3D生物打印在软骨修复中的应用*

关节软骨损伤后的自我修复是医学界一直在研究和探讨的难题。3D生物打印技术可以精准的分配载细胞生物材料,构建复杂的三维活体组织,在优化软骨缺损修复组织的内部结构、机械性能以及生物相容性上有很大优势,因此近年来成为软骨修复组织工程领域的研究热点。重点介绍了软骨生物3D生物打印的最新进展,包括软骨生物打印“墨水”材料的选择、种子细胞的来源以及3D生物打印技术的发展。此外,还阐述了3D生物打印技术在组织工程学应用上的部分局限性,并对其在软骨修复领域的发展与应用进行了预测。     

基于专利信息分析的中国3D生物打印技术发展与产业化研究*

目的:基于专利信息对我国3D生物打印技术的发展态势进行分析。方法:本文基于incopat和TDA两大专利分析平台对中国3D生物打印的专利发展态势从专利统计分析与专利计量分析两个维度进行了跨库组合分析,总结了我国3D生物打印技术的专利前沿动态特征。结果:研究发现,中国3D生物打印技术从2013年起进入专利激增态势,中国作为潜在技术市场的国际竞争日趋激烈,本文还从专利申请人、技术领域分布、专利文本关键词聚类、专利价值、专利合作等方面进行了深度挖掘分析。结论:最后,结合对中国3D生物打印专利申请人的专利产业化案例深度分析与专利特征总结,为中国3D生物打印技术发展与产业化提供参考建议。     

脱细胞基质生物墨水制备方法及应用进展

组织器官脱细胞后制备成的脱细胞基质 (Decellularized extracellular matrix,dECM) 含有许多蛋白质和生长因子,不仅能够为细胞提供三维支架还能够调控细胞再生,是目前最具有生物结构的生物材料。3D生物打印可以层层打印dECM和自体细胞的组合,构建载细胞组织结构。文中综述了不同来源的组织器官脱细胞基质生物墨水制备方法,包括脱细胞、交联等,以及脱细胞基质生物墨水在生物打印中的应用,并展望了其未来的应用前景。     

生物三维打印的研究进展

三维(3D)打印具有灵活性和精密性的特点,已在军工、航天等制造行业中发挥重要作用.随之兴起的生物3D打印在再生医学领域同样具有广泛的应用前景.生物3D打印是将打印的墨水改成含有活细胞的混合物,从而构建活体组织器官.目前生物3D打印更多的是应用于硬组织的仿生重建和新型给药装置的制备,但具有生物活性、更复杂的组织器官的重建还处于探索阶段.本文主要对3D打印在生物医学上的应用进行综述,讨论生物3D打印目前面临的问题,并探讨生物3D打印的未来发展方向.     

3D生物打印技术在微生物修复中的应用

排放到环境中的各种农药、多环芳烃、卤代芳烃等有机污染物以及阻燃剂等新兴污染物,对环境污染、农产品质量和环境安全造成了沉重负担。因此,有效去除环境中的有机污染物已成为迫在眉睫的挑战。3D生物打印技术已经在医学材料、制药等行业中发挥着重要作用。现在,越来越多的微生物被确定适合通过3D生物打印生产具有复杂结构和功能的生物材料。微生物的3D生物打印越来越受到环境微生物学家和生物技术专家的关注。本文综述了用于污染物微生物去除的不同3D生物打印技术的原理和优缺点,及用于微生物生物修复技术的可行性,并指出了可能遇到的限制和挑战。     

3D技术制备骨修复生物材料的功能和安全性评价

配制PLGA/HA复合生物材料,应用3D打印技术制造可移植入体内的骨支架,通过体外物理和生物学方法检测其性能,最后通过动物体内实验对其进行安全性评价。方法:使用3D打印技术打印PLGA/HA复合物立体支架生物材料,参照GB/T 1040和GB/T 9341检测支架材料的拉伸强度和弯曲强度,验证其支持h MSC的增殖及分化能力,并按照医疗器械生物学评价标准(GB/T16886)对支架材料进行体外和体内生物相容性及生物安全性评估。结果:成功制作了PLGA/HA复合材质的多孔3D支架材料;复合材料的机械拉伸强度和弯曲强度分别为38MPa和42MPa,是正常人软骨的5.35倍和5.25倍;体外细胞试验证明3D支架可支持h MSC增殖和分化为软骨细胞,生物安全性试验结果表明支架符合国家医疗器械生物学评价标准。     

