3D Printing of Customized Drug Delivery Systems with Controlled Architecture via Reversible Addition-Fragmentation Chain Transfer Polymerization

3D printing via reversible addition-fragmentation chain transfer (RAFT) polymerization has been recently developed to expand the scope of 3D printing technologies. A potentially high-impact but relatively unexplored opportunity that can be provided by RAFT-mediated 3D printing is a pathway toward personalized medicine through manufacturing bespoke drug delivery systems (DDSs). Herein, 3D printing of drug-eluting systems with precise geometry, size, drug dosage, and release duration/profiles is reported. This is achieved through engineering a range of 3D models with precise interconnected channel-pore structure and geometric proportions in architectural patterns. Notably, the application of the RAFT process is crucial in manufacturing materials with highly resolved macroscale features by confining curing to exposure precincts. This approach also allows spatiotemporal control of the drug loading and compositions within different layers of the scaffolds. The ratio between the polyethylene glycol units and the acrylate units in the crosslinkers is found to be a critical factor, with a higher ratio increasing swelling capacity, and thus enhancing the drug release profile, from the drug-eluting systems. This proof-of-concept research demonstrates that RAFT-mediated 3D printing enables the production of personalized drug delivery materials, providing a pathway to replace the “one-size-fits-all” approach in traditional health care.     

金属/陶瓷粉末3D打印技术及其应用

3D打印技术以数字化、网络化、个性化、定制化特点被认为将推动第3次革命技术,金属/陶瓷粉末构件的3D打印技术是目前先进制造技术的重要发展方向。主要介绍了3D打印成形金属/陶瓷粉末技术及其在航空航天等领域的应用现状和展望;详述了3D打印用金属粉末制备方法及不同工艺下粉末的特点及适用范围,进而综述了3D打印用金属粉末设备的工作原理。最后,对该方向的研究进展进行总结,并对其发展前景和主要发展方向进行展望。     

3D打印石墨烯制备技术及其在储能领域的应用研究进展

石墨烯优异的力学和物理性能使其成为理想的储能材料。因结构精确可控,易实现规模化制备,3D打印石墨烯材料有望在储能领域得到广泛应用。本文全面综述了3D打印石墨烯制备技术及其在储能领域的应用研究进展。石墨烯墨水的黏度和可打印性是实现石墨烯3D打印的制约因素。实现工艺简单、浓度可控、无黏结剂石墨烯墨水的规模化打印将成为3D打印石墨烯制备技术未来的研究热点。石墨烯超级电容器、锂硫电池、锂离子电池等储能元件一体化打印成型是3D打印石墨烯在储能领域应用的发展方向。     

高分子3D打印材料和打印工艺

3D打印技术亦称为增材制造,是基于三维数学模型数据,通过连续的物理层叠加,逐层增加材料来生成三维实体的技术。3D打印技术与传统材料加工技术相比有许多突出的优势,吸引了国内外工业界、投资界、学术界、新闻媒体和社会公众的热切关注。目前制约3D打印技术发展的因素主要有两个:打印工艺和打印材料。高分子聚合物在3D打印材料中占据主要地位。介绍了当前3D打印常用的高分子材料(热塑性高分子和光敏树脂)和与之相适应的打印工艺(FDM、SLS、SLA、Polyjet等),并对它们的特性和优缺点进行了评述,讨论了这些3D打印材料和工艺的开发面临的问题和挑战。     

Frontiers of 3D Printing/Additive Manufacturing: from Human Organs to Aircraft Fabrication

It has been more than three decades since stereolithography began to emerge in various forms of additive manufacturing and 3D printing. Today these technologies are proliferating worldwide in various forms of advanced manufacturing. The largest segment of the 3D printing market today involves various polymer component fabrications, particularly complex structures not attainable by other manufacturing methods.Conventional printer head systems have also been adapted to selectively print various speciated human cells and special molecules in attempts to construct human organs, beginning with skin and various tissue patches. These efforts are discussed along with metal and alloy fabrication of a variety of implant and bone replacement components by creating powder layers, which are selectively melted into complex forms(such as foams and other open-cellular structures) using laser and electron beams directed by CAD software. Efforts to create a "living implant" by bone ingrowth and eventual vascularization within these implants will be discussed briefly. Novel printer heads for direct metal droplet deposition as in other 3D printing systems are briefly described since these concepts will allow for the eventual fabrication of very large and complex products, including automotive and aerospace structures and components.     

