Abstract
In this study, blend nanofibrous scaffolds were electrospun from polycaprolactone/gelatin (PCL/Gel) blend solutions reinforced by bone morphogenetic protein (BMP)-modified graphene oxide (GO). SEM results showed that uniform and bead-less nanofibers with 270 nm average diameter were obtained from electrospun of PCL/Gel blend solutions. Tensile strength test and contact angle measurement demonstrated that addition of PCL led to higher mechanical and physical properties of the resulting nanofibers. The addition of PCL as well as GO in the blend supports the suitable mechanical strength in the body media. The loading of BMP-modified graphene in the Gel/PCL structure caused the formation of nanofibrous substrate with great resemblance to bone tissue. Gel/PCL-G hybrid nanofibers revealed good biocompatibility in the presence of human osteosarcoma cells, and no trace of cellular toxicity was observed. The cells grown on the scaffolds exhibited a spindle-like and broad morphology and almost uniformly covered the entire nanofiber scaffold.
Graphical abstract
Gel/PCL nanofibers reinforced by graphene oxide-immobilized bone morphogenetic protein was prepared as a promising safe and biocompatible nanofiber with high antibacterial activity for bone tissue engineering.
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Goudarzi ZM, Behzad T, Ghasemi-Mobarakeh L, Kharaziha M (2021) An investigation into influence of acetylated cellulose nanofibers on properties of PCL/Gelatin electrospun nanofibrous scaffold for soft tissue engineering. Polymer 213:123313
Kichi MK, Torkaman R, Mohammadi H, Toutounchi A, Kharaziha M, Alihosseini F (2020) Electrochemical and in vitro bioactivity behavior of poly (ε-caprolactone)(PCL)-gelatin-forsterite nano coating on titanium for biomedical application. Mater Today Commun 24:101326
Parham S, Kharazi AZ, Bakhsheshi-Rad HR, Ghayour H, Ismail AF, Nur H, Berto F (2020) Electrospun nano-fibers for biomedical and tissue engineering applications: a comprehensive review. Materials 13:2153
Liu J, Zou Q, Wang C, Lin M, Li Y, Zhang R, Li Y (2021) Electrospinning and 3D printed hybrid bi-layer scaffold for guided bone regeneration. Mater Des 210:110047
Ghosal K, Chandra A, Praveen G, Snigdha S, Roy S, Agatemor C, Thomas S, Provaznik I (2018) Electrospinning over solvent casting: tuning of mechanical properties of membranes. Sci Rep 8:1–9
Ghosal K, Kováčová M, Humpolíček P, Vajďák J, Bodík M, Špitalský Z (2021) Antibacterial photodynamic activity of hydrophobic carbon quantum dots and polycaprolactone based nanocomposite processed via both electrospinning and solvent casting method. Photodiagn Photodyn Ther 35:102455
Ghosal K, Manakhov A, Zajíčková L, Thomas S (2017) Structural and surface compatibility study of modified electrospun poly (ε-caprolactone)(PCL) composites for skin tissue engineering. AAPS PharmSciTech 18:72–81
Ghosal K, Thomas S, Kalarikkal N, Gnanamani A (2014) Collagen coated electrospun polycaprolactone (PCL) with titanium dioxide (TiO2) from an environmentally benign solvent: preliminary physico-chemical studies for skin substitute. J Polym Res 21:1–5
Ghosal K, Ghosh D, Das SK (2018) Preparation and evaluation of naringin-loaded polycaprolactone microspheres based oral suspension using Box-Behnken design. J Mol Liq 256:49–57
Gautam S, Sharma C, Purohit SD, Singh H, Dinda AK, Potdar PD, Chou CF, Mishra NC (2021) Gelatin-polycaprolactone-nanohydroxyapatite electrospun nanocomposite scaffold for bone tissue engineering. Mater Sci Eng C 119:111588
Bochicchio B, Barbaro K, De Bonis A, Rau JV, Pepe A (2020) Electrospun poly (d, l-lactide)/gelatin/glass-ceramics tricomponent nanofibrous scaffold for bone tissue engineering. J Biomed Mater Res Part A 108:1064–1076
