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Functionalize d 3D-printe d porous titanium scaffold induces in situ vascularized bone regeneration by orchestrating bone microenvironment

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Journal of Materials Science & Technology 2023年第22期153卷 92-105页

作者： Bo Yuan Pin Liu Rui Zhao Xiao Yang Zhanwen Xiao Kai Zhang Xiangdong Zhu Xingdong Zhang National Engineering Research Center for Biomaterials Sichuan UniversityChengdu 610064China College of Biomedical Engineering Sichuan UniversityChengdu 610064China

Titanium(Ti)and its alloys have been extensively explored for treating load-bearing bone ***-ever,high-stress shielding,weak osteogenic activity,and insufficient vascularization remain key chal-lenges for the long-term clinical outcomes of Ti-based ***,inspired by structural and func-tional cues of bone regeneration,a silicon-doped nano-hydroxyapatite(nSiHA)/titanium dioxide(TiO_(2))composite coating with a hierarchical micro/nano-network structure is constructed on the surface of a 3D-printed porous Ti scaffold via a combined strategy of acid-alkali(AA)treatment and electrochemi-cal deposition technique,which not only endows the scaffold with excellent osteoinduction ability but can also effectively immobilize and release vascular endothelial growth factor(VEGF).The results of the in vitro cell experiments show that the functionalized Ti scaffold significantly promotes osteogenesis in bone marrow mesenchymal stem cells(BMSCs)and angiogenesis in human umbilical vein endothelial cells(HUVECs)by activating the extracellular signal-regulated protein kinase(ERK)and HIF-1αsignaling *** being implanted into a rat femoral condyle defect model,the functionalized Ti scaffold can induce in situ vascularized bone regeneration by orchestrating the two coupled processes of angio-genesis and *** findings indicate that the functionalized Ti scaffold has great potential in bone tissue regeneration and is a promising candidate for load-bearing bone defect repair.

关键词： Porous titanium 3D-printing Hierarchical micro/nano-structure bone microenvironment Vascularization bone regeneration

A multifunctional nanocomposite hydrogel with controllable release behavior enhances bone regeneration

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Regenerative Biomaterials 2023年第1期10卷 1033-1047页

作者： Yingji Mao Yiwen Zhang Ying Wang Tao Zhou Bingxu Ma Pinghui Zhou Department of Orthopedics and Department of Plastic Surgery The First Affiliated Hospital of Bengbu Medical CollegeBengbuAnhui 233004China Anhui Province Key Laboratory of Tissue Transplantation School of Life SciencesBengbu Medical CollegeBengbuAnhui 233030China Department of Plastic Surgery and Burn Center Second Affiliated HospitalPlastic Surgery Institute of Shantou University Medical CollegeShantouGuangdong 515063China

Autologous and allogeneic bone grafts remain the gold standard for repairing bone ***,donor shortages and postoperative infections contribute to unsatisfactory treatment *** engineering technology that utilizes biologically active composites to accelerate the healing and reconstruction of segmental bone defects has led to new ideas for in situ bone *** nanocomposite hydrogels were constructed by covalently binding silver(Ag^(+))core-embedded mesoporous silica nanoparticles(Ag@MSN)to bone morphogenetic protein-2(BMP-2),which was encapsulated into silk fibroin methacryloyl(SilMA)and photo-crosslinked to form an Ag@MSN-BMP-2/SilMA hydrogel to preserve the biological activity of BMP-2 and slow its *** importantly,multifunctional Ag^(+)-containing nanocomposite hydrogels showed antibacterial *** hydrogels possessed synergistic osteogenic and antibacterial effects to promote bone defect ***@MSN-BMP-2/SilMA exhibited good biocompatibility in vitro and in vivo owing to its interconnected porosity and improved ***,the multifunctional nanocomposite hydrogel showed controllable sustained-release activity that promoted bone regeneration in repairing rat skull defects by inducing osteogenic differentiation and ***,Ag@MSN-BMP-2/SilMA hydrogels enrich bone regeneration strategies and show great potential for bone regeneration.

