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Evaluation of different crosslinking methods in altering the properties of extrusion-printed chitosan-basedmulti-material hydrogel composites

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Bio-Design and Manufacturing 2023年第2期6卷 150-173页

作者： Suihong Liu Haiguang Zhang Tilman Ahlfeld David Kilian Yakui Liu michael gelinsky Qingxi Hu Centre for Translational Bone Joint and Soft Tissue ResearchFaculty of Medicine and University Hospital Carl Gustav CarusTechnische Universität Dresden01307 DresdenGermany Rapid Manufacturing Engineering Center School of Mechatronic Engineering and AutomationShanghai UniversityShanghai 200444China Shanghai Key Laboratory of Intelligent Manufacturing and Robotics School of Mechatronic Engineering and AutomationShanghai UniversityShanghai 200444China National Demonstration Center for Experimental Engineering Training Education Shanghai UniversityShanghai 200444China

Three-dimensional printing technologies exhibit tremendous potential in the advancing fields of tissue engineering and regenerative medicine due to the precise spatial control over depositing the *** their widespread utilization and numerous advantages,the development of suitable novel biomaterials for extrusion-based 3D printing of scaffolds that support cell attachment,proliferation,and vascularization remains a ***-material composite hydrogels present incredible potential in this ***,in this work,a multi-material composite hydrogel with a promising formulation of chitosan/gelatin functionalized with egg white was developed,which provides good printability and shape *** addition,a series of comparative analyses of different crosslinking agents and processes based on tripolyphosphate(TPP),genipin(GP),and glutaraldehyde(GTA)were investigated and compared to select the ideal crosslinking strategy to enhance the physicochemical and biological properties of the fabricated *** of the results indicate that the composite hydrogel and the resulting scaffolds utilizing TPP crosslinking have great potential in tissue engineering,especially for supporting neo-vessel growth into the scaffold and promoting angiogenesis within engineered tissues.

关键词： Multi-material composite hydrogel Crosslinking mechanism Chitosan Gelatin Egg white 3D printing

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3D Printing of Cell-Container-Like Scaffolds for Multicell Tissue Engineering

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Engineering 2020年第11期6卷 1276-1284页

作者： Xiaoya Wang Meng Zhang Jingge Ma Mengchi Xu Jiang Chang michael gelinsky Chengtie Wu State Key Laboratory of High Performance Ceramics and Superfine Microstructure Shanghai Institute of CeramicsChinese Academy of SciencesShanghai 200050China Center of Materials Science and Optoelectronics Engineering University of Chinese Academy of SciencesBeijing 100049China Center for Translational Bone Joint and Soft Tissue Research.University Hospital Carl Gustav Carus&Faculty of MedicineTechnische Universitat DresdenDresden 01307Germany

The development of an engineered non-contact multicellular coculture model that can mimic the in v iv o cell microenvironment of human tissues remains *** this study,we successfully fabricated a cell-container-like scaffold composed of p-tricalcium phosphate/hydroxyapatite(p-TCP/HA)bioceramic that contains four different pore structures,including triangles,squares,parallelograms,and rectangles,by means of three-dimensional(3D)printing *** scaffolds can be used to simultaneously culture four types of cells in a non-contact *** engineered 3D coculture model composed of human bone-marrow-derived mesenchymal stem cells(HBMSCs),human umbilical vein endothelial cells(HUVECs),human umbilical vein smooth muscle cells(HUVSMCs),and human dermal fibroblasts(HDFs)with a spatially controlled distribution was constructed to investigate the individual or synergistic effects of these cells in osteogenesis and *** results showed that three or four kinds of cells cocultured in 3D cell containers exhibited a higher cell proliferation rate in comparison with that of a single cell *** studies into the cell-cell interactions between HBMSCs and HUVECs revealed that the 3D cell containers with four separate spatial structures enhanced the angiogenesis and osteogenesis of cells by amplifying the paracrine effect of the cocultured ***,the establishment of multicellular non-contact systems including three types of cells and four types of cells,respectively,cocultured in 3D cell containers demonstrated obvious advantages in enhancing osteogenic and angiogenic differentiation in comparison with monoculture modes and two-cell coculture *** study offers a new direction for developing a scaffold-based multicellular non-contact coculture system for tissue regeneration.