Sharahi M, Hivechi A, Bahrami SH, Hemmatinejad N, Milan PB (2021) Co-electrospinning of lignocellulosic nanoparticles synthesized from walnut shells with poly (caprolactone) and gelatin for tissue engineering applications. Cellulose 28:4943–4957
Al-Baadani MA, Yie KHR, Al-Bishari AM, Alshobi BA, Zhou Z, Fang K, Dai B, Shen Y, Ma J, Liu J, Shen X (2021) Co-electrospinning polycaprolactone/gelatin membrane as a tunable drug delivery system for bone tissue regeneration. Mater Des 209:109962
Samadian H, Khastar H, Ehterami A, Salehi M (2021) Bioengineered 3D nanocomposite based on gold nanoparticles and gelatin nanofibers for bone regeneration: in vitro and in vivo study. Sci Rep 11:1–11
Aunkor MTH, Raihan T, Prodhan SH, Metselaar HSC, Malik SUF, Azad AK (2020) Antibacterial activity of graphene oxide nanosheet against multidrug resistant superbugs isolated from infected patients. Royal Soc Open Sci 7:200640
Mohammed H, Kumar A, Bekyarova E, Al-Hadeethi Y, Zhang X, Chen M, Ansari MS, Cochis A, Rimondini L (2020) Antimicrobial mechanisms and effectiveness of graphene and graphene-functionalized biomaterials. A scope review. Front Bioeng Biotechnol 8:465
Mann R, Mitsidis D, Xie Z, McNeilly O, Ng YH, Amal R, Gunawan C (2021) Antibacterial activity of reduced graphene oxide. J Nanomater. https://doi.org/10.1155/2021/9941577
Kazemnejadi M, Mahmoudi B, Sharafi Z, Nasseri MA, Allahresani A, Esmaeilpour M (2019) Synthesis and characterization of a new poly α-amino acid Co (II)-complex supported on magnetite graphene oxide as an efficient heterogeneous magnetically recyclable catalyst for efficient free-coreductant gram-scale epoxidation of olefins with molecular oxygen. J Organomet Chem 896:59–69
Kazemnejadi M, Mahmoudi B, Sharafi Z, Nasseri MA, Allahresani A, Esmaeilpour M (2020) Copper coordinated-poly (α-amino acid) decorated on magnetite graphene oxide as an efficient heterogeneous magnetically recoverable catalyst for the selective synthesis of 5-and 1-substituted tetrazoles from various sources: a comparative study. Appl Organomet Chem 34:e5273
Halim A, Luo Q, Ju Y, Song G (2018) A mini review focused on the recent applications of graphene oxide in stem cell growth and differentiation. Nanomaterials 8:736
Zhou T, Zhou X, Xing D (2014) Controlled release of doxorubicin from graphene oxide based charge-reversal nanocarrier. Biomaterials 35:4185–4194
Fakhrali A, Poursharifi N, Nasari M, Semnani D, Salehi H, Ghane M, Mohammadi S (2021) Fabrication and characterization of PCL/Gel nanofibrous scaffolds incorporated with graphene oxide applicable in cardiac tissue engineering. Polym-Plast Technol Mater 60:2025–2041
Rohaniyan M, Davoodnia A, Beyramabadi SA, Khojastehnezhad A (2019) Phosphomolybdic acid supported on Schiff base functionalized graphene oxide nanosheets: preparation, characterization, and first catalytic application in the multi-component synthesis of tetrahydrobenzo[a]xanthene-11-ones. Appl Organomet Chem 33:e4881
Prakash J, Prema D, Venkataprasanna KS, Balagangadharan K, Selvamurugan N, Venkatasubbu GD (2020) Nanocomposite chitosan film containing graphene oxide/hydroxyapatite/gold for bone tissue engineering. Int J Biol Macromol 154:62–71
Even J, Eskander M, Kang J (2012) Bone morphogenetic protein in spine surgery: current and future uses. J Am Acad Orthop Surg 20:547–552
Ong KL, Villarraga ML, Lau E, Carreon LY, Kurtz SM, Glassman SD (2010) Off-label use of bone morphogenetic proteins in the United States using administrative data. Spine 35:1794–1800
Bigi A, Boanini E (2017) Functionalized biomimetic calcium phosphates for bone tissue repair. J Appl Biomater Funct Mater 15:313–325
Shuai C, Peng B, Feng P, Yu L, Lai R, Min A (2022) In situ synthesis of hydroxyapatite nanorods on graphene oxide nanosheets and their reinforcement in biopolymer scaffold. J Adv Res 35:13–24
