Ca-Ga Double Doping Strategy to Fabricate Hemostatic Mesoporous Silica Nanoparticles (MSN) with Antibacterial Activity

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ORIGINAL PAPER

Ca-Ga Double Doping Strategy to Fabricate Hemostatic Mesoporous Silica Nanoparticles (MSN) with Antibacterial Activity Sheng Ding 1 & Xiaohui Wei 1 & Kun Yang 1 & Song Lin 1 & Feng Tian 1

&

Fan Li 1

Received: 20 March 2020 / Accepted: 5 September 2020 # Springer Nature B.V. 2020

Abstract Hemostatic materials with antibacterial properties become increasingly significant in military and civilian trauma care. In recent years, some advanced inorganic hemostatic materials (e.g. QuikClot, Combat Gauze, and WoundStat) have been reported to have their own drawbacks and side effects. In the study, the mesoporous silica nanoparticles (MSN) doped with calcium and gallium (Ga0.5CaMSS) was explored for hemorrhage control together with good antibacterial properties. Transmission electron microscopy (TEM), the energy-dispersive X-ray spectrometer (EDS), Nitrogen gas adsorption-desorption measurements, X-Ray diffraction measurements (XRD) and the Fourier transform infrared (FTIR) spectra were used to characterize the coagulationpromoting surface chemistry, morphology and porous structure of the samples. The clotting blood tests (CBT), activated partial thromboplastin time (APTT) tests, prothrombin time (PT) tests, and thromboelastograph (TEG) analysis showed the much better hemostatic properties of the Ga0.5CaMSN compared with the control and blank MSN. Besides, Ga0.5CaMSN was found to have obvious antibacterial effect against both S. aureus and E. coli. Furthermore, the perfect biocompatibility of all samples was proved by hemolysis assay study and cytotoxicity test. Associated with the blood coagulation tests and antibacterial tests, it could be inferred that the stimulation of the blood coagulation and antibacterial activity of Ga0.5CaMSN were attributed to the incorporation of calcium ions and gallium ions. The Ga0.5CaMSN developed here can be a potent candidate for emergency treatment to control hemorrhage and wound infection pre-hospital. Keywords Mesoporous silica nanoparticles (MSN) . Calcium . Gallium . Hemorrhage control . Antibacterial properties

1 Introduction In modern war and pre-hospital period, excessive hemorrhage is still the main cause of death [1], and excessive hemorrhage accounts for 80% of early trauma deaths. Therefore, rapid hemorrhage control is essential for successful treatment. Meanwhile, the death of the wounded occurred in 5 days after injury is mainly due to the infection. It is reported that 2/3 to 3/4 of the post-war death is related to serious infections [2]. Therefore, the hemostatic materials with antibacterial properties will play an important role on treatments for the wounded pre-hospital.

* Feng Tian [email protected] * Fan Li [email protected] 1

Institute of Medical Support Technology, Academy of Military Sciences, Tianjin 300161, People’s Republic of China

Several clinical hemostatic agents have been applied to control hemorrhage, which were mainly divided into two parts: polymer materials (HemCon, Celox, Celox-D) and inorganic materials (QuikClot, WoundSta