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| 瑞士RegenHU打印机—活细胞组织三维打印制造最强音 活性细胞组织存活率99%以上！！ 常温、高低温等打印材料广泛！！ 接近体内自然环境的打印微环境极限控制！！ 打印速度极快！！ 生命与材料的完美结合!! Regenhu专注生物工程材料打印，特别是活性细胞组织、支架高要求的3D打印制造 瑞士RegenHU公司目前主要有两款产品，分别为3DDiscovery 和BioFactory系列。这两款产品都是生物打印领域中具有高性价比的3D生物打印平台，可以帮助研究者通过生物打印方法对有潜力的三维组织工程方法、材料、集成技术等进行研究。 瑞士RegenHU 所生产的3D生物打印与制造系统（3DDiscovery 和BioFactory系列）具有打印生物材料种类多、对细胞损伤率低、打印精度高、集成化程度好和操作方便等特点。相关数据显示，RegenHU三维生物打印机在生物材料兼容性、细胞打印特性等各项参数上处于全球领先地位。瑞士RegenHU 3D生物打印与制造系统已经广泛用于再生医学、组织工程、癌症、干细胞、医用高分子材料等科学领域的研究中。
性能良好的生物打印机必须解决以下问题： （1）打印力学方面方面，打印机在喷射过程中的剪切力和液滴的冲击力不会或者尽量少地对打印细胞活性造成冲击。 （2）生物支架材料的生物相容性问题，打印机打印的生物支架必须有良好的可降解性及降解速率，同时材料具有一定的机械力学强度以及最适孔径和孔隙率。同时生物支架还必须对细胞和 DNA 既无毒性，也不会引起不可逆的损伤，在整个打印过程中都要求是无菌化的。 （3）打印精度以及微结构控制能力，打印的支架与细胞混合体需要有稳定性的三维结构，不能在打印后出现溶解或坍塌。打印的构建物可以进行体外培养、增殖、分化、发育等后处理过程，要求构建模型是具有组织/器官三维特征的，能够模拟组织/器官特异性的微结构和微环境，这些对于大量细胞的种植、细胞和组织的生长、细胞外基质的形成、氧气和营养的传输、代谢物的排泄以及血管和神经的内生长起着决定作用。 瑞士RegenHU公司的3DDiscovery 和BioFactory系列产品完美地解决了以上问题，这两款产品通过在体外模拟内体生理条件，然后通过模块化、可选的多次分配技术、强大的BioCAD软件快速建模、微米级进程重复定位精度、纳升及皮升级别的高精度的打印流量控制、功能强大的多种打印喷头，可以帮助研究者快速、准确、个性化地制造复杂的生物实体。 目前，瑞士RegenHU公司的3DDiscovery 和BioFactory系列产品已经广泛应用于为生命科学、材料科学、药品研发、组织工程等诸多领域。其优异的性能为科研工作者在解决再生医学、组织工程、癌症、干细胞、医用高分子材料等领域的关键问题中提供了划时代的解决方案，相关文献已经在包括Nature，Acta Biomaterial，Biomaterials，Clin. Oral Impl. Res.，Journal of Laboratory Automation，Biomacromolecules等知名杂志发表，收到业内的广泛重视。 3DDiscovery打印机介绍 1、3DDiscovery三维运动及定位系统 3DDiscovery打印机采用的是基座作为Y轴，喷头作为X、Z轴的双驱动运动模式，运动精度更高。机械手臂精度控制在±10um之内，保证射出材料定位的高精度。对于生物打印来说，由于支架材料的微结构（microstructure）的空隙度需要控制在30-100um之间，输入文件的单层切片厚度一般在50--100um之间，所以±10um的控制精度足以满足所有的生物打印材料的需求。 2、3DDiscovery打印机喷头 3DDiscovery打印机喷头与“生物墨水”（bioink）之间具有良好的相容性，针对不同粘度的材料提供了不同挤出速率、针头孔径的喷头，喷头的设计符合流体力学的要求，包括黏滞性、密度、表面张力等重要参数。在3DDiscovery打印机的喷头设计中，喷头的孔径为150um—2mm之间，该设计可保证打印过程中所打印的细胞或分子保持液态，打印后又可以立即凝固，以维持黏弹性状态。这种液态到固态的变化保证不引起细胞、生物活性因子以及其他微粒的损伤，保证细胞的存活，从而有利于体外的培养。 采用气体压力来控制打印机的材料的挤出，控制精度是所有打印机中最高的一种。采用气压来作为动力的优势还在于满足保证细胞的存活率、无污染等生物方面的要求，三维打印喷头适应性强，操作简单，可以根据材料粘度调节适合的气体压力，进行不同粘度的成形材料的三维打印成形；另外喷头采用水平的排布方法，喷头间不易发生干扰。
3DDiscovery打印机喷头相关参数 喷头原理：电磁射流技术+微控阀门 喷嘴直径150um—2mm 喷射压强：2060 kPa（ Dispensing pressure ） 微控阀门喷射时间4001200 us（valve opening time ） 喷射点距：0.050.07 mm（dosing distance）
3、3DDiscovery打印机适合于不同的生物材料 3DDiscovery打印机可以使用聚乳酸（PLA）、聚乙醇酸（PGA）、聚乙二醇衍生物（PEG）、纤维蛋白、弹性蛋白（韧带及真皮中）、胶原蛋白、海藻酸钠、琼脂糖等。 也可以使用天然生物衍生材料，如脱钙骨基质、壳聚糖、藻酸盐凝胶等；另一类是人工合成生物高分子材料，主要有羟基***灰石、***酸三钙、生物活性玻璃等无机材料和以聚乳酸及其共聚物等为代表的有机材料。 也可以采用聚己酸内酯，***酸钙和水凝胶基体来形成生物相容性良好的骨骼。