关键词： 3D cell containers Non-contact multicellular coculture Interactions Angiogenesis Osteogenesis

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3D printing of patient-specific implants for osteochondral defects: workflow for an MRI-guided zonal design

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Bio-Design and Manufacturing 2021年第4期4卷 818-832页

作者： David Kilian Philipp Sembdner Henriette Bretschneider Tilman Ahlfeld Lydia Mika Jörg Lützner Stefan Holtzhausen Anja Lode Ralph Stelzer michael gelinsky Centre for Translational Bone Joint and Soft Tissue ResearchUniversity Hospital Carl Gustav Carus and Faculty of MedicineTechnische Universität DresdenDresdenGermany Institute of Machine Elements and Machine Design Faculty of Mechanical EngineeringTechnische Universität DresdenDresdenGermany University Center of Orthopaedic Trauma and Plastic SurgeryUniversity Hospital Carl Gustav CarusTechnische Universität DresdenDresdenGermany

Magnetic resonance imaging(MRI)is a common clinical practice to visualize defects and to distinguish different tissue types and pathologies in the human *** far,MRI data have not been used to model and generate a patient-specific design of multilayered tissue substitutes in the case of interfacial *** orthopedic cases that require highly individual surgical treatment,implant fabrication by additive manufacturing holds great ***-based techniques like 3D plot-ting allow the spatially defined application of several materials,as well as implementation of bioprinting *** the example of a typical multi-zonal osteochondral defect in an osteochondritis dissecans(OCD)patient,this study aimed to close the technological gap between MRI analysis and the additive manufacturing process of an implant based on dif-ferent biomaterial inks.A workflow was developed which covers the processing steps of MRI-based defect identification,segmentation,modeling,implant design adjustment,and implant generation.A model implant was fabricated based on two biomaterial inks with clinically relevant properties that would allow for bioprinting,the direct embedding of a patient’s own cells in the printing *** demonstrated by the geometric compatibility of the designed and fabricated model implant in a stereolithography(SLA)model of lesioned femoral condyles,a novel versatile CAD/CAM workflow was successfully established that opens up new perspectives for the treatment of multi-zonal(osteochondral)defects.

关键词： Additive manufacturing(AM) Magnetic resonance imaging(MRI) Computer-aided design(CAD) Osteochondritis dissecans(OCD) Bone cement Hydrogel

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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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3-D打印:一种个性化制备复杂支架和组织工程植入物的多功能快速成型技术(英文)

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中国修复重建外科杂志 2014年第3期28卷 279-285页

作者：罗永祥 Ashwini Rahul Akkineni Anja Lode michael gelinsky 德国德累斯顿工业大学移植骨关节和软组织研究中心中国科学院上海硅酸盐研究所生物材料和组织工程研究中心

目的对3-D打印技术构建的个性化生物支架和组织工程结构物的近期研究进展进行综述。方法广泛查阅近期采用3-D打印技术制备个性化生物支架和组织工程结构物的相关文献,并对作者课题组采用3-D打印技术用于组织工程领域的近期研究工作进行... 详细信息

目的对3-D打印技术构建的个性化生物支架和组织工程结构物的近期研究进展进行综述。方法广泛查阅近期采用3-D打印技术制备个性化生物支架和组织工程结构物的相关文献,并对作者课题组采用3-D打印技术用于组织工程领域的近期研究工作进行总结。结果相较于仅适用于特定生物材料的快速成型法,3-D打印技术适用于几乎所有膏状生物材料,为构建生物支架、多相支架甚至是包含活细胞的组织工程结构物提供了更多的可能和选择。结论 3-D打印技术是一种越来越重要的快速成型技术,该技术保证了生物材料的广泛选择应用,并使得直接打印敏感生物物质(如生长因子和细胞)成为可能。

关键词： 3-D打印技术快速成型法叠加制造个性化支架

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硅酸钙、β-磷酸三钙和羟基磷灰石三相陶瓷复合物与骨细胞活性的体外鉴定(英文)

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中国组织工程研究与临床康复 2010年第16期14卷 3033-3040页

作者： Anne Bernhardt Anja Lode Sivadasan Suresh Babu Antje Vogel Thomas Hanke Sebastian Thieme Hare Krishna Varma Angela Rosen-Wolff michael gelinsky Annie John Institute of Materials Science Max Bergmann Center forBiomaterials Dresden University of Technology Germany Biomedical Technology Wing Sree Chitra Tirunal Institute for Medical Sciences and Technology Thiruvananthapuram India Department of Pediatrics University Clinic Carl Gustav Carus Dresden University of Technology Dresden Germany

由于羟基磷灰石陶瓷与骨无机质的化学成份相似,所以10年来研究者对羟基磷灰石陶瓷在骨修复替换中的应用进行了深入的研究。羟基磷灰石因其高生物相容性和骨传导性已被广泛的应用,但羟基磷灰石的再吸收能力差。文章对由硅酸钙、β-磷酸... 详细信息

