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Fabrication of scaffolds in tissue engineering: A review

Peng ZHAO, Haibing GU, Haoyang MI, Chengchen RAO, Jianzhong FU, Lih-sheng TURNG

《机械工程前沿（英文）》 2018年第13卷第1期页码 107-119 doi: 10.1007/s11465-018-0496-8

摘要：

Tissue engineering (TE) is an integrated discipline that involves engineering and natural science in the development of biological materials to replace, repair, and improve the function of diseased or missing tissues. Traditional medical and surgical treatments have been reported to have side effects on patients caused by organ necrosis and tissue loss. However, engineered tissues and organs provide a new way to cure specific diseases. Scaffold fabrication is an important step in the TE process. This paper summarizes and reviews the widely used scaffold fabrication methods, including conventional methods, electrospinning, three-dimensional printing, and a combination of molding techniques. Furthermore, the differences among the properties of tissues, such as pore size and distribution, porosity, structure, and mechanical properties, are elucidated and critically reviewed. Some studies that combine two or more methods are also reviewed. Finally, this paper provides some guidance and suggestions for the future of scaffold fabrication.

关键词： tissue engineering scaffolds electrospinning 3D printing molding techniques conventional methods

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Current progress on scaffolds of tissue engineering heart valves

DONG Nianguo, SHI Jiawei, CHEN Si, HONG Hao, HU Ping

《医学前沿（英文）》 2008年第2卷第3期页码 229-234 doi: 10.1007/s11684-008-0043-9

摘要： Tissue engineering heart valves (TEHV) may be the most promising valve substitute, but the study has been relatively stagnant in the recent five years due to the special position, function and mechanical property of heart valves. It is one of the key factors to select an ideal scaffold material in the construction of TEHV. And this article will briefly review the current research and progress on the scaffolds of TEHV, especially based on Chinese works.

关键词： function scaffold promising research engineering

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New branched benign compounds including double antibiotic scaffolds: synthesis, simulation and adsorption

《化学科学与工程前沿（英文）》 2023年第17卷第2期页码 167-182 doi: 10.1007/s11705-022-2199-2

摘要： In this study, two novel environmental benign double antibiotic norfloxacin or ciprofloxacin scaffolds included branched molecules were prepared by multi-step routes and purified by simple performance, which were used as the target compounds (TCs). Meanwhile, a single norfloxacin or ciprofloxacin skeleton based molecules were synthesized as the reference compounds (RCs). The molecular geometry optimization and material simulation computation revealed that TCs presented smaller HOMO-LUMO energy gaps and larger binding energy levels on mild steel surface than RCs. The chemical adsorption of TCs on steel surface was confirmed by X-ray photoelectron spectroscopy, which could be processed by TCs chelation with iron ions. It was shown that TCs could be self-adsorbed on steel surface, which was demonstrated by atomic force microscopy and scanning electron microscopy. The anticorrosion of the studied compounds for mild steel in HCl solution was investigated by electrochemistry analysis. The results suggested that the anticorrosion efficiency could reach 95.86% (TC1) and 97.05% (TC2) at 0.050 mmol·L⁻¹ based on electrochemical impedance spectroscopy, which were much better than RCs (RC1, 69.23%; RC2, 74.16%). The adsorption isotherms of TCs on steel were further fitted, and a deep insight on adsorption was discussed.

关键词： branched compounds floxacin scaffold mild steel anticorrosion environmentally benign

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Cryo-copolymerization preparation of dextran-hyaluronate based supermacroporous cryogel scaffolds for

