scholarly journals Development of an anti-infective coating on the surface of intraosseous implants responsive to enzymes and bacteria

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Xin Liao ◽  
Xingfang Yu ◽  
Haiping Yu ◽  
Jiaqi Huang ◽  
Bi Zhang ◽  
...  

Abstract Background Bacterial proliferation on the endosseous implants surface presents a new threat to the using of the bone implants. Unfortunately, there is no effective constructed antibacterial coating which is bacterial anti-adhesion substrate-independent or have long-term biofilm inhibition functions. Methods Drug release effect was tested in Chymotrypsin (CMS) solution and S. aureus. We used bacterial inhibition rate assays and protein leakage experiment to analyze the in vitro antibacterial effect of (Montmorillonite/Poly-l-lysine-Chlorhexidine)10 [(MMT/PLL-CHX)10] multilayer film. We used the CCK-8 assay to analyze the effect of (MMT/PLL-CHX)10 multilayer films on the growth and proliferation of rat osteoblasts. Rat orthopaedic implant-related infections model was constructed to test the antimicrobial activity effect of (MMT/PLL-CHX)10 multilayer films in vivo. Results In this study, the (MMT/PLL-CHX)10 multilayer films structure were progressively degraded and showed well concentration-dependent degradation characteristics following incubation with Staphylococcus aureus and CMS solution. Bacterial inhibition rate assays and protein leakage experiment showed high levels of bactericidal activity. While the CCK-8 analysis proved that the (MMT/PLL-CHX)10 multilayer films possess perfect biocompatibility. It is somewhat encouraging that in the in vivo antibacterial tests, the K-wires coated with (MMT/PLL-CHX)10 multilayer films showed lower infections incidence and inflammation than the unmodified group, and all parameters are close to SHAM group. Conclusion (MMT/PLL-CHX)10 multilayer films provides a potential therapeutic method for orthopaedic implant-related infections.

2021 ◽  
Author(s):  
Xin Liao ◽  
Xingfang Yu ◽  
Haiping Yu ◽  
Jiaqi Huang ◽  
Bi Zhang ◽  
...  

Abstract BackgroundBacterial proliferation on the endosseous implants surface presents a new threat to the using of the bone implants. Unfortunately, there is no effective constructed antibacterial coating which is bacterial anti-adhesion substrate-independent or have long-term biofilm inhibition functions. MethodsDrug release effect was tested in CMS solution and S. aureus. We used bacterial inhibition rate assays and protein leakageexperiment to analyze the in vitro antibacterial effect of (MMT/PLL-CHX)10 multilayer film. We used the CCK-8 assay to analyze the effect of (MMT/PLL-CHX)10 multilayer films on the growth and proliferation of rat osteoblasts. Rat orthopaedic implant-related infections model was constructed to test the antimicrobial activity effect of (MMT/PLL-CHX)10 multilayer films in vivo.ResultsIn this study, the (MMT/PLL-CHX)10 multilayer films structure were progressively degraded and showed well concentration-dependent degradation characteristics following incubation with Staphylococcus aureus and CMS solution. Bacterial inhibition rate assays and protein leakageexperiment showed high levels of bactericidal activity. While the CCK-8 analysis proved that the (MMT/PLL-CHX)10 multilayer films possess perfect biocompatibility. It is somewhat encouraging that in the in vivo antibacterial tests, the K-wires coated with (MMT/PLL-CHX)10 multilayer films showed lower infections incidence and inflammation than the unmodified group, and all parameters are close to SHAM group. Conclusion(MMT/PLL-CHX)10 multilayer films provides a potential therapeutic method for orthopaedic implant-related infections.


Antibiotics ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 631
Author(s):  
Mengfan Peng ◽  
Wentao Tong ◽  
Zhen Zhao ◽  
Ling Xiao ◽  
Zhaoyue Wang ◽  
...  

