Engineering and optimisation of medically multi-functional mesoporous SiO2 fibers as effective wound...

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Engineering and optimisation of medically multi-functional mesoporous SiO2

fibers as effective wound dressing material†

Zhijun Ma,a Huijiao Ji,b Yu Teng,a Guoping Dong,cd Dezhi Tan,a Miaojia Guan,a Jiajia Zhou,a Junhua Xie,a

Jianrong Qiu*ac and Ming Zhang*b

Received 15th March 2011, Accepted 6th April 2011

DOI: 10.1039/c1jm11115a

In this paper, we propose a novel strategy for the preparation of flexible mesoporous SiO2 fibers

containing silver nanoparticles (Ag-cSiO2@mSiO2) as an effective wound dressing. The Ag-

cSiO2@mSiO2 was core–shell structured, composed of a condensed electrospun SiO2 nanofiber doped

with Ag NPs (silver nanoparticles) and a mesoporous SiO2 shell. Due to a high specific surface area and

large pore volume, the Ag-cSiO2@mSiO2 can substantially absorb exudates, the absorption capacity

for water and SBF (simulated body fluid) reached 267 wt% and 254 wt% of the sample, respectively.

Additionally, the mesopores can also act as hosts for the accommodation of drugs. The Loading

capacity of IBU (ibuprofen) reached up to 18 wt% of the sample, and its release was relatively fast, more

than 85% of the drug was released within 12 h. The condensed core of the SiO2 nanofiber not only

endowed the sample with a high flexibility, but also slowly released silver to possess a sustained

antibiotic effect. Considering its effective exudate-absorption ability, dual drug-release profiles (fast

release of IBU and sustained release of silver), together with its chemical and physical stability,

biocompatibility and high flexibility, Ag-cSiO2@mSiO2 could be a promising wound dressing material.

1. Introduction

In their daily lives, human beings are always under threat from

various kinds of infections. The skin plays an important role in

the prevention of infections from microbes and at the same time

keeping the homeostasis of the body. Once a trauma is suffered,

generally speaking, the damaged skin should be immediately

covered with a dressing. As a kind of high-quality wound

dressing, it should be able to maintain a moderately moist

environment for regeneration of the skin, prevent infection,

alleviate pain, allow gaseous exchange and remove excessive

exudates. In addition, a soft and flexible texture, chemical and

physical stability and biocompatibility are also required.1–3

However, wound dressing materials that are commercially

available only satisfy one or more of these standards. They are

aState Key Laboratory of Silicon Materials, Zhejiang University,Hangzhou, Zhejiang, 310027, People’s Republic of China. E-mail: [email protected]; Fax: +86-0571-88925079bCollege of Life Science, Zhejiang University, Hangzhou, 310058, People’sRepublic of China. E-mail: [email protected] Laboratory of Specially Functional Materials of Ministry ofEducation and Institute of Optical Communication Materials, SouthChina University of Technology, Guangzhou, Guangdong, 510640, P.R.ChinadShanghai Institute of Optics and Fine Mechanics, Chinese Academy ofSciences, Qinghe Road 390, Jiading District, Shanghai, 201800, People’sRepublic of China

† Electronic supplementary information (ESI) available. See DOI:10.1039/c1jm11115a

This journal is ª The Royal Society of Chemistry 2011

far from being ideal wound dressings. Recently, new investiga-

tions have been conducted on wound dressings with a dual drug

carrying-and-release ability.1,4–7 The biggest challenge in the

preparation of this kind of material is to obtain two different

drug release profiles (sustained release of antibiotic reagent and

fast release of anesthetic drugs) in one material.

