Graphene oxide/gallium nanoderivative as a multifunctional modulator of osteoblastogenesis and osteoclastogenesis for the synergistic therapy of implant-related bone infection

Currently, implant-associated bacterial infections account for most hospital-acquired infections in patients suffering from bone fractures or defects. Poor osseointegration and aggravated osteolysis remain great challenges for the success of implants in infectious scenarios. Consequently, developing...

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Main Authors: Ying Yang, Min Li, Bixia Zhou, Xulei Jiang, Dou Zhang, Hang Luo
Format: Article
Language:English
Published: KeAi Communications Co., Ltd. 2023-07-01
Series:Bioactive Materials
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2452199X22003139
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author Ying Yang
Min Li
Bixia Zhou
Xulei Jiang
Dou Zhang
Hang Luo
author_facet Ying Yang
Min Li
Bixia Zhou
Xulei Jiang
Dou Zhang
Hang Luo
author_sort Ying Yang
collection DOAJ
description Currently, implant-associated bacterial infections account for most hospital-acquired infections in patients suffering from bone fractures or defects. Poor osseointegration and aggravated osteolysis remain great challenges for the success of implants in infectious scenarios. Consequently, developing an effective surface modification strategy for implants is urgently needed. Here, a novel nanoplatform (GO/Ga) consisting of graphene oxide (GO) and gallium nanoparticles (GaNPs) was reported, followed by investigations of its in vitro antibacterial activity and potential bacterium inactivation mechanisms, cytocompatibility and regulatory actions on osteoblastogenesis and osteoclastogenesis. In addition, the possible molecular mechanisms underlying the regulatory effects of GO/Ga nanocomposites on osteoblast differentiation and osteoclast formation were clarified. Moreover, an in vivo infectious microenvironment was established in a rat model of implant-related femoral osteomyelitis to determine the therapeutic efficacy and biosafety of GO/Ga nanocomposites. Our results indicate that GO/Ga nanocomposites with excellent antibacterial potency have evident osteogenic potential and inhibitory effects on osteoclast differentiation by modulating the BMP/Smad, MAPK and NF-κB signaling pathways. The in vivo experiments revealed that the administration of GO/Ga nanocomposites significantly inhibited bone infections, reduced osteolysis, promoted osseointegration located in implant-bone interfaces, and resulted in satisfactory biocompatibility. In summary, this synergistic therapeutic system could accelerate the bone healing process in implant-associated infections and can significantly guide the future surface modification of implants used in bacteria-infected environments.
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spelling doaj.art-6a20fc077429419988dcf96ce7089e632023-03-24T04:23:01ZengKeAi Communications Co., Ltd.Bioactive Materials2452-199X2023-07-0125594614Graphene oxide/gallium nanoderivative as a multifunctional modulator of osteoblastogenesis and osteoclastogenesis for the synergistic therapy of implant-related bone infectionYing Yang0Min Li1Bixia Zhou2Xulei Jiang3Dou Zhang4Hang Luo5Department of Plastic Surgery, Xiangya Hospital, Central South University, Changsha, 410008, China; State Key Laboratory of Powder Metallurgy, Central South University, Changsha, 410083, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, China; Corresponding author. Department of Plastic Surgery, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, 410008, Hunan, PR China.Department of Oncology, Changsha Central Hospital, University of South China, Changsha, 410006, ChinaDepartment of Plastic Surgery, Xiangya Hospital, Central South University, Changsha, 410008, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, ChinaDepartment of Plastic Surgery, Xiangya Hospital, Central South University, Changsha, 410008, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, ChinaState Key Laboratory of Powder Metallurgy, Central South University, Changsha, 410083, ChinaState Key Laboratory of Powder Metallurgy, Central South University, Changsha, 410083, China; Corresponding author. State Key Laboratory of Powder Metallurgy, Central South University, 932 South Lushan Road, Changsha, 410083, Hunan, China.Currently, implant-associated bacterial infections account for most hospital-acquired