关键词： tissue engineering nanocomposite multifunctional hydrogels drug release antibacterial capacity bone regeneration

MicroRNA-21a-5p-modified macrophage exosomes as natural nanocarriers promote bone regeneration by targeting GATA2

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Regenerative Biomaterials 2023年第1期10卷 1413-1428页

作者： Xin Luo Chunxiu Meng Yujue Zhang Qicui Du Caiyao Hou Huifen Qiang Kun Liu Zhaoyong Lv Jun Li Fengzhen Liu Biomaterials Laboratory Liaocheng People’s HospitalLiaocheng Hospital affiliated to Shandong First Medical UniversityLiaocheng 252000China Department of Materials Science and Engineering Liaocheng UniversityLiaocheng 252000China

bone immune responses based on macrophages are critical in the osteogenesis of bone *** general,M2 macrophage facilitate the promotion of osteogenesis,as well,M1 macrophage play an important role in early bone healing,as confirmed by previous ***,it is not clear how M1 macrophage are involved in the bone immune ***-21a-5p is a highly expressed microRNA in M1 macrophage in contrast to ***,the current work sought to ascertain the influence of M1 macrophage on bone healing via exosomal miR-21a-5p and the probable *** discovered that injecting M1 macrophage exosomes overexpressing miR-21a-5p into bone defect locations enhanced bone regeneration in ***,by directly targeting GATA2,miR-21a-5p accelerated MC3T3-E1 osteogenic *** findings showed that exosomal miR-21a-5p from M1 macrophage may be transported to osteoblasts and target GATA2 to enhance bone defect healing.

关键词： exosomes miR-21a-5p GATA2 macrophages bone regeneration

Metal-Doped Brushite Cement for bone regeneration

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Journal of Bionic Engineering 2023年第6期20卷 2716-2731页

作者： Muhammad Aqib Aneela Anwar Humayun Ajaz Samina Akbar Ahsan Manzoor Maham Abid Zohaib Waheed Qudsia Kanwal Department of Chemistry University of Engineering and TechnologyGT RoadLahore54890Pakistan Department of Chemistry University of LahoreLahore5400Pakistan

For the past several years,calcium phosphate cement was used in the biomedical *** biocompatibility,good bioactivity,self-setting qualities,minimum setting degree,appropriate toughness,and simple shape to accommodate any difficult geometry are among their most notable *** phosphate has some types and brushite is one of the most attractive mineral for bone repair *** is extensively employed in filling fractures and trauma treatments as a bone substituted *** kind of material can potentially be used as a medicine delivery *** replacement of metal,such as magnesium,zinc,and strontium ions,into the calcium phosphate structure is a major research topic these *** cement has low mechanical strength and quick setting *** is possible to produce biomaterials with higher mechanical *** adding metal that are great potential in controlling cellular density when included into *** a result,it is a successful method to develop quite well regenerative *** paper provides a detailed summary of the present achievements of metal-doped brushite cement for bone repair and healing *** major purpose of this work is to give a simple but thorough analysis of current successes in brushite cement doped with Zn,Mg,Sr,and other ions as well as to highlight new advancements and *** impact of metal replacement on cement physical and chemical properties,including microstructure,setting time,injectability,mechanical property,and ion release,is *** metal-doped cement has osteogenesis,angiogenesis,and antibacterial properties,as well as their prospective utility as drug carriers,also considered.

关键词： Calcium phosphate Brushite bone cement Metal dopants bone regeneration

Enhancing osteogenic bioactivities of coaxial electrospinning nanoscaffolds through incorporating iron oxide nanoparticles and icaritin for bone regeneration

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Nano Research 2024年第7期17卷 6430-6442页

作者： Peng Wang Qianjin Wang Dengxian Wu Yunyang Zhang Shixiong Kang Xucai Wang Jiayu Gu Hao Wu Zhihong Xu Qing Jiang School of Biomedical Engineering and Informatics Nanjing Medical UniversityNanjing 211166China State Key Laboratory of Pharmaceutical Biotechnology Department of Sports Medicine and Adult Reconstructive SurgeryNanjing Drum Tower HospitalThe Affiliated Hospital of Nanjing University Medical SchoolNanjing 210008China Center of Modem Analysis Nanjing UniversityNanjing 210008China State Key Laboratory of Bioelectronics Jiangsu Key Laboratory for Biomaterials and DevicesSchool of Biological Science and Medical EngineeringSoutheast UniversityNanjing 210009China Co-Innovation Center for Efficient Processing and Utilization of Forest Resources College of Chemical EngineeringNanjing Forestry UniversityNanjing 210037China Jiangsu Institute of Metrology Nanjing 210023China