In this experiment, the quorum quenching gene ytnP of Bacillus licheniformis T-1 was cloned and expressed, and the effect against infection of Aeromonas hydrophila ATCC 7966 was evaluated in vitro and vivo. The BLAST results revealed a 99% sequence identity between the ytnP gene of T-1 and its homolog in B.subtilis sub sp. BSP1, and the dendroGram showed that the similarity in the YtnP protein in T-1 was 100% in comparison with B.subtilis 3610, which was categorized as the Aidc cluster of the MBL family. The AHL lactonase activity of the purified YtnP was detected as 1.097 ± 0.7 U/mL with C6-HSL as the substrate. Otherwise, purified YtnP protein could significantly inhibit the biofilm formation of A.hydrophila ATCC 7966 with an inhibition rate of 68%. The MIC of thiamphenicol and doxycycline hydrochloride against A. hydrophila reduced from 4 μg/mL and 0.5 μg/mL to 1 μg/mL and 0.125 μg/mL, respectively, in the presence of YtnP. In addition, YtnP significantly inhibited the expression of five virulence factors hem, ahyB, ast, ep, aerA of A. hydrophila ATCC 7966 as well (p < 0.05). The results of inhibition on virulence showed a time-dependence tendency, while the strongest anti-virulence effects were within 4–24 h. In vivo, when the YtnP protein was co-injected intraperitoneally with A. hydrophila ATCC 7966, it attenuated the pathogenicity of A. hydrophila and the accumulated mortality was 27 ± 4.14% at 96 h, which was significantly lower than the average mortality of 78 ± 2.57% of the Carassius auratus injected with 108 CFU/mL of A. hydrophila ATCC 7966 only (p < 0.001). In conclusion, the AHL lactonase in B. licheniformis T-1 was proven to be YtnP protein and could be developed into an agent against infection of A. hydrophila in aquaculture.


2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Fatemeh Ostadhossein ◽  
Parikshit Moitra ◽  
Esra Altun ◽  
Debapriya Dutta ◽  
Dinabandhu Sar ◽  
...  

AbstractDental plaques are biofilms that cause dental caries by demineralization with acidogenic bacteria. These bacteria reside inside a protective sheath which makes any curative treatment challenging. We propose an antibiotic-free strategy to disrupt the biofilm by engineered clustered carbon dot nanoparticles that function in the acidic environment of the biofilms. In vitro and ex vivo studies on the mature biofilms of Streptococcus mutans revealed >90% biofilm inhibition associated with the contact-mediated interaction of nanoparticles with the bacterial membrane, excessive reactive oxygen species generation, and DNA fragmentation. An in vivo examination showed that these nanoparticles could effectively suppress the growth of S. mutans. Importantly, 16S rRNA analysis of the dental microbiota showed that the diversity and richness of bacterial species did not substantially change with nanoparticle treatment. Overall, this study presents a safe and effective approach to decrease the dental biofilm formation without disrupting the ecological balance of the oral cavity.


1991 ◽  
Vol 261 (6) ◽  
pp. H1872-H1879 ◽  
Author(s):  
P. Kubes ◽  
M. B. Grisham ◽  
J. A. Barrowman ◽  
T. Gaginella ◽  
D. N. Granger

The overall objective of this study was to determine whether leukocyte adherence and/or emigration is a prerequisite for the increased vascular protein leakage associated with acute inflammation. An in vivo preparation was used to monitor intestinal vascular protein leakage as well as polymorphonuclear leukocyte (PMN) adhesion and emigration in feline mesenteric microvessels exposed to platelet-activating factor (PAF) and leukotriene B4 (LTB4). Local intra-arterial infusion of PAF (4 ng/min) produced a fourfold increase in vascular protein leakage. A 50-fold higher concentration of LTB4 had no effect on vascular protein efflux. LTB4, however, did potentiate the PAF-induced vascular protein leakage. Both inflammatory mediators caused leukocytes to adhere to endothelial cells in postcapillary venules; however, leukocyte emigration was observed only in the presence of PAF. PAF-induced leukocyte adhesion and emigration and the increased vascular protein leakage were inhibited by a monoclonal antibody (MoAb IB4) directed against the common beta-subunit of the adhesive glycoprotein complex CD11/CD18. MoAb IB4 also prevented LTB4-induced leukocyte adhesion. Both PAF and LTB4 caused degranulation of cat PMNs in vitro, yet superoxide production was stimulated by PAF only. The data derived from these in vivo and in vitro studies indicate that leukocyte adhesion per se does not necessarily lead to increased vascular protein leakage and leukocyte emigration. Adhesion-dependent PMN functions such as emigration and superoxide production may play an important role in producing the alterations in vascular integrity observed in inflamed microvessels.


