- Email: [email protected]
Study on antibacterial performance and biocompatibility of a novel phosphorus-magnesium fiber
Accepted Manuscript Study on antibacterial performance and biocompatibility of a novel phosphorusmagnesium fiber Wei Wu, Jia Chen, Da Sun, Xiangjun Kong, Dake xu, Yi Wang, Li Luo, Kun Zhang, Keshen Xiao, Guixue Wang PII: DOI: Reference:
S0167-577X(17)31298-3 http://dx.doi.org/10.1016/j.matlet.2017.08.099 MLBLUE 23076
To appear in:
Materials Letters
Received Date: Revised Date: Accepted Date:
6 May 2017 21 August 2017 23 August 2017
Please cite this article as: W. Wu, J. Chen, D. Sun, X. Kong, D. xu, Y. Wang, L. Luo, K. Zhang, K. Xiao, G. Wang, Study on antibacterial performance and biocompatibility of a novel phosphorus-magnesium fiber, Materials Letters (2017), doi: http://dx.doi.org/10.1016/j.matlet.2017.08.099
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
1
Study on antibacterial performance and biocompatibility of a novel phosphorus-magnesium fiber
Wei Wu a, †, Jia Chen a, b, †, Da Sun c, †,* Xiangjun Kong d, Dake xu e, Yi Wang a, Li Luo a, Kun Zhang a, Keshen Xiao e,*, Guixue Wang a,* a
Key Laboratory for Biorheological Science and Technology of Ministry of Education, State and
Local Joint Engineering Laboratory for Vascular Implants, Bioengineering College of Chongqing University, Chongqing University, Chongqing 400044, China b
Institute of Laboratory Animals of Sichuan Academy of Medical Science & Sichuan Provincial
People's Hospital, Chengdu 610000, China c
Institute of Life Sciences, Wenzhou University, Wenzhou 325000, China
d
Institute of Chinese Medical Sciences, State Key Laboratory of Quality Research in Chinese
Medicine, University of Macau, Macau 999078, China e
Institute of Metal Research, Chinese Academic of Sciences, Shenyang 110016, China
† These authors contributed equally to this work.
* Corresponding author: Tel: +86 13108982986, Email: [email protected] (Guixue Wang); Tel: +86 13066776442, Email: [email protected] (Keshen Xiao); Tel: +86 18358782040, Email: [email protected] (Da Sun).
2
Abstract The present study was intended to investigate the antibacterial performance and biocompatibility of a novel phosphorus-magnesium fiber (PMF). The PMF was found to exhibit excellent antibacterial performance against methicillin-resistant Staphylococcus aureus and Candida albicans, exceeding 95% when the PMF concentration was higher than 500 µg mL-1. MTS analysis was performed to assess the in vitro cytotoxicity of PMF, which showed PMF with a concentration range of 100-1000 mg L-1 had no significant toxic effects on L929 fibroblast cells. In addition, the in vivo toxicity assay of PMF was studied in zebrafish (Danio rerio) embryos, and the results confirmed little toxicity at effective antibacterial concentration. Hence, PMF was proved to be a potential coating or filling material with promising antibacterial performance for in implantable medical devices. Keywords:
Biomaterials;
Nanoparticles;
phosphorous-magnesium
fiber;
antibacterial
performance; zebrafish.
1. Introduction
To treat bone defect and osteoporosis, bone filling has emerged as required. Autologous bone grafts are considered to represent the gold standard of the bone filling. However, they are practically limited by insufficient volume available for those who suffer from widespread orthopaedic diseases 1. For the good bio-compatibility, degradability, and tenacity, various graft substitutes, such as bioceramics, magnesium alloys, and bone cement, have been widely applied in orthopaedic surgery over the past years 2. While in the process, a very serious problem is to prevent bacterial infections. In general, infections occurring after orthopaedic transplantation are resulted by the bacteria that reach the surface of implants faster than host cells, and subsequently form biofilms under the action of bacteria and their fiber proteins. Numerous strategies involving appropriate use of antibiotics and antibiotics coatings on the materials are subjected to potential solutions to the preceding problem 3,4. Nevertheless, the adhesion and stability of coatings might
3
not be satisfactory for burst release in the body fluids, especially for the modifications of scaffold materials. In addition, improving the surgical technique and reducing intraoperative pollution are also fail to avoid postoperative infection completely. The aim of this study was to prepare a novel phosphorus-magnesium fiber (PMF) and investigate its antibacterial performance, cytocompatibility, and in vivo toxicity, then to evaluate its potential application in orthopedic transplants using bone substitutes and scaffold.