Dongjiao ZHOU, Shaochuan SHEN, Junxian YUN, Kejian YAO, Dong-Qiang LIN

《化学科学与工程前沿（英文）》 2012年第6卷第3期页码 339-347 doi: 10.1007/s11705-012-1209-1

摘要： Dextran-hyaluronate (Dex-HA) based supermacroporous cryogel scaffolds for soft tissue engineering were prepared by free radical cryo-copolymerization of aqueous solutions containing the dextran methacrylate (Dex-MA) and hyaluronate methacrylate (HA-MA) at various macromonomer concentrations under the freezing condition. It was observed that the suitable total concentration of macromonomers for the preparation of Dex-HA cryogel scaffold with satisfied properties was 5% (w/w) at the HA-MA concentration of 1% (w/v), which was then used to produce the test scaffold. The obtained cryogel scaffold with 5% (w/w) macromonomer solution had high water permeability (5.1 × 10 m ) and high porosity (92.4%). The pore diameter examined by scanning electron microscopy (SEM) was in a broad range of 50–135 μm with the mean pore diameter of 91 μm. Furthermore, the cryogel scaffold also had good elastic nature with the elastic modulus of 17.47±1.44 kPa. The culture of 3T3-L1 preadipocyte within the scaffold was investigated and observed by SEM. Cells clustered on the pore walls and grew inside the scaffold indicating the Dex-HA cryogel scaffold could be a promising porous biomaterial for applications in tissue engineering.

关键词： cryogel scaffold tissue engineering dextran hyaluronate 3T3-L1 preadipocyte

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Hemocompatible polyurethane/gelatin-heparin nanofibrous scaffolds formed by a bi-layer electrospinning

Heyun WANG, Yakai FENG, Marc BEHL, Andreas LENDLEIN, Haiyang ZHAO, Ruofang XIAO, Jian LU, Li ZHANG, Jintang GUO

《化学科学与工程前沿（英文）》 2011年第5卷第3期页码 392-400 doi: 10.1007/s11705-011-1202-0

摘要： In this paper, a scaffold, which mimics the morphology and mechanical properties of a native blood vessel is reported. The scaffold was prepared by sequential bi-layer electrospinning on a rotating mandrel-type collector. The tubular scaffolds (inner diameter 4 mm, length 3 cm) are composed of a polyurethane (PU) fibrous outer-layer and a gelatin-heparin fibrous inner-layer. They were fabricated by electrospinning technology, which enables control of the composition, structure, and mechanical properties of the scaffolds. The microstructure, fiber morphology and mechanical properties of the scaffolds were examined by means of scanning electron microscopy (SEM) and tensile tests. The PU/gelatin-heparin tubular scaffolds have a porous structure. The scaffolds achieved a breaking strength (3.7±0.13 MPa) and an elongation at break (110±8%) that are appropriate for artificial blood vessels. When the scaffolds were immersed in water for 1 h, the breaking strength decreased slightly to 2.2±0.3 MPa, but the elongation at break increased to 145±21%. In platelet adhesion tests the gelatin-heparin fibrous scaffolds showed a significant suppression of platelet adhesion. Heparin was released from the scaffolds at a fairly uniform rate during the period of 2 day to 9 day. The scaffolds are expected to mimic the complex matrix structure of native arteries, and to have good biocompatibility as an artificial blood vessel owing to the heparin release.

关键词： electrospinning artificial blood vessels scaffold polyurethane gelatin nanofiber hemocompatibility

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组织工程模板中的生物相容性途径 Perspective

David F. Williams

《工程（英文）》 2018年第4卷第2期页码 286-290 doi: 10.1016/j.eng.2018.03.007

摘要：

组织工程通过系统结合分子信号和力学信号对特定靶细胞进行有意可控刺激以组建新的组织，通常需要借助由生物材料构建的结构传递这些信号，并对生成的组织块塑形。这些结构之前被称为支架，如今被更准确地命名为模板，其规范却难以定义，主要因为该规范必须涉及为细胞组建新组织提供适宜的微环境，以及细胞与模板材料的相互作用符合构建新型可存活组织的需求。这些特点统称为生物相容性。然而，传统生物相容性的理论和公认机制（大多通过可移植的医学装置进行实验得出）不足以解释在组织工程过程中的现象。本文作者近期在特定的基于材料、生物学的途径方面重新定义了生物相容性。本文以上述途径为前提讨论了组织工程生物相容性的机制。

关键词：生物材料支架机械力转导炎症拓扑

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Progress of three-dimensional macroporous bioactive glass for bone regeneration

Lijun JI, Yunfeng SI, Ailing LI, Wenjun WANG, Dong QIU, Aiping ZHU

《化学科学与工程前沿（英文）》 2012年第6卷第4期页码 470-483 doi: 10.1007/s11705-012-1217-1

摘要： Bioactive glasses (BGs) are ideal materials for macroporous scaffolds due to their excellent osteoconductive, osteoinductive, biocompatible and biodegradable properties, and their high bone bonding rates. Macroporous scaffolds made from BGs are in high demand for bone regeneration because they can stimulate vascularized bone ingrowth and they enhance bonding between scaffolds and surrounding tissues. Engineering BG/biopolymers (BP) composites or hybrids may be a good way to prepare macroporous scaffolds with excellent properties. This paper summarizes the progress in the past few years in preparing three-dimensional macroporous BG and BG/BP scaffolds for bone regeneration. Since the brittleness of BGs is a major problem in developing macroporous scaffolds and this limits their use in load bearing applications, the mechanical properties of macroporous scaffolds are particularly emphasized in this review.

