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Presently, there is a recognized and imperative need for bioartificial organs. The technological advances in transgenosis, tissue engineering, and rapid prototyping have led to the development of spatially complex tissues. An ideal artificial organ should provide nutrient transport system, mechanical stable architecture, and synergetic multicellular organization in one construct. The multinozzle rapid prototyping technique simultaneously assembles vascular systems including hierarchical multicellular structures in an automated and reproducible manner and offers an effective way for treating organ failures. In this article, a brief overview of the recent trends and outstanding challenges in organ manufacturing is provided. From the viewpoint of disciplinary crossing, integration, and development, future directions in the coming years were pointed out.

The rapid prototyping and manufacturing technology (RPM), is an integration of many different disciplines. It is based on an advanced dispersed-accumulated forming principle and originated from 1980s. It generates an entity by first forming a series of layers according to the dispersed section information of the digital model, and then piling the formed layers sequentially together. It is capable of forming parts with complicated structures and non-homogeneous materials. Traditional RPM techniques are mainly used as prototypes in product invention process, such as stereolithography, three-dimensional printing, laminated object manufacturing, and fused deposition modeling. Later, with the progress of material and enabling technology, many new RPM techniques emerged out and have been already applied in the fields such as rapid tooling/moulding, direct formed usable part, nano-/micro-RPM, and biomanufacturing. This high flexible digital manufacturing method has a likely ability to become an almighty forming technology.

A functional-region/separate-interface/single-cell-type of tissue engineering pathway was evaluated to regenerate osteochondral defects that are deep in the marrow cavity. A gradient osteochondral scaffold fabricated via a rapid prototyping technology, called multi-nozzle low-temperature deposition manufacturing, was composed of three parts with different materials and pore-structures, respectively, for bone, cartilage and a separate interface between them. The separate interface was composed of micro-pores, that were less than 5 urn and with low porosity, to reduce or to avoid the destruction of the micro-environment in vivo by preventing blood and cells and reducing the amount of oxygen and nutrients moving from the marrow cavity to the articulate marrow. The preliminary results after 6 weeks of implantation into 4 mm diameter osteochondral defects in the knee joints of rabbits showed that the defects with the scaffold/cells composition had bone-like or cartilage-like tissue filling the defects with smooth surface, while the defects with nothing (blank) showed only fibrous tissue.

In this study, a two-step crosslinking method derived from commercial rapid prototyping equipment was used to fabricate a gradient hydrogel scaffold in vitro. This system contained two types of nozzles; one was double-nozzle unit, used for relatively simple gradient hydrogel scaffold composed of two nonmiscible hydrogel materials. The other was single nozzle that was used for mixing a gradient hydrogel scaffold composed of two types of hydrogel materials. Different types of scaffolds were formed by modifying the gradient in one of the relevant nozzles. To improve the extrusion controlling effect, accessorial parameters were introduced. A 3D gradient construct containing neuron cells and Schwann cells was fabricated and cultured for 7 days. This construct was helpful in designing a gradient mode to observe the relationship between different cells in vitro. This work has improved tissue-engineering techniques for later manufacturing of very complicated organ analogs.

A novel 3D hybrid construct was developed for liver manufacturing by depositing biodegradable polyurethane (PU) and a naturally derived polymer gelatin simultaneously via a double nozzle rapid prototyping (RP) technique. A grid object was produced by precisely and simultaneously dispersing the PU and gelatin to form 3D constructs with interconnected macro-channels at a low temperature (-28°C). Micro-pores were formed by freeze-drying the constructs. The PU polymer provided mechanical support while gelatin provided accommodation for implant cells. The hydrophilicity of the hybrid constructs was between the pure PU and pure gelatin structures. The interconnected channels allow nutrients and oxygen to be supplied throughout the construct as well as provide space for the attachment of cells. The design and fabrication strategies, used to create complex physical objects directly from computer aided design (CAD) models, represent a promising technique for implantable bioartificial livers. It is anticipated that these PU-gelatin hybrid constructs will serve as a useful model for bioartificial liver manufacturing.

A precise control over the internal architecture was essential for manufacture of complex organs. To create vascular systems that mimic human livers, we designed and fabricated complex 3D objects with an intrinsic network of interconnected channels. A new elastomeric polyurethane, mainly based on polycaprolactone and poly(ethylene glycol) with excellent biocompatibility and tunable biodegradation properties, was used to fabricate these vascular systems using a low temperature deposition system based on the layer-by-layer manufacturing principle. A specific model was selected via computer aided design (CAD), solid free form fabrication processes are conducted under computer direction. Two example object patterns were produced by precision controlled dispensing of a biodegradable polyurethane into 3D multi-micro-tunnels with multi-micro-pores at a low temperature (-28°C). The design and fabrication strategies used to create physical objects directly from CAD models represent a promising route for the establishment of complex organ vascular systems.

