Large bone defects face a high risk of pathogen exposure due to open wounds,which leads to high infection rates and delayed bone union.To promote successful repair of infectious bone defects,fabrication of a scaffold ...Large bone defects face a high risk of pathogen exposure due to open wounds,which leads to high infection rates and delayed bone union.To promote successful repair of infectious bone defects,fabrication of a scaffold with dual functions of osteo-induction and bacterial inhibition is required.This study describes creation of an engineered progenitor cell line(C3H10T1/2)capable of doxycycline(DOX)-mediated release of bone morphogenetic protein-2(BMP2).Three-dimensional bioprinting technology enabled creation of scaffolds,comprising polycaprolactone/mesoporous bioactive glass/DOX and bioink,containing these engineered cells.In vivo and in vitro experiments confirmed that the scaffold could actively secrete BMP2 to significantly promote osteoblast differentiation and induce ectopic bone formation.Additionally,the scaffold exhibited broad-spectrum antibacterial capacity,thereby ensuring the survival of embedded engineered cells when facing high risk of infection.These findings demonstrated the efficacy of this bioprinted scaffold to release BMP2 in a controlled manner and prevent the occurrence of infection;thus,showing its potential for repairing infectious bone defects.展开更多
Bone defects caused by trauma,tumor,congenital abnormality and osteoarthritis,etc.have been substantially impacted the lives and health of human.Artificial bone implants,like bioceramic-based scaffolds,provide signifi...Bone defects caused by trauma,tumor,congenital abnormality and osteoarthritis,etc.have been substantially impacted the lives and health of human.Artificial bone implants,like bioceramic-based scaffolds,provide significant benefits over biological counterparts and are critical for bone repair and regeneration.However,it is highly probable that bacterial infections occur in the surgical procedures or on bioceramic-based scaffolds.Therefore,it is of great significance to obtain bioceramic-based scaffolds with integrative antibacterial and osteogenic functions for treating bone implant-associated infection and promoting bone repair.To fight against infection problems,bioceramic-based scaffolds with various antibacterial strategies are developed for bone repair and regeneration and also have made great progresses.This review summarizes recent progresses in bioceramic-based scaffolds with antibacterial function,which include drug-induced,ion-mediated,physical-activated and their combined antibacterial strategies according to specific antibacterial mechanism.Finally,the challenges and opportunities of antibacterial bioceramic-based scaffolds are discussed.展开更多
For the therapy and regeneration of bone defects resulting from malignant bone tumors, it is necessary to develop multifunctional biomaterials that are able to deliver therapeutic drugs, monitor drug release, and stim...For the therapy and regeneration of bone defects resulting from malignant bone tumors, it is necessary to develop multifunctional biomaterials that are able to deliver therapeutic drugs, monitor drug release, and stimulate bone formation. Herein, a multifunctional mesoporous bioactive glass （MBG）/upconversion nanoparticle （UCNP） nanocomposite [UCNPs@SiO2@mSiO2-XCa （X = 0, 5, 10, 15, and 20）] with the ability to deliver anti-cancer drugs, monitor drug release, and stimulate osteogenic differentiation of bone marrow stromal cells （BMSCs） was successfully prepared using a layer-by-layer strategy. The nanocomposite spheres possess a core--sheU structure composed of UCNPs and a mesoporous SiO2/Ca layer with a uniform size distribution of 100 nm. The incorporation of Ca into the nanocomposites induced phase transformation from a pure hexagonal phase to a cubic phase, and facilitated the occurrence of red emission, which significantly improved fluorescence penetration for deep tissue imaging. In addition, since the red emission strongly overlaps with the maximum absorbance of the anti-cancer drug zinc phthalocyanine （ZnPc）, red luminescence could be strongly quenched by ZnPc. Consequently, drug release could be quantified by monitoring changes in fluorescence intensity. Furthermore, the incorporation of Ca into MBG/UCNP nanocomposites remarkably improved bioactivity, i.e., it stimulated apatite mineralization in simulated body fluids and enhanced cell proliferation and bone-related gene expression in BMSCs for the concentration range of 200-500 ~g/mL. Our results suggest that the prepared MBG/UCNP nanocomposites are useful for the therapy and regeneration of bone defects resulting from malignant bone tumors owing to their distinct multifunctionality, including strong red emission and functions in drug-delivery monitoring and osteostimulation.展开更多
基金supported by the National Key R&D Program(grant no.2016YFC1102100)a NSFC grant(grant no.81921002)the Shanghai Science and Technology Development Fund(grant no.18DZ2291200 and 18441902700).
