Electrospun homogeneous silk fibroin/poly (ɛ-caprolactone) nanofibrous scaffolds by addition of acetic acid for tissue engineering

Abstract

In this study, we investigated the phase separation phenomenon of silk fibroin/poly (ɛ-caprolactone) electrospinning solution to improve the performance of silk fibroin/poly (ɛ-caprolactone) electrospun nanofibers. It showed that phase separation does occur in just a few hours in the silk fibroin/poly (ɛ-caprolactone)/formic acid mixture solution. Acetic acid, small molecule nonsolvent for silk fibroin, was first introduced to silk fibroin/poly (ɛ-caprolactone)/formic acid solution, a homogeneous solution without separation for over several days was achieved after mixing for 5 h. The morphology and composition of the silk fibroin/poly (ɛ-caprolactone) and acetic acid-modified silk fibroin/poly (ɛ-caprolactone) fibrous scaffolds were examined by scanning electron microscopy, Fourier transform infrared spectroscopy and thermal gravimetric analyzer. Attachment and proliferation of mouse osteoblast MC3T3-E1 cells were tested by scanning electron microscopy and cytotoxity assay. The results indicated that the phase separation of silk fibroin/poly (ɛ-caprolactone) solution might led to inhomogeneous morphology and composition of the composite scaffolds, and the inhomogeneity of the silk fibroin/poly (ɛ-caprolactone) scaffolds with formic acid as solvent had a remarkable difference on cell adhesion and proliferation. In contrast, there was no significant difference among the silk fibroin/poly (ɛ-caprolactone) scaffolds with formic acid/acetic acid as solvent because of their good consistency in fiber morphology and composition. These obtained silk fibroin/poly (ɛ-caprolactone) nanofibers had small average diameter of 190 ± 40 nm. The obtained results proved that this study provided a facile and effective approach to achieve compositionally homogeneous silk fibroin/poly (ɛ-caprolactone) scaffolds with formic acid as solvent for effective applications.

Keywords

Electrospinning silk fibroin poly (ɛ-caprolactone)formic acid acetic acid phase separation

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References

Goldberg

Langer

Jia

. Nanostructured materials for applications in drug delivery and tissue engineering. J Biomater Sci Polym Ed 2007; 18: 241–268.

Agarwal

Wendorff

Greiner

. Use of electrospinning technique for biomedical applications. Polymer 2008; 49: 5603–5621.

Barnes

Sell

Boland

. Nanofiber technology: designing the next generation of tissue engineering scaffolds. Adv Drug Deliv Rev 2007; 59: 1413–1433.

Wang

Zhang

Shao

. Electrospinning system with tunable collector for fabricating three-dimensional nanofibrous structures. Micro Nano Lett 2014; 9: 24–27.

Reneker

Yarin

. Electrospinning jets and polymer nanofibers. Polymer 2008; 49: 2387–2425.

Greiner

Wendorff

. Electrospinning: A fascinating method for the preparation of ultrathin fibers. Angew Chem Int Ed 2007; 46: 5671–5703.

Sill

von Recum

. Electrospinning: applications in drug delivery and tissue engineering. Biomaterials 2008; 29: 1989–2006.

Khadka

Haynie

. Insoluble synthetic polypeptide mats from aqueous solution by electrospinning. ACS Appl Mater Interfaces 2010; 2: 2728–2732.

Bhattarai

Gunn

. Natural-synthetic polyblend nanofibers for biomedical applications. Adv Mater 2009; 21: 2792–2797.

10.

Feng

Duan

. Effect of inhomogeneity of the electrospun fibrous scaffolds of gelatin/polycaprolactone hybrid on cell proliferation. J Biomed Mater Res A 2015; 103: 431–438.

11.

Feng

Yuan

. Acetic-acid-mediated miscibility toward electrospinning homogeneous composite nanofibers of GT/PCL. Biomacromolecules 2012; 13: 3917–3925.

12.

Zhang

Feng

Huang

. Fabrication of porous electrospun nanofibres. Nanotechnology 2006; 17: 901–908.

13.

Powell

Boyce

. Engineered human skin fabricated using electrospun collagen–PCL blends: morphogenesis and mechanical properties. Tissue Eng Part A 2009; 15: 2177–2187.