Ordered mesoporous SiO2 is one kind of useful material for

diverse medical and biological applications, including bio-

separation,8,9 gene transfection,10,11 enzyme immobilization12,13

and drug delivery,14,15 due to its regular mesopores, large specific

surface area, high pore volume, stable chemical and physical

properties and biocompatibility. Its surface is hydrophilic and

can easily be functionalized with organic groups, due to the

existence of abundant hydroxyl groups.16,17,18 Recently, meso-

porous silica nanospheres, used for efficient haemorrhage

control, have been reported.18 The scheme of relevant investi-

gations were mainly based on the fast and abundant absorption

of blood by mesoporous silica nanospheres. Silver ions were also

added in mesoporous silica nanospheres using an ion exchanging

method to obtain an antibiotic effect. From this point, it seems

that mesoporous SiO2 fibers (MSFs) can perhaps be applied as

a kind of high-quality wound dressing material, now that they

actually satisfy several of the chief requirements for a prominent

wound dressing. However, MSFs prepared with traditional

methods, such as acidic hydrolyzing, mechanic drawing and

template self-assembly, are usually with an entirely homogeneous

mesoporous structure or not long enough.19–23 Consequently,

they are fragile rather than flexible, thus are difficult to be

J. Mater. Chem., 2011, 21, 9595–9602 | 9595

http://dx.doi.org/10.1039/c1jm11115a






http://pubs.rsc.org/en/journals/journal/JM

http://pubs.rsc.org/en/journals/journal/JM?issueid=JM021026

Fig. 1 Schematic illustration of the preparation process of the Ag-

cSiO2@mSiO2.

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patterned into a film for a wound dressing. In addition, such

a homogeneous mesoporous structure also made the different

release of antibiotic reagent and anesthetic drugs more difficult.

A new strategy has to be designed, beforeMSFs can be applied as

wound dressings.

To explore the possibility of using MSFs as wound dressings,

we proposed a novel design for the preparation of MSFs with

a soft and flexible texture and dual drug releasing profiles. The

MSF prepared in our investigation is continuously long and has

a core–shell structure. It is composed of a condensed core of SiO2

nanofiber prepared with electrospinning and a mesoporous SiO2

shell synthesized with a modified St€ober method. The condensed

SiO2 nanofiber not only provides a template for the formation of

the mesoporous shell but also endows the whole fiber with high

flexibility. The mesoporous SiO2 shell substantially enhances the

pore volume and the specific surface area of the fiber (which is

beneficial for the absorption of exudates or blood and prolifer-

ation of skin cells) and accommodates drugs. Silver nanoparticles

(Ag NPs) are incorporated in the condensed SiO2 nanofiber to

obtain a sustained antibiotic effect. The sample is denoted as Ag-

cSiO2@mSiO2 (‘‘c’’ means condensed and ‘‘m’’ means meso-

porous). We studied the morphology, structure and porosity of

the Ag-cSiO2@mSiO2. Meanwhile, we investigated its silver-

release profile and exudate-absorption ability. We also studied

the drug-loading capacity and release profile of the Ag-

cSiO2@mSiO2 using IBU (ibuprofen) as the model drug, and

evaluated its antibiotic ability with E. coli as the model

microorganism.

Materials and methods

2.1. Synthesis of precursor SiO2 solution

SiO2 solution was synthesized according to the method used in

ref. 24. In a typical process, TEOS (tetraethoxysilane, 30 mL)

and EtOH (ethanol, 30 mL) were mixed in a 100 mL glass vessel.

Then HCl (hydrochloric, 30 wt%, 4.8 mL) was added drop wise

through vigorous magnetic stirring. After being stirred for 30

min, the glass vessel was shifted into an oil bath, and the solution

was hydrolyzed under 80 �C until it was suitable for electro-

spinning. Then an ethanol solution of AgNO3 (silver nitrate)

with different concentrations (0, 0.05, 0.1 or 0.15 g silver nitrate

dissolved in 3 mL EtOH) was added with magnetic stirring for 5

min.

2.2. Electrospinning of Ag-cSiO2 nanofiber

Electrospinning was carried out in a home-made setup with

a motor controlled aluminum drum as the collector. Parameters

were set as follows: the feeding rate was 0.8 mL h�1; the applied

DC voltage was 12 kV; and the rotational speed of the collector

was 1000 rpm. The whole process proceeded under room

temperature and room humidity. After 1 h of collection, the

surface of the aluminum drum was covered by a thin layer of

white nanofiber, which was then peeled off and dried in air under

room temperature overnight. The obtained fiber was named as

xAg-cSiO2 (x ¼ 0, 0.05, 0.1 and 0.15, which meant that the

corresponding samples were prepared with the SiO2 solution

doped with 0 g, 0.05 g, 0.1 g and 0.15 g AgNO3, respectively, and

it is similar for the nomination of the following samples)

9596 | J. Mater. Chem., 2011, 21, 9595–9602

2.3. Fabrication of Ag-cSiO2@mSiO2 fiber

Electrospun xAg-cSiO2 fibers (0.15 g) were dispersed in a mixture

of ethanol (120 mL) and deionized water (75 mL) through

vigorous magnetic stirring, then CTAB (cetyltrimethy-

lammonium bromide, 0.36 g), NH3$H2O (ammonium hydroxide,

28 wt %, 0.4 mL) and TEOS (0.38 mL) were added sequentially.

