The bone defect repair is a complex process including immune regulation,stem cell osteogenic differentiation and extracellu-lar matrix mineralization.Current bone tissue engineering approaches often fail to adapt thro...The bone defect repair is a complex process including immune regulation,stem cell osteogenic differentiation and extracellu-lar matrix mineralization.Current bone tissue engineering approaches often fail to adapt throughout the above osteogenic process,resulting in suboptimal repair outcomes.To address this problem,a 3D-printed scaffold with multistage osteogenic activity based on shape-memory elastomer and electroactive material is developed.The scaffold exhibits excellent shape memory performance and can trigger shape recovery by physio-logical temperature.The physiological temperature-triggered shape-memory behavior makes the scaffold promising for mini-mally invasive implantation.After electric field polarization,the scaffold’s surface carries the negative charge,which can activate the PI3K/Akt signaling pathway to promote the polarization of macrophages to M2 phenotype and activate the FAK/ERK signaling pathway to promote osteogenic differentiation of bone marrow mesenchymal stem cells(BMSCs),indicating that the scaffold can effectively participate in immune microenvironment regulation and stem cell osteogenic differentiation.Additionally,the negative charge on the scaffold’s surface can attract calcium and phos-phate ions,forming a mineralized matrix and promoting late-stage extracellular matrix mineralization by continuously supplying mineralizing ions such as calcium and phosphate.Overall,this study introduces a 3D-printed scaffold with multistage osteogenic ac-tivity,offering a promising strategy for bone defect repair.展开更多
In situ monitoring of bone regeneration enables timely diagnosis and intervention by acquiring vital biological parameters.However,an existing gap exists in the availability of effective methodologies for continuous a...In situ monitoring of bone regeneration enables timely diagnosis and intervention by acquiring vital biological parameters.However,an existing gap exists in the availability of effective methodologies for continuous and dynamic monitoring of the bone tissue regeneration process,encompassing the concurrent visualization of bone formation and implant degradation.Here,we present an integrated scaffold designed to facilitate real-time monitoring of both bone formation and implant degradation during the repair of bone defects.Laponite(Lap),CyP-loaded mesoporous silica(CyP@MSNs)and ultrasmall superparamagnetic iron oxide nanoparticles(USPIO@SiO2)were incorporated into a bioink containing bone marrow mesenchymal stem cells(BMSCs)to fabricate functional scaffolds denoted as C@M/GLU using 3D bioprinting technology.In both in vivo and in vitro experiments,the composite scaffold has demonstrated a significant enhancement of bone regeneration through the controlled release of silicon(Si)and magnesium(Mg)ions.Employing near-infrared fluorescence(NIR-FL)imaging,the composite scaffold facilitates the monitoring of alkaline phosphate(ALP)expression,providing an accurate reflection of the scaffold’s initial osteogenic activity.Meanwhile,the degradation of scaffolds was monitored by tracking the changes in the magnetic resonance(MR)signals at various time points.These findings indicate that the designed scaffold holds potential as an in situ bone implant for combined visualization of osteogenesis and implant degradation throughout the bone repair process.展开更多
The repair of large load-bearing bone defects requires superior mechanical strength,a feat that a single hydrogel scaffold cannot achieve.The objective is to seamlessly integrate optimal microarchitecture,mechanical r...The repair of large load-bearing bone defects requires superior mechanical strength,a feat that a single hydrogel scaffold cannot achieve.The objective is to seamlessly integrate optimal microarchitecture,mechanical robustness,vascularisation,and osteoinductive biological responses to effectively address these critical load-bearing bone defects.To confront this challenge,three-dimensional(3D)printing technology was employed to prepare a polycaprolactone(PCL)-based integrated scaffold.Within the voids of 3D printed PCL scaffold,a methacrylate gelatin(GelMA)/methacrylated silk fibroin(SFMA)composite hydrogel incorporated with parathyroid hormone(PTH)peptide-loaded mesoporous silica nanoparticles(PTH@MSNs)was embedded,evolving into a porous PTH@MSNs/GelMA/SFMA/PCL(PM@GS/PCL)scaffold.The feasibility of fabricating this functional scaffold with a customised hierarchical structure was confirmed through meticulous chemical and physical characterisation.Compression testing unveiled an impressive strength of 17.81±0.83 MPa for the composite scaffold.Additionally,in vitro angiogenesis potential of PM@GS/PCL scaffold was evaluated through Transwell and tube formation assays using human umbilical vein endothelium,revealing the superior cell migration and tube network formation.The alizarin red and alkaline phosphatase staining assays using bone marrow-derived mesenchymal stem cells clearly illustrated robust osteogenic differentiation properties within this scaffold.Furthermore,the bone repair potential of the scaffold was investigated on a rat femoral defect model using micro-computed tomography and histological examination,demonstrating enhanced osteogenic and angiogenic performance.This study presents a promising strategy for fabricating a microenvironment-matched composite scaffold for bone tissue engineering,providing a potential solution for effective bone defect repair.展开更多
基金supported by the National Natural Science Foundation of China(32271412,32071350 and 32171404)Natural Science Foundation of Shanghai(21ZR1403100)Science and Technology Commission of Shanghai Municipality(20DZ2254900).
