Vancomycin containing PLLA/β-TCP controls experimental osteomyelitis in vivo

Kankilic, Berna; Bilgiç, Elif; Korkusuz, Petek; Korkusuz, Feza

doi:10.1186/s13018-014-0114-3

Cited by 20 publications

(32 citation statements)

References 27 publications

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“…Among the bacteria species isolated from osteomyelitis, S. aureus (Staphylococcus) is the most prevalent bacterial subtype, accounting for approximately 80% of all osteomyelitis pathogen, especially for septic osteomyelitis due to trauma (2). Although our understanding towards the pathophysiology and treatment of osteomyelitis has progressed significantly, it remains a clinical conundrum for orthopedic surgeons, especially cases caused by open fracture trauma (3).…”

Section: Introductionmentioning

confidence: 99%

Inhibition of pyroptosis attenuates Staphylococcus aureus-induced bone injury in traumatic osteomyelitis

Zhu

Zhang

et al. 2019

Ann. Transl. Med

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Background: Osteomyelitis is a severe bone infection and typically leads to progressive bone resorption, destruction and dysfunction. Pyroptosis is a form of programmed cell death involved in various infectious diseases. However, the identification of pyroptosis and the role it plays in osteomyelitis remains to be clarified. In this study, we investigated the expression of pyroptosis-associated proteins in osteomyelitis and the effects of inhibiting pyroptosis on S. aureus-induced osteomyelitis both in vitro and in vivo. Methods: The expression of pyroptosis-associated protein-NLRP3 (NLR Family Pyrin Domain Containing 3), Caspase1 and GSDMD (GasderminD) were examined in murine and human infectious bone fragments by western blot. Bone destruction was evaluated by microcomputed tomography (μCT). The concentration of inflammatory factors was tested by Enzyme linked Immunosorbent Assay (ELISA). The expression of pyroptosis-associated gene was detected by real-time quantitative polymerase chain reaction (RT-qPCR). Results: The expression of pyroptosis-associated proteins in infectious bone fragments from patients with osteomyelitis was significantly higher than uninfected bone. Additionally, in S. aureus-induced murine osteomyelitis model, higher expression of pyroptosis-associated proteins was noticed. Furthermore, the inhibitors of pyroptosis-associated proteins alleviated S. aureus-induced pyroptosis both in vivo and in vitro. More importantly, the inhibition of pyroptosis restored the bone formative property, attenuated the aberrant activation of osteoclast in vitro and reversed bone injury in vivo. Conclusions: Our study identified pyroptosis as a key pathway in osteomyelitis and elaborated that the inhibition of pyroptosis could attenuate S. aureus-induced bone destruction in osteomyelitis, providing a potential treatment target to osteomyelitis.

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Section: Introductionmentioning

confidence: 99%

Inhibition of pyroptosis attenuates Staphylococcus aureus-induced bone injury in traumatic osteomyelitis

Zhu

Zhang

et al. 2019

Ann. Transl. Med

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“…Em contrapartida, como desvantagem ao uso de polímero biodegradável como carreador para um fármaco, temos a possível "bomba" inicial de liberação antimicrobiana no local (Kankilic et al, 2014). Esse grande percentual de liberação inicial poderá dificultar uma liberação contínua e estável em níveis inibitórios desejáveis até a degradação polimérica.…”

Section: Sistemas De Liberação De Fármacosunclassified

“…Sabemos que por ser in vitro o estudo oferece limitações inerentes ao estabelecimento de condições experimentais e possibilidade do número de análises (Kankilic et al, 2014). Desta forma, se fazem necessários futuros estudos in vivo e, posteriormente, testes clínicos em maior escala que permitam confirmar a viabilidade de aplicação destes polímeros.…”

Section: Análise Estruturalunclassified

Análise in vitro de um dispositivo polimérico como alternativa para o uso de antimicrobiano sistêmico em Odontologia