The mixture was magnetically stirred under room temperature

for 4 h, then the fibers were separated out with filtration, washed

with ethanol and deionized water several times, then dried in air

under 120 �C for 5 h. Thoroughly dried fibers were heated to 600�C at a heating rate of 3 �C min�1 from room temperature and

then calcined at 600 �C for 2 h, and finally cooled to room

temperature in air. The fibers were further heated to 400 �C with

a heating rate of 5 �C min�1 from room temperature and

annealed at 400 �C for 2 h and finally cooled to room tempera-

ture in a reducing atmosphere (5% H2, 95% N2) in order to

reduce the silver ions. Corresponding samples were denoted as

xAg-cSiO2@mSiO2. The whole preparation process of Ag-

cSiO2@mSiO2 is shown in Fig. 1.

2.4. Characterization

2.4.1. Morphology, structure, composition and porosity of the

sample. SEM (Scanning electron microscopy) and TEM

(Transmission electron microscopy) images were recorded with

a Hitachi S-4800 scanning electron microscope and a CM200UT

transmission electron microscope, respectively; XRD (X-ray

diffraction) and EDS (Energy-dispersive spectroscopy) patterns

were tested using a RIGAKU D/MAX 2550/PC polycrystalline

X-Ray diffractometer and an EMAX 350 energy disperse spec-

trometer; N2 (Nitrogen) adsorption–desorption isotherms were

measured with an AUTOSORB-1-C micromeritics instrument;

the specific surface area and pore size distribution of the Ag-

cSiO2@mSiO2 were calculated with a Brunauer–Emmett–Teller

(BET) method and Barrett–Joyner–Halenda (BJH) method

according to the N2 adsorption–desorption isotherms; FT-IR

spectra (Fourier transform infrared spectroscopy) were tested

with a NICOTCT Fourier transform infrared spectroscopy,

while TGA (Thermal gravity analysis) was carried out with

a Pyris 1 TGA thermogravimetric analyzer.

2.4.2. Release of silver. The releasing profile of silver was

investigated in PBS (phosphate-buffered saline, pH ¼ 7.4). 1 g

0.1Ag-cSiO2@mSiO2 was dispersed in 100 mL PBS in a vial, then

the vial was shifted into an oil bath and gently stirred under



Fig. 2 SEM images of electrospun Ag-cSiO2 prepared using the

precursor SiO2 solution with different hydrolyzing times ((a): 140 min;

(b): 155 min; (c): 165 min; (d): 170 min).

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a maintained temperature of 37 �C. At selected time intervals,

aliquots (5 mL) were extracted and filtrated with filter paper to

remove the fibers, and the silver-containing solution was prop-

erly diluted for measurement of the silver concentration. The

silver concentration was measured using an ICE3500 atomic

absorption spectrometer.

2.4.3. Absorption of water and SBF. Deionized water and

freshly prepared SBF were applied to evaluate the exudate-

absorption ability of the sample. 0.1 g of thoroughly dried 0.1Ag-

cSiO2@mSiO2 was patterned into a small disk with a diameter of

2 cm. The small disk was completely immersed in 10 mL of

deionized water or SBF for 10 min, then was picked out and

placed on a stainless sieve until no liquid dripped. The mass of

the sample was weighed by a Mettler Toledo EL204 electronic

balance. The absorption ability of the sample was evaluated from

the ratio (Wwet � Wdry)/Wdry, where Wdry and Wwet refer to the

weight of the sample before and after absorption of water or

SBF, respectively. Commercial gauze was used as control.

2.4.4. Antibiotic ability of the sample. The antibiotic ability of

Ag-cSiO2@mSiO2 with different doping concentrations of Ag

NPs was investigated by measuring the inhibition zones for

E. coli. Briefly, xAg-cSiO2@mSiO2 (x¼ 0, 0.05, 0.1, 0.15) (0.05 g)

was compacted into a small disk with a diameter of 2 cm. 100 mL

of E. coli strain DH5a culture suspension in logarithmic phase

diluted to OD (optical density) 0.500 was added to the surface of

a glass dish containing 10 ml of congealed agarose LB medium

(composed of 10 g tryptone, 5 g yeast extract, and 5 g NaCl per

liter). The as-made xAg-cSiO2@mSiO2 disks were immediately

overlaid on the medium/bacterial surface separately. The dish

was incubated under 37 �C overnight.