ABSTRACT: In this study, a bioink that combines the outstanding shear thinning properties of nanobrillated cellulose (NFC) with the fast cross-linking ability of alginate was formulated for the 3D bioprinting of living soft tissue with cells. Printability was evaluated with concern to printer parameters and shape delity. The shear thinning behavior of the tested bioinks enabled printing of both 2D gridlike structures as well as 3D constructs. Furthermore, anatomically shaped cartilage structures, such as a human ear and sheep meniscus, were 3D printed using MRI and CT images as blueprints. Human chondrocytes bioprinted in the noncytotoxic, nanocellulose-based bioink exhibited a cell viability of 73% and 86% after 1 and 7 days of 3D culture, respectively. On the basis of these results, we can conclude that the nanocellulose-based bioink is a suitable hydrogel for 3D bioprinting with living cells. This study demonstrates the potential use of nanocellulose for 3D bioprinting of living tissues and organs. （2）Markus Rimanna, et al. 3D Bioprinted Muscle and Tendon Tissues for Drug Development. Chimia 69 (2015) 65–67
图3-10蜘蛛丝蛋白水凝胶生成的三维细胞加载结构 生物墨水的生物印刷适应性是生物打印的目前最大的瓶颈之一。文章报道了使用了重组蜘蛛丝蛋白作为生物墨水，发现其具有能够对细胞生存和增殖具有良好的适应能力，不需要交联剂、机械稳定添加剂或增稠剂。在这项研究中, 重组蜘蛛丝蛋白水凝胶可以自动生成的三维细胞加载结构，证明重组蜘蛛丝水蛋白凝胶在生物打印中具有良好的应用前景。 BioFactory三维生物打印机系统介绍 瑞士RegenHU BIOFACTORY是目前已知的三维打印机中功能最为强大的生物打印机，产品一经推出，立即受到组织工程领域的科学家的重视。其强大的动力系统、独特的转盘式选择定位系统、可扩展到8只打印头的材料选择平台，都为科学家的研究能力增加了强大的保障。 1、BioFactory系统动力系统介绍 2、BioFactory配置不同型号的打印头 配备多达5种不同型号的打印头，可以实现组织工程支架打印、细胞打印和对高分子，如蛋白质和多种有机大分子的打印。
4、BioFactory打印环境控制能力 Flow box提供了灭菌功能，可以控制温度、湿度、光照、氧气/二氧化碳浓度。 5、BioFactory的主要优势
6、相关案例参考 （1）Lenke Horva , Yuki Umehara, Corinne Jud, et al. Engineering an in vitro air-blood barrier by 3D bioprinting, Nature,22 January 2015 2015年Nature杂志专门刊发RegenHU BioFactory的应用文章，介绍其在构建体外血液-空气组织屏障方面的应用 研究人员成功利用BioFactory的打印精度优势，采用内皮细胞和上皮细胞构建了肺泡体外三维模型，为研究血-空气屏障的体外组织提供了非常好的途径。 （2）Kesti M, Müller M, Becher J, et al. A versatile bioink for three-dimensional printing of cellular scaffolds based on thermally and photo-triggered tandem gelation. Acta Biomater. 2015 Jan;11:162-72 BioINK® / OsteoINK®生物材料介绍 瑞士RegenHU公司提供2种不同型号的打印水凝胶BioINK® / OsteoINK® BioINK® / OsteoINK®对于大量细胞的种植、细胞和组织的生长、细胞外基质的形成、氧气和营养的传输、代谢物的排泄以及血管和神经的内生长均有良好的表现。
BioINK® / OsteoINK®材料能够同时满足多项活细胞3D打印的需求：速度快，可以达到秒级成型；条件温和，过程完全在生理条件下完成，不涉及化学反应以及能够对细胞造成伤害的外界刺激；强度、通透性好，打印出来的产品最终尺寸可以达到厘米级别以上的尺度，不变形和软化，还能够保证细胞生长所需营养物质的输送；具有良好的触变性和自修复性能，在细胞生长的同时可以不断改变自身的结构，能够在保证对细胞提供足够支撑的情况下不限制其扩增；可以根据需要迅速分解不残留，这些特点为将来3D打印器官的活体移植创造了条件。 |
代理nscrypt品牌3D组织工程支架打印系统
Human Tissue TechnologiesEquipment & Experience
Human Tissue Engineering Equipment
With our TE series of micro dispense pump direct print equipment, nScrypt offers laboratory-ready computer aided engineering equipment capable of true 3D printing humand tissue scaffolds. We offer two models: the Tabletop Series and 3D-300 Series.
CAB/CAM Technology
