最近发表在《杂志》上的论文Biomaterials回顾了不同器官系统中再生疗法的三维生物打印（3DBP）的新进展。
学习：用于再生医学和维特罗模型的组织/器官3D生物打印的进展。图片来源：luchschenf/shutterstock.com
Background
Organ/tissue shortage has emerged as a significant challenge in the medical field due to patient immune rejections and donor scarcity. Moreover, mimicking or predicting the human disease condition in the animal models is difficult during preclinical trials owing to the differences in the disease phenotype between animals and humans.
3DBP has gained significant attention as a highly-efficient multidisciplinary technology to fabricate 3D biological tissue with complex composition and architecture. This technology allows precise assembly and deposition of biomaterials with donor/patient’s cells, leading to the successful fabrication of organ/tissue-like structures, preclinical implants, and in vitro models.
In this study, researchers reviewed the 3DBP strategies currently used for regenerative therapy in eight organ systems, including urinary, respiratory, gastrointestinal, exocrine and endocrine, integumentary, skeletal, cardiovascular, and nervous systems. Researchers also focused on the application of 3DBP to fabricate in vitro models. The concept of in situ 3DBP was discussed.
3DBP使用的常见生物打印技术
挤出生物打印
In this extensively used low-cost bioprinting method, rotating screw gear or pressurized air is used without or with temperature to extrude a continuous stream of thermoplastic or semisolid material. Different materials can be printed at a high fabrication speed using this technology. However, low cell viability and the need for post-processing are the major drawbacks of extrusion bioprinting.
Inkjet Bioprinting
在这种方法中，液滴通过声学或热力在底物上排出。该技术的主要优势是高制造速度，小液滴体积和相互连接的微孔隙率梯度。但是，有限的印刷材料和堵塞是喷墨生物打印的最大缺点欧洲杯足球竞彩。
Laser-assisted Bioprinting
激光用于在激光辅助生物打印方法中诱导生物材料的正向转移。欧洲杯足球竞彩高细胞活力和无喷嘴的非接触过程是激光辅助生物打印的最大优势，而金属颗粒污染和打印过程的耗时性质是主要缺点。
3DBP在不同器官系统中应用于再生治疗
神经系统
Several studies were performed involving the development of neuronal tissues using the 3DBP method. The pressure extrusion/syringe extrusion (PE/SE) bioprinting technique was used for central nervous tissue (CNS) tissue replacement. The layered porous structure was fabricated using glial cells derived using human induced pluripotent stem cell (iPSC) and a novel bioink based on agarose, alginate, and carboxymethyl chitosan (CMC) formed synaptic networks and displayed a bicuculline-induced enhanced calcium response.
同样，立体光刻（SLA）用于制造CNS的3D支架，并评估了脚手架的可行性以进行再生医学应用。使用聚（乙二醇）二丙烯酸二丙烯酸甲酯（PEGDA-Gelma）和大鼠E14神经祖细胞（NPCS）打印分层的线性微通道。3D支架恢复了突触接触，并显着改善了功能结果。在交联期间，环己烷用于将聚苯乙烯纤维粘合到基质束末端。
心血管系统
多光子激发3维打印（MPE-3DP）用于心肌组织的再生。使用gelma/钠4- [2-（4-甲氧杆菌）苯甲酰基-2-二甲基氨基] - 丁基苯甲磺酸盐（MBS）和人类HCIPSC衍生的心肌细胞（CMS），内皮细胞（ECS），内皮细胞（ECS），使用gelma/ sodiuim [2-（4-甲氧杆菌）苯甲酰-2-二甲基氨基]制造逐层结构。和平滑肌细胞（SMC）。交联是通过光激活进行的。该结构促进了机电耦合，并改善了细胞增殖，血管和心脏功能。
融合沉积建模（FDM）和PE/SE生物打印方法用于复杂的组织和器官再生。使用聚乙烯醇（PVA），琼脂糖，藻酸钠和富含血小板的血浆以及大鼠H9C2细胞以及人类脐静脉内皮细胞（HUVECS）制造微流体网络心形结构。在交联机制期间使用了2％二氯化钙。制造的结构具有具有空心机械性能和自定义高度的情人心脏。
SE打印用于使用胶原蛋白型胶原蛋白胶和人类成纤维细胞和ECS用于血管中的应用。制造的网络具有内皮网络，并在成纤维细胞层之间发芽。
Skeletal System
可以使用3DBP技术对骨，软骨和骨骼肌组织进行修复和再生。例如，FDM打印用于打印多功能治疗脚手架以治疗骨骼。使用透明质酸（HA）/氧化铁纳米颗粒（离子）/米诺环素和人类MG-63和人骨髓基质细胞（HBMSC）制造丝源投射（PLA）平台（HA）/氧化铁纳米颗粒（离子）/米诺环素（HBMSC），从欧洲杯猜球平台和哈。
PE/SE method was used to fabricate disks and cuboid-shaped scaffolds using α- tricalcium phosphate (TCP) microgel and human fetal osteoblast (hFOB) and bone marrow-derived mesenchymal stem cell (BM-MSC) for bone repair, multicellular delivery, and disease model. The fabricated structures promoted osteogenesis.