模拟微重力条件下心肌细胞的体外三维固定化培养

观察心肌细胞体外培养形成三维(3D)组织结构的能力和过程及心肌细胞在模拟微重力状态下的3D固定化培养效果。应用酶消化法从新生的乳鼠心室肌组织获取心肌细胞,以Cytodex3为心肌细胞的3D固定化培养载体,将心肌细胞固定化培养于Spinnerflask中,用扫描电镜观察心肌细胞体外培养形成的3D组织结构;以心肌细胞的代谢效率和细胞搏动强度为观察指标,比较心肌细胞在Spinnerflask及HARV(highaspectratevessel)生物反应器中3D固定化培养的差异。结果显示,心肌细胞不仅能贴附于Cytodex3上生长,且形成了具有同步自律收缩的3D组织样结构;心肌细胞在两种不同培养体系中的细胞接种效率和细胞形态没有明显差异,培养于HARV中的心肌细胞的代谢效率和细胞搏动强度均明显高于Spinnerflask培养体系。体外培养的乳鼠心肌细胞具有形成同步自律收缩的3D组织结构的能力;模拟微重力的培养环境有利于改善心肌细胞3D组织样培养物的代谢和功能 。     

组织工程皮肤生物反应器的研究与设计

目的设计一套生物反应器,能针对不同支架材料———细胞复合物进行构建组织工程皮肤。方法根据皮肤的自身生长特点和不同支架材料-细胞复合物的特性,模拟皮肤的生长环境和力学环境,通过生物反应器解决组织工程皮肤构建中支架的装夹和气液界面问题。结果生物反应器由控制系统和生物反应器主体两部分构成,能提供对多种皮肤细胞复合物的动态培养。结论皮肤生物反应器能够满足不同组织工程皮肤产品的需要。能够形成气液界面和模拟生物力学的刺激。     

用于药物评价的体外心脏组织模型研究进展

候选药物对心脏的毒副作用是其在开发过程中被淘汰的重要原因之一.传统药物评价所采用的动物模型存在种属差异、成本高、效率低等缺陷.因此,近年来随着干细胞和生物打印等技术的快速发展,体外心脏组织模型的构建受到了越来越多地关注.本文追踪体外心脏模型构建的起源与发展,综述模型所利用的心肌细胞来源以及二维、三维模型构建的相关技术与方法,着重阐述心肌组织模型血管化的重要性及研究进展,并对该领域未来的发展方向进行展望,以期为体外心肌组织模型在药物评价方面的研究和应用提供新思路.     

三维肝细胞模型及其在化学性肝损伤评价中的应用

肝脏是机体代谢外源性化学物的主要场所,也是化学物及其代谢产物毒作用的重要靶器官。为了更加快速、准确地对化学物引起的肝损伤进行评估,选择贴近人体的细胞模型和培养方法至关重要。近年来研究发展了多种人源体外肝细胞模型,其中新兴的三维(3D)肝细胞体外模型具有类似体内肝脏表型、代谢能力,并适于长期体外培养,为药物等化学物的肝毒性测试提供了有力的体外评价工具。本文主要介绍目前常用的肝细胞模型的特点,以及球体模型、生物反应器、3D打印和肝脏芯片等3D培养系统,概述了这些模型在化学性肝损伤评估中的应用进展。     

Controlling the Three-Dimensional Printing Mechanical Properties of Nostoc Sphaeroides System

The main purpose of this paper is to explore the opportunities for fresh Nostoc sphaeroides (N. sphaeroides) to be applied to 3D food printing. N. sphaeroides is rich in nutrients and its paste possesses shear thinning properties. It was found the product obtained by 3D food printing with fresh N. sphaeroides had poor printability and was easy to collapse. In this study, we compared the addition of different potato starch (2%, 4%, 6% and 8%) to the characteristics of 3D printing of the N. sphaeroides gel system. The results obtained from the rheological analysis showed that the 6% potato starch added to of N. sphaeroides gel can be utilized for 3D food printing. The addition of potato starch increased the viscosity of the mixture so the printed lines were not easily broken, and the “self-supporting ability” of the material itself was enhanced to maintain a good shape without collapse. Texture profile analysis also showed that the 6% starch added printed product had the best gumminess parameter. In order to get a better printed product, the effects of printing parameters (nozzle diameter (Dn), extrusion rate (Vd) and nozzle moving speed (Vn)) on material printing performance and product formability was tested. When Dn, Vd, Vn were = 1.2 mm, 20 mm³/s, 25 mm/s, respectively, the printed product was having similar to the target product, with less breakage and less the changing of shape. Overall results show that 3D printing technology is a rising method for producing N. sphaeroides-based new products.