nScrypts Computer Aided Biology (CAB)/Computer Aided Machining (CAM) technology represents the first real opportunity to offer real-time mass customization of various human tissue and human organs on demand using our micro dispense pump direct print manufacturing machines.
Materials Experience
Weve worked with a variety of biomaterials for human tissue technologies.
Micro Dispense Pump Human Tissue EngineeringDirect Print Manufacturing Tools
3D 组织支架打印系统
Standard Features
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Controlled micro environment for temp and air
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Controlled macro environment for air and humidity
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HEPA filtration (3D-300 only)
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Mixing nozzles
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CAD interface for *.dwg input
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X/Y/Z stage accuracy: ±0.0004”
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Z-scanning for precise placement (3D-300 only)
The TE subseries of nScrypts Tabletop series dispensing tool is a laboratory-ready tool capable of true 3D scaffolds:
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Vary micro porosity via material science
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Vary macro porosity via structural printing
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ECM’s with a diverse material, protein and nutrient matrix.
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Cell printing is gentle and promotes extremely high viability
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Cell clusters with varying sizes for precise placement and layering
Advantages of nScrypt’s Micro Dispense Pump Printing Tools and Processes
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Very wide range of viscosities, from a few centipoise to 1 million centipoise
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Conformal and true direct print 3D printing and builds
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nScrypts software user interface is designed for bio users, not computer scientists
Xie, B., R.L. Parkhill, W.L. Warren, Smay, J.E., "Synthesis Direct Writing of Three Dimensional Polymer Scaffolds Using Colloidal Gels," Advanced Functional Materials, 16(13), 1685-1693, 2006
Tabletop Series Micro Dispense Pump Machine Technical Specifications
Computer and Software
- Pentium? 4 with CD-ROM Drive; 17” LCD Monitor and 10” Video Monitor; ASC11 Keyboard/Trackball
- Create and organize printing jobs for high throughput manufacturing with our customizable, user-friendly software.
