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Intelligent Vascularized 3D/4D/5D/6D‑Printed Tissue Scaffolds

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纳微快报:英文版 2023年第12期15卷 376-418页

作者： Xiaoyu Han qimanguli saiding Xiaolu Cai Yi Xiao Peng Wang Zhengwei Cai Xuan Gong Weiming Gong Xingcai Zhang Wenguo Cui Department of Orthopaedics Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint DiseasesShanghai Institute of Traumatology and OrthopaedicsRuijin HospitalShanghai Jiao Tong University School of Medicine197 Ruijin 2nd RoadShanghai 200025People’s Republic of China Department of Orthopedics Jinan Central HospitalShandong First Medical University and Shandong Academy of Medical Sciences105 Jiefang RoadLixia DistrictJinan 250013ShandongPeople’s Republic of China Department of Biomedical Engineering College of Life Science and TechnologyHuazhong University of Science and TechnologyWuhan 430074HubeiPeople’s Republic of China School of Engineering and Applied Sciences Harvard UniversityCambridgeMA 02138USA University of Texas Southwestern Medical Center DallasTX 75390‑9096USA

Blood vessels are essential for nutrient and oxygen delivery and waste ***-repairing materials with functional vascular networks are widely used in bone tissue *** manufacturing is a manufacturing technology that creates three-dimensional solids by stacking substances layer by layer,mainly including but not limited to 3D printing,but also 4D printing,5D printing and 6D *** can be effectively combined with vascularization to meet the needs of vascularized tissue scaffolds by precisely tuning the mechanical structure and biological properties of smart vascular ***,the development of neovascularization to vascularization to bone tissue engineering is systematically discussed in terms of the importance of vascularization to the ***,the research progress and future prospects of vascularized 3D printed scaffold materials are highlighted and presented in four categories:functional vascularized 3D printed scaffolds,cell-based vascularized 3D printed scaffolds,vascularized 3D printed scaffolds loaded with specific carriers and bionic vascularized 3D printed ***,a brief review of vascularized additive manufacturing-tissue scaffolds in related tissues such as the vascular tissue engineering,cardiovascular system,skeletal muscle,soft tissue and a discussion of the challenges and development efforts leading to significant advances in intelligent vascularized tissue regeneration is presented.

关键词： Intelligent Additive manufacturing Tissue engineering Vascularization Osteogenesis

Enhancement of critical-sized bone defect regeneration by magnesium oxide-reinforced 3D scaffold with improved osteogenic and angiogenic properties

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Journal of Materials Science & Technology 2023年第4期135卷 186-198页

作者： Bo Chen Zhengjie Lin qimanguli saiding Yongcan Huang Yi Sun Xinyun Zhai Ziyu Ning Hai Liang Wei Qiao Binsheng Yu Kelvin W.K.Yeung Jie Shen Department of Orthopaedics Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint DiseasesShanghai Institute of Traumatology and OrthopaedicsRuijin HospitalShanghai Jiao Tong University School of MedicineShanghai 200025China D Printing Clinical Translational and Regenerative Medicine Center Shenzhen Qianhai Shekou Free Trade Zone HospitalShenzhen 518067China Shenzhen Key Laboratory of Spine Surgery Department of Spine SurgeryPeking University Shenzhen HospitalShenzhen 518036China Department of Orthopaedics and Traumatology the University of Hong KongChina Hong Kong Special Administrative RegionChina Shenzhen Key Laboratory for Innovative Technology in Orthopaedic Trauma the University of Hong Kong Shenzhen HospitalShenzhen 518053China School of Materials Science and Engineering Nankai UniversityTianjin 300071China Department of Pathology Guangdong Provincial People’s HospitalGuangdong Academy of Medical SciencesGuangzhou 510080China Department of Stomatology Shenzhen Qianhai Shekou Free Trade Zone HospitalShenzhen 518067China Applied Oral Sciences and Community Dental Care Faculty of Dentistrythe University of Hong KongChina Hong Kong Special Administrative RegionChina China Orthopaedic Regenerative Medicine Group(CORMed) Hangzhou 310000China

The healing of critical-sized bone defects(CSD)remains a challenge in orthopedic *** recent years,scaffolds with sophisticated microstructures fabricated by the emerging three-dimensional(3D)printing technology have lighted up the treatment of the CSD due to the elaborate microenvironments and support they may ***,we established a magnesium oxide-reinforced 3D-printed biocompos-ite scaffold to investigate the effect of magnesium-enriched 3D microenvironment on CSD *** composite was prepared using a biodegradable polymer matrix,polycaprolactone(PCL),and the disper-sion phase,magnesium oxide(MgO).With the appropriate surface treatment by saline coupling agent,the MgO dispersed homogeneously in the polymer matrix,leading to enhanced mechanical performance and steady release of magnesium ion(Mg^(2+))for superior cytocompatibility,higher cell viability,advanced osteogenic differentiation,and cell mineralization capabilities in comparison with the pure *** in-vivo femoral implantation and critical-sized cranial bone defect studies demonstrated the importance of the 3D magnesium microenvironment,as a scaffold that released appropriate Mg^(2+) exhibited remarkably increased bone volume,enhanced angiogenesis,and almost recovered CSD after 8-week ***,this study suggests that the magnesium-enriched 3D scaffold is a potential candidate for the treatment of CSD in a cell-free therapeutic approach.