14.

Kwon

Matsuda

. Co-electrospun nanofiber fabrics of poly (L-lactide-co-ɛ-caprolactone) with type I collagen or heparin. Biomacromolecules 2005; 6: 2096–2105.

15.

Cho

. Molecular weight distribution and solution properties of silk fibroins with different dissolution conditions. Int J Biol Macromol 2012; 51: 336–341.

16.

Park

. Electrospun silk fibroin scaffolds with macropores for bone regeneration: an in vitro and in vivo study. Tissue Eng Part A 2010; 16: 1271–1279.

17.

Park

Kim

. Development of 3-D nanofibrous fibroin scaffold with high porosity by electrospinning: implications for bone regeneration. Biotechnol Lett 2008; 30: 405–410.

18.

Chutipakdeevong

Ruktanonchai

Supaphol

. Hybrid biomimetic electrospun fibrous mats derived from poly (ɛ-caprolactone) and silk fibroin protein for wound dressing application. J Appl Polym Sci 2015; 132: Article ID 41653–Article ID 41653.

19.

Chen

Ahmed

EIS

. Dexamethasone loaded core–shell SF/PEO nanofibers via green electrospinning reduced endothelial cells inflammatory damage. Colloids Surf B Biointerfaces 2015; 126: 561–568.

20.

Qiao

Sun

. Mechanical and viscoelastic properties of novel silk fibroin fiber/poly (ɛ-caprolactone) biocomposites. J Appl Polym Sci 2008; 110: 134–139.

21.

Buasri

Chaiyut

Loryuenyong

. Mechanical and thermal properties of silk fiber reinforced poly (lactic acid) biocomposites. Optoelectron Adv Mat 2013; 7: 938–942.

22.

Zhang

. Current research on electrospinning of silk fibroin and its blends with natural and synthetic biodegradable polymers. Front Mater Sci 2013; 7: 129–142.

23.

Zhang

Yin

Huang

. Degradation of electrospun SF/P (LLA-CL) blended nanofibrous scaffolds in vitro. Polym Degrad Stabil 2011; 96: 2266–2275.

24.

Zhang

Wang

Huang

. Fabrication of silk fibroin blended P (LLA-CL) nanofibrous scaffolds for tissue engineering. J Biomed Mater Res A 2010; 93: 984–993.

25.

Gunn

Zhang

. Polyblend nanofibers for biomedical applications: perspectives and challenges. Trends Biotechnol 2010; 28: 189–197.

26.

Lim

Kim

. Fabrication and evaluation of poly (epsilon-caprolactone)/silk fibroin blend nanofibrous scaffold. Biopolymers 2012; 97: 265–275.

27.

Yuan

Shi

Qiu

. Mechanical property and biological performance of electrospun silk fibroin-polycaprolactone scaffolds with aligned fibers. J Biomater Sci Polym Ed 2016; 27: 263–275.

28.

Sridhar

Venugopal

Sridhar

. Cardiogenic differentiation of mesenchymal stem cells with gold nanoparticle loaded functionalized nanofibers. Colloids Surf B Biointerfaces 2015; 134: 346–354.

29.

Chen

Zhu

. Promoting epithelium regeneration for esophageal tissue engineering through basement membrane reconstitution. ACS Appl Mater Interfaces 2014; 6: 4954–4964.

30.

Kim

Park

Kim

. Effect of nanofiber content on bone regeneration of silk fibroin/poly (ɛ-caprolactone) nano/microfibrous composite scaffolds. Int J Nanomed 2015; 10: 485–502.

31.

McClure

Sell

Ayres

. Electrospinning-aligned and random polydioxanone–polycaprolactone–silk fibroin-blended scaffolds: geometry for a vascular matrix. Biomed Mater 2009; 4: 6142–6149.

32.

Wolfe

Madurantakam

Garg

. Evaluation of thrombogenic potential of electrospun bioresorbable vascular graft materials: acute monocyte tissue factor expression. J Biomed Mater Res A 2010; 92: 1321–1328.

33.

Pham

Sharma

Mikos

. Electrospun poly(ɛ-caprolactone) microfiber and multilayer nanofiber/microfiber scaffolds: Characterization of scaffolds and measurement of cellular infiltration. Biomacromolecules 2006; 7: 2796–2805.