infections in patients suffering from bone fractures or defects. Poor osseointegration and aggravated osteolysis remain great challenges for the success of implants in infectious scenarios. Consequently, developing an effective surface modification strategy for implants is urgently needed. Here, a novel nanoplatform (GO/Ga) consisting of graphene oxide (GO) and gallium nanoparticles (GaNPs) was reported, followed by investigations of its in vitro antibacterial activity and potential bacterium inactivation mechanisms, cytocompatibility and regulatory actions on osteoblastogenesis and osteoclastogenesis. In addition, the possible molecular mechanisms underlying the regulatory effects of GO/Ga nanocomposites on osteoblast differentiation and osteoclast formation were clarified. Moreover, an in vivo infectious microenvironment was established in a rat model of implant-related femoral osteomyelitis to determine the therapeutic efficacy and biosafety of GO/Ga nanocomposites. Our results indicate that GO/Ga nanocomposites with excellent antibacterial potency have evident osteogenic potential and inhibitory effects on osteoclast differentiation by modulating the BMP/Smad, MAPK and NF-κB signaling pathways. The in vivo experiments revealed that the administration of GO/Ga nanocomposites significantly inhibited bone infections, reduced osteolysis, promoted osseointegration located in implant-bone interfaces, and resulted in satisfactory biocompatibility. In summary, this synergistic therapeutic system could accelerate the bone healing process in implant-associated infections and can significantly guide the future surface modification of implants used in bacteria-infected environments.http://www.sciencedirect.com/science/article/pii/S2452199X22003139NanocompositesAntimicrobial potencyImplant-associated bone infectionsOsteogenesisOsteoclastogenesis
spellingShingle Ying Yang
Min Li
Bixia Zhou
Xulei Jiang
Dou Zhang
Hang Luo
Graphene oxide/gallium nanoderivative as a multifunctional modulator of osteoblastogenesis and osteoclastogenesis for the synergistic therapy of implant-related bone infection
Bioactive Materials
Nanocomposites
Antimicrobial potency
Implant-associated bone infections
Osteogenesis
Osteoclastogenesis
title Graphene oxide/gallium nanoderivative as a multifunctional modulator of osteoblastogenesis and osteoclastogenesis for the synergistic therapy of implant-related bone infection
title_full Graphene oxide/gallium nanoderivative as a multifunctional modulator of osteoblastogenesis and osteoclastogenesis for the synergistic therapy of implant-related bone infection
title_fullStr Graphene oxide/gallium nanoderivative as a multifunctional modulator of osteoblastogenesis and osteoclastogenesis for the synergistic therapy of implant-related bone infection
title_full_unstemmed Graphene oxide/gallium nanoderivative as a multifunctional modulator of osteoblastogenesis and osteoclastogenesis for the synergistic therapy of implant-related bone infection
title_short Graphene oxide/gallium nanoderivative as a multifunctional modulator of osteoblastogenesis and osteoclastogenesis for the synergistic therapy of implant-related bone infection
title_sort graphene oxide gallium nanoderivative as a multifunctional modulator of osteoblastogenesis and osteoclastogenesis for the synergistic therapy of implant related bone infection
topic Nanocomposites
Antimicrobial potency
Implant-associated bone infections
Osteogenesis
Osteoclastogenesis
url http://www.sciencedirect.com/science/article/pii/S2452199X22003139
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AT minli grapheneoxidegalliumnanoderivativeasamultifunctionalmodulatorofosteoblastogenesisandosteoclastogenesisforthesynergistictherapyofimplantrelatedboneinfection
AT bixiazhou grapheneoxidegalliumnanoderivativeasamultifunctionalmodulatorofosteoblastogenesisandosteoclastogenesisforthesynergistictherapyofimplantrelatedboneinfection
AT xuleijiang grapheneoxidegalliumnanoderivativeasamultifunctionalmodulatorofosteoblastogenesisandosteoclastogenesisforthesynergistictherapyofimplantrelatedboneinfection
AT douzhang grapheneoxidegalliumnanoderivativeasamultifunctionalmodulatorofosteoblastogenesisandosteoclastogenesisforthesynergistictherapyofimplantrelatedboneinfection
AT hangluo grapheneoxidegalliumnanoderivativeasamultifunctionalmodulatorofosteoblastogenesisandosteoclastogenesisforthesynergistictherapyofimplantrelatedboneinfection