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3D-printed Mechanically Strong calcium phosphate cement Scaffold with Metformin/Stem Cell-encapsulating Alginate Microbeads for Bone Tissue Engineering

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Journal of Bionic Engineering 2022年第6期19卷 1658-1670页

作者： Xiong Xiong Yuanyuan Chen Rupan Yuan Gengtao Qiu Michael D.Weir Hockin H.K.Xu Jin Liu Jianping Ruan Xiaofeng Chang Shuxin Qu School of Life Science and Engineering Southwest Jiaotong UniversityChengdu610031China Sichuan Engineering Research Center for Biomimetic Synthesis of Natural Drugs School of Life Science and EngineeringSouthwest Jiaotong UniversityChengdu610031China Key Lab of Advanced Technologies of Materials Ministry of EducationSchool of Materials Science and EngineeringSouthwest Jiaotong UniversityChengdu610031China Department of Advanced Oral Sciences and Therapeutics University of Maryland School of DentistryBaltimoreMD21201USA Center for Stem Cell Biology and Regenerative Medicine University of Maryland School of MedicineBaltimoreMD21201USA University of Maryland Marlene and Stewart Greenebaum Cancer Center University of Maryland School of MedicineBaltimoreMD21201USA Key Laboratory of Shannxi Province for Craniofacial Precision Medicine Research Clinical Research Center of Shannxi Province for Dental and Maxillofacial DiseasesCollege of StomatologyXi’an Jiaotong UniversityXi’anShannxi710004China

The utilization of calcium phosphate cement(CPC)is limited due to its low mechanical strength and difficulty to seed cells deep into the *** objectives of this study were to:(1)develop a 3D-printed CPC-dopamine-metformin scaffold encapsulating human periodontal ligament stem cells(hPDLSCs),(2)investigate the effect of dopamine on the performance of CPC,and(3)evaluate the effect of microbead degradation and metformin release on the osteogenic differentiation of the released *** mechanical property of the CPC scaffolds was elevated by adding dopamine,and the CPC scaffold with 7 wt.%dopamine had the highest compressive strength(7.35 MPa).Four types of microbeads with different content of alginate(oxidized alginate),hPDLSCs,and 2%metformin were *** and cell counting kit tests confirm that the hPDLSCs are protected by microbeads encapsulation during the CPC setting *** alkaline phosphatase test indicates that the osteogenic differentiation of hPDLSCs was enhanced by the fast release of cells and *** microbeads consisting of 2%oxidized alginate and 2%metformin were optimal for cell delivery due to favorable cell release and osteogenic *** CPC scaffold is promising used for bone regeneration in dental,craniofacial,and orthopedic applications.

关键词： calcium phosphate cement 3D Printing Bionic Alginate microbeads Metformin

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Effect of Additives on the Morphology of the Hydrated Product and Physical Properties of a calcium phosphate cement

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Journal of Materials Science & Technology 2008年第2期24卷 285-288页

作者： Xiupeng WANG Jiandong YE Yingjun WANG Key Laboratory of Specially Functional Materials （Ministry of Education） and School of Materials Science and Engineering South China University of Technology Guangzhou 510641 China

The morphology of a hydrated calcium phosphate cement （CPC） doped with several normally used additives was investigated by scanning electron microscopy （SEM） and the compressive strength of the cement was determined in this study. The hydrated products of CPC without additives was rod-like hydroxyapatite （HA） grains with around 2-5 μm in length and 100 nm in width. The addition of Sr obviously decreased the crystal size of the rod-like grains. CPCs containing carbonate, collagen and gelatin showed flake-like crystal morphology. Crylic acid-containing CPC presented flocculus-like structure. And malic acid-containing CPC exhibited oriented flake-like structure. The X-ray diffraction （XRD） analysis showed that the additives used in this study did not alter the hydration products of the cement. The compressive strength tests indicated that the compressive strength of the cement with rod-like morphology HA crystals was much higher than that of the cement with flake-like morphology HA crystals, and the cement with oriented flake-like morphology HA crystals exhibited the poorest compressive strength.