由于羟基磷灰石陶瓷与骨无机质的化学成份相似,所以10年来研究者对羟基磷灰石陶瓷在骨修复替换中的应用进行了深入的研究。羟基磷灰石因其高生物相容性和骨传导性已被广泛的应用,但羟基磷灰石的再吸收能力差。文章对由硅酸钙、β-磷酸三钙和羟基磷灰石组成的三相陶瓷复合物进行了研究。在三相陶瓷复合物环境下,采用不同比率硅酸钙、β-磷酸三钙和羟基磷灰石对骨髓夹源间充质干细胞进行体外研究。细胞在加入和没有加入成骨细胞的情况下培养28d。采用碱性磷酸酶活性、碱性磷酸酶基因码转录和骨唾液蛋白Ⅱ表达评估成骨分化水平。成骨细胞和破骨细胞在陶瓷复合80%羟基磷灰石材料上完成预实验。将鼠颅盖骨成骨细胞与人单核细胞共同培养以分析其向破骨细胞分化的可能性。结果显示人骨髓间充质干细胞在陶瓷复合物材料上表现出快速黏附和高度增殖率,在所有实验材料上,成骨诱导的骨髓间充质干细胞碱性磷酸酶活性增加,碱性磷酸酶基因码转录和骨唾液酸蛋白Ⅱ的表达在3种材料上同样增加。扫描电镜和聚焦激光扫描显微镜结果证明在陶瓷复合80%羟基磷灰石材料上的人单核细胞向破骨样细胞分化。结果提示制备的三相陶瓷复合材料支持人骨髓间充质干细胞的黏附、增殖和成骨分化,以及人单核细胞与成骨细胞联合培养条件下破骨细胞形成。

关键词：羟基磷灰石陶瓷 β-磷酸三钙复合物材料骨细胞活性人骨髓间充质干细胞细胞碱性磷酸酶活性硅酸体外鉴定

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3D打印细胞容器样支架在多细胞组织工程中的应用研究

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Engineering 2020年第11期6卷 155-173页

作者：王晓亚张猛马景阁徐梦驰常江 michael gelinsky 吴成铁 State Key Laboratory of High Performance Ceramics and Superfine Microstructure Shanghai Institute of Ceramics Chinese Academy of Sciences Center of Materials Science and Optoelectronics Engineering University of Chinese Academy of Sciences Center for Translational Bone Joint and Soft Tissue Research University Hospital Carl Gustav Carus & Faculty of Medicine Technische Universit?t Dresden

人工设计的非接触式多细胞共培养模型可以模仿人体组织的细胞内微环境,但其发展始终面临各种挑战。本研究利用3D打印技术,成功制得了一种含β-磷酸三钙/羟基磷灰石(β-TCP/HA)的细胞容器样支架,该支架设计了四种不同形状的微孔结构:三... 详细信息

人工设计的非接触式多细胞共培养模型可以模仿人体组织的细胞内微环境,但其发展始终面临各种挑战。本研究利用3D打印技术,成功制得了一种含β-磷酸三钙/羟基磷灰石(β-TCP/HA)的细胞容器样支架,该支架设计了四种不同形状的微孔结构:三角形、正方形、平行四边形和长方形微孔结构。这些支架可以在非接触的方式下同时培养四种细胞。本研究构建了一种由人骨髓间质干细胞(HBMSC)、人脐静脉内皮细胞(HUVEC)、人脐静脉平滑肌细胞(HUVSMC)、人真皮成纤维细胞(HDF)组成的3D共培养模型,用以研究这些细胞在促进骨生成和血管生成过程中细胞的个体效应与协同效应。结果表明,相较于在3D细胞容器中仅培养一种细胞,共培养三种或四种细胞展现出了更高的细胞增殖率。HBMSC与HUVEC的细胞间相互作用的研究表明,含有四种独立空间结构的3D细胞容器可以通过放大共培养细胞的旁分泌效应促进细胞的骨生成和血管生成能力。此外,在3D细胞容器中建立多细胞非接触体系,特别是含有三种或四种细胞的共培养体系,相对于单细胞培养模式与两种细胞共培养模式来说,在促进细胞成骨分化和成血管分化方面展现出明显的优势。本研究为基于支架的多细胞非接触式共培养体系的发展提供了新的研究方向。

关键词： 3D细胞容器非接触式多细胞共培养相互作用血管生成骨生成

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