Quantitative evaluation of the antibiotic effect of the Ag-

cSiO2@mSiO2 was investigated by studying the growth kinetics

of E. coli in LB liquid media. 100 mL of E. coli strain DH5a

culture suspension in the logarithmic phase diluted to OD 0.500

was added to 5 ml of liquid LB medium in glass tubes. A gradient

concentration of 0.1Ag-cSiO2@mSiO2 was added into the glass

tube, and the tube was incubated in a 200 rpm shaker under

a maintained temperature of 37 �C. Absorbance at a 600 nm

wavelength was measured at selected time intervals with an

Eppendorf Bio Photometer.

2.4.5. Investigation of cytotoxicity of the sample. BMSCs

(bone mesenchymal stem cells) were cultured in H-DMEM

medium (Invitrogen, USA) containing 10% heat-inactivated FBS

(fetal bovine serum) at a maintained temperature of 37 �C in

a humidified atmosphere with 5% CO2. The cells were seeded in

96-well plates at a density of 8 � 103 cells cm�2 and grown

overnight prior to studies. Then, the cells were incubated with

fresh media containing gradient concentrations of 0.1Ag-

cSiO2@mSiO2 (from 0.1 mg cm�2 to 100 mg cm�2). After incu-

bation for 4 days, 20 mL MTT (thiazolyl blue tetrazolium

bromide, 10 mg mL�1, Sigma-Aldrich, USA) solution was added

to each well of the plate, then the plate was incubated at 37 �C for

4 h. Finally, the cells were lysed using DMSO (Sigma, USA). A

microplate reader (Bio-Rad 680, USA) was applied to monitor

the absorbance of the supernatants at 570 nm. This experiment

was repeated three times.


2.4.6. Drug loading capacity and releasing profile of the

sample. IBU (Ibuprofen) was used as the model drug. Briefly,

0.1Ag-cSiO2@mSiO2 (0.15 g) was dispersed in a hexane solution

of IUB (50 mg mL�1, 30 mL). The mixture was magnetically

stirred under room temperature for 12 h, then the fibers were

centrifuged out and dried in air under 60 �C for 10 h. The

loading-capacity of the sample was evaluated with TGA and

EDS. For testing of the drug-releasing profile, 9 pieces of IBU-

loading samples (every piece of sample weighed 0.01 � 0.002 g)

was separately immersed in 5 mL of SBF (simulated body fluid),

and the mixture was gently stirred under a maintained temper-

ature of 37 �C. At selected time intervals, the fibers were centri-

fuged out, and the solution was left for measuring of the IBU

concentration.

3. Results and discussion

3.1. Structure, composition and morphology of the samples

For the SiO2 solution used in this investigation, the hydrolyzing

time is an important parameter that determines the sample

morphology. Fig. 2 shows the morphological evolution of elec-

trospun 0.1Ag-cSiO2 as a function of hydrolyzing time. When

hydrolyzing time changed from 140 min to 155 min, then to 165

min, and finally to 170 min, the morphology of the sample

changed from fine beads to tailed beads, then to beaded fibers,

and finally to long and uniform fibers.

According to previous investigations24,25 and our experience,

when the molar ratio of H2O : TEOS and HCl : TEOS is around

2 and 0.003, respectively, it is much easier to obtain a spinnable

SiO2 solution. In the hydrolyzing procedure of the SiO2 solution,

prolonging the hydrolyzing time in a certain range will increase

the length of the molecule chain and the evaporation of the

solvent, which will consequently raise the viscosity and adjust

the electric conductivity of the solution. Consequently, the

morphology of the products changed substantially with the

hydrolyzing time.

Fig. 3(a) and Fig. 3(b) show SEM images of 0.1Ag-cSiO2 and

0.1Ag-cSiO2@mSiO2, respectively. After coverage of the meso-

porous silica shell the average diameter of the fibers increased

markedly, changing from 300 nm to 880 nm. Fig. 3(c) and Fig. 3

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(d) show the highly magnified SEM images of one single 0.1Ag-

cSiO2@mSiO2 fiber observed from the side and the tip, respec-

tively. In Fig. 3(c), small-pore-like structures with a relatively

uniform pore size could be observed on the wall of the shell, and

the chiseled core–shell structure is clearly shown in Fig. 3(d).