2. Materials and Methods
2.1 Materials: The novel PMF was obtained from the surface of high-purity Mg (99.99%) soaking in the etching solution (Table S1) provided by the Chinese academy of sciences, and the temperature of reaction was around 80 oC. The investigations on relevant physical properties of PMF were conducted using X-ray diffractometer (XRD), dynamic light scattering (DLS), scanning electron microscope (SEM) and corresponding energy dispersion spectrum (EDS) analysis. 2.2 Antibacterial tests: 1 mL bacterial suspensions with approximately 106 CFU mL-1 of methicillin-resistant Staphylococcus aureus (MRSA; ATCC 33591) and Candida albicans (C. albicans; ATCC 10231) were respectively transferred to the entrifuge tubes containing different concentrations of PMF dissolved in 0.9% (w/v) NaCl solutions (100, 500, 1000, 1500 µg mL-1). Both S.aureus and C. albicans are pathogens capable of causing life-threatening infections, which frequently located in implantable devices
5,6
. After co-incubation at 37 oC for 24 h, bacterial
suspensions were diluted to approximately 103 CFU mL-1, and 0.1 ml of the diluted bacterial suspensions were used to coat agar plates. The plates were then incubated at 37 oC for 24 h before counting the bacterial colonies. In the control group, PMF was replaced with 0.9% (w/v) NaCl solution, and the remaining steps were the same 6,7. The antibacterial rate C was determined by the following equation:
4
C (%) = 100 × (A - B) / A
(1)
where A was the bacteria number of CFU in the control NaCl solution and B in the PMF solution. 2.3 Hemolysis experiments: Fresh blood was collected from healthy rabbit using anticoagulative tubes, and then diluted with 0.9% NaCl to get the final solutions about 1.0 mg mL-1 8. Weigh the PMF and dip it into a tube containing 0.9% NaCl to get the different concentration (100, 500, 1000, 1500 µg mL-1). Preheat the PMF solutions for 72 h at 37 °C. After that, they were filtered through 0.22 µm sterile membranes, and added into the tubes containing 0.2 mL diluted blood. Then co-incubate them for 60 min at 37 °C. NaCl solution and deionized water were used as the blank control and positive control, respectively. These samples were centrifuged for 5 min at 3000 rpm, and the supernatant was carefully obtained to conduct an ultraviolet spectrophotometer analysis at 545 nm. The hemolysis effects was calculated as the following formula based on average absorbance values of three replicates 9. Hemolysis = (ODt − ODnc) / (ODpc – ODnc) × 100%
(2)
where OD means optical density. Specifically, ODt represents the optical density of the PMF test groups, ODnc was that of 0.9% NaCl control group, and ODpc was that of deionized water group. 2.4 In vitro cytotoxicity studies: L929 cells (103 per well) with same amount were treated with different concentrations of PMF, with different incubation periods of 24, 48, and 72 h, to detect their
effects
on
cell
viability.