文摘The bone defect repair is a complex process including immune regulation,stem cell osteogenic differentiation and extracellu-lar matrix mineralization.Current bone tissue engineering approaches often fail to adapt throughout the above osteogenic process,resulting in suboptimal repair outcomes.To address this problem,a 3D-printed scaffold with multistage osteogenic activity based on shape-memory elastomer and electroactive material is developed.The scaffold exhibits excellent shape memory performance and can trigger shape recovery by physio-logical temperature.The physiological temperature-triggered shape-memory behavior makes the scaffold promising for mini-mally invasive implantation.After electric field polarization,the scaffold’s surface carries the negative charge,which can activate the PI3K/Akt signaling pathway to promote the polarization of macrophages to M2 phenotype and activate the FAK/ERK signaling pathway to promote osteogenic differentiation of bone marrow mesenchymal stem cells(BMSCs),indicating that the scaffold can effectively participate in immune microenvironment regulation and stem cell osteogenic differentiation.Additionally,the negative charge on the scaffold’s surface can attract calcium and phos-phate ions,forming a mineralized matrix and promoting late-stage extracellular matrix mineralization by continuously supplying mineralizing ions such as calcium and phosphate.Overall,this study introduces a 3D-printed scaffold with multistage osteogenic ac-tivity,offering a promising strategy for bone defect repair.
基金support from various resources,including the National Natural Science Foundation of China (grant numbers 32071350,32271412,32171404)the Shanghai Rising-Star Program (grant numbers 22QA1400100)+1 种基金the Fundamental Research Funds for the Central Universities (grant numbers 2232019A3-06,2232021D-10)the Science and Technology Commission of Shanghai Municipality (grant numbers 21ZR1403100,19440741600,20DZ2254900).
文摘In situ monitoring of bone regeneration enables timely diagnosis and intervention by acquiring vital biological parameters.However,an existing gap exists in the availability of effective methodologies for continuous and dynamic monitoring of the bone tissue regeneration process,encompassing the concurrent visualization of bone formation and implant degradation.Here,we present an integrated scaffold designed to facilitate real-time monitoring of both bone formation and implant degradation during the repair of bone defects.Laponite(Lap),CyP-loaded mesoporous silica(CyP@MSNs)and ultrasmall superparamagnetic iron oxide nanoparticles(USPIO@SiO2)were incorporated into a bioink containing bone marrow mesenchymal stem cells(BMSCs)to fabricate functional scaffolds denoted as C@M/GLU using 3D bioprinting technology.In both in vivo and in vitro experiments,the composite scaffold has demonstrated a significant enhancement of bone regeneration through the controlled release of silicon(Si)and magnesium(Mg)ions.Employing near-infrared fluorescence(NIR-FL)imaging,the composite scaffold facilitates the monitoring of alkaline phosphate(ALP)expression,providing an accurate reflection of the scaffold’s initial osteogenic activity.Meanwhile,the degradation of scaffolds was monitored by tracking the changes in the magnetic resonance(MR)signals at various time points.These findings indicate that the designed scaffold holds potential as an in situ bone implant for combined visualization of osteogenesis and implant degradation throughout the bone repair process.
基金supported by the National Natural Science Foundation of China(Nos.32071350,32171404)Fundamental Research Funds for the Central Universities(No.2232019A3-06)+3 种基金International Cooperation Fund of the Science and Technology Commission of Shanghai Municipality(No.19440741600)Natural Science Foundation of Shanghai(No.21ZR1403100)Science and Technology Commission of Shanghai Municipality(No.20DZ2254900)Biomaterials and Regenerative Medicine Institute Cooperative Research Project by Shanghai Jiao Tong University School of Medicine(No.2022LHB03).
文摘The repair of large load-bearing bone defects requires superior mechanical strength,a feat that a single hydrogel scaffold cannot achieve.The objective is to seamlessly integrate optimal microarchitecture,mechanical robustness,vascularisation,and osteoinductive biological responses to effectively address these critical load-bearing bone defects.To confront this challenge,three-dimensional(3D)printing technology was employed to prepare a polycaprolactone(PCL)-based integrated scaffold.Within the voids of 3D printed PCL scaffold,a methacrylate gelatin(GelMA)/methacrylated silk fibroin(SFMA)composite hydrogel incorporated with parathyroid hormone(PTH)peptide-loaded mesoporous silica nanoparticles(PTH@MSNs)was embedded,evolving into a porous PTH@MSNs/GelMA/SFMA/PCL(PM@GS/PCL)scaffold.The feasibility of fabricating this functional scaffold with a customised hierarchical structure was confirmed through meticulous chemical and physical characterisation.Compression testing unveiled an impressive strength of 17.81±0.83 MPa for the composite scaffold.Additionally,in vitro angiogenesis potential of PM@GS/PCL scaffold was evaluated through Transwell and tube formation assays using human umbilical vein endothelium,revealing the superior cell migration and tube network formation.The alizarin red and alkaline phosphatase staining assays using bone marrow-derived mesenchymal stem cells clearly illustrated robust osteogenic differentiation properties within this scaffold.Furthermore,the bone repair potential of the scaffold was investigated on a rat femoral defect model using micro-computed tomography and histological examination,demonstrating enhanced osteogenic and angiogenic performance.This study presents a promising strategy for fabricating a microenvironment-matched composite scaffold for bone tissue engineering,providing a potential solution for effective bone defect repair.
