Electrospun silk biomaterial scaffolds for regenerative medicine

Abstract

Electrospinning is a versatile technique that enables the development of nanofiber-based biomaterial scaffolds. Scaffolds can be generated that are useful for tissue engineering and regenerative medicine since they mimic the nanoscale properties of certain fibrous components of the native extracellular matrix in tissues. Silk is a natural protein with excellent biocompatibility, remarkable mechanical properties as well as tailorable degradability. Integrating these protein polymer advantages with electrospinning results in scaffolds with combined biochemical, topographical and mechanical cues with versatility for a range of biomaterial, cell and tissue studies and applications. This review covers research related to electrospinning of silk, including process parameters, post treatment of the spun fibers, functionalization of nanofibers, and the potential applications for these material systems in regenerative medicine. Research challenges and future trends are also discussed.

Fig. 1

Schematic diagram of electrospinning setup.

Fig. 2

Scanning electron micrographs (A) and distributions of diameters (B) of non-woven silk fibers from of non-woven silk fibers from (a) 7 wt% silk/HFA solution, 1.3 kV/cm; (b) 5 wt% silk/HFA solution, 1.6 kV/cm; (c) 5 wt% silk/HFA solution, 1.0 kV/cm and (d) 3 wt% silk/HFA solution, 1.0 kV/cm. (From Ref. [68] with permission)

Fig. 3

Scanning electron micrographs of electrospun silk fibers with applied voltage at 20 kV and (A) 17%, (B) 28% and (C) 39%. (D) Rheological behavior of silk fibroin aqueous solutions with different concentrations. Scale bar = 1μm. (From Ref. [70] with permission)

Fig. 4

Effects of electrical field, polymer concentration and spinning distance on electrospun silk fiber diameter. (A) The relationship between fiber diameter and electrical field with concentration of 15% at spinning distances of 5, 7 and 10 cm. (B) The relationship between fiber diameter and silk concentration at three electric fields (2, 3, 4 kV/cm) with fixed spinning distance. (From Ref. [78] with permission)

Fig. 5

Effects of different solvent vapor treatment and temperature on confomational change of silk nanofiber. (A) Changes of area ratios of silk II and silk I structures (A_II/A_I) of the amide I region of silk nanofibers, determined from IR spectra during solvent vapor treatments at 35°C ((▲) water; (◆) methanol; (▼) ethanol; (●) propanol). (B) Changes in peak position of amide I band (β-sheet conformation) of regenerated silk nanofibers treated with water vapor at: (a) 25°C, (b) 35°C, (c) 45°C and (d) 55°C (From Ref. [94] with permission)

Fig. 6

Schematic of (A) side-by-side and (B) coaxial nozzle configurations. (From Ref. [18] with permission)

Fig. 7

Scanning electron micrographs of osteoblast attachment on (a–c) 2-D and (d–f) 3-D silk nanofibrous scaffolds 1 day after cell seeding. Scale bar = 100 μm. Arrows indicate pores and cells in the scaffolds. (From Ref. [100] with permission)

Fig. 8

TEM images of elctrospun silk/nHAP fibers. Scale bar = 0.2μm (From Ref. [104] with permission)

Fig. 9

SEM images of crystallized and PEO-extracted elctrospun silk nanofibers (a) before and (b) after the adsorption of the MWCNTs. (c) macroscopic images of non-woven silk membrane before (left) and afer (right) adsorption of the MWCNTs. (From Ref. [106] with permission)

Fig. 10

(A) Macroscopic image of tubular electrospun silk fibroin scaffold. (B) Internal pressure change of tubular scaffold as function of time. (C) Smooth muscle cell and (D) endothelial cell morphology on the electrospun silk mats stained with Live/Dead kit. (From Ref. [125] and [21] with permission)

Fig. 11

(A) Schematic structure of chitin/silk fibroin biocomponent nanofibrous scaffolds. (B) Cell attachment (a) and relative spreading area (b) of normal human keratinocytes on chitin/SF blend and hybrid nanofibrous matrices without coating for 0, 1, 3, and 7 days of culture. The relative spreading levels were obtained by normalize the spreading area with that from cells cultured on pure chitin nanofibrous matrix for 1 day. Data are expressed as the mean ± S.E. (n = 30). S.E.: standard error of the mean. (From Ref. [134] with permission)

Fig. 12

Histological observation of silk fibroin (SF) nanofiber membrane in rabbit calvarial defects: control group at (A) 4, (C) 8 and (E) 12 weeks (20 ×); SF nanofiber membrane implanted group at (B,H) 4, (D,I) 8 and (F,G) 12 weeks at (B,D,F) lower (20×) and (H,I,G) higher (100×) magnification. M: the SF nanofiber membrane; NB: new bone; OB: old bone; Arrow: wound edge. The samples were stained with multiple stain solution. (From Ref. [138] with permission)

Fig. 13

Comparison between SEM micrographs of hMSCs cultured on silk fibroin electrospun fibrous mats (a,b) without and (c–e) with incorporation of BMP-2 for 31 days. (From Ref. [104] with permission)