关键词： bioactive glass biopolymer bone regeneration macroporous scaffolds tissue engineering

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支架与组织的设计及3D打印 Review

安佳, Joanne Ee Mei Teoh, Ratima Suntornnond, Chee Kai Chua

《工程（英文）》 2015年第1卷第2期页码 261-268 doi: 10.15302/J-ENG-2015061

摘要：

目前，组织工程学中应用3D打印工艺的情况越来越多。本文介绍3D打印技术在组织工程学应用领域的最前沿研究，尤其侧重于计算机辅助支架设计系统的开发、功能梯度支架的直接3D打印、选择性激光烧结 (SLS) 和熔融沉积成型 (FDM) 工艺建模、利用微观和宏观特征进行支架间接增材制造、生物反应器的开发，以及3D/4D生物打印。本文还讨论3D打印的技术限制，进而突出新3D打印方法在组织工程学领域得到进一步改善的可能性。

关键词：快速原型制造 3D打印增材制造组织工程生物打印

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募集抗原特异性T细胞的3D打印支架促进血管化 Article

李翠笛, 马振江, 李文韬, 颉天阳, 钟丽萍, 陈宏方, 王文豪, 王金武, 崔文国, 赵永祥

《工程（英文）》 2022年第17卷第10期页码 183-195 doi: 10.1016/j.eng.2021.05.018

摘要：

3D打印支架植入后激起的免疫反应是组织修复效果的主要决定性因素。因此，巧妙调控免疫反应的支架材料具有高效修复组织的潜能。本研究受抗原特异性免疫反应对血管新生促进作用的启发，通过动态共价键将介孔二氧化硅微棒（MSR）/聚乙烯亚胺（PEI）/卵清蛋白（OVA）自组装疫苗与3D打印自固化磷酸钙骨水泥（CPC）基支架结合，构建了一种具有调控局部体液免疫反应功能的组织修复支架。通过局部释放OVA激活体液免疫反应，支架可有效募集抗原特异性CD4⁺ 2 型辅助性T细胞（Th2 细胞），从而促进支架植入早期的血管新生；在提供充足和丰富的血供环境的同时，MSR微棒中释放的硅离子还能有效加速骨再生。在室温下稳定成型的自固化磷酸钙基打印浆料能够促进功能性氧化透明质酸在材料中的均匀分布和结构保持，并构建具有均匀连通孔道的支架。将MSR/PEI 作为抗原载体共价结合于富含醛基的支架，可实现OVA的稳定释放。在体外实验中，该疫苗负载支架有效募集并激活了树突细胞使树突细胞呈递抗原，还促进了骨髓间充质干细胞（BMSC）成骨分化。在皮下包埋实验中，疫苗负载支架增加了Th2 细胞在脾脏中的比例，局部募集了抗原特异性T细胞并促进了支架内的血管新生。此外，原位颅骨缺损修复模型结果表明，负载疫苗的支架可促进血管化骨组织再生。总之，该方法为具有促进血管新生功能个性化植入体的设计提供了一种新思路。

关键词： 3D打印免疫微环境调控血管新生骨再生

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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 Article

王晓亚, 张猛, 马景阁, 徐梦驰, 常江, Michael Gelinsky, 吴成铁

《工程（英文）》 2020年第6卷第11期页码 1276-1284 doi: 10.1016/j.eng.2020.08.001

摘要：

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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基于液滴微流控的分级结构反蛋白石多孔支架用于仿生三维细胞共培养 Article