关键词： 3D printing Magnesium Critical-sized defect Bone regeneration Angiogenesis Scaffold

Local bone metabolism balance regulation via double-adhesive hydrogel for fixing orthopedic implants

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Bioactive Materials 2022年第6期7卷 169-184页

作者： Wei Jiang Fushan Hou Yong Gu qimanguli saiding Pingping Bao Jincheng Tang Liang Wu Chunmao Chen Cailiang Shen Catarina Leite Pereira Marco Sarmento Bruno Sarmento Wenguo Cui Liang Chen Department of Orthopaedic Surgery Orthopedic InstituteThe First Affiliated Hospital of Soochow University708 Renmin RdSuzhouJiangsu215006PR China Department of Orthopedics The Second Hospital of Shanxi Medical UniversityNo.382 Wuyi RoadTaiyuanShanxi030001PR China Department of Orthopaedics Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint DiseasesShanghai Institute of Traumatology and OrthopaedicsRuijin HospitalShanghai Jiao Tong University School of Medicine197 Ruijin 2nd RoadShanghai200025PR China Department of Electrocardiography The First Affiliated Hospital of Anhui Medical University218 Jixi RoadShushan DistrictHefeiAnhui230022PR China Department of Orthopedics The First Affiliated Hospital of Anhui Medical University218 Jixi RoadShushan DistrictHefeiAnhui230022PR China i3S-Instituto de Investigacao e Inovacao em Saude and INEB-dica Universidade do PortoRua Alfredo Allen 2084200-393PortoPortugal CESPU-Institute for Research and Advanced Training in Health Sciences and Technologies Rua Central de Gandra 13174585-116GandraPortugal Faculty of Medicine Universidade de LisboaAvenida Professor Egas Moniz1649-028LisboaPortugal

The effective osteointegration of orthopedic implants is a key factor for the success of orthopedic ***,local metabolic imbalance around implants under osteoporosis condition could jeopardize the fixation *** by the bone structure and the composition around implants under osteoporosis condition,alendronate(A)was grafted onto methacryloyl hyaluronic acid(H)by activating the carboxyl group of methacryloyl hyaluronic acid to be bonded to inorganic calcium phosphate on trabecular bone,which is then integrated with aminated bioactive glass(AB)modified by oxidized dextran(O)for further adhesion to organic collagen on the trabecular *** hybrid hydrogel could be solidified on cancellous bone in situ under UV irradiation and exhibits dual adhesion to organic collagen and inorganic apatite,promoting osteointegration of orthopedic implants,resulting in firm stabilization of the implants in cancellous bone *** vitro,the hydrogel was evidenced to promote osteogenic differentiation of embryonic mouse osteoblast precursor cells(MC3T3-E1)as well as inhibit the receptor activator of nuclear factor-κB ligand(RANKL)-induced osteoclast differentiation of macrophages,leading to the upregulation of osteogenic-related gene and protein *** a rat osteoporosis model,the bone-implant contact(BIC)of the hybrid hydrogel group increased by 2.77,which is directly linked to improved mechanical stability of the orthopedic ***,this organic-inorganic,dual-adhesive hydrogel could be a promising candidate for enhancing the stability of orthopedic implants under osteoporotic conditions.

关键词： Hydrogels Osteoporosis Osseointegration Dual-functional Peri-implant

From “organs on a chip” to “patient on a chip”

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The Innovation 2022年第5期3卷 17-18页

作者： qimanguli saiding Jingyun Ma Chunhai Ke Wenguo Cui Ningbo Institute of Innovation for Combined Medicine and Engineering Ningbo Medical Center Li Huili Hospital57 Xingning RoadNingboZhejiang 315100China Department of Orthopaedics Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint DiseasesShanghai Institute of Traumatology and OrthopaedicsRuijin HospitalShanghai Jiao Tong University School of Medicine197 Ruijin 2nd RoadShanghai 200025China

CONVENTIONAL MODELS FOR DRUG SCREENING :The increasing cost of drug safety is attributed to the inappropriate pre-clinical models with unrepresentative pharmacokinetic and pharmacodynamic profiles that blur drug efficacy and ***,the commercial drugs designed by impromper disease models could cause potential multi-organ side *** worse,in some cases,unqualified drug screening is the cause of unexpected hospitalization in *** urgent yet unsolved issues push scholars to reform monolayer cell culture and traditional animal models for drug validation.1 Then,in vitro three-dimensional(3D)cell culture models followed,but these are mainly limited to cell capsulation in defined hydrogels,spheroid systems,and engineered *** surprisingly,the 3D cell aggregates are still far from real organs,invalidating the drug kinetics.

