm 499:110–118. https://doi.org/10.1016/j.ijpharm.2015.12.070CrossRefPubMed

Roushangar Zineh B, Shabgard MR, Roshangar L (2018) Mechanical and biological performance of printed alginate/methylcellulose/halloysite nanotube/polyvinylidene fluoride bio-scaffolds. Mater Sci Eng C Mater Biol Appl 92:779–789. https://doi.org/10.1016/j.msec.2018.07.035CrossRefPubMed

Satué M, del Arriero MM, Monjo M, Ramis JM (2013) Quercitrin and taxifolin stimulate osteoblast differentiation in MC3T3-E1 cells and inhibit osteoclastogenesis in RAW 264.7 cells. Biochem Pharmacol 86:1476–1486. https://doi.org/10.1016/j.bcp.2013.09.009CrossRefPubMed

Sedghi R, Shaabani A, Sayyari N (2020) Electrospun triazole-based chitosan nanofibers as a novel scaffolds for bone tissue repair and regeneration. Carbohydr Polym 230:115707. https://doi.org/10.1016/j.carbpol.2019.115707CrossRefPubMed

Shikov AN, Pozharitskaya ON, Miroshnyk I et al (2009) Nanodispersions of taxifolin: impact of solid-state properties on dissolution behavior. Int J Pharm 377:148–152. https://doi.org/10.1016/j.ijpharm.2009.04.044CrossRefPubMed

Sunil C, Xu B (2019) An insight into the health-promoting effects of taxifolin (dihydroquercetin). Phytochemistry 166:112066. https://doi.org/10.1016/j.phytochem.2019.112066CrossRefPubMed

Tang Y, Wang X, Li Y et al (2010) Production and characterisation of novel injectable chitosan/methylcellulose/salt blend hydrogels with potential application as tissue engineering scaffolds. Carbohydr Polym 82:833–841. https://doi.org/10.1016/j.carbpol.2010.06.003CrossRef

Tarahovsky YS, Selezneva II, Vasilieva NA et al (2007) Acceleration of fibril formation and thermal stabilization of collagen fibrils in the presence of taxifolin (dihydroquercetin). Bull Exp Biol Med 144:791–794. https://doi.org/10.1007/s10517-007-0433-zCrossRefPubMed

Terekhov RP, Selivanova IA, Tyukavkina NA et al (2020) Assembling the puzzle of taxifolin polymorphism. Molecules. https://doi.org/10.3390/molecules25225437CrossRefPubMedPubMedCentral

Tian F, Hosseinkhani H, Hosseinkhani M et al (2008) Quantitative analysis of cell adhesion on aligned micro- and nanofibers. J Biomed Mater Res Part A 84A:291–299. https://doi.org/10.1002/jbm.a.31304CrossRef

Vergaro V, Abdullayev E, Lvov YM et al (2010) Cytocompatibility and uptake of halloysite clay nanotubes. Biomacromolecules 11:820–826. https://doi.org/10.1021/bm9014446CrossRefPubMed

Vergaro V, Lvov YM, Leporatti S (2012) Halloysite clay nanotubes for resveratrol delivery to cancer cells. Macromol Biosci 12:1265–1271. https://doi.org/10.1002/mabi.201200121CrossRefPubMed

Walmsley GG, Ransom RC, Zielins ER et al (2016) Stem cells in bone regeneration. Stem Cell Rev Rep 12:524–529. https://doi.org/10.1007/s12015-016-9665-5CrossRefPubMed

Wang Y-J, Zhang H-Q, Han H-L et al (2017) Taxifolin enhances osteogenic differentiation of human bone marrow mesenchymal stem cells partially via NF-κB pathway. Biochem Biophys Res Commun 490:36–43. https://doi.org/10.1016/j.bbrc.2017.06.002CrossRefPubMed

Wasupalli GK, Verma D (2020) Injectable and thermosensitive nanofibrous hydrogel for bone tissue engineering. Mater Sci Eng C Mater Biol Appl 107:110343. https://doi.org/10.1016/j.msec.2019.110343CrossRefPubMed