- Ethernet Network Port and RS232
Conveyor System
- O-ring style or belt driven conveyer
- SMEMA-compatible
- PCB, JEDEC tray or auer-style boat handling
Vision System
- Digital camera link and firewire cameras
- Fixed focal length telecentric or highmagnificationlenses
- Inspection for pattern matching or partpresence
- Detect and measure colorimetric/monochromatic variations
- 2D and 3D complex feature gauging/measurement
- Inspection for aesthetic part variation
Conformal Mapping
- Laser sensor for normal and extended working distance
- Target Mapping: z-data of specific points on a given substrate
- Grid Mapping: coplanarity surface measurement over a symmetric grid
- Path Mapping: provides z-data along a custom predefined path
Dispense Pump
- Smart Pump?: servo driven
- Direct print dynamic flow control allows for adjustment as material properties change over time
- Precise starting and stopping without tailing; tight volumetric control
Motion System
- 3-axis brushless DC servo motor
- X/Y/Z accuracy: ±10μm
- X/Y repeatability: ±2μm
- X/Y resolution: 0.5μm
- X/Y Velocity: 304mm/sec (12"/sec)
- Travel X/Y: 304mm x 152mm (12" x 6")
- Travel Z: 101mm (4")
Installation Requirements
- Air Supply: 80 PSI to 120 PSI
- Power: 120 volts at 30 amps
Computer Aided Biology / Computer Aided Machining Technologies
nScrypt′s Computer Aided Biology/Computer Aided Machining technology represents the first real opportunity to offer real-time mass customization of human tissue and human organs on demand. We have shown that CAB/CAM is able to build precise, direct print 3D printing of biological structures, indicating that it is possible for the first time to identify and reproduce the mechanisms for growth and repair of human tissues as they occur in nature.
Click the play button above to watch video of nScrypt Bioengineer Cindy Smith discussing nScrypt′s tissue engineering technology.
Connecting Engineering Science with Medical Science
Tissue engineering and nScrypts Computer Aided Biology/Computer Aided Machining (CAB/CAM) technology are the result of connecting the engineering sciences with medical science. With the natural extension of the CAB/CAM technology, biocompatible, engineered whole organs will be realizable in years and not decades. CAB/CAM will permit developing curative medical treatments and biological constructs — engineered neo-organs that can be used to detect, prevent, and cure diseases.
Regenerative medicine is the new frontier, unlocking the code of how the body repairs itself. Tissues within the body are complex structures of multiple cell types and extracellular matrix (ECM) within a dynamic three-dimensional microenvironment. The specific architecture of the cells and matrix within a tissue is important in directing numerous biological functions, such as tissue development, organ formation, wound healing, and homeostasis. We imagine being able to lay down cells and matrix in a defined three-dimensional architecture, triggering a response to repair a diseased kidney or a failing heart in the same way that this would happen in natural biological systems.
Human Tissue Biomedical Constructs Materials Experience
| Biomaterial | Summary |
|---|---|
| Poly(caprolactone) (PCL) | This commonly used biodegradable polymer can be used to form a rigid direct 3D printing scaffold structure with pores and struts. It can also be used for cytokine, antigen, or drug delivery. |
| Collagen type I | This biological, partially soluble, hydrogel can be used for cell encapsulation within 3D constructs, or as part of the scaffold structure. |
| Hyaluronic acid (HA) | This biological hydrogel is thicker than collagen, and can be used to encapsulate cells or for layering different cell types within the scaffold structure. |
| Poly(propylene fumarate-co-ethylene glycol) (PPFa€“PEG) | PPF has the ability to crosslink in situ to make strong, porous scaffolds. Adding PEG hydrogel creates a more flexible construct for cell encapsulation. |
| Pluronic F-127 (PF-127) | Made from poly(ethylene oxide) (PEO) and poly(propylene oxide) (PPO), this is an excellent shape-holding hydrogel due to inverse-temperature gelation; it is also a good drug carrier. |
| Poly(ethylene oxide) (PEO) and poly(ethylene glycol) (PEG) | PEO and PEG hydrogels are easily soluble and can hold shape very well. |
| Fibrinogen and thrombin | Put together, these materials form fibrin, an insoluble, stable, biodegradable hydrogel found in blood clots. |
| Poly-3-hydroxybutyrate (P3HB) and poly-4-hydroxybutyrate (P4HB) | A strong, naturally produced, biodegradable plastic with a range of melting points, from low (60?°C for P4HB) to high (> 175?°C for P3HB), used in cardiovascular applications. |
| (PLGA-co-PEG)-triblock-dimethacrylate (PPTD) | PLGA is a popular biomaterial with good constructive properties, and combining it with PEG dimethacrylate makes it a good hydrogel biomaterial. |
| Extracellular matrices (ECMs): Small intestine submucosa (SIS) and urinary bladder mucosa (UBM) | Natural and biodegradable materials that can be used for scaffolds, but may require additional processing such as homogenization. |
| Calfskin gelatin | A good biodegradable material for scaffold fabrication, when deposited warm. |