Author(s):  
Amanda P. Mattos ◽  
Fabricio P. Povh ◽  
Bruna B. Rissato ◽  
Vítor V. Schwan ◽  
Kátia R. F. Schwan-Estrada

Aims: This study is aimed to evaluate the in vitro antifungal activity effect of the crude aqueous extract (CAE), hydrolate (HY) and essential oil (EO) of Corymbia citriodora, Cymbopogon citratus, Cymbopogon flexuosus and Curcuma longa against the phytopathogenic fungi Alternaria steviae, Botryosphaeria dothidea, Colletotrichum gloeosporioides and Sclerotium rolfsii, and assess, in situ, the effectiveness of CAE of medicinal plants in reducing the severity of the cucumber anthracnose. Methodology: The EOs and HYs were obtained by hydrodistillation. The CAEs were prepared by the turbolysis method. Mycelial growth of the fungi was measured daily, by the diametrically opposite method. In the in vivo test, the CAEs were sprayed on the cotyledon leaves of healthy cucumber plants with three days after were inoculated with C. lagenarium. The severity of assessment of the disease was based on a scale of notes. Results: The medicinal plants studied showed antifungal activity against all or almost all pathogens. In general, treatment with CAE and HY of C. longa revealed the highest inhibition against the fungi tested. With the exception of the EO of C. longa, the other EOs showed total inhibition against all the fungi and in all the concentrations tested. Compared to control, in in vivo assays CAE of C. citratus presents a potential for control of cucumber anthracnose reducing the severity of the disease. Conclusion: The medicinal plants studied produce compounds associated with antimicrobial activity.


2020 ◽  
Vol 477 (12) ◽  
pp. 2383-2399
Author(s):  
Fengyi Zhao ◽  
Wen Lu ◽  
Yuanyuan Xu ◽  
Li Xu ◽  
Jingjing Zhang ◽  
...  

Several bioactive dehydroabietylamine Schiff-bases (L1−L4), amides (L5−L11) and complex CuL3(NO3)2, Cu(L5)3, Co(L6)2Cl2 had been synthesized successfully for developing more efficient but lower toxic antiproliferative compounds. Their antiproliferative activities to Hela (cervix), HepG2 (liver), MCF-7 (breast), A549 (lung) and HUVEC (umbilical vein, normal cell) were investigated in vitro. The toxicity of all compounds was less than dehydroabietylamine (L0). For HepG2 cells, L1, L2 and L3 had higher anti-HepG2 activity, especially L1 (0.52 µM) had highest anti-HepG2 activity but low toxicity. For MCF-7 cells, L1, L2, L3 and L4 had higher anti-MCF-7 activity, especially L3(0.49 µM) had highest anti-MCF-7 activity but low toxicity. For A549 cells, L2 and L3 had higher anti-A549 activity. Furthermore, L1 and L3 may be the great promise antiproliferative drugs with nontoxic side effects, due to the high anti-HepG2 and anti-MCF-7 inhibition rate in vivo, 65% and 61%, respectively. L1, L2 and L3 could induce apoptosis through intercalating into DNA.


Author(s):  
Cong Yao ◽  
Meisong Zhu ◽  
Xiuguo Han ◽  
Qiang Xu ◽  
Min Dai ◽  
...  

Post-operative infections in orthopaedic implants are severe complications that require urgent solutions. Although conventional antibiotics limit bacterial biofilm formation, they ignore the bone loss caused by osteoclast formation during post-operative orthopaedic implant-related infections. Fortunately, enoxacin exerts both antibacterial and osteoclast inhibitory effects, playing a role in limiting infection and preventing bone loss. However, enoxacin lacks specificity in bone tissue and low bioavailability-related adverse effects, which hinders translational practice. Here, we developed a nanosystem (Eno@MSN-D) based on enoxacin (Eno)-loaded mesoporous silica nanoparticles (MSN), decorated with the eight repeating sequences of aspartate (D-Asp8), and coated with polyethylene glycol The release results suggested that Eno@MSN-D exhibits a high sensitivity to acidic environment. Moreover, this Eno@MSN-D delivery nanosystem exhibited both antibacterial and anti-osteoclast properties in vitro. The cytotoxicity assay revealed no cytotoxicity at the low concentration (20 μg/ml) and Eno@MSN-D inhibited RANKL-induced osteoclast differentiation. Importantly, Eno@MSN-D allowed the targeted release of enoxacin in infected bone tissue. Bone morphometric analysis and histopathology assays demonstrated that Eno@MSN-D has antibacterial and antiosteoclastic effects in vivo, thereby preventing implant-related infections and bone loss. Overall, our study highlights the significance of novel biomaterials that offer new alternatives to treat and prevent orthopaedic Staphylococcus aureus-related implantation infections and bone loss.