关键词： calcium phosphate cement Morphology Apatite

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Treatment of critical bone defects using calcium phosphate cement and mesoporous bioactive glass providing spatiotemporal drug delivery

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Bioactive Materials 2023年第10期28卷 402-419页

作者： Richard Frank Richter Corina Vater Margarete Korn Tilman Ahlfeld Martina Rauner Winnie Pradel Bernd Stadlinger Michael Gelinsky Anja Lode Paula Korn Centre for Translational Bone Joint and Soft Tissue ResearchUniversity Hospital Carl Gustav Carus and Faculty of MedicineTechnische Universitat DresdenDresdenGermany Department of Oral and Maxillofacial Surgery University Hospital Carl Gustav CarusTechnische Universitat DresdenGermany Department of Medicine III and Center for Healthy Aging University Hospital Carl Gustav CarusTechnische Universitat DresdenGermany Clinic of Cranio-Maxillofacial and Oral Surgery Center of Dental MedicineUniversity of ZurichSwitzerland

calcium phosphate cements (CPC) are currently widely used bone replacement materials with excellent bioactivity, but have considerable disadvantages like slow degradation. For critical-sized defects, however, an improved degradation is essential to match the tissue regeneration, especially in younger patients who are still growing. We demonstrate that a combination of CPC with mesoporous bioactive glass (MBG) particles led to an enhanced degradation in vitro and in a critical alveolar cleft defect in rats. Additionally, to support new bone formation the MBG was functionalized with hypoxia conditioned medium (HCM) derived from rat bone marrow stromal cells. HCM-functionalized scaffolds showed an improved cell proliferation and the highest formation of new bone volume. This highly flexible material system together with the drug delivery capacity is adaptable to patient specific needs and has great potential for clinical translation.

关键词： Drug delivery 3D plotting Alveolar cleft defect calcium phosphate cement Mesoporous bioactive glass

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Microstructure and Mechanical Properties of calcium phosphate cement/Gelatine Composite Scaffold with Oriented Pore Structure for Bone Tissue Engineering

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Journal of Wuhan University of Technology(Materials Science) 2012年第1期27卷 92-95页

作者： QI Xiaopeng HE Fupo YE Jiandong School of Materials Science and Engineering South China University of Technology School of Material and Chemical Engineering Jiangxi University of Science and Technology

The macroporous calcium phosphate（CPC） cement with oriented pore structure was prepared by freeze casting. SEM observation showed that the macropores in the porous calcium phosphate cement were interconnected aligned along the ice growth direction. The porosity of the as-prepared porous CPC was measured to be 87.6% by Archimede＇s principle. XRD patterns of specimens showed that poorly crystallized hydroxyapatite was the main phase present in the hydrated porous calcium phosphate cement. To improve the mechanical properties of the CPC scaffold, the 15% gelatine solution was infiltrated into the pores under vacuum and then the samples were freeze dried to form the CPC/gelatine composite scaffolds. After reinforced with gelatine, the compressive strength of CPC/gelatine composite increased to 5.12 MPa, around fifty times greater than that of the unreinforced macroporous CPC scaffold, which was only 0.1 MPa. And the toughness of the scaffold has been greatly improved via the gelatine reinforcement with a much greater fracture strain. SEM examination of the specimens indicated good bonding between the cement and gelatine. Participating the external load by the deformable gelatine, patching the defects of the CPC pores wall, and crack deflection were supposed to be the reinforcement mechanisms. In conclusion, the calcium phosphate cement/gelatine composite with oriented rmre structure nrenared in this work might be a potential scaffold for bone tissue engineerinm

关键词： calcium phosphate cement scaffold gelatine oriented pores mechanical properties

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Evaluation of calcium phosphate cement As a Root Canal Sealer Filling Material

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Journal of Wuhan University of Technology(Materials Science) 2001年第4期16卷 14-18页

作者：戴红莲 Wuhan Univ Technol Biomed Mat & Engn Res Ctr Wuhan 430070 Peoples R China Hubei Med Univ Stomatol Hosp Wuhan Peoples R China

calcium phosphate cement for root end sealing was obtained by in mixing alpha-tricalcium phosphate and additives with an aqueous solation of citric. Powder and liquid were mixed at a ratio of 1.25g/mL. The biocompatibility of this material was investigated primarily by subcutaneous implantation tests. Then calcium phosphate cement was used to fill three adult dogs' root canal, both calcium hydroxide paste and hydroxyapatite paste as control. The animals were killed at 4, 12, 20 weeks postoperatively respectively. The effects of different materials on the apical closure, restoration of periapical tissues and adaptability to the dentinal surface were examined by optical and electronic microscope. The observation at 20 weeks shows that the calcium phosphate cement has the potentialities of being a root canal sealer filling material available for pulpless teeth with open-apex and destructive periapical tissue.