Welch AA, Hardcastle AC (2014) The effects of flavonoids on bone. Curr Osteoporos Rep 12:205–210. https://doi.org/10.1007/s11914-014-0212-5CrossRefPubMed

Wu Y, Zhang Y, Ju J et al (2019) Advances in halloysite nanotubes-polysaccharide nanocomposite preparation and applications. Polym (Basel). https://doi.org/10.3390/polym11060987CrossRefPubMedCentral

Zhang H-Q, Wang Y-J, Yang G-T et al (2019) Taxifolin inhibits receptor activator of NF-κB ligand-induced osteoclastogenesis of human bone marrow-derived macrophages in vitro and prevents lipopolysaccharide-induced bone loss in vivo. Pharmacology 103:101–109. https://doi.org/10.1159/000495254CrossRefPubMed

Zhou W, Guo B, Liu M et al (2009) Poly(vinyl alcohol)/Halloysite nanotubes bionanocomposite films: Properties and in vitro osteoblasts and fibroblasts response. J Biomed Mater Res A 93:1574–1587. https://doi.org/10.1002/jbm.a.32656CrossRef

Zhu J, Marchant RE (2011) Design properties of hydrogel tissue-engineering scaffolds. Expert Rev Med Devices 8:607–626. https://doi.org/10.1586/erd.11.27CrossRefPubMedPubMedCentral

Zu S, Yang L, Huang J et al (2012) Micronization of taxifolin by supercritical antisolvent process and evaluation of radical scavenging activity. Int J Mol Sci 13:8869–8881. https://doi.org/10.3390/ijms13078869CrossRefPubMedPubMedCentral

Zu Y, Wu W, Zhao X et al (2014) The high water solubility of inclusion complex of taxifolin-γ-CD prepared and characterized by the emulsion solvent evaporation and the freeze drying combination method. Int J Pharm 477:148–158. https://doi.org/10.1016/j.ijpharm.2014.10.027CrossRefPubMed

Zu Y, Wu W, Zhao X et al (2014) Enhancement of solubility, antioxidant ability and bioavailability of taxifolin nanoparticles by liquid antisolvent precipitation technique. Int J Pharm 471:366–376. https://doi.org/10.1016/j.ijpharm.2014.05.049CrossRefPubMed

Title: Thermo-responsive hydrogels based on methylcellulose/Persian gum loaded with taxifolin enhance bone regeneration: an in vitro/in vivo study
Authors: Zahra Sadat Sajadi-Javan
Jaleh Varshosaz
Mina Mirian
Maziar Manshaei
Atousa Aminzadeh
Publication date: 24-01-2022
Publisher: Springer Netherlands
Published in: Cellulose / Issue 4/2022
Print ISSN: 0969-0239
Electronic ISSN: 1572-882X
DOI: https://doi.org/10.1007/s10570-021-04383-8

Springer Professional

Abstract

Graphical abstract

Please log in to get access to your license.

Dont have a licence yet? Then find out more about our products and how to get one now:

Springer Professional "Technik"

Springer Professional "Wirtschaft+Technik"

Other articles of this Issue 4/2022

Conversion of cellulose into 5-hydroxymethylfurfural in an H2O/tetrahydrofuran/cyclohexane biphasic system with Al2(SO4)3 as the catalyst

Chitosan-covalent organic framework dual-layer membrane with high efficiency of iodine capture

A natural antibacterial agent based on modified chitosan by hinokitiol for antibacterial application on cotton fabric

Fabrication of a 2,6-diaminopurine-grafted cellulose nanocrystal composite with high proton conductivity

Green nanoarchitectonics for next generation electronics devices: patterning of conductive nanowires on regenerated cellulose substrates

Correction to: A facile approach for the synthesis of spinel zinc ferrite/cellulose as an effective photocatalyst for the degradation of methylene blue in aqueous solution