Comparison of silk fibroin electrospun scaffolds with poloxamer and honey additives for burn wound applications

Abstract

A primary aim in wound-healing research is to construct an inexpensive, biodegradable dermal regeneration template with heightened moisture retention and permeability properties. The presence of moisture is important for optimal burn wound healing as it creates an environment for re-epithelialization and minimizes the risk of infections. Permeability can be achieved through a process known as electrospinning. This scaffold fabrication technique creates a mat of randomly oriented nanofibers that can readily mimic native extracellular matrix. Novel electrospun silk fibroin scaffolds were fabricated with poloxamer 407 (P407) and Manuka honey additives for a burn wound dermal regeneration template application. Enhanced human dermal fibroblast adhesion and cell infiltration were observed with the inclusion of P407, and scaffolds incorporated with Manuka honey demonstrated increased water uptake and a higher cell density within the scaffolds at the end of a 28-day period. Overall, this study established that both the silk fibroin/P407 and silk fibroin/Manuka honey scaffolds have the potential to be successful dermal regeneration templates, with P407 increasing surface wettability and Manuka honey modulating moisture retention.

Keywords

Silk fibroin electrospinning dermal regeneration template Manuka honey poloxamer

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References

Pan

Liu

Sun

et al . Preparation and characterization of electrospun PLCL/Poloxamer nanofibers and dextran/gelatin hydrogels for skin tissue engineering. PLoS ONE 2014; 9(11): e112885.

Moyer

Yezhelyev

Ingram

WL.

Bilayer dermal matrix for the treatment of painful burn scars. Wounds 2011; 23(8): 236–242.

Shores

Gabriel

Gupta

Skin substitutes and alternatives: a review. Adv Skin Wound Care 2007: 20(9 Pt. 1): 493–508; quiz 509–510.

Woodroof

EA.

The search for an ideal temporary skin substitute: AWBAT. Eplasty 2009; 9: e10.

Halim

Khoo

Mohd Yussof

SJ.

Biologic and synthetic skin substitutes: an overview. Indian J Plast Surg 2010. 43(Suppl): S23–S28.

Zhong

Zhang

Lim

CT.

Tissue scaffolds for skin wound healing and dermal reconstruction. Wiley Interdiscip Rev Nanomed Nanobiotechnol 2010; 2(5): 510–525.

Rho

Jeong

Lee

et al . Electrospinning of collagen nanofibers: effects on the behavior of normal human keratinocytes and early-stage wound healing. Biomaterials 2006; 27(8): 1452–1461.

Matthews

Wnek

Simpson

et al . Electrospinning of collagen nanofibers. Biomacromolecules 2002; 3(2): 232–238.

Sell

Wolfe

Garg

et al . The use of natural polymers in tissue engineering: a focus on electrospun extracellular matrix analogues. Polymers 2010; 2(4): 522.

10.

Pham

Sharma

Mikos

AG.

Electrospinning of polymeric nanofibers for tissue engineering applications: a review. Tissue Eng 2006; 12(5): 1197–1211.

11.

Bhardwaj

Kundu

SC.

Electrospinning: a fascinating fiber fabrication technique. Biotechnol Adv 2010; 28(3): 325–347.

12.

Lannutti

Reneker

et al . Electrospinning for tissue engineering scaffolds. Mater Sci Eng 2007; 27(3): 504–509.

13.

Ingavle

Leach

JK.

Advancements in electrospinning of polymeric nanofibrous scaffolds for tissue engineering. Tissue Eng Part B Rev 2014; 20(4): 277–293.

14.

El-Hadidy

Bhaa

et al . Role of epidermal stem cells in repair of partial-thickness burn injury after using Moist Exposed Burn Ointment (MEBO((R))) histological and immunohistochemical study. Tissue Cell 2014; 46(2): 144–151.

15.

Rockwood

Preda

Yücel

et al . Materials fabrication from Bombyx mori silk fibroin. Nat Protoc 2011; 6(10): 1612–1631.

16.

Min

B-M

Lee

Kim

et al . Electrospinning of silk fibroin nanofibers and its effect on the adhesion and spreading of normal human keratinocytes and fibroblasts in vitro. Biomaterials 2004; 25(7–8): 1289–1297.

17.

Vepari

Kaplan

DL.

Silk as a biomaterial. Prog Polym Sci 2007; 32(8–9): 991–1007.