关键词： calcium phosphate cement histocompatibility apical closure

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Hyaluronic acid facilitates bone repair effects of calcium phosphate cement by accelerating osteogenic expression

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Bioactive Materials 2021年第11期6卷 3801-3811页

作者： Xu Cui Chengcheng Huang Zhizhen Chen Meng Zhang Chunyu Liu Kun Su Jianyun Wang Li Li Renxian Wang Bing Li Dafu Chen Changshun Ruan Deping Wang William W.Lu Haobo Pan Center for Human Tissues and Organs Degeneration Shenzhen Institutes of Advanced TechnologyChinese Academy of ScienceShenzhen518055PR China Shenzhen Healthemes Biotechnology Co.Ltd Shenzhen518102PR China Department of Orthopedics Fourth Affiliated Hospital of Guangxi Medical University/Liu Zhou WorkerLiuzhou545005PR China Laboratory of Bone Tissue Engineering Beijing Laboratory of Biomedical MaterialsBeijing Research Institute of Orthopaedics and TraumatologyBeijing Jishuitan HospitalBeijing100035PR China Schools of Materials Science and Engineering Tongji UniversityShanghai201804PR China Department of Orthopaedics and Traumatology The University of Hong KongHong Kong SARPR China

calcium phosphate cements(CPC)are widely anticipated to be an optimum bone repair substitute due to its satisfied biocompatibility and degradability,suitable to be used in minimally invasive treatment of bone *** the clinical application of CPC is still not satisfied by its poor cohesiveness and mechanical properties,in particular its *** acid reinforced calcium phosphate cements(HA/CPC)showed extroadinary potential not only enhancing the compressive strength of the cements but also significantly increasing its *** our study,the compressive strength of HA/CPC increased significantly when the cement was added 1%hyaluronic acid(denoted as 1-HA/CPC).In the meantime,hyaluronic acid obviously promoted ALP activity,osteogenic related protein and mRNA expression of hBMSCs(human bone marrow mesenchymal stem cells)in vitro,cement group of HA/CPC with 4%hyaluronic acid adding(denoted as 4-HA/CPC)showed optimal enhancement in hBMSCs *** being implanted in rat tibial defects,4-HA/CPC group exhibited better bone repair ability and bone growth promoting factors,comparing to pure CPC and 1-HA/CPC *** underlying biological mechanism of this stimulation for HA/CPC may be on account of higher osteogenic promoting factors secretion and osteogenic genes expression with hyaluronic acid *** results indicate that hyaluronic acid is a highly anticipated additive to improve physicochemical properties and osteoinductivity performance of CPCs for minimally invasive healing of bone defects.

关键词： Hyaluronic acid calcium phosphate cement Physicochemical properties Osteogenic activity

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The In-situ Reinforcement of calcium phosphate cement and Its Micro-structural Analysis

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Journal of Wuhan University of Technology(Materials Science) 2005年第B12期20卷 19-21页

作者：万鹏 Institute of Analytical and Biomedical Sciences School of Chemistry and Molecular Sciences Wuhan University Wuhan 430072 China

Carbon nanotubes （ CNTs ） and polyacrylic acid were employed to modify the setting process and hydration products of β-TCP/TTCP calcium phosphate cement. The micro-structure of hydration product and the fashion of how additives and hydration particles interconnected were investigated. With the modification effect of CNTs , the setting particles and CNTs got winded and interconnected and thus made the composite more compact and denser.

关键词： calcium phosphate cement CNTs polyacrylic acid microstructure

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Preparation of a Novel calcium phosphate cement Using N-methylene Phosphonic Chitosan as a Gelling Agent

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Journal of Wuhan University of Technology(Materials Science) 2005年第B12期20卷 304-307页

作者：耿燕丽 Department of Materials Science and Technology Nanjing University of Technology Nanjing 210009 China

A modified chitosan （ N-methylene phosphonic Chitosan, NMPC） was synthesized to improve solubility and ability to bind calcium ion. The properties of the raw material chitosan and its derivative NMPC were characterised using FTIR , ^1H- NMR . The aim of this study was to enhance the compressive CPC by reinforcing with NMPC. A formulation consisting of CPC powder , buffer solution and gelling agent was used for preparation of the CPC. CPC powder coasisted of tetracalcium phosphate（ TTCP ） and dicalcium phosphate anhydrous （ DCPA ）. NMPC which acted as the gelling ageut was dissohed into KH2PO4-Na2 HPO4 buffer solution. Each specimen in the mold was sandciched between two fritted glass sides and kept for 24 hours. Compressive strengths were determined, the setting product was identified using X-ray diffraction and scanning electron microscopy was used to investigate the hydroxyapatite particles size and porosity. The experimental results showed that the dominating influence on the compressive strengths of CPC-AMPC was the HA panicle size, its uniformity and appropriate porosity.