3D Printed Functional and Biological Materials on Moving Freeform Surfaces

Conventional 3D printing technologies typically rely on open‐loop, calibrate‐then‐print operation procedures. An alternative approach is adaptive 3D printing, which is a closed‐loop method that combines real‐time feedback control and direct ink writing of functional materials in order to fabricate devices on moving freeform surfaces. Here, it is demonstrated that the changes of states in the 3D printing workspace in terms of the geometries and motions of target surfaces can be perceived by an integrated robotic system aided by computer vision. A hybrid fabrication procedure combining 3D printing of electrical connects with automatic pick‐and‐placing of surface‐mounted electronic components yields functional electronic devices on a free‐moving human hand. Using this same approach, cell‐laden hydrogels are also printed on live mice, creating a model for future studies of wound‐healing diseases. This adaptive 3D printing method may lead to new forms of smart manufacturing technologies for directly printed wearable devices on the body and for advanced medical treatments.     

3D打印技术对工业产品形态的影响分析

目的 给处于发展瓶颈中的工业产品企业和传统工艺作坊,提供产品形态创新发展的思路。方法 以部分行业领域的3D打印创新作品为例,通过对案例中的3D打印技术创新进行介绍与其社会价值进行分析,得出3D打印工业产品形态的主体框架一体化趋势、产品形态轻量化趋势和产品造型多样化趋势。 结论 未来的定制化3D打印工业产品,将会呈现出更多个性化的形态,对于处于发展瓶颈的工业产品企业与传统手工艺作坊来说,需要用互联网思维认识和思考3D打印技术对产品形态的影响,结合民生需求,通过3D打印技术创新,赋予产品更多的形态可能,从而焕发新生。     

Recent Development of Printed Micro-Supercapacitors: Printable Materials,Printing Technologies,and Perspectives

The rapid progression of portable and wearable electronics has necessitated the development of high-performing, miniaturized energy-storage devices with flexible form factors and high energy and power delivery. Printed micro-supercapacitors (MSCs), with in-plane interdigital configurations, is touted as a promising choice to fulfill these requirements. New printing technologies can assemble MSCs with fiscal and environmental benefits, large form factors, and at high throughputs, qualities not afforded with conventional microfabrication technologies. Here, recent progress in the preparation of functional ink systems for wearable MSCs, encompassing electrode materials, conductor materials, and electrolytes, is presented. First, a comprehensive background of the fundamentals of printing technology is introduced, with discussions focusing on methods of improving ink functionality while simultaneously retaining good printability. Second, various printing techniques to ensure manufacturable scaling of wearable MSCs with high areal electrochemical performance and small footprint are explored. Within the scope of these two topics, various issues that hinder the full materialization of widespread adoption of printed MSC and next steps to overcome these issues are discussed. Further deep dives in scientific and technical challenges are also presented, including limited functionality of the inks, low printing resolution, overlay accuracy, and complex encapsulation.     