Carnaval¹

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“…Atualmente, existe uma grande variedade de biomateriais que podem ser empregados para a administração local de antibióticos e sua eficácia tem sido demonstrada Kwon, 2011). Assim, o PLLA pode ser utilizado tanto como um dispositivo de matriz de suporte celular quanto como um liberador de fármaco local (Zhang et al, 2015;Kankilic et al, 2014;Wu et al, 2014).…”

Section: Lista De Abreviaturas E Siglasunclassified

“…Como um potencial sistema de administração de fármacos, o uso de biomateriais poliméricos, como o PLLA, em associação com antimicrobianos tem sido estudado (Kankilic et al, 2014;Wu et al,2014;Zhang et al, 2015 (Liu et al, 2004;Nair;Laurencin, 2007;Qi et al, 2013;Lafzi et al, 2016;).…”

Section: Amoxicilinaunclassified

Análise in vitro da citotoxicidade em osteoblastos de dispositivos poliméricos incorporados com antimicrobianos para uso local

Lage¹

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Lage TC. In vitro analysis of cytotoxicity in osteoblasts of polymer devices incorporated with antimicrobials for local use [dissertation] São Paulo: Universidade de São Paulo, Faculdade de Odontologia; 2017. Versão Corrigida. Osteoblasts are mesenquima originated cells, which are involved in the bone formation. These cells may suffer alterations due to traumas, interventions and infeccions. The infections can be minimized by the handling of antimicrobials. Poly (L-lactide) or PLLA is a synthetic polymer known for its biocompatibility and absorption, which can be used as a local pharmacological releaser, as an alternative to the systemic antimicrobial therapy. This polymer also can be frequently used as a supporting structure to cellular matrix in the bone tissue engineering as it can be used for support in repair and regeneration. The particle incorporation in this polymer can create side effects, therefore, we need to certificate that the polymeric device incorporated with antimicrobials are not cytotoxic. Proposition: Analyse the structure and cytotoxicity in osteoblasts of PLLA polymeric devices associated with antimicrobials, being them: Amoxicillin, Azithromycin, Clindamycin and Metronidazole. Methods: For this study 270 polymerical devices were manufactured with 6mm diameter of PLLA with a 20% antimicrobials incorporation of Amoxicillin (AM), Azithromycin (AZ), Clindamycin (CL) and Metronidazole (ME) that have been produced through two methods: eletrospinning (mesh) or casting (film). Afterwards a MTT cytotoxicity test was made over the periods of 24, 48 and 72 hours of experiment. To make a structural analysis of the device a macroscopic analysis was performed through photographs and microscopic imaging with scanning electron microscope (SEM). Results: The cytotoxicity reaction exhibited that meshes and films incorporated with antimicrobials are comparable with the osteoblasts culture, indicating that there was no cytotoxicity in any moment (p < 0.05). In the phothograph we could observe that the devices showed a similar coloration among the meshes and different coloration for the films depending on the incorporated antimicrobial. The SEM analysis displayed a difference in the surface appearance of the films. The AM films displayed an irregular and porous appearance, meanwhile, AZ looked smooth with few grains, the CL and ME have rough surfaces and PLLA presents smooth surfaces. As for the meshes, we noticed that all the samples had microfibers and pores that mimic the extracellular matrix, differing only in the thickness of the fibers. Osteoblasts were present in all films but AM did not induce proliferation, with only isolated cells emerging. In meshes osteoblasts were only found in AM, ME and PLLA. Conclusion: Polymeric devices made with PLLA incorporated with antimicrobials can be used in bone repair and regeneration given that they did not offer cytotoxicity for osteoblasts.

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Vancomycin containing PLLA/β-TCP controls experimental osteomyelitis in vivo

Cited by 20 publications

References 27 publications

Inhibition of pyroptosis attenuates Staphylococcus aureus-induced bone injury in traumatic osteomyelitis

Inhibition of pyroptosis attenuates Staphylococcus aureus-induced bone injury in traumatic osteomyelitis

Análise in vitro de um dispositivo polimérico como alternativa para o uso de antimicrobiano sistêmico em Odontologia

Análise in vitro da citotoxicidade em osteoblastos de dispositivos poliméricos incorporados com antimicrobianos para uso local

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