PE/SE生物打印也用于使用藻酸盐/明胶/HA，大鼠骨髓间充质干细胞（BMSC）和牛心脏祖细胞（CPC）制造复杂的多孔层状软骨样结构。CPC上调蛋白聚糖4（PRG4），SRY-box转录因子9（SOX9）和胶原蛋白II的基因表达。
PE/SE printing was also used to fabricate multinucleated, highly-aligned myotube structures using polyurethane (PU), poly(ε-caprolactone) (PCL), and mouse C2C12 myoblasts and NIH/3T3 fibroblasts for in-situ expansion and differentiation of skeletal muscle tendon. The fabricated constructs demonstrated more than 80% cell viability with initial tissue differentiation and development.
外皮系统
SLA bioprinting technique was used to fabricate bi-layered epidermis-like structure using collagen type I, mouse NIH 3T3 fibroblast cells, and human keratinocyte cells for tissue model and engineering. The fabricated constructs effectively imitated the tissue functions.
Similarly, PE was employed to fabricate microporous structures using human amniotic mesenchymal stem cells (AFSCs) and heparin-HA-PEGDA for wound healing. The construct improved the wound closure and reepithelialization, increased extracellular matrix synthesis and vascularization, and prolonged the cell paracrine activity.
PE technique was utilized to prepare a multilayered cornea-like structure using human keratocytes and methacrylated collagen (ColMA)-alginate. The cell viability of the keratocytes decreased from 90% to 83% after printing.
Gastrointestinal, Respiratory, and Urinary Systems
PE/SE bioprinting was utilized to bioprint multilayered liver-like structures using GeIMA and human HepG2/C3A for liver tissue engineering. Similarly, hepatocytes were also bioprinted to fabricate multiple organ precursors with branching vasculature. A small intestine model with improved intestinal function and high cell proliferation was fabricated using caco-2 cell-loaded polyethylene vinyl acetate (PEVA) scaffold.
Spheroids of mesenchymal stem cells (MSCs) and chondrocytes and lung endothelial cells were utilized to fabricate scaffold-free tracheal transplant. After implantation in the rat model, the matured spheroids displayed excellent vasculogenesis, chondrogenesis, and mechanical strength. FDM technique was used to fabricate a glomerular structure for kidneys using human iPSCs and hydrogel and a hollow porous network using poly(lactic-co-glycolic acid (PLGA)/PCL/tumor-associated endothelial cells (TECs) for the urethra.
In-situ Bioprinting
在原位生物涂纸中，组织直接印在体内的特定缺陷或伤口部位，以进行再生和修复治疗。该方法提供了明确定义的结构，并减少了宿主植入物接口之间的差距。原位生物打印胜于体外生物打印技术，因为患者的身体是天然的生物反应器，提供了天然的微环境。
几项研究评估了该技术的组织再生。例如，使用纤维蛋白/胶原蛋白/HA和人成纤维细胞细胞，使用PE/SE方法用于猪和小鼠的皮肤组织再生。在生物材料快速交联后，形成了一致成分，厚度和宽度的皮肤板。PE/SE技术还用于使用琼脂糖/CMC/藻酸盐和人IPSC的小鼠的神经组织再生。
体外模型的生物打印
体外模型为理解治疗和疾病病理生理学机理提供了重要帮助。最近，使用3DBP技术对人体组织和器官进行体外模型进行安全评估和药物测试。
结论和未来前景
在器官和组织的3DBP中，生物材料在维持细胞活力，提供支持和长期接受度中起着欧洲杯足球竞彩至关重要的作用。具体而言，生物界必须具有独特的特性，例如细胞生长促进和结构稳定性，可以优化用于临床使用。此外，生物界必须与打印机兼容，以进行高精度快速原型制作。
Bioinks fulfilling all of these requirements are yet to be identified. Moreover, managing the time during the bioprinting of the constructs is another major challenge, as the time required to fabricate them is often more than the survival time of cells. A bioreactor platform that supports organoid growth and provides time for tissue remodeling can be used to overcome this challenge. Ethical challenges and issues are also a hurdle since fabricating internal tissues/organs can lead to liability and biosafety concerns.
In the future, 3DBP can provide novel solutions to engineer organs/tissues and revolutionize modern healthcare and medicine if these challenges can be addressed.
来自Azom的更多信息：建立耐用和可持续的期货与[电子邮件保护]
Source
Jain，P.，Kathuria，H.，Dubey，N。用于再生医学和维特罗模型的组织/器官3D生物打印的进步。Biomaterials2022。https://www.sciencedirect.com/science/article/abs/pii/S0142961222002794?via%3Dihub
Disclaimer: The views expressed here are those of the author expressed in their private capacity and do not necessarily represent the views of AZoM.com Limited T/A AZoNetwork the owner and operator of this website. This disclaimer forms part of theTerms and conditionsof use of this website.