关键词： N-methylene phosphonic chitosan calcium phosphate cement compressive strength

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Tissue-engineered calcium phosphate cement in rabbit femoral condylar bone defects

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Chinese Medical Journal 2012年第11期125卷 1993-1998页

作者： LIU Chun-rong MIAO Jun XIA Qun HUANG Hong-chao GONG Chen YANG Qiang LI Lan-ying Key Laboratory of Hormones and Development （Ministry of Health） Metabolic Diseases Hospital and Tianjin Institute of Endocrinology Tianjin Medical University Tianjin 300070 China Department of Spinal Surgery Tianjin Hospital Tianjin 300211 China

Background calcium phosphate cement （CPC） is a favorable bone-graft substitute, with excellent biocompatibility and osteoconductivity. However, its reduced osteoinductive ability may limit the utility of CPC. To increase its osteoinductive potential, this study aimed to prepare tissue-engineered CPC and evaluate its use in the repair of bone defects. The fate of transplanted seed cells in vivo was observed at the same time. Methods Tissue-engineered CPC was prepared by seeding CPC with encapsulated bone mesenchymal stem cells （BMSCs） expressing recombinant human bone morphogenetic protein-2 （rhBMP-2） and green fluorescent protein （GFP）. Tissue-engineered CPC and pure CPC were implanted into rabbit femoral condyle bone defects respectively. Twelve weeks later, radiographs, morphological observations, histomorphometrical evaluations, and in vivo tracing were performed. Results The radiographs revealed better absorption and faster new bone formation for tissue-engineered CPC than pure CPC. Morphological and histomorphometrical evaluations indicated that tissue-engineered CPC separated into numerous small blocks, with active absorption and reconstruction noted, whereas the residual CPC area was larger in the group treated with pure CPC. In the tissue-engineered CPC group, in vivo tracing revealed numerous cells expressing both GFP and rhBMP-2 that were distributed in the medullar cavity and on the surface of bony trabeculae. Conclusion Tissue-engineered CPC can effectively repair bone defects, with allogenic seeded cells able to grow and differentiate in vivo after transplantation.

关键词： calcium phosphate cement bone tissue engineering bone defect,recombinant human bone morphogenetic protein-2

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Delivering MC3T3-E1 cells into injectable calcium phosphate cement through alginate-chitosan microcapsules for bone tissue engineering

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2014年第4期15卷 382-392页

作者： Peng-yan QIAO Fang-fang LI Li-min DONG Tao XU Qiu-fei XIE Department of Prosthodontics Peking University School and Hospital of Stomatology Beijing Key Lab of Fine Ceramics Institute of Nuclear and New Energy TechnologyTsinghua University Department of Preventive Dentistry Peking University School and Hospital of Stomatology National Engineering Laboratory for Digital and Material Technology of Stomatology Peking University School and Hospital of Stomatology

Objective： To deliver cells deep into injectable calcium phosphate cement（CPC） through alginate-chitosan（AC） microcapsules and investigate the biological behavior of the cells released from microcapsules into the ***： Mouse osteoblastic MC3T3-E1 cells were embedded in alginate and AC microcapsules using an electrostatic droplet *** two types of cell-encapsulating microcapsules were then mixed with a CPC ***3T3-E1 cell viability was investigated using a Wst-8 kit,and osteogenic differentiation was demonstrated by an alkaline phosphatase（ALP） activity *** attachment in CPC was observed by an environment scanning electron ***： Both alginate and AC microcapsules were able to release the encapsulated MC3T3-E1 cells when mixed with CPC *** released cells attached to the setting CPC scaffolds,survived,differentiated,and formed mineralized *** grew in the pores concomitantly created by the AC microcapsules in situ within the *** Day 21,cellular ALP activity in the AC group was approximately four times that at Day 7 and exceeded that of the alginate microcapsule group（P0.05）.Pores formed by the AC microcapsules had a diameter of several hundred microns and were spherical compared with those formed by alginate ***： AC microcapsule is a promising carrier to release seeding cells deep into an injectable CPC scaffold for bone engineering.

关键词： Injectable scaffold calcium phosphate cement Osteoblast Microencapsulation Cell release Chitosan

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