After
incubation
for
designed
intervals,
20
µL
3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) solution (0.5 mg mL-1) was added to the cells and then incubated for 2 h at 37 oC. Finally, the absorbance of cells was detected at 490 nm using the EL × 800 microplate reader (BioTek
5
Instruments Inc.) with the plain cell culture media as the control. L929 cell viability was calculated by the formula based on five replicates: Cell viability = (ODt - ODb) / (ODc - ODb) × 100%
(3)
where ODt was the optical density of test groups, ODc was that of media incubated with L929 cells, and ODb was that of media without any cells. The statistical analysis of MTS assay was conducted by SPSS version 22.0 software. 2.5 In vivo toxicity studies: Weigh and suspend the PMF in egg water to prepare the working solutions, and then transfer the solutions to the 24-well plates. Twenty healthy embryos (eight-cell stage) of wild-type zebrafish were added to each well of the working solutions. Several aspects including hatching rates, growth states, abnormality and survival rates of embryos, and touch responses of larval zebrafish, were investigated to detect the developmental influences of PMF.
3. Results and discussion
Fig.1 shows PMF shows long rod needlelike shapes with widths at micro- or nano-sizes and lengths greater than 200 µm, which has large specific surface area. Meanwhile, the ratio of diameter/length of the PMF was larger than 10. Owing to this structure, PMF may exhibit a certain degree of nano-character
10
. The XRD data and possible chemical composition formula were
provided in Supplementary Material (Fig. S1). Preliminary DLS analysis indicated that the size distribution of PMF at a concentration of 500 µg mL-1 was 701.1 ± 69.53 nm (Fig. S2).
6
Fig. 1. SEM image of PMF and its corresponding EDS analysis. As shown in Fig. 2 the antibacterial rates under co-incubation with high concentrations of the PMF were all above 95%. Therefore, it can be concluded that a higher concentration than 500 µg mL-1 is necessary to guarantee a strong antibacterial performance against these common pathogens reported in clinical practice. Whereas undesirable hemolysis ratio increased as the PMF concentration increase, and exceeded 5% when the PMF concentration reaches 1500 µg mL-1. The PMF at low concentrations (< 1000 µg mL-1 ) could be classified as a non-hemolytic material, and PMF (1000 ~ 1500 µg mL-1) could be classified as a slightly-hemolytic material according to the American Society for Testing and Materials 11.
Fig. 2. Antibacterial rates and hemolysis ratios of the PMF Fig. 3a shows that the viabilities of L929 cells co-incubated within the PMF concentration range of 10-1000 µg mL-1 were not significantly different (P > 0.05) compared with control groups. However, PMF exhibited cytotoxinic to L929 cells when the concentration reached 1500 µg mL-1. Therefore, PMF was cytotoxic to L929 cells in a concentration-dependent manner. Thus, the concentration range (500-1000 µg mL-1) was selected for in vivo cytotoxicity evaluation.
7
Fig. 3. The in vitro L929 cell proliferation assay obtained with PMF incubation (a), In vivo toxicity analysis: hatched embryos at 72 h with 500 (b) and 1000 µg mL-1 (c) PMF. In the in vivo cytotoxicity evaluation, the hatching rates and touch responses of the zebrafish are similar in the control and the PMF-treated groups. No delay in hatching was observed for the control and PMF test groups. There were no malformations on embryos and larval zebrafish while observing under microscope (Fig 3b, c). In the range of the studied concentration, our results suggested that the PMF might not impact the early development of zebrafish.
4. Conclusions
This study confirmed that PMF possessed both good bactericidal ability and biocompatibility at the concentration range from 500 to 1000 µg mL-1, implying that the PMF had great potential for various applications in orthopedics, such as the coating or filling material of implantable medical devices with excellent antibacterial performance.
Acknowledgements
This work was supported by the National Natural Science Foundation of China (11332003, 31370949, 81400329, 51603023), the National Key Research and Development Program (2016YFC1102305),
the
(106112016CDJXY230002,
Fundamental
Research
Funds
106112016CDJXY230001),
the
for
the
China
Central
Universities
Postdoctoral
Science
Foundation (2016M602656, 2017T100682) and the Chongqing Postdoctoral Scientific Research Foundation (Xm2016011), the Chongqing Research Program of Basic research and Frontier Technology (cstc2017jcyjAX0186), as well as the Chongqing Engineering Laboratory in Vascular
8
Implants and the Public Experiment Center of State Bioindustrial Base (Chongqing).
References
1.
