Journal Pre-proofs Joint wound healing using polymeric dressing of chitosan/strontium-doped titanium dioxide with high antibacterial activity Li Chen, Hong Pan, Caifeng Zhuang, Mengyao Peng, Li Zhang PII: DOI: Reference:
S0167-577X(20)30260-3 https://doi.org/10.1016/j.matlet.2020.127555 MLBLUE 127555
To appear in:
Materials Letters
Received Date: Revised Date: Accepted Date:
4 February 2020 21 February 2020 21 February 2020
Please cite this article as: L. Chen, H. Pan, C. Zhuang, M. Peng, L. Zhang, Joint wound healing using polymeric dressing of chitosan/strontium-doped titanium dioxide with high antibacterial activity, Materials Letters (2020), doi: https://doi.org/10.1016/j.matlet.2020.127555
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Joint wound healing using polymeric dressing of chitosan/strontium-doped titanium dioxide with high antibacterial activity Li Chenb, Hong Panc, Caifeng Zhuangb, Mengyao Pengb, and Li Zhang*a a
Department of Emergency, Rizhao City Hospital of Traditional Chinese Medicine,
Rizhao 276000, Shandong, China E-mail:
[email protected] b
Department of Spinal Surgery, People’s hospital of RiZhao, Rizhao 276800,
Shandong, China c
Department of General Surgery, People’s hospital of RiZhao, Rizhao 276800,
Shandong, China
Abstract: Treatment against bacterial infection is of great significance for joint wound healing in medical nursing care. Thus, it is urgent to develop efficient antibacterial agent with excellent wound healing capability. In this research, a two-step strategy was employed for the development of novel chitosan scaffold reinforced by strontium doped TiO2 nanoparticles (CS/Sr-TiO2). The antibacterial activity of CS/Sr-TiO2 against Escherichia coli, and Staphylococcus aureus were evaluated with the zone of inhibition method. Wound healing properties of CS/Sr-TiO2 were tested in rabbit joint wound, and the Sr-doping is able to achieve a high wound healing rate near 93 % after 12 days. Hence the results strongly demonstrate that the CS/Sr-TiO2 nanocomposites may be the promising materials for wound healing application in nursing care with enhanced antibacterial activity and high biocompatibility. 1
Key words Polymer; strontium doped titanium dioxide; biomaterials; composite materials; joint wound healing
1 Introduction The nursing care of wound after surgery or injury is a complex but critical biological procedure, in which variety of inter/intra-cellular pathways need to be activated for reducing the infection risk and promoting the wound healing. 1, 2 In recent years, tissue engineering method have been accepted as an effective way for skin wound through dermal repair and regeneration.
3, 4
The essential demands for an ideal dressing
biomaterial are biocompatible, non-allergenic, and can be easily removed from wound area without trauma.5 In addition, a moist environment with the porous structure is required for gaseous exchange, tissue regeneration, and removal of excess exudates. 6, 7
More importantly, the designed dressing biomaterial should possess excellent
antibacterial effect to protect the wound from further infection accompanied with fast wound healing ability. 8 Chitosan (CS) is an important scaffold biopolymer for tissue engineering because of its impressive biodegradability, biocompatibility, antibacterial and hemostatic activity. 9, 10
It is able to be processed into various forms including nanofibers, 11 hydrogels, 12
films, 13 and sponges. 14 Nevertheless, the wound healing ability of CS is largely limited for poor antimicrobial activity at neutral environment.
15
Incorporation of external
antibacterial agents into CS scaffold is a promising approach. For example, Zhai et al. presented porous chitosan/ZnO nanocomposite hydrogel as bandages for burn wound healing, the nanocomposite shown improved bactericidal activity. 2
16
You eat al.
introduced Ag nanoparticle into the collagen/chitosan hybrid scaffold for burn wounds, which displayed promoted anti-inflammatory and wound healing ability.
17
Among
various metallic antibacterial agents, TiO2 has received extensive interests thanks to the non-toxicity, high antibacterial activity, and outstanding physical and chemical stability. 18-21
Thus, the rational design and construction of chitosan scaffold incorporated with
TiO2 agent hold great potential for effective skin wound healing in nursing care. In this study, a facile two-step strategy was applied for the development of the welldispersed inorganic-organic hybrid Chitosan/strontium doped TiO2 (CS/Sr-TiO2) nanocomposite film. Microscopic morphology and structural conformation of CS/SrTiO2 film was investigated by scanning electron microscope (SEM), Powder X-ray diffraction (XRD), and X-ray photoelectron spectroscopy (XPS) techniques. The obtained CS/Sr-TiO2 nanocomposites film demonstrates improved antibacterial activity and superior joint wound healing property in nursing care.
2 Experimental section The Sr-TiO2 nanoparticles were prepared through hydrothermal method. Typically, 1.0 mL of tetrabutyl titanate (TTIP) and 0.1 mmol of Sr(NO3)2 was dissolved in 25.0 mL ethylene glycol (EG) under vigorous stirring, followed by dropwise adding of deionized water (50 mL) into the above solution at room temperature. Next, the suspension was transferred to the 100 mL Teflon-lined autoclave and hydrothermally heated at 180 °C for 10 h. After reaction, the pale precipitate was collected by washing with ethanol and water several times to thoroughly remove the surface EG. Finally, the Sr-TiO2 product 3
was vacuum dried at 85 ° C overnight. Additionally, the pure TiO2 sample has been prepared without the adding of Sr(NO3)2.