Fig. 4(a) and Fig. 4(b) are TEM images of 0.1Ag@nSiO2 under

different magnifications. Relatively big Ag NPs (dark black dots)

with occasional distribution can be observed in Fig. 4(b),

however its population was very small. By magnifying one bare

area of a fiber in Fig. 4(a), a large population of much smaller Ag

NPs with relatively uniform size and homogenous distribution

can be observed, as shown in Fig. 4(b). Fig. 4(c), Fig. 4(d) and

Fig. 4(e) are TEM images of 0.1Ag-cSiO2@mSiO2. In Fig. 4(c),

a clear core–shell structure of 0.1Ag-cSiO2@mSiO2 with

a homogenous SiO2 shell can be observed. From the curvature of

the fiber in Fig. 4(c), it can be seen that the Ag-cSiO2@mSiO2 is

flexible. The mesoporous shell of the fibers is uniform, and its

average thickness is about 290 nm. Some big Ag NPs can be

observed in the mesoporous SiO2 shell. However, small Ag NPs

cannot be observed even with higher magnification, as shown in

Fig. 4(d), due to the detection limit of the instrument. Fig. 4(e) is

a magnified TEM image of one single fiber in Fig. 4(c), in which

the homogeneous mesoporous structure of the shell can be

observed more clearly. Fig. 4(f) is a HRTEM (high resolution

TEM) image of one single Ag NP. Due to its crystal fringes, we

can determine that the Ag NP was poly-crystalline.

Fig. 5 shows the XRD patterns of the Ag-cSiO2@mSiO2. The

big broadened peak at about 2q¼ 22� originates from the typical

diffraction of amorphous silica. The small peaks at about

2q¼ 38.3�, 44.3�, 64.5� and 77.5� correspond to diffractions from

[111], [200], [220] and [311] faces of cubic Ag NPs. Peak intensity

increased with doping concentration of silver nitrate, indicating

a quantitative increase of Ag NPs. The SAXRD (small-angle

X-ray diffraction) pattern of the 0.1Ag-cSiO2@mSiO2 is shown

in Fig. 6. The diffraction peak at 2q¼ 2.84� should be ascribed to

diffraction from the mesoporous SiO2 shell. According to

Bragg’s diffraction equation, the cell (one mesopore together

with its wall is defined as a cell) diameter was calculated to be

about 3.15 nm.

Fig. 3 SEM images of (a): electrospun Ag-cSiO2 fiber; (b): Ag-

cSiO2@mSiO2 fiber; (c) and (d): one single Ag-cSiO2@mSiO2 fiber

observed from the side and the tip, respectively.

9598 | J. Mater. Chem., 2011, 21, 9595–9602

Fig. 7 shows the N2 adsorption–desorption isotherms of

0.1Ag-cSiO2@mSiO2. An IV-type adsorption isotherm without

hysteresis loops can be discerned, implying that the mesopores

of the sample are highly uniform. The inset in Fig. 7 shows the

size distribution of the mesopores. Only one narrow and sharp

peak at about 1.97 nm can be seen, indicative of a narrow size

distribution of the mesopores. The average pore diameter,

Brunauer–Emmett–Teller (BET) surface area and total pore

volume of the sample were calculated to be 1.73 nm, 766.9 m2

g�1 and 0.29 cc g�1, respectively. According to previous inves-

tigations,26,27 the BJH method is known to underestimate the

pore size of the porous materials. So, the actual average pore

diameter of the Ag-cSiO2@mSiO2 in this investigation should

be larger. In the above paragraph, we have calculated the

cell diameter to be about 3.15 nm, thus we can estimate that

average wall thickness of the mesopores was about 1.42 nm

((average wall thickness) ¼ (average cell diameter) � (average

pore diameter)).

3.2. Release of silver from the sample

Fig. 8 shows the release profile of silver from 0.1Ag-

cSiO2@mSiO2. The whole release process can be divided into

two stages: the fast release stage before 5 h and the sustained

release stage after 5 h. From TEM images, it was observed that

some of the Ag NPs were just grafted or embedded on the fiber

surface, once exposed to magnetic stirring, they departed from

the fibers and dispersed into the water. It was a fast and rela-

tively short-time process, thus the first fast release stage

happened. This part of the released silver was composed mainly

of Ag NPs, which was verified by UV absorption spectrum (see

ESI, Fig. S1†). The second sustained release stage should be

ascribed to the Ag NPs in the condensed SiO2 core of the

sample. Because of the condensed structure of the cSiO2 fiber,

release of silver ions became slow and long-lasting. These

different silver release profiles of silver in one material can

endow the sample with dual antibiotic ability: on one hand, the

first fast release stage can cause fierce and immediate steriliza-

tion once the wound dressing is placed on the skin (now that the

antibiotic effect of Ag NPs has been proved to be one order

higher than its ionized counterpart28). On the other hand, the

sustained release of silver ions can lead to a consistent and long-

lasting antibiotic effect, avoiding infection in the regeneration

process of the damaged skin.