基于熔融沉积3D打印聚乳酸基复合材料的研究进展

目的 半结晶性聚乳酸(PLA)因透明性好、力学性能优异、能生物降解等优点,在加工领域表现出适用范围广等特性,因此对PLA基复合材料在3D打印技术中的研究应用及最新进展状况进行总结,以期提供借鉴与参考。方法 以熔融沉积成型(FDM)、PLA基体为主线,在查阅近年中外文献基础上,分别从PLA结构性能、3D打印成型工艺、PLA基复合材料改性等方面进行了探讨,着重分析工艺参数的技术优化,以及复合材料的结构改性最新研究进展。结果 FDM制备PLA基复合材料的研究取得了丰硕的成果,在3D打印行业中表现优异,潜力巨大,商品化程度越来越高。结论 低廉、高效、可定制的3D打印受到国内外科研工作者广泛关注与青睐,随着新技术的不断探索和突破,以及纳米材质和新型聚合物材料等新型材质应用,使3D打印在成型加工技术上占据绝对优势。     

数字印刷技术的发展及现状

随着计算机技术、喷墨打印技术、高精度喷涂装置、超细染料制备等技术、装备和原料的不断发展、更新,明显地加速了数字印刷的工业化和实用化。在2008年德鲁巴国际印展会（Drupa）上,数字印刷成为最大的亮点,而喷墨数字印刷更成为亮点中的亮点。本文较全面地阐述了数字印刷和数字印刷技术,重点介绍了喷墨数字印刷技术和各种品牌的数字印刷机,并对数字印刷技术的发展前景进行了展望。     

3D打印腰部健康护具设计研究

目的 通过对3D打印材料与技术的概述、腰部健康护具市场需求的分析,探索3D打印技术与传统医疗护具设计结合的可能性,思考个性与适应性、艺术与功能性、单价与制造速度的平衡与协调。方法 以腰部健康护具为研究切入点,借助SLS、SLA打印技术,重点关注可成型工艺(同一材料的3D打印设计改良),对增加造型可塑性以及更为概念性的设计方略层面进行研究。结果 基于使用、技术、个性三方面的需求,设计了具备磁疗功效和定制特点的3D打印腰部健康护具。经实验测试,佩戴性良好,各项指标达到了设计预期。结论 未来的3D打印发展方向,材料研究仍将是重点,除了材料的多元化、智慧化,技术的互动、增效也会进一步刷新人类社会的制造观念;有效利用3D打印技术的便捷性特点和可定制特点,势必成为未来“可定制化”无障碍产品设计重要的研发和探索方向。     

Freeform,Reconfigurable Embedded Printing of All‐Aqueous 3D Architectures

Aqueous microstructures are challenging to create, handle, and preserve since their surfaces tend to shrink into spherical shapes with minimum surface areas. The creation of freeform aqueous architectures will significantly advance the bioprinting of complex tissue‐like constructs, such as arteries, urinary catheters, and tracheae. The generation of complex, freeform, three‐dimensional (3D) all‐liquid architectures using formulated aqueous two‐phase systems (ATPSs) is demonstrated. These all‐liquid microconstructs are formed by printing aqueous bioinks in an immiscible aqueous environment, which functions as a biocompatible support and pregel solution. By exploiting the hydrogen bonding interaction between polymers in ATPS, the printed aqueous‐in‐aqueous reconfigurable 3D architectures can be stabilized for weeks by the noncovalent membrane at the interface. Different cells can be separately combined with compartmentalized bioinks and matrices to obtain tailor‐designed microconstructs with perfusable vascular networks. The freeform, reconfigurable embedded printing of all‐liquid architectures by ATPSs offers unique opportunities and powerful tools since limitless formulations can be designed from among a breadth of natural and synthetic hydrophilic polymers to mimic tissues. This printing approach may be useful to engineer biomimetic, dynamic tissue‐like constructs for potential applications in drug screening, in vitro tissue models, and regenerative medicine.     