1987 ◽  
Author(s):  
T J Williams ◽  
M Rampart ◽  
S Nourshargh ◽  
P G Hellewell ◽  
S D Brain ◽  
...  

The mechanisms involved in the accumulation of polymorphonuclear leukocytes (PMNs) in an inflammatory reaction are complex. A key phase in this process is the attachment of the PMN to the microvascular (venular in most tissues) endothelial cell, initiated by the extravascular generation of a chemical mediator. Experiments in vitro suggest that mediators, such as C5a, may act in vivo by stimulating the increased expression of the CD18 complex on the surface of the PMN within the venule lumen (1), whereas IL-1 may act by causing the expression of an adhesive molecule on the endothelial cell (2). In vitro the former process is rapid whereas the latter is slow in onset. We have measured the local accumulation of intravenously-injected Ulln-PMNs in response to intradermally-injected mediators in the rabbit, in order to investigate possible mechanisms in vivo. PMN accumulation was found to be rapid in onset in response to C5a, the rate of accumulation falling progressively to low levels by 4 hours. In contrast PMN accumulation in response to IL-1 was slow in onset, reaching a peak rate at 3-4 hours. Intradermal injection of the vasodilator prostaglandins PGI2; PGE2 and the neuropeptides VIP and CGRP caused a marked potentiation of the rate of leukocyte accumulation. PMN accumulation induced by C5a was associated with increased microvascular permeability, as indicated by the leakage of intravenously-injected 125I-albumin with a time-course in parallel with the rate of PMN accumulation enhanced by intradermally-injected vasodilators. Depletion of circulating PMNs abolishes these responses to C5a (3). In contrast, leukocyte accumulation induced by IL-1 was associated with little plasma protein leakage, even in the presence of intradermal vasodilators. This observation indicates that PMN emigration itself does not lead to increased microvascular permeability. C5a, but not IL-1, may stimulate emigrating PMNs to secrete an endogenous factor that increases permeability by an action on endothelial cells (3). This factor does not appear to be the phospholipid PAF (4). In contrast to the enhancing effects of local PGI2, intravenously-infused PGI2 inhibited PMN accumulation induced by C5a and IL-1, and plasma protein leakage induced by C5a (5). This effect is probably mediated by elevation of cyclic AMP in intravascular PMNs. We have shown that C5a stimulation of PMNs in contact with endothelial cells in vitro induces endothelial cell PGI2 secretion (6). Thus, PGI2 may be part of a negative feedback system in vivo to control interactions between PMNs and endothelial cells.These observations provide some clues to the intricacies of mechanisms of leukocyte accumulation in vivo.


2018 ◽  
Vol 100-B (1_Supple_A) ◽  
pp. 9-16 ◽  
Author(s):  
E. P. Su ◽  
D. F. Justin ◽  
C. R. Pratt ◽  
V. K. Sarin ◽  
V. S. Nguyen ◽  
...  

The development and pre-clinical evaluation of nano-texturised, biomimetic, surfaces of titanium (Ti) implants treated with titanium dioxide (TiO2) nanotube arrays is reviewed. In vitro and in vivo evaluations show that TiO2 nanotubes on Ti surfaces positively affect the osseointegration, cell differentiation, mineralisation, and anti-microbial properties. This surface treatment can be superimposed onto existing macro and micro porous Ti implants creating a surface texture that also interacts with cells at the nano level. Histology and mechanical pull-out testing of specimens in rabbits indicate that TiO2 nanotubes improves bone bonding nine-fold (p = 0.008). The rate of mineralisation associated with TiO2 nanotube surfaces is about three times that of non-treated Ti surfaces. In addition to improved osseointegration properties, TiO2 nanotubes reduce the initial adhesion and colonisation of Staphylococcus epidermidis. Collectively, the properties of Ti implant surfaces enhanced with TiO2 nanotubes show great promise. Cite this article: Bone Joint J 2018;100-B(1 Supple A):9–16.


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