3.3. Exudate-absorption ability of the sample

As a kind of high-quality wound dressing, the material should

have the ability to massively absorb excessive exudates from the

wound to keep a suitably moist environment for regeneration of

the skin. A high specific surface area and large pore volume imply

that Ag-cSiO2@mSiO2 could have a superior exudate-absorption

ability. Fig. 9 shows the performance of the sample on absorp-

tion of deionized water and SBF. The absorption ratio of

deionized water and SBF for Ag-cSiO2@mSiO2 was 267 wt% and

254 wt%, respectively. For the gauze, the corresponding value

became 185 wt% and 159 wt%, respectively. Obviously, Ag-

cSiO2@mSiO2 performed better on absorption of both deionized

water and SBF than the gauze did.



Fig. 4 (a) and (b): TEM images of an Ag-cSiO2 fiber at low and high magnification; (c), (d) and (e): TEM images of an Ag-cSiO2@mSiO2 fiber at low

and high magnification; (f): HRTEM image of one Ag NP partly embedded in the mesoporous shell.

Fig. 5 XRD patterns of xAg-cSiO2@mSiO2 (x ¼ 0.05, 0.1, 0.15).

Fig. 6 SAXRD (small-angle X-ray diffraction) pattern of 0.1Ag-

cSiO2@mSiO2.

Fig. 7 N2 adsorption–desorption isotherms of Ag-cSiO2@mSiO2; the

inset shows the size distribution of the mesopores.


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3.4. Performance of antibiotic effect

Fig. 10 shows the digital images of inhibition zones against

E.coli. Samples inFig.10(b) toFig. 10(d)are0.05Ag-cSiO2@mSiO2,

0.1Ag-cSiO2@mSiO2 and 0.15Ag-cSiO2@mSiO2, respectively. As

can be seen, along with the increase of silver concentration, the

area of the inhibition zone increased rapidly, changing from 4

mm2 to 50 mm2 and then to 128 mm2. Fig. 10(a) shows the

antibiotic effect of the control (0Ag-cSiO2@mSiO2). No inhibi-

tion zone can be observed, indicating that the inhibition ability of

the sample should be ascribed to the doped Ag NPs.

Fig. 11 shows the proliferation curves of E. coli cultured with

0.1Ag-cSiO2@mSiO2 of different sample-dosage as a function

of incubation time. Obviously, the proliferation of E. coli

shows a sensitive dose-dependent antibiotic effect of the

sample. Along with the increase of the sample concentration,

the lag phase of the growth curve was prolonged gradually.

When the sample concentration reached 500 ppm, the lag phase

J. Mater. Chem., 2011, 21, 9595–9602 | 9599


Fig. 8 Releasing profile of silver from a 0.1Ag-cSiO2@mSiO2 fiber in

SBF as a function of immersing time. Two releasing stages can be dis-

cerned: the fast release stage before 10 h and the sustained release stage

after 10 h.

Fig. 9 Water and SBF absorption ratio of Ag-cSiO2@mSiO2 and gauze.

Performance of Ag-cSiO2@mSiO2 on the absorption of water and SBF

exhibited little difference, and both of them were better than the ones of

the gauze.

Fig. 10 Inhibition zones of xAg-cSiO2@mSiO2 (from (a) to (d), x ¼ 0,

0.05, 0.1 and 0.15) against proliferation of E. coli. Along with the increase

of the silver dose, the area of the inhibition zone increased substantially.

Fig. 11 Growth curves of E. coli incubated with the 0.1Ag-cSiO2@m-

SiO2 fibers. Gradient concentrations of 0.1Ag-cSiO2@mSiO2 fibers were

added to the culture of E. coli. The duration of the lag phase increased

with the increase of sample concentration, and the bacterial growth was

completely inhibited when the sample concentration reached 1000 ppm.

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was extended to more than 12 h. The proliferation of E. coli

was completely inhibited during the whole incubation process,

when the sample concentration reached 1000 ppm, indicating

that the sample possesses a long-term antibiotic ability, whi-

ch is an important property for application as a wound

dressing.

3.5. Result of cytotoxicity investigation

As shown in Fig. 12, the 0.1Ag-cSiO2@mSiO2 exhibited little

influence on the viability and proliferation of BMSCs in the

concentration range of 0.1–100 mg cm�2. In the antibacterial

efficiency test, 0.1Ag-cSiO2@mSiO2 of 1000 ppm (equivalent to

�13 mg cm�2) exhibited nearly 100% antibacterial efficiency (see

ESI, Fig. S2†). Even when the concentration of the sample

reached up to 100 mg cm�2, the viability of the cells was only

slightly reduced with no significance. These results indicated that

the Ag-cSiO2@mSiO2 is biocompatible with human cells, and, at

the same time, has an effective antibiotic ability.