Rapid prototyping (RP) technologies are a set of manufacturing processes that can produce very complex structures directly from computer-aided design models without structure-specific tools or knowledge. These technologies might eventually enable the manufacture of human livers to create functional substitutes for treating liver failure or dysfunctionality. However, the approaches used currently face many challenges, such as the complex branched vascular and bile ductular systems and the variety of cell types, matrices and regulatory factors involved in liver development. Here, we discuss the challenges and provide evidence for the usefulness of RP in overcoming them.

We have recently developed an organ manufacturing technique that enables us to form cell/biomaterial complex three-dimensional (3D) architectures in designed patterns. This technique employs a highly accurate 3D micropositioning system with a pressue-controlled syringe to deposit cell/biomaterial structures with a lateral resolution of 10 microm. The pressure-activated micro-syringe is equipped with a fine-bore exit needle using which a wide variety of 3D patterns with different arrays of channels (through-holes) were created. The channels can supply living cells with nutrients and allow removing the cell metabolites. The embedded cells remain viable and perform biological functions as long as the 3D structures are retained. The new technology has the potential for eventual high-throughput production of artificial human tissues and organs.

PurposeAims to provide information on organism manufacturing engineering (OME), a newly proposed interdisciplinary research area.Design/methodology/approachA conceptual discussion and approach are taken.FindingsOME is based on layer‐by‐layer RP principles and the integration of the new advancement of manufacturing science, biomaterials, cell molecular biology and developmental biology. OME aims to construct live tissues and organs through controlled assembly of 3D cell structure with the principles and methods of modern manufacturing science and life science.Originality/valueFocuses on important processes for indirect and direct cell assembly using OME approaches.

This paper introduces a new subject called bio‐manufacturing. Bio‐manufacturing combines life science with manufacturing science, and uses manufacturing method to form materials with bio‐activity and bio‐degradability into scaffolds. In this paper, we discuss the hierarchy of bio‐manufacturing: the lower grade uses undegradable bio‐material to form permanent organ replacement such as auricular cartilage and the higher grade uses biodegradable bio‐materials to repair organ damage or organ replacement which degrades after embedded in the human body. They all adopt jetting/extrusion deposition process (fused deposition modelling or 3D printer), the distinct different point being the temperature of the forming chamber. The samples of bones and auricular cartilage produced by those processes had been practiced on dogs and rabbits, repaired their damage.

Ra = 3.2, and it can be improved to better that Ra = 1.6 by polishing. The dimensional accuracy relative to size is about ±0.1 mm for dimensions less than 200 mm.

In the race to fabricate a product to market with increases in speed, cost and quality, the drive to economically decrease tooling lead times becomes more important. Rapid tooling (RT) fabricated at Tsinghua University uses a metal plasma spraying process and rapid prototyping (RP) to form a metal tool. The process uses plasma spraying as the heat pool to melt metal powder and then deposit molten metal on to the substrate made by RP. It provides a quick, accurate, simple and relatively cost effective route for producing metal parts or tools, especially for large tools. The process and key technologies are analysed and described in detail. Applications illustrate that the total costs and lead times for new products can be reduced.

The technique of precision rapid mould by transferred coating forming is an innovative rapid tooling (RT) process. It combines many techniques such as transferred coating and rapid prototyping. The main advantages of this process compared with other RT processes are low investment and production cost, shorter production cycles and many kinds of scale tool. The manufacturing process and the coating materials have been researched. The results of application show that net shape production may be fabricated in 2–7 days. The surface roughness of tools, Ra, can reach 1.6–6.3 äm, and dimensional accuracy may attain CT4-CT6.

Continuously jetting method and discretely jetting method were tested in study and development of the process, ‘Rapid ice prototype forming’ (RIPF). The two jetting methods show substantial differences in jetting pressure threshold, flow rate, response sensitivity, forming precision, etc., in our experiments. This paper compared the differences based on the experiments’ result and analysed the reasons. This paper also addressed the characteristics of the two jetting methods and pointed out the suitable application fields of the two jetting methods, respectively.

To produce the metal die of an automobile deck part of high quality at low cost with a short cycle, a new method of manufacturing the die, based on rapid prototyping and rapid tooling, is proposed in this paper. First, the technological process of rapid processing (RP) technology and the large-scale rapid processing and manufacture (RP&M) equipment SSM-1600 that is based on the innovative idea of concurrent processing in a divided field are introduced. The SSM-1600 equipment supplies a gap in the field of making large prototypes. The technology of the unbaked ceramic mold casting process based on RP technology is also introduced. The method of 3D non-linear coupled thermo-mechanical FEM analysis is adopted to analyze the dimensional accuracy of the die of an automobile deck part during the casting solidification process. The simulation result can be used to modify the CAD model to further improve the precision of the die. The system of manufacturing the die of an automobile deck part based on rapid prototyping has gained success by the verification of practical production.