Ocular preparations: the formulation approach

The main aim of pharmacotherapeutics is the attainment of an effective drug concentration at the intended site of action for a sufficient period of time to elicit the response. A major problem being faced in ocular therapeutics is the attainment of an optimal concentration at the site of action. Poor bioavailability of drugs from ocular dosage forms is mainly due to the tear production, non-productive absorption, transient residence time, and impermeability of corneal epithelium. This article reviews: [1] the barriers that decrease the bioavailability of an ophthalmic drug; [2] the objectives to be considered in producing optimal formulations; and [3] the approaches being used to improve the corneal penetration of a drug molecule and delay its elimination from the eye. The focus of this review is on the recent developments in topical ocular drug delivery systems, the rationale for their use, their drug release mechanism, and the characteristic advantages and limitations of each system. In addition, the review attempts to give various analytical procedures including the animal models and other models required for bioavailability and pharmacokinetic studies. The latter can aid in the design and predictive evaluation of newer delivery systems.

The dosage forms are divided into the ones which affect the precorneal parameters, and those that provide a controlled and continuous delivery to the pre- and intraocular tissues. The systems discussed include: (a) the commonly used dosage forms such as gels, viscosity imparting agents, ointments, and aqueous suspensions; (b) the newer concept of penetration enhancers, phase transition systems, use of cyclodextrins to increase solubility of various drugs, vesicular systems, and chemical delivery systems such as the prodrugs; (c) the developed and under-development controlled/continuous drug delivery systems including ocular inserts, collagen shields, ocular films, disposable contact lenses, and other new ophthalmic drug delivery systems; and (d) the newer trends directed towards a combination of drug delivery technologies for improving the therapeutic response of a non-efficacious drug. The fruitful resolution of the above-mentioned technological suggestions can result in a superior dosage form for both topical and intraocular ophthalmic application.     

Mucoadhesive Drug Delivery Systems

Mucoadhesion in drug delivery systems has recently gained interest among pharmaceutical scientists as a means of promoting dosage form residence time as well as improving intimacy of contact with various absorptive membranes of the biological system. Besides acting as platforms for sustained-release dosage forms, bioadhesive polymers can themselves exert some control over the rate and amount of drug release, and thus contribute to the therapeutic advantage of such systems. This paper describes some aspects of bioadhesion such as mucus layer, mucoadhesion, and theories of bioadhesion to explain the adhesion mechanism. The factors important to mucoadhesion, the methods used to study bioadhesion, and bioadhesive polymers are described. The methods that evaluate the mucoadhesive dosage forms and finally the bioadhesive drug delivery systems designed for several therapeutic purposes are presented.     

Biodegradable Electronic Systems in 3D,Heterogeneously Integrated Formats

Biodegradable electronic systems represent an emerging class of technology with unique application possibilities, from temporary biomedical implants to “green” consumer gadgets. This paper introduces materials and processing methods for 3D, heterogeneously integrated devices of this type, with various functional examples in sophisticated forms of silicon‐based electronics. Specifically, techniques for performing multilayer assembly by transfer printing and for fabricating layer‐to‐layer vias and interconnects by lithographic procedures serve as routes to biodegradable, 3D integrated circuits composed of functional building blocks formed using specialized approaches or sourced from commercial semiconductor foundries. Demonstration examples range from logic gates and analog circuits that undergo functional transformation by transience to systems that integrate multilayer resistive sensors for in situ, continuous electrical monitoring of the processes of transience. The results significantly expand the scope of engineering options for biodegradable electronics and other types of transient microsystem technologies.     

Three‐Dimensional Printing of Multifunctional Nanocomposites: Manufacturing Techniques and Applications

The integration of nanotechnology into three‐dimensional printing (3DP) offers huge potential and opportunities for the manufacturing of 3D engineered materials exhibiting optimized properties and multifunctionality. The literature relating to different 3DP techniques used to fabricate 3D structures at the macro‐ and microscale made of nanocomposite materials is reviewed here. The current state‐of‐the‐art fabrication methods, their main characteristics (e.g., resolutions, advantages, limitations), the process parameters, and materials requirements are discussed. A comprehensive review is carried out on the use of metal‐ and carbon‐based nanomaterials incorporated into polymers or hydrogels for the manufacturing of 3D structures, mostly at the microscale, using different 3D‐printing techniques. Several methods, including but not limited to micro‐stereolithography, extrusion‐based direct‐write technologies, inkjet‐printing techniques, and popular powder‐bed technology, are discussed. Various examples of 3D nanocomposite macro‐ and microstructures manufactured using different 3D‐printing technologies for a wide range of domains such as microelectromechanical systems (MEMS), lab‐on‐a‐chip, microfluidics, engineered materials and composites, microelectronics, tissue engineering, and biosystems are reviewed. Parallel advances on materials and techniques are still required in order to employ the full potential of 3D printing of multifunctional nanocomposites.     