Kazemnejadi M, Alavi SA, Rezazadeh Z, Nasseri MA, Allahresani A, Esmaeilpour M (2020) Fe3O4@SiO2 nanoparticles–functionalized Cu(II) Schiff base complex with an imidazolium moiety as an efficient and eco-friendly bifunctional magnetically recoverable catalyst for the Strecker synthesis in aqueous media at room temperature. Appl Organomet Chem 34:e5388
Abbasi A, Nasef MM, Takeshi M, Faridi-Majidi R (2014) Electrospinning of nylon-6,6 solutions into nanofibers: Rheology and morphology relationships. Chin J Polym Sci 32:793–804
Le Moigne N, van Den Oever M, Budtova T (2011) A statistical analysis of fibre size and shape distribution after compounding in composites reinforced by natural fibres. Compos A 42:1542–1550
Kazemnejadi M, Shakeri A, Nikookar M, Shademani R, Mohammadi M (2018) Selective and metal-free epoxidation of terminal alkenes by heterogeneous polydioxirane in mild conditions. Royal Soc Open Sci 5:171541
Kazemnejadi M, Shakeri A, Nikookar M, Mohammadi M, Esmaeilpour M (2017) Co(II) Schiff base complex decorated on polysalicylaldehyde as an efficient, selective, heterogeneous and reusable catalyst for epoxidation of olefins in mild and self-coreductant conditions. Res Chem Intermed 43:6889–6910
Panahi F, Fareghi-Alamdari R, Khajeh Dangolani S, Khalafi-Nezhad A, Golestanzadeh M (2017) Graphene grafted N-methyl-4-pyridinamine (G-NMPA): an efficient heterogeneous organocatalyst for acetylation of alcohols. ChemistrySelect 2:474–479
Ilican S, Caglar Y, Caglar M, Yakuphanoglu F (2006) Electrical conductivity, optical and structural properties of indium-doped ZnO nanofiber thin film deposited by spray pyrolysis method. Phys E (Amsterdam, Neth) 35:131–138
Chawla S, Naraghi M, Davoudi A (2013) Effect of twist and porosity on the electrical conductivity of carbon nanofiber yarns. Nanotechnology 24:255708
Kim MH, An HW, Park KO, Yeo SI, Yang DJ, Park GB (2009) Biological evaluation of biodegradable PCL-BCP/PCL bi-layered GBR membrane. Bioceramics 22:703–706
Sheibley DW, LL Rieker LC Hsu, MA Manzo, U.S. Pat., 1982, 4,357,402.
Wan Y, Huang W, Wang Z, Zhu XX (2004) Preparation and characterization of high loading porous crosslinked poly(vinyl alcohol) resins. Polymer 45:71–77
Wang Z, Luo J, Zhu XX, Jin S, Tomaszewski MJ (2004) Functionalized cross-linked poly (vinyl alcohol) resins as reaction scavengers and as supports for solid-phase organic synthesis. J Comb Chem 6:961–966
Datkhile KD, Patil SR, Patil MN, Durgawale PP, Jagdale NJ, Deshmukh VN (2020) Studies on phytoconstituents, In vitro antioxidant, antibacterial, and cytotoxicity potential of Argemone mexicana Linn. (Family: Papaveraceae). J Nat Sci Biol Med 11:198
Chen ST, Faller EM, Kobata K, Fadli MA, Yeoh CS (2018) Effect of collagen-related compound on cell proliferation and matrix production with cultured human dermal fibroblasts. Int J Med Toxicol Leg Med 21:269–273
Kim SH, Lee HS, Ryu DS, Choi SJ, Lee DS (2011) Antibacterial activity of silver-nanoparticles against Staphylococcus aureus and Escherichia coli. Microbiol Biotechnol Lett 39:77–85
Birla SS, Tiwari VV, Gade AK, Ingle AP, Yadav AP, Rai MK (2009) Fabrication of silver nanoparticles by Phoma glomerata and its combined effect against Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus. Lett Appl Microbiol 48:173–179
Montevecchi M, Dorigo A, Cricca M, Checchi L (2013) Comparison of the antibacterial activity of an ozonated oil with chlorhexidine digluconate and povidone-iodine. A disk diffusion test. New Microbiol 36:289–302
Al-Shawi SG, Andreevna Alekhina N, Aravindhan S, Thangavelu L, Elena A, Viktorovna Kartamysheva N, Rafkatovna Zakieva R (2021) Synthesis of NiO nanoparticles and sulfur, and nitrogen co doped-graphene quantum dots/nio nanocomposites for antibacterial application. J Nanostruct 11:181–188