bone tissue engineering provides a promising strategy for the treatment of bone ***,the clinical utilization of biomaterial-based scaffolds is constrained by their inadequate mechanical strength and absence of osteo-inductive ***,we proposed to endow nano-scaffold(NS)constructed by coaxial electrospinning technique with enhanced osteogenic bioactivities and mechanical properties by incorporating biocompatible magnetic iron oxide nanoparticles(IONPs)and icaritin(ICA).Four types of nano-scaffolds(NS,ICA@NS,NS-IONPs and ICA@NS-IONPs)were *** incorporation of ICA and IONPs minimally impact their surface morphological and chemical *** enhanced the mechanical properties of NS scaffolds,including hardness,tensile strength,and elastic *** vitro assessments demonstrated that ICA@NS-IONPs exhibited enhanced osteogenic bioactivities towards mouse calvarial pre-osteoblast cell line MC3T3-E1 as evidenced by detecting the alkaline phosphatase(ALP)activity level,expressions of osteogenesis-related genes and proteins as well as mineralized nodule *** investigations revealed that MEK/ERK(MAP kinase-ERK kinase(MEK)/extracellularsignal-regulated kinase(ERK))signaling pathway could offer a plausible explanation for the osteogenic differentiation of MC3T3-E1 cells induced by ICA@***,the implantation of nano-scaffolds in rat skull defects exhibited a substantial improvement in in vivo bone ***,IONPs and ICA incorporated coaxial electrospinning nano-scaffolds present a novel strategy for the optimization of scaffolds for bone tissue engineering.

关键词： iron oxide nanoparticles icaritin coaxial electrospinning nano-scaffolds MEK/ERK signaling pathway bone regeneration

Bio-inspired dual-adhesive particles from microfluidic electrospray for bone regeneration

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Nano Research 2023年第4期16卷 5292-5299页

作者： Lei Yang Xiaocheng Wang Yunru Yu Luoran Shang Wei Xu Yuanjin Zhao Department of Rheumatology and Immunology Nanjing Drum Tower HospitalSchool of Biological Science and Medical EngineeringSoutheast UniversityNanjing 210096China Oujiang Laboratory(Zhejiang Lab for Regenerative Medicine Vision and Brain Health)Wenzhou InstituteUniversity of Chinese Academy of SciencesWenzhou 325001China Shanghai Xuhui Central Hospital Zhongshan-Xuhui Hospitaland the Shanghai Key Laboratory of Medical Epigeneticsthe International Colaboratory of Medical Epigenetics and Metabolism(Ministry of Science and Technology)Institutes of Biomedical SciencesFudan UniversityShanghai 200032China Department of Orthopedics Tongren HospitalShanghai Jiao Tong University School of MedicineShanghai 200336China

Bioadhesive hydrogels have demonstrated great potential in bone ***,the relatively simple adhesion mechanism and lack of intricate structural design restrict their further ***,inspired by multiple adhesion mechanisms of pollen particles and marine mussels,we present a novel type of dual-adhesive hydrogel particles fabricated from microfluidic electrospray for bone *** the particles are rapidly solidified via liquid nitrogen-assisted cryogelation,they exhibit pollen-mimicking hierarchical porous morphology and gain structure-related ***,the particles are further coated by polydopamine(PDA)to achieve molecular-level adhesion especially to physiological wet surfaces of bone *** from such dual-adhesion mechanisms,the particles can strongly adhere to bone tissue defects,and function as porous ***,the dual-adhesive particles can serve as effective vehicles to release key growth factors more than two *** vitro experiments showed that the growth factors-loaden particles have excellent biocompatibility and more significantly promote angiogenesis(~2-fold)and osteogenic differentiation(~3-fold)than *** vivo experiments indicated that the dual-adhesive particles could significantly enhance bone regeneration(~4-fold)than control by coupling osteogenesis and angiogenesis *** on these features,the bio-inspired dual-adhesive particles have great potentials for bone repair and wound healing applications.

关键词： microfluidics particles growth factors adhesion bone regeneration

3D-printed,bi-layer,biomimetic artificial periosteum for boosting bone regeneration

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Bio-Design and Manufacturing 2022年第3期5卷 540-555页

作者： Yage Sun Ziwei Gao Xiaoping Zhang Ziyang Xu Yahan Zhang Binbin He Rong Yang Qian Zhang Qiang Yang Wenguang Liu School of Material Science and Engineering Tianjin Key Laboratory of Composite and Functional MaterialsTianjin UniversityTianjin 300350China Department of Spine Surgery Tianjin HospitalTianjin UniversityTianjin 300211China