9600 | J. Mater. Chem., 2011, 21, 9595–9602

3.6. Drug-loading and releasing of Ag-cSiO2@mSiO2 fibers

The drug-loading capacity and releasing profile of the sample

were evaluated with a widely used anesthetic drug: IBU

(ibuprofen), whose molecular size is smaller than 1 nm. Fig. 13

shows the FTIR spectra of the sample before and after loading of

IBU. As can be seen, after loading of IBU, the typical vibration

peak at 1722 cm�1, which originated from the vibration of

COOH, together with the bending mode of –OH at 1634 cm�1,

CHx bonds at 2873 cm�1 and 2954 cm�1, can be clearly observed,

indicating the successful loading of IBU.

Fig. 14 shows the TG curve of IBU-loading 0.1Ag-

cSiO2@mSiO2. Four weight loss stages can be observed,

including room temperature to 70 �C, 70 �C to 200 �C, 200 �C to

430 �C and 430 �C to 630 �C. The first stage can be ascribed to the

evaporation of the remaining solvent, while the second one may



Fig. 12 Cytotoxicity of Ag-cSiO2@mSiO2 nanostructure. The viability

of BMSCs incubated with gradient concentrations of 0.1Ag-cSiO2@m-

SiO2 for 4 days. Each data point represents the mean values from at least

three independent experiments.

Fig. 13 FTIR spectra of Ag-cSiO2@mSiO2 before and after loading of

IBU. Appearance of characteristic absorption peaks of IBU on the red

curve indicated the successful loading of IBU on Ag-cSiO2@mSiO2.

Fig. 14 TG curve of IBU-loading Ag-cSiO2@mSiO2. From this result,

the drug-loading capacity of the Ag-cSiO2@mSiO2 was measured to be

about 18 wt% of the sample

Fig. 15 Releasing curve of IBU in SBF as a function of immersing time.

Two releasing stages can be discerned: the burst releasing stage before 12

h and the relatively slow releasing stage after 12 h.

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originate from partial sublimation of the IBU that was adsorbed

on the fiber surface. The last two stages should be ascribed to the

preliminary departure and terminal decomposition of the IBU

that was accommodated in the mesopores. Drug-loading

capacity of the Ag-cSiO2@mSiO2 was estimated to be about 18

wt%.

Besides loading capacity, the release profile is another

important criterion for application as a drug carrier. Fig. 15

shows the release profile of IBU from 0.1Ag-cSiO2@mSiO2 in

SBF, which was plotted from the integrated intensity of the

absorption peak of IBU at 263 nm (see ESI, Fig. S3†). More than

85% of the drug was released within 12 h. This release stage

should originate from the rapid leaching of free IBU from the

outer surfaces or pore entrances. After 12 h, the release profile of

the rest drug became relatively mild, which should be ascribed to

the interaction between the COOH groups of IBU and the OH

groups of the fiber. Considering the relatively fast release profile

of Ag-cSiO2@mSiO2, immediate relief of pain can be anticipated,

when it is applied as a wound dressing.


4. Conclusion

In summary, core–shell structured flexible mesoporous SiO2

fibers doped with Ag NPs (Ag-cSiO2@mSiO2) were successfully

prepared through electrospinning and a modified St€ober method,

and their feasibility as high-quality wound dressings was inves-

tigated. The results showed that Ag-cSiO2@mSiO2 can effec-

tively absorb water and SBF, implying that it has a large

absorption capacity for exudates. The mesoporous shell of the

Ag-cSiO2@mSiO2 can accommodate drugs conveniently, and its

drug release was relatively fast, making immediate relief of pain

possible. Due to the condensed structure of the electrospun SiO2

nanofiber, the release of silver from Ag-cSiO2@mSiO2 was very

slow, endowing the sample with a sustained antibiotic effect. In

addition, the condensed core of SiO2 nanofiber also endowed the

Ag-cSiO2@mSiO2 with high flexibility, making it easy to be

patterned into film to be used as a wound dressing. Considering

the various advantages of the sample, we believe Ag-cSiO2@m-

SiO2 could be a promising material for wound dressings. To the

best of knowledge, this is the first time that mesoporous SiO2

fibers as wound dressings has been investigated.