     

3D打印技术在骨科临床应用中的感知研究

目的 了解医院骨科医师和管理者对3D打印技术在骨科应用的安全性、有效性、经济性和伦理性的感知。方法 对上海市4所三级综合性医院的所有骨科临床医师和相关管理部门的负责人或管理者进行问卷调查,并邀请4名骨科专家进行定性访谈。结果 3所被调查医院在骨科领域应用了3D打印技术,但使用量有限。被调查的医师和管理者认为：骨科3D打印主要优点是手术时间短、增加手术便利性和手术成功率高,主要缺点是费用高且价格昂贵、缺乏相关规范标准和整个过程相对复杂且耗时长。结论 3D打印技术在骨科临床应用的安全性和有效性需长期评价,骨科3D打印技术的临床应用需要规制。     

Composite 3D printed scaffold with structured electrospun nanofibers promotes chondrocyte adhesion and infiltration

Additive manufacturing, also called 3D printing, is an effective method for preparing scaffolds with defined structure and porosity. The disadvantage of the technique is the excessive smoothness of the printed fibers, which does not support cell adhesion. In the present study, a 3D printed scaffold was combined with electrospun classic or structured nanofibers to promote cell adhesion. Structured nanofibers were used to improve the infiltration of cells into the scaffold. Electrospun layers were connected to 3D printed fibers by gluing, thus enabling the fabrication of scaffolds with unlimited thickness. The composite 3D printed/nanofibrous scaffolds were seeded with primary chondrocytes and tested in vitro for cell adhesion, proliferation and differentiation. The experiment showed excellent cell infiltration, viability, and good cell proliferation. On the other hand, partial chondrocyte dedifferentiation was shown. Other materials supporting chondrogenic differentiation will be investigated in future studies.     

3D打印股骨远端内侧个性化解剖型接骨板的研究进展

目前,比较复杂的股骨远端C3型骨折和膝外翻的矫形手术都需要应用到独立的股骨内侧接骨板。以往术者都是将对侧股骨的外侧接骨板进行预弯曲,以达到贴近骨骼自然形态的目的,而这种冷变形会改变接骨板的金相结构,进而破坏接骨板的生物力学,接骨板螺钉孔的位置有时也会影响到骨折的愈合情况。与传统制造技术相对比,3D打印技术作为"第三次工业革命"的核心技术,不必事先制造模具,不必在制造过程中去除大量的材料,也不必通过复杂的锻造工艺就可以得到最终产品,更适合于难加工材料的制造、外形设计检查、装配检验和快速反求工程等。本文将股骨远端内侧接骨板的个性化设计与3D打印技术相结合,从接骨板的应用、3D打印技术的现况及其应用于制作股骨远端内侧个性化解剖型接骨板的前景等方面进行了综述。     

Structural and congenital heart disease interventions: the role of three-dimensional printing

Advances in catheter-based interventions in structural and congenital heart disease have mandated an increased demand for three-dimensional (3D) visualisation of complex cardiac anatomy. Despite progress in 3D imaging modalities, the pre- and periprocedural visualisation of spatial anatomy is relegated to two-dimensional flat screen representations. 3D printing is an evolving technology based on the concept of additive manufacturing, where computerised digital surface renders are converted into physical models. Printed models replicate complex structures in tangible forms that cardiovascular physicians and surgeons can use for education, preprocedural planning and device testing. In this review we discuss the different steps of the 3D printing process, which include image acquisition, segmentation, printing methods and materials. We also examine the expanded applications of 3D printing in the catheter-based treatment of adult patients with structural and congenital heart disease while highlighting the current limitations of this technology in terms of segmentation, model accuracy and dynamic capabilities. Furthermore, we provide information on the resources needed to establish a hospital-based 3D printing laboratory.     