18.

Quan

et al . Electrospun poly (ɛ-caprolactone)/silk fibroin core-sheath nanofibers and their potential applications in tissue engineering and drug release. Int J Biol Macromol 2011; 49(2): 223–232.

19.

Samal

Kaplan

Chiellini

Ultrasound sonication effects on silk fibroin protein. Macromol Mater Eng 2013; 298(11): 1201–1208.

20.

Batrakova

Kabanov

AV.

Pluronic block copolymers: evolution of drug delivery concept from inert nanocarriers to biological response modifiers. J Control Release 2008; 130(2): 98–106.

21.

Webb

Hlady

Tresco

PA.

Relative importance of surface wettability and charged functional groups on NIH 3T3 fibroblast attachment, spreading, and cytoskeletal organization. J Biomed Mater Res 1998; 41(3): 422–430.

22.

Ruardy

Schakenraad

Van der Mei

et al . Adhesion and spreading of human skin fibroblasts on physicochemically characterized gradient surfaces. J Biomed Mater Res 1995; 29(11): 1415–1423.

23.

Van der Valk

Van Pelt

AWJ

Busscher

et al . Interaction of fibroblasts and polymer surfaces: relationship between surface free energy and fibroblast spreading. J Biomed Mater Res 1983; 17(5): 807–817.

24.

Jeong

Bae

Lee

et al . Biodegradable block copolymers as injectable drug-delivery systems. Nature 1997; 388(6645): 860–862.

25.

Kwon

Han

Lee

et al . Biocompatibility of poloxamer hydrogel as an injectable intraocular lens: a pilot study. J Cataract Refract Surg 2005; 31(3): 607–613.

26.

Eteraf-Oskouei

Najafi

Traditional and modern uses of natural honey in human diseases: a review. Iran J Basic Med Sci 2013; 16(6): 731–742.

27.

Schmidlin

English

Duncan

et al . Antibacterial potential of Manuka honey against three oral bacteria in vitro. Swiss Dent J 2014; 124(9): 922–924.

28.

Mandal

Honey: its medicinal property and antibacterial activity. Asian Pac J Trop Biomed 2011; 1(2): 154–160.

29.

Jin

Chen

Karageorgiou

et al . Human bone marrow stromal cell responses on electrospun silk fibroin mats. Biomaterials 2004; 25(6): 1039–1047.

30.

Kadakia

Jain

Hixon

et al . Sonication induced silk fibroin cryogels for tissue engineering applications. Mater Res Express 2016; 3(5): 055401.

31.

Wongpanit

Tabata

Rujiravanit

Miscibility and biodegradability of silk fibroin/carboxymethyl chitin blend films. Macromol Biosci 2007; 7(12): 1258–1271.

32.

Zhang

Zuo

et al . Preparation and characterization of electrospun silk fibroin nanofiber with addition of 1-ethyl-3-(3-dimethylarainopropyl) carbodiimide. Polym Sci Ser A+ 2011; 53(5): 397–402.

33.

Kearns

MacIntosh

Crawford

et al . Silk-based biomaterials for tissue engineering. Top Tissue Eng 2008; 4(5): 1–19.

34.

Mandal

Kundu

SC.

Non-bioengineered silk fibroin protein 3D scaffolds for potential biotechnological and tissue engineering applications. Macromol Biosci 2008; 8(9): 807–818.

35.

Shyu

et al . Fabrication and characterization of a sponge-like asymmetric chitosan membrane as a wound dressing. Biomaterials 2001; 22(2): 165–173.

36.

Minden-Birkenmaier

Neuhalfen

Janowiak

et al . Preliminary investigation and characterization of electrospun polycaprolactone and manuka honey scaffolds for dermal repair. J Eng Fibers Fabrics 2015; 10(4): 126–138.

37.

Sell

Wolfe

Spence

et al . A preliminary study on the potential of manuka honey and platelet-rich plasma in wound healing. Int J Biomater 2012; 2012: 1–14.

38.

Sigma-Aldrich. Enzymatic method for determining hydroxyproline (Hydroxyproline assay), 2016, http://www.sigmaaldrich.com/technical-documents/protocols/biology/hydroxyproline-assay-kit-mak008.html

39.

Xia

et al . Controlled water vapor transmission rate promotes wound-healing via wound re-epithelialization and contraction enhancement. Sci Rep 2016; 6: 24596.