3. Results and discussion The TEM results of the as-synthesized Sr-TiO2 nanoparticles were provided in Fig. 1a, they presented high dispersibility and uniform particle size of about 20 nm. The inset HRTEM image revealed the highly crystallized feature of the particle associated with the clear interplanar spacing of 0.35 nm, which was assigned to the (1 0 1) lattice plane of anatase TiO2. 22 The Sr-TiO2 products with different Sr-doping amount have been synthesized, and the Sr dopant concentration was determined from the inductively coupled plasma optical emission spectroscopy (ICP-OES). The EDS spectrum for 1.2% At. % Sr-TiO2 sample was exhibited in Fig. 1b. It clearly presents the existence of Ti, O and Sr elements, suggesting the Sr has been successfully doped in the TiO2 phase. The atomic content of Sr is 1.19%, which is consistent with the ICP-OES results. The elemental valence and chemical composition information of CS/Sr-TiO2 nanocomposite dressing were detected by XPS measurement. The Sr 3d core level XPS spectrum in Fig. 1c also confirms the presence of strontium in all doped samples, while the peak intensities of the Sr 3d are observed to decrease with reducing the Sr content. The main peak located at 133.7 eV is belong to Sr 3d3/2 and the shoulder peak positioned at 135.5 eV stands for Sr 3d5/2. 23 Fig. 1d depicts O 1s spectra at 530.2 eV for un-doped TiO2 product which is ascribed to Ti-O bond in anatase TiO2. Also, a shoulder peak is observed in Sr spectrum as the dopant content is increased, which is attributed to the 4
cationic Sr2+ in the form of Sr-O band. The Ti 2p photoemission spectra are provided in Fig. 1e, two obvious peaks at 465.1 eV and 459.4 eV correspond to Ti 2p1/2 and Ti 2p3/2, respectively. The spin orbit splitting of 5.7 eV in all samples confirms the signal of Ti4+ in titanium oxidation state have remained unchanged by the doping at different levels. 24, 25 As we can see from Fig. 1f, chitosan nanofibers shown smooth surfaces and concentrated distributions of diameter (100-200 nm). Fig. 1g gave the microscopic morphology of Sr-TiO2 samples, the nonuniform Sr-TiO2 nanoparticles were anchored by the PLA matrixes. The CS/Sr-TiO2 fiber networks were illustrated in Fig. 1h, which displayed homogeneous dispersion of Sr-TiO2 nanoparticles without obvious agglomeration with the help of chitosan. The satisfied incorporation of Sr-TiO2 nanoparticles into CS scaffold and the abundant porosity of the nanocomposite dressing are able to exhibit ideal antibacterial activity and superior skin wound healing property in nursing care. The therapeutic efficacy of the different as-prepared dressings for in vivo joint wound healing was evaluated using the rabbit full-thickness joint wound models. Fig. 2a illustrated the optical photographs of the traumas after days 1, 6, and 12. Importantly, the rabbit joint wound treated with CS/Sr-TiO2 composite dressing grown fresh skin and the wound became smoother when compared to the control, and CS/TiO2 dressings. Moreover, after the 12-day surgery with the dressing of CS/Sr-TiO2 nanocomposite, the skin wound of the rat almost recovered to normal, showing better healing ability than other parallel-controlled treatments. The wound healing rate after treatment with 5
different dressings were shown in Fig. 2b. Obviously, the rabbits received therapy with CS/TiO2 and CS/Sr-TiO2 dressings displayed distinctive would healing effect. The Srdoping is able to further promote the wound care, leading to the highest wound healing rate near 93 % after 12 days for CS/Sr-TiO2 treated rabbits.
4. Conclusion In summary, a novel chitosan scaffold reinforced by Sr-TiO2 nanoparticles (near 20 nm in diameter) was fabricated via a two-step strategy for wound healing in nursing care. The microscopic morphology and composition of the prepared CS/Sr-TiO2 nanocomposite dressing was characterized by SEM, XRD, and XPS analysis. Antibacterial activity of CS/Sr-TiO2 against Escherichia coli, and Staphylococcus aureus were in vitro evaluated with the zone of inhibition method. The in vivo assessment for rabbit joint wound healing revealed that CS/Sr-TiO2 nanocomposite dressing shown a highest wound healing rate near 93 % after 12 days compared to that of the pure chitosan and CS/TiO2. This study strongly demonstrates that the CS/Sr-TiO2 nanocomposites may be the promising materials for wound healing application in nursing care with enhanced antibacterial activity and high biocompatibility.
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Figures
Fig. 1. (a) TEM images of the Sr-TiO2 nanoparticles. (b) EDX profile of Sr-TiO2 sample. XPS spectra for different Sr-TiO2 samples showing Sr 3d (c), O 1S (d), and Ti 2p (e). SEM images of the chitosan (f), TiO2 (g), and CS/Sr-TiO2 nanocomposite dressing (h).
Fig. 2. (a) In vivo evaluation of control, CS/TiO2, and CS/Sr-TiO2 nanocomposite as wound dressing, scale bar: 5mm, and their wound healing rate (b).
Conflicts of interest There are no conflicts to declare. 8
Author contributions Li Chen: Resources, Synthesis, Writing. Hong Pan: Formal analysis, characterization. Caifeng Zhuang: Formal analysis. Mengyao Peng: Characterization Li Zhang: Resources, Writing, Review, Editing.
Declaration of Interest Statement The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Highlights
The Sr-TiO2 nanoparticles with uniform morphology were fabricated through hydrothermal method. The polymeric chitosan based dressings combined with Sr-TiO2 nanoparticles were prepared for joint wound healing. The CS/Sr-TiO2 dressings shown high antimicrobial activity and improved wound healing effect. The CS/Sr-TiO2 dressings are promising materials for joint wound healing application in nursing care.
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