Three‐dimensional imaging technologies: a priority for the advancement of tissue engineering and a challenge for the imaging community

Tissue engineering/regenerative medicine (TERM) is an interdisciplinary field that applies the principle of engineering and life sciences to restore/replace damaged tissues/organs with in vitro artificially‐created ones. Research on TERM quickly moves forward. Today newest technologies and discoveries, such as 3D‐/bio‐printing, allow in vitro fabrication of ex‐novo made tissues/organs, opening the door to wide and probably never‐ending application possibilities, from organ transplant to drug discovery, high content screening and replacement of laboratory animals. Imaging techniques are fundamental tools for the characterization of tissue engineering (TE) products at any stage, from biomaterial/scaffold to construct/organ analysis. Indeed, tissue engineers need versatile imaging methods capable of monitoring not only morphological but also functional and molecular features, allowing three‐dimensional (3D) and time‐lapse in vivo analysis, in a non‐destructive, quantitative, multidimensional analysis of TE constructs, to analyze their pre‐implantation quality assessment and their fate after implantation. This review focuses on the newest developments in imaging technologies and applications in the context of requirements of the different steps of the TERM field, describing strengths and weaknesses of the current imaging approaches.

     

A Simple,Low-Cost Conductive Composite Material for 3D Printing of Electronic Sensors

3D printing technology can produce complex objects directly from computer aided digital designs. The technology has traditionally been used by large companies to produce fit and form concept prototypes (‘rapid prototyping’) before production. In recent years however there has been a move to adopt the technology as full-scale manufacturing solution. The advent of low-cost, desktop 3D printers such as the RepRap and emoH@baF has meant a wider user base are now able to have access to desktop manufacturing platforms enabling them to produce highly customised products for personal use and sale. This uptake in usage has been coupled with a demand for printing technology and materials able to print functional elements such as electronic sensors. Here we present formulation of a simple conductive thermoplastic composite we term ‘carbomorph’ and demonstrate how it can be used in an unmodified low-cost 3D printer to print electronic sensors able to sense mechanical flexing and capacitance changes. We show how this capability can be used to produce custom sensing devices and user interface devices along with printed objects with embedded sensing capability. This advance in low-cost 3D printing with offer a new paradigm in the 3D printing field with printed sensors and electronics embedded inside 3D printed objects in a single build process without requiring complex or expensive materials incorporating additives such as carbon nanotubes.     

3D打印技术在植物繁殖生态学中的应用进展与评述

3D打印(3D printing)是以数字化模型为基础,运用粉末状金属或塑料等可粘合材料,通过逐层打印的方式构造物体的一项技术。由于3D打印具有灵活和精密的特点,这一技术已经在军工、航天等制造行业中发挥了重要作用。鉴于3D打印的独特优势,该技术也可以在植物繁殖生态学研究中发挥作用而且具有广阔的应用前景,但目前还处于探索阶段。该文概述了3D打印技术以及植物繁殖生态学的花特征进化研究,同时总结了3D打印技术在植物繁殖生态学领域的最新研究进展,并探讨将来可能的发展方向。     

Osteoinduction and survival of osteoblasts and bone-marrow stromal cells in 3D biphasic calcium phosphate scaffolds under static and dynamic culture conditions

In many tissue engineering approaches, the basic difference between in vitro and in vivo conditions for cells within three‐dimensional (3D) constructs is the nutrition flow dynamics. To achieve comparable results in vitro, bioreactors are advised for improved cell survival, as they are able to provide a controlled flow through the scaffold. We hypothesize that a bioreactor would enhance long‐term differentiation conditions of osteogenic cells in 3D scaffolds. To achieve this either primary rat osteoblasts or bone marrow stromal cells (BMSC) were implanted on uniform‐sized biphasic calcium phosphate (BCP) scaffolds produced by a 3D printing method. Three types of culture conditions were applied: static culture without osteoinduction (Group A); static culture with osteoinduction (Group B); dynamic culture with osteoinduction (Group C). After 3 and 6 weeks, the scaffolds were analysed by alkaline phosphatase (ALP), dsDNA amount, SEM, fluorescent labelled live‐dead assay, and real‐time RT‐PCR in addition to weekly alamarBlue assays. With osteoinduction, increased ALP values and calcium deposition are observed; however, under static conditions, a significant decrease in the cell number on the biomaterial is observed. Interestingly, the bioreactor system not only reversed the decreased cell numbers but also increased their differentiation potential. We conclude from this study that a continuous flow bioreactor not only preserves the number of osteogenic cells but also keeps their differentiation ability in balance providing a suitable cell‐seeded scaffold product for applications in regenerative medicine.