40.

Kliment

Englert

Crum

et al . A novel method for accurate collagen and biochemical assessment of pulmonary tissue utilizing one animal. Int J Clin Exp Pathol 2011; 4(4): 349–355.

41.

Wang

Effects of working parameters on electrospinning. In: Li

Wang

(eds) One-dimensional nanostructures: electrospinning technique and unique nanofibers. Berlin, Heidelberg: Springer, 2013, pp. 15–28.

42.

Pillay

Dott

Choonara

et al . A review of the effect of processing variables on the fabrication of electrospun nanofibers for drug delivery applications. J Nanomater 2013; 2013: 1–22.

43.

Imaizumi

Matsumoto

Suzuki

et al . Phenolic resin-based carbon thin fibers prepared by electrospinning: additive effects of poly(vinyl butyral) and electrolytes. Polym J 2009; 41(12): 1124–1128.

44.

Zhang

Zuo

Fan

et al . Mechanisms and control of silk-based electrospinning. Biomacromolecules 2012; 13(3): 798–804.

45.

Loh

Choong

Three-dimensional scaffolds for tissue engineering applications: role of porosity and pore size. Tissue Eng Part B Rev 2013; 19(6): 485–502.

46.

Harley

Yannas

. Skin Tissue Engineering for Regeneration. Encyclopedia of Medical Devices and Instrumentation 2006. DOI: 10.1002/0471732877.

47.

Hartman

Zhang

Adams

et al . Microfabricated electrospun collagen membranes for 3-D cancer models and drug screening applications. Biomacromolecules 2009; 10(8): 2019–2032.

48.

Newton

Mahajan

Ayres

et al . Regulation of material properties in electrospun scaffolds: role of cross-linking and fiber tertiary structure. Acta biomater 2009; 5(1): 518–529.

49.

Pawlaczyk

Lelonkiewicz

Wieczorowski

Age-dependent biomechanical properties of the skin. Postȩpy Dermatol Alergol 2013; 30(5): 302–306.

50.

Lapeer

Gasson

Karri

Simulating plastic surgery: from human skin tensile tests, through hyperelastic finite element models to real-time haptics. Prog Biophys Mol Biol 2010; 103(2–3): 208–216.

51.

Zhou

Xie

Knight

et al . Effects of pH and calcium ions on the conformational transitions in silk fibroin using 2D Raman correlation spectroscopy and 13C solid-state NMR. Biochemistry 2004; 43(35): 11302–11311.

52.

Zhou

Cao

et al . In vitro and in vivo degradation behavior of aqueous-derived electrospun silk fibroin scaffolds. Polym Degrad Stabil 2010; 95(9): 1679–1685.

53.

Lamke

Nilsson

Reithner

HL.

The evaporative water loss from burns and the water-vapour permeability of grafts and artificial membranes used in the treatment of burns. Burns 1977; 3(3): 159–165.

54.

Queen

Gaylor

JDS

Evans

et al . The preclinical evaluation of the water vapour transmission rate through burn wound dressings. Biomaterials 1987; 8(5): 367–371.

55.

Wright

Andric

Freeman

JW.

Utilizing NaCl to increase the porosity of electrospun materials. Mater Sci Eng 2011; 31(1): 30–36.

56.

McClure

Wolfe

Simpson

et al . The use of air-flow impedance to control fiber deposition patterns during electrospinning. Biomaterials 2012; 33(3): 771–779.

57.

Giliberti

White

Dee

KC.

Control of cell-biomaterial interactions. In: Dumitriu

(ed.) Polymeric biomaterials, revised and expanded. New York: CRC Press, 2001, pp. 361–376

58.

Förch

Schönherr

Tobias

et al . Appendix C: contact angle goniometry. In: Förch

Schönherr

Tobias

et al . (eds) Surface design: applications in bioscience and nanotechnology. New York: Wiley, 2009, pp. 471–473.

59.

Kim

J-H

Yoon

J-Y

. Protein adsorption on polymer particles. Ency Sur Colloid Sci 2002; 1: 4373-4381.

60.

Yaghoobi

Kazerouni

Evidence for clinical use of honey in wound healing as an anti-bacterial, anti-inflammatory anti-oxidant and anti-viral agent: a review. Jundishapur J Nat Pharm Prod 2013; 8(3): 100–104.