J. Mater. Chem., 2011, 21, 9595–9602 | 9601


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Acknowledgements

This work was financially supported by the National Natural

Science Foundation of China (Grant Nos. 50872123 and

50802083), the National Basic Research Program of China

(2006CB806000b), and the Program for Changjiang Scholars

and Innovative Research Team in University (IRT0651).

Reference

1 R. A. Thakur, C. A. Florek, J. Kohn and B. B. Michniak, Int. J.Pharm., 2008, 364, 87.

2 J. J. Elsner and M. Zilberman, Acta Biomater., 2009, 5, 2872.3 S. Lu, W. Gao and H. Y. Gu, Burns, 2008, 34, 623.4 D. Liang, B. S. Hsiao and B. Chu, Adv. Drug Delivery Rev., 2007, 59,1392.

5 N. Adhirajan, N. Shanmugasundaram, S. Shanmuganathan andM. Babu, Eur. J. Pharm. Sci., 2009, 36, 235.

6 B. B. Mandal and S. C. Kundu, Biomaterials, 2009, 30, 5170.7 H. S. Yoo, T. G. Kim and T. G. Park, Adv. Drug Delivery Rev., 2009,61, 1033.

8 Y. Zhu, S. Kaskel, J. Shi, T. Wage and K. H. V. P�ee, Chem. Mater.,2007, 19, 6408.

9 T. Sen, A. Sebastianelli and I. J. Bruce, J. Am. Chem. Soc., 2006, 128,7130.

10 F. Torney, B. G. Trewyn, V. S. Y. Lin and K. Wang, Nat.Nanotechnol., 2007, 2, 295.

11 I. Y. Parka, I. Y. Kia, M. K. Yoo, Y. J. Choi, M. H. Cho andC. S. Cho, Int. J. Pharm., 2008, 359, 280.

12 Y. Wang and F. Caruso, Chem. Mater., 2005, 17, 953.

9602 | J. Mater. Chem., 2011, 21, 9595–9602

13 J. Lee, H. B. Na, B. C. Kim, J. H. Lee, B. Lee, J. H. Kwak, Y. Hwang,J. G. Park, M. B. Gu, J. Kim, J. Joo, C. H. Shin, J. W. Grate,T. Hyeon and J. Kim, J. Mater. Chem., 2009, 19, 7864.

14 Y. Zhu, J. Shi, W. Shen, X. Dong, J. Feng, M. Ruan and Y. Li,Angew. Chem., Int. Ed., 2005, 44, 5083.

15 I. I. Slowing, B. G. Trewyn, S. Giri and V. S. Y. Lin, Adv. Funct.Mater., 2007, 17, 1225.

16 H. Yoshitake, T. Yokoi and T. Tatsumi, Chem. Mater., 2003, 15,1713.

17 A. M. Burke, J. P. Hanrahan, D. A. Healyd, J. R. Sodeaud,J. D. Holmes and M. A. Morris, J. Hazard. Mater., 2009, 164, 229.

18 C. Dai, Y. Yuan, C. Liu, J. Wei, H. Hong, X. Li and X. Pan,Biomaterials, 2009, 30, 5364.

19 F. Kleitz, F. Marlow, G. D. Stucky and F. Schuth, Chem. Mater.,2001, 13, 3587.

20 J. Wang, J. Zhang, B. Y. Asoo and G. D. Stucky, J. Am. Chem. Soc.,2003, 125, 13966.

21 P. Yang, D. Zhao, B. F. Chmelka and G. D. Stucky, Chem. Mater.,1998, 10, 2033.

22 P. J. Bruinsma, A. Y. Kim, J. Liu and S. Baskaran, Chem. Mater.,1997, 9, 2507.

23 Z. Gong, G. Ji, M. Zheng, X. Chang, W. Dai, L. Pan, Y. Shi andY. Zheng, Nanoscale Res. Lett., 2009, 4, 1257.

24 T. Yamaguchi, S. Sakai and K. Kawakami, J. Sol-Gel Sci. Technol.,2008, 48, 350.

25 K. Kamiya and T. Yoko, J. Mater. Sci., 1986, 21, 842.26 E. P. Barrett, L. G. Joyner and P. H. Halenda, J. Am. Chem. Soc.,

1951, 73, 373.27 P. I. Ravikovitch and A. V. Neimark, Colloids Surf., A, 2001, 187–

188, 11–21.28 C. N. Lok, C. M. Ho, R. Chen, Q. Y. He, W. Y. Yu, H. Sun,

P. K. H. Tam, J. F. Chiu and C. M. Che, J. Proteome Res., 2006, 5,916.



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