3D打印技术探究

3D打印技术是将三维数字模型分解成若干层平面切片,然后由3D打印机把粉末状、液状或丝状可粘合材料按切片图形逐层叠加,最终堆积成完整物体的技术。文章对3D打印的技术原理、步骤、常用材料、主要技术、发展及建议进行了深层次的探讨。与传统制造技术相比,3D打印技术有很多优势,目前已广泛应用于建筑、工业设计等领域。该技术将会带来全球制造业经济的重大变革。     

Ocular Preparations: The Formulation Approach

ABSTRACT

The main aim of pharmacotherapeutics is the attainment of an effective drug concentration at the intended site of action for a sufficient period of time to elicit the response. A major problem being faced in ocular therapeutics is the attainment of an optimal concentration at the site of action. Poor bioavailability of drugs from ocular dosage forms is mainly due to the tear production, non-productive absorption, transient residence time, and impermeability of corneal epithelium. This article reviews: the barriers that decrease the bioavailability of an ophthalmic drug; the objectives to be considered in producing optimal formulations; and the approaches being used to improve the corneal penetration of a drug molecule and delay its elimination from the eye. The focus of this review is on the recent developments in topical ocular drug delivery systems, the rationale for their use, their drug release mechanism, and the characteristic advantages and limitations of each system. In addition, the review attempts to give various analytical procedures including the animal models and other models required for bioavailability and pharmacokinetic studies. The latter can aid in the design and predictive evaluation of newer delivery systems.

The dosage forms are divided into the ones which affect the precorneal parameters, and those that provide a controlled and continuous delivery to the pre- and intraocular tissues. The systems discussed include: (a) the commonly used dosage forms such as gels, viscosity imparting agents, ointments, and aqueous suspensions; (b) the newer concept of penetration enhancers, phase transition systems, use of cyclodextrins to increase solubility of various drugs, vesicular systems, and chemical delivery systems such as the prodrugs; (c) the developed and under-development controlled/continuous drug delivery systems including ocular inserts, collagen shields, ocular films, disposable contact lenses, and other new ophthalmic drug delivery systems; and (d) the newer trends directed towards a combination of drug delivery technologies for improving the therapeutic response of a non-efficacious drug. The fruitful resolution of the above-mentioned technological suggestions can result in a superior dosage form for both topical and intraocular ophthalmic application.     

Pharmaceutical Applications of Hot-Melt Extrusion: Part I

Interest in hot-melt extrusion techniques for pharmaceutical applications is growing rapidly with well over 100 papers published in the pharmaceutical scientific literature in the last 12 years. Hot-melt extrusion (HME) has been a widely applied technique in the plastics industry and has been demonstrated recently to be a viable method to prepare several types of dosage forms and drug delivery systems. Hot-melt extruded dosage forms are complex mixtures of active medicaments, functional excipients, and processing aids. HME also offers several advantages over traditional pharmaceutical processing techniques including the absence of solvents, few processing steps, continuous operation, and the possibility of the formation of solid dispersions and improved bioavailability. This article, Part I, reviews the pharmaceutical applications of hot-melt extrusion, including equipment, principles of operation, and process technology. The raw materials processed using this technique are also detailed and the physicochemical properties of the resultant dosage forms are described. Part II of this review will focus on various applications of HME in drug delivery such as granules, pellets, immediate and modified release tablets, transmucosal and transdermal systems, and implants.