Goldstein, J. A., Paliga, J. T. & Bartlett, S. P. Cranioplasty: indications and advances. Curr. Opin. Otolaryngol. Head Neck Surg. 21, 400–409 (2013).
2.
Wang, W., Ouyang, Y. & Poh, C. K. Orthopaedic Implant Technology: Biomaterials from Past to Future. Ann. Acad. Med. Singap. 40, 237–244 (2011).
3.
Cook, G. E. et al. Infection in Orthopaedic. J. Orthop. Trauma 12, 19–23 (2015).
4.
Sun, D., Babar Shahzad, M., Li, M., Wang, G. & Xu, D. Antimicrobial materials with medical applications. Mater. Technol. 30, B90–B95 (2014).
5.
Li, J. et al. Biofilm formation of Candida albicans on implant overdenture materials and its removal. J. Dent. 40, 686–92 (2012).
6.
Sun, D. et al. An investigation of the antibacterial ability and cytotoxicity of a novel cu-bearing 317L stainless steel. Sci. Rep. 6, 29244 (2016).
7.
Wang, S., Yang, C., Ren, L., Shen, M. & Yang, K. Study on antibacterial performance of Cu-bearing cobalt-based alloy. Mater. Lett. 129, 88–90 (2014).
8.
Bender, E. A. et al. Hemocompatibility of poly(ɛ-caprolactone) lipid-core nanocapsules stabilized with polysorbate 80-lecithin and uncoated or coated with chitosan. Int. J. Pharm. 426, 271–279 (2012).
9.
Li, Y. et al. Biocompatibility of Fe3O4@Au composite magnetic nanoparticles in vitro and in vivo. Int. J. Nanomedicine 6, 2805–2819 (2011).
10. Gleiter, H. Nanostructured materials: Basic concepts and microstructure. Acta Mater. 48,
9
1–29 (2000). 11. Andrade, F. K. et al. Studies on the hemocompatibility of bacterial cellulose. J. Biomed. Mater. Res. A 98A, 554–566 (2011).
10
1. The PMF with excellent antibacterial effect and biocompatibility has been manufactured; 2. The PMF is potential to utilize in bone filling to reduce the risk of bacterial infection; 3. The PMF showed no in vivo toxicity evaluated with zebra fish model.
S0167-577X(17)31298-3 http://dx.doi.org/10.1016/j.matlet.2017.08.099 MLBLUE 23076
To appear in:
Materials Letters
Received Date: Revised Date: Accepted Date:
6 May 2017 21 August 2017 23 August 2017
Please cite this article as: W. Wu, J. Chen, D. Sun, X. Kong, D. xu, Y. Wang, L. Luo, K. Zhang, K. Xiao, G. Wang, Study on antibacterial performance and biocompatibility of a novel phosphorus-magnesium fiber, Materials Letters (2017), doi: http://dx.doi.org/10.1016/j.matlet.2017.08.099
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
1
Study on antibacterial performance and biocompatibility of a novel phosphorus-magnesium fiber
Wei Wu a, †, Jia Chen a, b, †, Da Sun c, †,* Xiangjun Kong d, Dake xu e, Yi Wang a, Li Luo a, Kun Zhang a, Keshen Xiao e,*, Guixue Wang a,* a
Key Laboratory for Biorheological Science and Technology of Ministry of Education, State and
Local Joint Engineering Laboratory for Vascular Implants, Bioengineering College of Chongqing University, Chongqing University, Chongqing 400044, China b
Institute of Laboratory Animals of Sichuan Academy of Medical Science & Sichuan Provincial
People's Hospital, Chengdu 610000, China c
Institute of Life Sciences, Wenzhou University, Wenzhou 325000, China
d
Institute of Chinese Medical Sciences, State Key Laboratory of Quality Research in Chinese
Medicine, University of Macau, Macau 999078, China e
Institute of Metal Research, Chinese Academic of Sciences, Shenyang 110016, China
† These authors contributed equally to this work.