Periosteum,a membrane covering the surface of the bone,plays an essential role in maintaining the function of bone tissue—and especially in providing nourishment and vascularization during the bone regeneration ***,most artificial periostea have relatively weak mechanical strength and a rapid degradation rate,and they lack integrated angiogenesis and osteogenesis *** this study,a bi-layer,biomimetic,artificial periosteum composed of a methacrylated gelatin–nano-hydroxyapatite(GelMA-nHA)cambium layer and a poly(N-acryloyl 2-lycine)(PACG)-GelMA-Mg^(2+)fibrous layer was fabricated via 3D *** GelMA-nHA layer is shown to undertake the function of improving osteogenic differentiation of rat bone marrow mesenchymal stem cells with the sustainable release of Ca^(2+) from nHA *** hydrogen-bonding-strengthened P(ACG-GelMA-L)-Mg^(2+)hydrogel layer serves to protect the inner defect site and prolong degradation time(60 days)to match new bone ***,the released magnesium ion exhibits a prominent effect in regulating the polarization phenotype of macrophage cells into theM2 phenotype and thus promotes the angiogenesis of the human umbilical vein endothelial cells in *** bi-layer artificial periosteum was implanted into a critical-sized cranial bone defect in rats,and the 12-week post-operative outcomes demonstrate optimal new bone regeneration.

关键词： 3D printing Bi-layer periosteum scaffold Immune regulation bone regeneration

Injectable composite hydrogel based on carbon particles for photothermal therapy of bone tumor and bone regeneration

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Journal of Materials Science & Technology 2022年第23期118卷 64-72页

作者： Chengxiong Wei Xin Jin Chengwei Wu Wei Zhang State Key Laboratory of Structure Analysis for Industrial Equipment Department of Engineering MechanicsDalian University of TechnologyDalian 116024China

Surgical resection,as the most efficient treatment for bone tumor,still faces a dilemma between the complete removal of tumor tissue and the maximum reservation of healthy bone *** response to this,an injectable composite hydrogel with chitosan/hyaluronic acid/β-sodium glycerophosphate as the matrix and carbon particles as the photothermal agent is *** to the temperature sensitivity,the composite hydrogel can be injected into the irregular bone defect and exhibit the sol-gel phase transition upon body temperature,facilitating the conformal *** composite hydrogel can ablate the human osteosarcoma on Balb/c nude mice model with the tumor inhibition rate of 98.4%after near-infrared laser irradiation(808 nm).The assessment of bone regeneration on calvarial-defect model of Sprague-Dawley rats reveals that the composite hydrogel can promote new bone formation with the bone volume/total volume ratio of 76.2%after 8 weeks,in sharp contrast to the control group of 23.9%.)

关键词： Hydrogel Carbon particle Photothermal therapy bone regeneration

bone-targeted lipoplex-loaded three-dimensional bioprinting bilayer scaffold enhanced bone regeneration

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Regenerative Biomaterials 2024年第4期3卷 138-148页

作者： Woo-Jin Kim Jeong-Hyun Ryu Ji Won Kim Ki-Tae Kim Hye-Rim Shin Heein Yoon Hyun-Mo Ryoo Young-Dan Cho Department of Molecular Genetics School of Dentistry and Dental Research InstituteSeoul National UniversitySeoul03080Republic of Korea Department of Periodontology School of Dentistry and Dental Research InstituteSeoul National University and Seoul National University Dental HospitalSeoul03080Republic of Korea

Clinical bone-morphogenetic protein 2(BMP2)treatment for bone regeneration,often resulting in complications like soft tissue inflammation and ectopic ossification due to high dosages and non-specific delivery systems,necessitates research into improved biomaterials for better BMP2 stability and *** tackle this challenge,we introduced a groundbreaking bone-targeted,lipoplex-loaded,three-dimensional bioprinted bilayer scaffold,termed the polycaprolactone-bioink-nanoparticle(PBN)scaffold,aimed at boosting bone *** encapsulated BMP2 within the fibroin nanoparticle based lipoplex(Fibroplex)and functionalized it with DSS6 for bone tissue-specific targeting.3D printing technology enables customized,porous PCL scaffolds for bone healing and soft tissue growth,with a two-step bioprinting process creating a cellular lattice structure and a bioink grid using gelatin-alginate hydrogel and DSS6-Fibroplex,shown to support effective nutrient exchange and cell growth at specific pore *** PBN scaffold is predicted through in silico analysis to exhibit biased BMP2 release between bone and soft tissue,a finding validated by in vitro osteogenic differentiation *** PBN scaffold was evaluated for critical calvarial defects,focusing on sustained BMP2 delivery,prevention of soft tissue cell infiltration and controlled fiber membrane pore size in *** PBN scaffold demonstrated a more than eight times longer BMP2 release time than that of the collagen sponge,promoting osteogenic differentiation and bone regeneration in a calvarial defect *** findings suggest that the PBN scaffold enhanced the local concentration of BMP2 in bone defects through sustained release and improved the spatial arrangement of bone formation,thereby reducing the risk of heterotopic ossification.

关键词： 3D bioprinting bone-targeting lipoplex BMP2 bone regeneration