34.

Kumbar

Nukavarapu

James

. Electrospun poly(lactic acid- co -glycolic acid) scaffolds for skin tissue engineering. Biomaterials 2008; 29: 4100–4107.

35.

Wang

. Electrospun silk fibroin nanofibers in different diameters support neurite outgrowth and promote astrocyte migration. J Biomed Mater Res A 2013; 101: 2667–2678.

36.

Kumbar

James

Nukavarapu

. Electrospun nanofiber scaffolds: engineering soft tissues. Biomed Mater 2008; 3: 3750–3756.

37.

Jeong

Lee

Park

. Effect of solvent on the characteristics of electrospun regenerated silk fibroin nanofibers. Key Eng Mater 2007; 342–343: 813–816.

38.

Noh

Lee

Kim

. Electrospinning of chitin nanofibers: Degradation behavior and cellular response to normal human keratinocytes and fibroblasts. Biomaterials 2006; 27: 3934–3944.

39.

Katsogiannis

KAG

Vladisavljević

Georgiadou

. Porous electrospun polycaprolactone (PCL) fibres by phase separation. Eur Polym J 2015; 69: 284–295.

40.

Kim

Hyun

. Electrospun three-dimensional silk fibroin nanofibrous scaffold. J Appl Polym Sci 2007; 106: 3922–3928.

41.

Hanaor

Michelazzi

Leonelli

. The effects of carboxylic acids on the aqueous dispersion and electrophoretic deposition of ZrO₂. J Eur Ceram Soc 2012; 32: 235–244.

42.

Kim

Park

Hammond

. Hydrogen-bonding layer-by-layer assembled biodegradable polymeric micelles as drug delivery vehicles from surfaces. Acs Nano 2008; 2: 386–392.

43.

Miroiu

Stefan

Visan

. Composite biodegradable biopolymer coatings of silk fibroin–Poly (3-hydroxybutyric-acid-co-3-hydroxyvaleric-acid) for biomedical applications. Appl Surf Sci 2015; 355: 1123–1131.

44.

Ouyang

Sun

. The antioxidant activities and the amino acid analysis of soybean protein hydrolysates. Food Sci Technol 2015; 40: 263–267.

45.

Tan

Han

. Fabrication of silk fibroin/cellulose whiskers–chitosan composite porous scaffolds by layer-by-layer assembly for application in bone tissue engineering. J Mater Sci 2016; 51: 4399–4410.

46.

Chen

Lai

. Preparation and characterization of biomimetic silk fibroin/chitosan composite nanofibers by electrospinning for osteoblasts culture. Nanoscale Res Lett 2012; 7: 1–11.

47.

Hofmann

Hagenmüller

Koch

. Control of in vitro tissue-engineered bone-like structures using human mesenchymal stem cells and porous silk scaffolds. Biomaterials 2007; 28: 1152–1162.

48.

Melke

Midha

Ghosh

. Silk fibroin as biomaterial for bone tissue engineering. Acta Biomater 2015; 31: 1–16.

49.

Ribeiro

Almeida

Martins

. Influence of different surface modification treatments on silk biotextiles for tissue engineering applications. J Biomed Mater Res Part B 2016; 104B: 496–507.

50.

Xiao

Nichol

. Synthesis and characterization of photocrosslinkable gelatin and silk fibroin interpenetrating polymer network hydrogels. Acta Biomater 2011; 7: 2384–2393.

51.

Wang

Zhang

Wang

. Fabrication and properties of the electrospun polylactide/silk fibroin-gelatin composite tubular scaffold. Biomacromolecules 2009; 10: 2240–2244.

52.

Zhang

Chen

. Electrospun scaffolds from silk fibroin and their cellular compatibility. J Biomed Mater Res Part A 2009; 93: 976–983.

53.

Cui

Wang

. Biomimetic composite scaffolds based on mineralization of hydroxyapatite on electrospun poly(ɛ-caprolactone)/nanocellulose fibers. Carbohydr Polym 2016; 143: 270–278.

54.

Qian

Jiang

. The use of hyaluronan to regulate protein adsorption and cell infiltration in nanofibrous scaffolds. Biomaterials 2012; 33: 3428–3445.