* Corresponding author: Tel: +86 13108982986, Email: [email protected] (Guixue Wang); Tel: +86 13066776442, Email: [email protected] (Keshen Xiao); Tel: +86 18358782040, Email: [email protected] (Da Sun).
2
Abstract The present study was intended to investigate the antibacterial performance and biocompatibility of a novel phosphorus-magnesium fiber (PMF). The PMF was found to exhibit excellent antibacterial performance against methicillin-resistant Staphylococcus aureus and Candida albicans, exceeding 95% when the PMF concentration was higher than 500 µg mL-1. MTS analysis was performed to assess the in vitro cytotoxicity of PMF, which showed PMF with a concentration range of 100-1000 mg L-1 had no significant toxic effects on L929 fibroblast cells. In addition, the in vivo toxicity assay of PMF was studied in zebrafish (Danio rerio) embryos, and the results confirmed little toxicity at effective antibacterial concentration. Hence, PMF was proved to be a potential coating or filling material with promising antibacterial performance for in implantable medical devices. Keywords:
Biomaterials;
Nanoparticles;
phosphorous-magnesium
fiber;
antibacterial
performance; zebrafish.
1. Introduction
To treat bone defect and osteoporosis, bone filling has emerged as required. Autologous bone grafts are considered to represent the gold standard of the bone filling. However, they are practically limited by insufficient volume available for those who suffer from widespread orthopaedic diseases 1. For the good bio-compatibility, degradability, and tenacity, various graft substitutes, such as bioceramics, magnesium alloys, and bone cement, have been widely applied in orthopaedic surgery over the past years 2. While in the process, a very serious problem is to prevent bacterial infections. In general, infections occurring after orthopaedic transplantation are resulted by the bacteria that reach the surface of implants faster than host cells, and subsequently form biofilms under the action of bacteria and their fiber proteins. Numerous strategies involving appropriate use of antibiotics and antibiotics coatings on the materials are subjected to potential solutions to the preceding problem 3,4. Nevertheless, the adhesion and stability of coatings might
3
not be satisfactory for burst release in the body fluids, especially for the modifications of scaffold materials. In addition, improving the surgical technique and reducing intraoperative pollution are also fail to avoid postoperative infection completely. The aim of this study was to prepare a novel phosphorus-magnesium fiber (PMF) and investigate its antibacterial performance, cytocompatibility, and in vivo toxicity, then to evaluate its potential application in orthopedic transplants using bone substitutes and scaffold.
2. Materials and Methods
2.1 Materials: The novel PMF was obtained from the surface of high-purity Mg (99.99%) soaking in the etching solution (Table S1) provided by the Chinese academy of sciences, and the temperature of reaction was around 80 oC. The investigations on relevant physical properties of PMF were conducted using X-ray diffractometer (XRD), dynamic light scattering (DLS), scanning electron microscope (SEM) and corresponding energy dispersion spectrum (EDS) analysis. 2.2 Antibacterial tests: 1 mL bacterial suspensions with approximately 106 CFU mL-1 of methicillin-resistant Staphylococcus aureus (MRSA; ATCC 33591) and Candida albicans (C. albicans; ATCC 10231) were respectively transferred to the entrifuge tubes containing different concentrations of PMF dissolved in 0.9% (w/v) NaCl solutions (100, 500, 1000, 1500 µg mL-1). Both S.aureus and C. albicans are pathogens capable of causing life-threatening infections, which frequently located in implantable devices
5,6
. After co-incubation at 37 oC for 24 h, bacterial
suspensions were diluted to approximately 103 CFU mL-1, and 0.1 ml of the diluted bacterial suspensions were used to coat agar plates. The plates were then incubated at 37 oC for 24 h before counting the bacterial colonies. In the control group, PMF was replaced with 0.9% (w/v) NaCl solution, and the remaining steps were the same 6,7. The antibacterial rate C was determined by the following equation:
4
C (%) = 100 × (A - B) / A
(1)