关键词： organs culture attributed

Capturing dynamic biological signals via bio-mimicking hydrogel for precise remodeling of soft tissue

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Bioactive Materials 2021年第12期6卷 4506-4516页

作者： Zhengwei Cai qimanguli saiding Liang Cheng Liucheng Zhang Zhen Wang Fei Wang Xinliang Chen Gang Chen Lianfu Deng Wenguo Cui Department of Orthopaedics Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint DiseasesShanghai Institute of Traumatology and OrthopaedicsRuijin HospitalShanghai Jiao Tong University School of Medicine197 Ruijin 2nd RoadShanghai200025PR China Jiaxing Key Laboratory of Basic Research and Clinical Translation on Orthopedic Biomaterials Department of OrthopaedicsThe Second Affiliated Hospital of Jiaxing University1518 North Huancheng RoadJiaxing314000China Shanghai Key Laboratory of Embryo Original Diseases The International Peace Maternal and Child Health HospitalSchool of MedicineShanghai Jiao Tong University910 Hengshan RoadShanghai200030PR China

Soft tissue remodeling is a sophisticated process that sequentially provides dynamic biological signals to guide cell ***,capturing these signals within hydrogel and directing over time has still been unrealized owing to the poor comprehension of physiological ***,a bio-mimicking hydrogel is designed via thiol-ene click reaction to capture the early physical signal triggered by inflammation,and the chemical signals provided with chemokine and natural adhesion sites,which guaranteed the precise soft tissue *** bio-mimicking hydrogel efficiently facilitated cell anchoring,migration,and invasion in the 3D matrix due to the permissive space and the interaction with integrin ***,the covalently grafted chemokine-like peptide is optimal for colonization and functional differentiation of endothelial cells through a HIF-1αdependent signal ***,the early polarization of macrophages,collagen deposition and angiogenesis in rat acute wound model,and the increased blood perfusion in mouse skin flap model have confirmed that the bio-mimicking hydrogel realized precise soft tissue remodeling and opens new avenues for the phased repair of different tissues such as nerve,myocardium,and even bone.

关键词： Biological signals Physiological phase Hydrogel Chemotactic Soft tissue remodeling

Lotus seedpod-inspired internal vascularized 3D printed scaffold for bone tissue repair

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Bioactive Materials 2021年第6期6卷 1639-1652页

作者： Xiaoyu Han Mingjie Sun Bo Chen qimanguli saiding Junyue Zhang Hongliang Song Lianfu Deng Peng Wang Weiming Gong Wenguo Cui Department of Orthopedics Jinan Central HospitalShandong First Medical University&Shandong Academy of Medical Sciences105 Jiefang RoadLixia DistrictJinanShandong250013PR China Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases Shanghai Institute of Traumatology and OrthopedicsRuijin HospitalShanghai Jiao Tong University School of Medicine197 Ruijin 2nd RoadShanghai200025PR China

In the field of bone defect repair,3D printed scaffolds have the characteristics of personalized customization and accurate internal ***,how to construct a well-structured vascular network quickly and effectively inside the scaffold is essential for bone repair after ***,inspired by the unique biological structure of“lotus seedpod”,hydrogel microspheres encapsulating deferoxamine(DFO)liposomes were prepared through microfluidic technology as“lotus seeds”,and skillfully combined with a three-dimensional(3D)printed bioceramic scaffold with biomimetic“lotus”biological structure which can internally grow blood *** this composite scaffold system,DFO was effectively released by 36%in the first 6 h,which was conducive to promote the growth of blood vessels inside the scaffold *** the following 7 days,the release rate of DFO reached 69%,which was fundamental in the formation of blood vessels inside the scaffold as well as osteogenic differentiation of bone mesenchymal stem cells(BMSCs).It was confirmed that the composite scaffold could significantly promote the human umbilical vein endothelial cells(HUVECs)to form the vascular morphology within 6 h in *** vivo,the composite scaffold increased the expression of vascularization and osteogenic related proteins Hif1-α,CD31,OPN,and OCN in the rat femoral defect model,significantly cutting down the time of bone *** sum up,this“lotus seedpod”inspired porous bioceramic 3D printed scaffold with internal vascularization functionality has broad application prospects in the future.

关键词： 3D scaffolds Drug release Neovascularization Osteogenesis Regeneration