文摘Large bone defects face a high risk of pathogen exposure due to open wounds,which leads to high infection rates and delayed bone union.To promote successful repair of infectious bone defects,fabrication of a scaffold with dual functions of osteo-induction and bacterial inhibition is required.This study describes creation of an engineered progenitor cell line(C3H10T1/2)capable of doxycycline(DOX)-mediated release of bone morphogenetic protein-2(BMP2).Three-dimensional bioprinting technology enabled creation of scaffolds,comprising polycaprolactone/mesoporous bioactive glass/DOX and bioink,containing these engineered cells.In vivo and in vitro experiments confirmed that the scaffold could actively secrete BMP2 to significantly promote osteoblast differentiation and induce ectopic bone formation.Additionally,the scaffold exhibited broad-spectrum antibacterial capacity,thereby ensuring the survival of embedded engineered cells when facing high risk of infection.These findings demonstrated the efficacy of this bioprinted scaffold to release BMP2 in a controlled manner and prevent the occurrence of infection;thus,showing its potential for repairing infectious bone defects.
基金the National Natural Science Foundation of China(No.51872185,52072246,32130062)Science and Technology Commission of Shanghai Municipality(No.20442420300)China Postdoctoral Science Foundation(No.2021M703332).
文摘Bone defects caused by trauma,tumor,congenital abnormality and osteoarthritis,etc.have been substantially impacted the lives and health of human.Artificial bone implants,like bioceramic-based scaffolds,provide significant benefits over biological counterparts and are critical for bone repair and regeneration.However,it is highly probable that bacterial infections occur in the surgical procedures or on bioceramic-based scaffolds.Therefore,it is of great significance to obtain bioceramic-based scaffolds with integrative antibacterial and osteogenic functions for treating bone implant-associated infection and promoting bone repair.To fight against infection problems,bioceramic-based scaffolds with various antibacterial strategies are developed for bone repair and regeneration and also have made great progresses.This review summarizes recent progresses in bioceramic-based scaffolds with antibacterial function,which include drug-induced,ion-mediated,physical-activated and their combined antibacterial strategies according to specific antibacterial mechanism.Finally,the challenges and opportunities of antibacterial bioceramic-based scaffolds are discussed.
基金Funding for this study was provided by the China Postdoctroal Science Foundation funded project （No. 2014M561526）, the Recruitment Program of Global Young Talent, China （Dr. Wu）, the National High-tech R＆D Program of China （No. SS2015AA020302）, the National Natural Science Foundation of China （No. 81190132）, Program of Shanghai Outstanding Academic Leaders （No. 15XD1503900）, and the Key Research Program of Chinese Academy of Sciences （No. KGZD- EW-T06）.
文摘For the therapy and regeneration of bone defects resulting from malignant bone tumors, it is necessary to develop multifunctional biomaterials that are able to deliver therapeutic drugs, monitor drug release, and stimulate bone formation. Herein, a multifunctional mesoporous bioactive glass （MBG）/upconversion nanoparticle （UCNP） nanocomposite [UCNPs@SiO2@mSiO2-XCa （X = 0, 5, 10, 15, and 20）] with the ability to deliver anti-cancer drugs, monitor drug release, and stimulate osteogenic differentiation of bone marrow stromal cells （BMSCs） was successfully prepared using a layer-by-layer strategy. The nanocomposite spheres possess a core--sheU structure composed of UCNPs and a mesoporous SiO2/Ca layer with a uniform size distribution of 100 nm. The incorporation of Ca into the nanocomposites induced phase transformation from a pure hexagonal phase to a cubic phase, and facilitated the occurrence of red emission, which significantly improved fluorescence penetration for deep tissue imaging. In addition, since the red emission strongly overlaps with the maximum absorbance of the anti-cancer drug zinc phthalocyanine （ZnPc）, red luminescence could be strongly quenched by ZnPc. Consequently, drug release could be quantified by monitoring changes in fluorescence intensity. Furthermore, the incorporation of Ca into MBG/UCNP nanocomposites remarkably improved bioactivity, i.e., it stimulated apatite mineralization in simulated body fluids and enhanced cell proliferation and bone-related gene expression in BMSCs for the concentration range of 200-500 ~g/mL. Our results suggest that the prepared MBG/UCNP nanocomposites are useful for the therapy and regeneration of bone defects resulting from malignant bone tumors owing to their distinct multifunctionality, including strong red emission and functions in drug-delivery monitoring and osteostimulation.