where A was the bacteria number of CFU in the control NaCl solution and B in the PMF solution. 2.3 Hemolysis experiments: Fresh blood was collected from healthy rabbit using anticoagulative tubes, and then diluted with 0.9% NaCl to get the final solutions about 1.0 mg mL-1 8. Weigh the PMF and dip it into a tube containing 0.9% NaCl to get the different concentration (100, 500, 1000, 1500 µg mL-1). Preheat the PMF solutions for 72 h at 37 °C. After that, they were filtered through 0.22 µm sterile membranes, and added into the tubes containing 0.2 mL diluted blood. Then co-incubate them for 60 min at 37 °C. NaCl solution and deionized water were used as the blank control and positive control, respectively. These samples were centrifuged for 5 min at 3000 rpm, and the supernatant was carefully obtained to conduct an ultraviolet spectrophotometer analysis at 545 nm. The hemolysis effects was calculated as the following formula based on average absorbance values of three replicates 9. Hemolysis = (ODt − ODnc) / (ODpc – ODnc) × 100%
(2)
where OD means optical density. Specifically, ODt represents the optical density of the PMF test groups, ODnc was that of 0.9% NaCl control group, and ODpc was that of deionized water group. 2.4 In vitro cytotoxicity studies: L929 cells (103 per well) with same amount were treated with different concentrations of PMF, with different incubation periods of 24, 48, and 72 h, to detect their
effects
on
cell
viability.
After
incubation
for
designed
intervals,
20
µL
3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) solution (0.5 mg mL-1) was added to the cells and then incubated for 2 h at 37 oC. Finally, the absorbance of cells was detected at 490 nm using the EL × 800 microplate reader (BioTek
5
Instruments Inc.) with the plain cell culture media as the control. L929 cell viability was calculated by the formula based on five replicates: Cell viability = (ODt - ODb) / (ODc - ODb) × 100%
(3)
where ODt was the optical density of test groups, ODc was that of media incubated with L929 cells, and ODb was that of media without any cells. The statistical analysis of MTS assay was conducted by SPSS version 22.0 software. 2.5 In vivo toxicity studies: Weigh and suspend the PMF in egg water to prepare the working solutions, and then transfer the solutions to the 24-well plates. Twenty healthy embryos (eight-cell stage) of wild-type zebrafish were added to each well of the working solutions. Several aspects including hatching rates, growth states, abnormality and survival rates of embryos, and touch responses of larval zebrafish, were investigated to detect the developmental influences of PMF.
3. Results and discussion
Fig.1 shows PMF shows long rod needlelike shapes with widths at micro- or nano-sizes and lengths greater than 200 µm, which has large specific surface area. Meanwhile, the ratio of diameter/length of the PMF was larger than 10. Owing to this structure, PMF may exhibit a certain degree of nano-character
10
. The XRD data and possible chemical composition formula were
provided in Supplementary Material (Fig. S1). Preliminary DLS analysis indicated that the size distribution of PMF at a concentration of 500 µg mL-1 was 701.1 ± 69.53 nm (Fig. S2).
6
Fig. 1. SEM image of PMF and its corresponding EDS analysis. As shown in Fig. 2 the antibacterial rates under co-incubation with high concentrations of the PMF were all above 95%. Therefore, it can be concluded that a higher concentration than 500 µg mL-1 is necessary to guarantee a strong antibacterial performance against these common pathogens reported in clinical practice. Whereas undesirable hemolysis ratio increased as the PMF concentration increase, and exceeded 5% when the PMF concentration reaches 1500 µg mL-1. The PMF at low concentrations (< 1000 µg mL-1 ) could be classified as a non-hemolytic material, and PMF (1000 ~ 1500 µg mL-1) could be classified as a slightly-hemolytic material according to the American Society for Testing and Materials 11.
Fig. 2. Antibacterial rates and hemolysis ratios of the PMF Fig. 3a shows that the viabilities of L929 cells co-incubated within the PMF concentration range of 10-1000 µg mL-1 were not significantly different (P > 0.05) compared with control groups. However, PMF exhibited cytotoxinic to L929 cells when the concentration reached 1500 µg mL-1. Therefore, PMF was cytotoxic to L929 cells in a concentration-dependent manner. Thus, the concentration range (500-1000 µg mL-1) was selected for in vivo cytotoxicity evaluation.