Bao Q, Zhang H, Yang JX, Wang S, Tang DY, Jose R, Ramakrishna R, Lim CT, Loh KP (2010) Graphene-polymer nanofiber membrane for ultrafast photonics. Adv Funct Mater 20:782–791
Şamlı M, Bayraktar O, Korel F (2014) Characterization of silk fibroin based films loaded with rutin–β-cyclodextrin inclusion complexes. J Incl Phenom Macrocycl Chem 80:37–49
Higashi T, Tajima A, Motoyama K, Arima H (2012) Cyclodextrin/poly(ethylene glycol) polypseudorotaxane hydrogels as a promising sustained-release system for lysozyme. J Pharm Sci 101:2891–2899
Marusic A, Grcevic D, Katavic V, Kovacic N, Lukic IK, Kalajzic I, Lorenzo JA (2000) Role of B lymphocytes in new bone formation. Lab Invest 80:1761–1774
Gao S, Guo W, Chen M, Yuan Z, Wang M, Zhang Y, Liu S, Xi T, Guo Q (2017) Fabrication and characterization of electrospun nanofibers composed of decellularized meniscus extracellular matrix and polycaprolactone for meniscus tissue engineering. J Mater Chem B 5:2273–2285
Dejob L, Toury B, Tadier S, Grémillard L, Gaillard C, Salles V (2021) Electrospinning of in situ synthesized silica-based and calcium phosphate bioceramics for applications in bone tissue engineering: A review. Acta Biomater 123:123–153
Siddiqui N, Kishori B, Rao S, Anjum M, Hemanth V, Das S, Jabbari E (2021) Electropsun polycaprolactone fibres in bone tissue engineering: a review. Mol Biotechnol 63:363–388
Ramazani S, Karimi M (2014) Electrospinning of poly(ε-caprolactone) solutions containing graphene oxide: effects of graphene oxide content and oxidation level. Polym Compos 37:131–140
Jin G, Li K (2014) The electrically conductive scaffold as the skeleton of stem cell niche in regenerative medicine. Mater Sci Eng C 45:671–681
Unal S, Arslan S, Gokce T, Atasoy BM, Karademir B, Oktar FN, Gunduz O (2019) Design and characterization of polycaprolactone-gelatin-graphene oxide scaffolds for drug influence on glioblastoma cells. Eur Polym J 115:157–165
Wan C, Chen B (2011) Poly(ε-caprolactone)/graphene oxide biocomposites: mechanical properties and bioactivity. Biomed Mater 6:055010
Tan GZ, Zhou Y (2020) Electrospinning of biomimetic fibrous scaffolds for tissue engineering: a review. Int J Polym Mater Polym Biomater 69:947–960
Tarafder S, Bose S (2014) Polycaprolactone-coated 3D printed tricalcium phosphate scaffolds for bone tissue engineering: in vitro alendronate release behavior and local delivery effect on in vivo osteogenesis. ACS Appl Mater Interfaces 6:9955–9965
Yu YH, Chan ChCh, Lai YCh, Lin YY, Huang YCh, Chi WF, Kuo ChW, Lin HM, Chen PCh (2014) Biocompatible electrospinning poly(vinyl alcohol) nanofibres embeddedwith graphene-based derivatives with enhanced conductivity, mechanical strength and thermal stability. RSC Adv 4:56373–56384
Luo Y, Shen H, Fang Y, Cao Y, Huang J, Zhang M, Dai J, Shi X, Zhang Z (2015) Enhanced proliferation and osteogenic differentiation of mesenchymal stem cells on graphene oxide-incorporated electrospun poly(lactic-co-glycolic acid) nanofibrous mats. ACS Appl Mater Interfaces 7:6331–6339
Sayyar S, Murray E, Thompson BC, Gambhir S, Officer DL, Wallace GG (2013) Covalently linked biocompatible graphene/ polycaprolactone composites for tissue engineering. Carbon 52:296–304
Ma H, Su W, Tai Z, Sun D, Yan X, Liu B, Xue Q (2012) Preparation and cytocompatibility of polylactic acid/ hydroxyapatite/graphene oxide nanocomposite fibrous membrane. Chin Sci Bull 57:3051–3058
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Kadhim, M.M., Bokov, D.O., Ansari, M.J. et al. Bone morphogenetic protein (BMP)-modified graphene oxide-reinforced polycaprolactone–gelatin nanofiber scaffolds for application in bone tissue engineering. Bioprocess Biosyst Eng 45, 981–997 (2022). https://doi.org/10.1007/s00449-022-02717-9
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DOI: https://doi.org/10.1007/s00449-022-02717-9