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Irisin-loaded electrospun core-shell nanofibers as calvarial periosteum accelerate vascularized bone regeneration by activating the mitochondrial SIRT3 pathway

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Regenerative Biomaterials 2024年第1期3卷 44-57页

作者： Xi Hua Mingzhuang Hou Lei Deng Nanning Lv Yong Xu Xuesong Zhu Huilin Yang Qin Shi Hao Liu Fan He Department of orthopaedics The First Affiliated Hospital of Soochow UniversitySoochow UniversitySuzhou 215006China Orthopaedic Institute Suzhou Medical CollegeSoochow UniversitySuzhou 215000China Department of Orthopedics Suzhou Wuzhong People’s HospitalSuzhouJiangsu Province 215128China Department of Orthopedic Surgery Lianyungang Clinical College of Xuzhou Medical UniversityLianyungang 222003China

The scarcity of native periosteum poses a significant clinical barrier in the repair of critical-sized bone *** challenge of enhancing regenerative potential in bone healing is further compounded by oxidative stress at the fracture ***,the introduction of artificial periosteum has demonstrated its ability to promote bone regeneration through the provision of appropriate mechanical support and controlled release of proosteogenic *** this study,a poly(L-lactic acid)(PLLA)/hyaluronic acid(HA)-based nanofibrous membrane was fabricated using the coaxial electrospinning *** incorporation of irisin into the core-shell structure of PLLA/HA nanofibers(PLLA/HA@Irisin)achieved its sustained *** vitro experiments demonstrated that the PLLA/HA@Irisin membranes exhibited favorable *** osteogenic differentiation of bone marrow mesenchymal stem cells(BMMSCs)was improved by PLLA/HA@Irisin,as evidenced by a significant increase in alkaline phosphatase activity and matrix ***,PLLA/HA@Irisin significantly enhanced the mitochondrial function of BMMSCs via the activation of the sirtuin 3 antioxidant *** assess the therapeutic effectiveness,PLLA/HA@Irisin membranes were implanted in situ into critical-sized calvarial defects in *** results at 4 and 8 weeks post-surgery indicated that the implantation of PLLA/HA@Irisin exhibited superior efficacy in promoting vascularized bone formation,as demonstrated by the enhancement of bone matrix synthesis and the development of new blood *** results of our study indicate that the electrospun PLLA/HA@Irisin nanofibers possess characteristics of a biomimetic periosteum,showing potential for effectively treating critical-sized bone defects by improving the mitochondrial function and maintaining redox homeostasis of BMMSCs.

关键词： periosteum irisin mitochondrial function critical-sized bone defect redox homeostasis

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3D-bioprinted anisotropic bicellular living hydrogels boost osteochondral regeneration via reconstruction of cartilage–bone interface

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The Innovation 2024年第2期5卷 88-97页

作者： Yijian Zhang Duo Li Yang Liu Liuqi Peng Dongdong Lu Pinpin Wang Dongxu Ke Huilin Yang Xuesong Zhu Changshun Ruan Department of orthopaedics The First Affiliated Hospital of Soochow UniversitySoochow UniversitySuzhou 215006China Research Center for Human Tissue and Organ Degeneration Institute of Biomedicine and BiotechnologyShenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhen 518055China University of Chinese Academy of Sciences Beijing 100049China Novaprint Therapeutics suzhou Co. Ltd.Room 605B1 BuildingBioBayNo.218 Xinghu StreetSuzhou Industrial ParkSuzhou 215000China

Reconstruction of osteochondral(OC)defects represents an immense challenge due to the need for synchronous regeneration of special stratified *** revolutionary innovation of bioprinting provides a robust method for precise fabrication of tissue-engineered OCs with hierarchical structure;however,their spatial living cues for simultaneous fulfilment of osteogenesis and chondrogenesis to reconstruct the cartilage-bone interface of OC are ***,inspired by natural OC bilayer features,anisotropic bicellular living hydrogels(ABLHs)simultaneously embedding articular cartilage progenitor cells(ACPCs)and bone mesenchymal stem cells(BMSCs)in stratified layers were precisely fabricated via two-channel extrusion *** optimum formulation of the 7%GelMA/3%AlgMA hydrogel bioink was demonstrated,with excellent printability at room temperature and maintained high cell ***,the chondrogenic ability of ACPCs and the osteogenic ability of BMSCs were demonstrated in vitro,confirming the inherent differential spatial regulation of ABLHs.

关键词： printing stratified boost

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Vanillin-based functionalization strategy to construct multifunctional microspheres for treating inflammation and regenerating intervertebral disc

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Bioactive Materials 2023年第10期28卷 167-182页

作者： Zhuang Zhu Qifan Yu Hanwen Li Feng Han Qianping Guo Heng Sun He Zhao Zhengdong Tu Zhuang Liu Caihong Zhu Bin Li Orthopedic Institute Department of Orthopedic SurgeryThe First Affiliated HospitalSchool of Biology&Basic Medical SciencesSuzhou Medical CollegeSoochow UniversitySuzhouJiangsu215007China Institute of Functional Nano&Soft Materials Jiangsu Key Laboratory for Carbon-Based Functional Materials and DevicesSoochow UniversitySuzhouJiangsu215123China Children’s Hospital of Soochow University Pediatric Research Institute of Soochow UniversitySuzhouJiangsu215123China

Intervertebral disc degeneration(IVDD)is one of the main causes of low back *** local delivery strategies using biomaterial carriers have shown potential for IVDD treatment,it remains challenging for intervention against multiple adverse contributors by a single delivery *** the present work,we propose a new functionalization strategy using vanillin,a natural molecule with anti-inflammatory and antioxidant properties,to develop multifunctional gelatin methacrylate(GelMA)microspheres for local delivery of transforming growth factorβ3(TGFβ3)toward IVDD *** vitro,functionalized microspheres not only improved the release kinetics of TGFβ3 but also effectively inhibited inflammatory responses and promoted the secretion of extracellular matrix(ECM)in lipopolysaccharide-induced nucleus pulposus(NP)*** vivo,functionalized platform plays roles in alleviating inflammation and oxidative stress,preserving the water content of NP and disc height,and maintaining intact structure and biomechanical functions,thereby promoting the regeneration of ***-throughput sequencing suggests that inhibition of the phosphatidylinositol 3-kinase(PI3K)-Akt signaling might be associated with their therapeutic *** summary,the vanillin-based functionalization strategy provides a novel and simple way for packaging multiple functions into a single delivery platform and holds promise for tissue regeneration beyond the IVD.

关键词： Intervertebral disc degeneration Microsphere Vanillin Transforming growth factorβ3 Regeneration

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