7
Fig. 3. The in vitro L929 cell proliferation assay obtained with PMF incubation (a), In vivo toxicity analysis: hatched embryos at 72 h with 500 (b) and 1000 µg mL-1 (c) PMF. In the in vivo cytotoxicity evaluation, the hatching rates and touch responses of the zebrafish are similar in the control and the PMF-treated groups. No delay in hatching was observed for the control and PMF test groups. There were no malformations on embryos and larval zebrafish while observing under microscope (Fig 3b, c). In the range of the studied concentration, our results suggested that the PMF might not impact the early development of zebrafish.
4. Conclusions
This study confirmed that PMF possessed both good bactericidal ability and biocompatibility at the concentration range from 500 to 1000 µg mL-1, implying that the PMF had great potential for various applications in orthopedics, such as the coating or filling material of implantable medical devices with excellent antibacterial performance.
Acknowledgements
This work was supported by the National Natural Science Foundation of China (11332003, 31370949, 81400329, 51603023), the National Key Research and Development Program (2016YFC1102305),
the
(106112016CDJXY230002,
Fundamental
Research
Funds
106112016CDJXY230001),
the
for
the
China
Central
Universities
Postdoctoral
Science
Foundation (2016M602656, 2017T100682) and the Chongqing Postdoctoral Scientific Research Foundation (Xm2016011), the Chongqing Research Program of Basic research and Frontier Technology (cstc2017jcyjAX0186), as well as the Chongqing Engineering Laboratory in Vascular
8
Implants and the Public Experiment Center of State Bioindustrial Base (Chongqing).
References
1.
Goldstein, J. A., Paliga, J. T. & Bartlett, S. P. Cranioplasty: indications and advances. Curr. Opin. Otolaryngol. Head Neck Surg. 21, 400–409 (2013).
2.
Wang, W., Ouyang, Y. & Poh, C. K. Orthopaedic Implant Technology: Biomaterials from Past to Future. Ann. Acad. Med. Singap. 40, 237–244 (2011).
3.
Cook, G. E. et al. Infection in Orthopaedic. J. Orthop. Trauma 12, 19–23 (2015).
4.
Sun, D., Babar Shahzad, M., Li, M., Wang, G. & Xu, D. Antimicrobial materials with medical applications. Mater. Technol. 30, B90–B95 (2014).
5.
Li, J. et al. Biofilm formation of Candida albicans on implant overdenture materials and its removal. J. Dent. 40, 686–92 (2012).
6.
Sun, D. et al. An investigation of the antibacterial ability and cytotoxicity of a novel cu-bearing 317L stainless steel. Sci. Rep. 6, 29244 (2016).
7.
Wang, S., Yang, C., Ren, L., Shen, M. & Yang, K. Study on antibacterial performance of Cu-bearing cobalt-based alloy. Mater. Lett. 129, 88–90 (2014).
8.
Bender, E. A. et al. Hemocompatibility of poly(ɛ-caprolactone) lipid-core nanocapsules stabilized with polysorbate 80-lecithin and uncoated or coated with chitosan. Int. J. Pharm. 426, 271–279 (2012).
9.
Li, Y. et al. Biocompatibility of Fe3O4@Au composite magnetic nanoparticles in vitro and in vivo. Int. J. Nanomedicine 6, 2805–2819 (2011).
10. Gleiter, H. Nanostructured materials: Basic concepts and microstructure. Acta Mater. 48,
9
1–29 (2000). 11. Andrade, F. K. et al. Studies on the hemocompatibility of bacterial cellulose. J. Biomed. Mater. Res. A 98A, 554–566 (2011).
10
1. The PMF with excellent antibacterial effect and biocompatibility has been manufactured; 2. The PMF is potential to utilize in bone filling to reduce the risk of bacterial infection; 3. The PMF showed no in vivo toxicity evaluated with zebra fish model.