邵长敏, 刘羽霄, 池俊杰, 叶方富, 赵远锦

《工程（英文）》 2021年第7卷第12期页码 1778-1785 doi: 10.1016/j.eng.2020.06.031

摘要：

三维（3D）细胞培养具有更好地模拟天然组织特异性的优势，在药物开发、毒性测试和组织工程中发挥着重要作用。然而，现有的3D细胞培养的支架或微载体通常尺寸有限，并且在模拟生物体内血管复合体方面表现不佳。因此，本研究提出了一种通过简单的微流控方法制备的新型分级结构反蛋白石多孔支架，用于促进3D细胞共培养。该支架是基于微流控乳液液滴模板和惰性聚合物聚合的复合概念构建的。研究结果表明，该支架能够保证细胞培养过程中的营养供给，从而实现大面积的细胞培养。此外，通过在该支架中连续种植不同的细胞，本文还开发了内皮细胞包裹肝细胞的3D细胞共培养系统，用于构建功能化组织。研究结果表明，该支架用于细胞共培养系统，有助于维持肝细胞特定的体内功能。该分级结构反蛋白石多孔支架为3D细胞培养甚至仿生组织的构建奠定了基础。

关键词：微流控反蛋白石细胞培养液滴生物材料

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一种新型生物材料——玉米醇溶蛋白多孔支架的质量监控

张玥, 李伟迎, 兰润, 王瑾晔

《工程（英文）》 2017年第3卷第1期页码 130-135 doi: 10.1016/J.ENG.2017.01.001

摘要：

我们之前的研究显示玉米醇溶蛋白具有良好的生物相容性和机械特性。由玉米醇溶蛋白多孔支架制成的第一个产品——一种可吸收的骨替代物，已经通过了国家食品药品监督管理总局医疗器械的生物学评价(ISO 10993)。然而，作为一种三类医疗器械，在其进入市场前需要进行质量监控，这些监控包括原材料的质量监控、灭菌方法的选择和生物相容性的评价。在本文中，我们通过氨基酸分析(AAA) 和十二烷基硫酸钠–聚丙烯酰氨凝胶电泳(SDS-PAGE) 研究了四种玉米醇溶蛋白，来监控其组成和纯度，以控制原材料的质量。我们用SDS-PAGE 研究了三种灭菌方式对玉米醇溶蛋白多孔支架的影响，并比较了在不同γ 射线剂量下SDS-PAGE 图谱的变化。我们发现在剂量20~30 kGy 范围内，γ 射线灭菌过程中玉米醇溶蛋白的肽链没有发生断裂或聚合，这表明γ 射线灭菌对于玉米醇溶蛋白多孔支架是适用的。对于细胞相容性，我们发现使用MTT 实验和CCK-8 实验来评估玉米醇溶蛋白膜上细胞的增殖是有区别的，由于在CCK-8 实验中背景的吸光度差异较小，我们认为CCK-8 实验更为适合。

关键词：玉米醇溶蛋白氨基酸分析十二烷基硫酸钠&ndash 聚丙烯酰氨凝胶电泳 &gamma 射线灭菌 MTT 实验 CCK-8 实验

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增材制造可降解镁合金植入物面临的挑战及其对策 Article

王银川, 付彭怀, 王南清, 彭立明, 康斌, 曾晖, 袁广银, 丁文江

《工程（英文）》 2020年第6卷第11期页码 1267-1275 doi: 10.1016/j.eng.2020.02.015

摘要：

增材制造（AM）技术具有制备复杂几何结构的能力，为可降解金属植入物的制备提供了前所未有的机会，尤其对具有合适力学性能和良好生物相容性的可降解镁合金。然而，AM可降解镁基植入物面临着许多挑战，如镁粉制备困难以及AM过程中的粉体飞溅和裂纹形成。本文分析了AM可降解镁合金所面临的挑战，并提出了相应的应对策略，成功制备了一种表面光滑且圆整度好的新型镁合金（JDBM）粉体，然后对其AM参数进行了优化。在优化参数的基础上，采用选区激光熔化（SLM）技术制备了三种不同结构（仿生、金刚石和极小曲面）的JDBM多孔支架，并分析了其力学性能和降解行为。最后，筛选出性能最优的极小曲面支架进行透钙磷石（DCPD）涂层处理，该涂层极大地抑制了支架降解速率，并提高了其细胞相容性。AM镁合金支架展现了作为骨组织工程支架的临床应用前景。

关键词：增材制造选区激光熔化可降解镁合金组织工程支架表面改性