A mathematical model to predict the layered process error and an optimization algorithm to define the fabricating orientation based on the minimum process error for layered manufacturing fabrication has been developed. Case studies to determine the preferred orientation candidates for fabricating spherical objects, cube objects and objects with irregular geometrical shapes have been conducted and the results were used to validate the sensitivity, accuracy, and capability of the developed model and optimization algorithm. Different orientation candidates determined by minimum processing error and by minimum processing time were also compared. The developed model and the optimization algorithm can be used, in conjunction with other processing parameters such as processing time and support structure, to define an optimal processing planning for layered manufacturing fabrication.

A mathematical model to describe the principle of layered manufacturing and layered fabrication error is presented in this paper. In this model, the layered manufacturing process is characterized by the model decomposition and material accumulation. A 3D design model is represented by a set of points with sequence functions to correlate the layered processing information. Iso‐sequence planes are defined as the processing layers to collect points with the same processing sequence and to define the material accumulation along its gradient direction. Examples of using the proposed model to describe the layered manufacturing to process flat and no‐flat surfaces and the description of the layered processing error are also presented.

Melted extrusion modeling (MEM) is one kind of rapid prototyping technology which is widely used in many areas. The bonding between the material path in MEM is the key to prototypes’ strength. To analyze the relationship between the bonding strength and the forming parameters easily, bonding potential, a variable which measures the bonding interface status, is proposed. The tensile experiments and the bonding potential calculations of test samples were done. The regression function between bonding potential and strength was obtained. According to the bonding potential analysis, this paper has presented the forming parameters determining rules.

Rapid Freezing Prototyping (RFP) with water is a novel solid freeform fabrication technique that can generate three-dimensional ice objects by depositing and rapidly freezing water layer by layer. It provides a means to build a solid part (ice part) with the potential of better performance than other solid freeform fabrication techniques in many aspects. The support, where necessary, is made of brine whose freezing point is lower than pure water. After building the part, the support can be removed by utilizing the melting temperature difference between brine and water. Preliminary experiments have shown that the ice patterns can be used for design visualization and silicone molding. This paper will present the concept and some experimental results of the RFP process as well as its potential applications.

Multi‐functional rapid prototyping manufacturing system (M‐RPMS) is an important potential developing field and tendency of RP technique. Application area of the M‐RPMS has been discussed in this paper. It is believed that the M‐RPMS has to be developed both for industrial and academic purposes. The openness of software and hardware, the diversity of RP processes and the highest function/cost ratio are the outstanding speciality of the M‐RPMS. This paper also introduces the design principle of the M‐RPMS, the calculation method for function integration degree (FID), the running of SLS in the M‐RPMS and the key of early stage rapid feedback design system.

Processing accuracy is an important area studied in rapid prototyping (RP) research. It is mainly dependent on the processing parameters, material characteristics and many other factors. Studies on processing accuracy can be divided into two categories: in-plane processing accuracy and vertical processing accuracy (that determines the staircase on the surfaces of prototypes). This work focuses on the in-plane processing accuracy. Similar to laminated object manufacturing (LOM) process, slicing solid manufacturing (SSM) uses paper and CO2 laser as material and energy source, respectively. This paper introduces an integrated method that combines orthogonal experimental design and analysis, and neural network analysis to determine the optimal processing conditions. The key processing parameters and their degree of influences on the processing accuracy, and the quantitative relations between input parameters and output accuracy will be investigated. This method of experimental design and analysis is not only effective for the SSM process, but also applicable to other RP processes that use the principle of 3D layered manufacture.

A new technique for preparing double-layer polyurethane (PU)-collagen nerve conduits for peripheral nerve repair via a double-nozzle, low-temperature, deposition manufacturing (DLDM) system has been developed. The DLDM system is based on a digital prototyping approach, and uses a combination of thermally induced phase separation and freeze-drying. With this system, two kinds of biomaterials with different properties can be combined to produce scaffold structures with good biocompatibility in the inner layer and with the desired mechanical strength protruded by the outer. The forming precision is high, the wall thickness can be controlled, and a tight connection between the two layers can be achieved. The effects of changing the processing parameters and the material temperature on the structure of the scaffolds have been investigated. Additionally, the effect of material concentration on the mechanical strength and hydrophilic properties of the scaffolds has also been studied. Ideal peripheral nerve repair conduits, comprising an outer microporous layer of PU and internal oriented filaments of collagen, have been manufactured through optimizing the processing parameters and the biomaterial concentrations.

Using rapid prototyping technology, three-dimensional (3D) structures composed of hepatocytes and gelatin hydrogel have been formed. This technique employs a highly accurate 3D micropositioning system with a pressure-controlled syringe to deposit cell/biomaterial structures with a lateral resolution of 10 microm. The pressure-activated micro-syringe is equipped with a fine-bore exit needle for which a wide variety of 3D patterns with different arrays of channels (through-holes) were created. More than 30 layers of a hepatocyte/gelatin mixture were laminated into a high spacial structure using this method. The laminated hepatocytes remained viable and performed biological functions in the construct for more than 2 months. The rapid prototyping technology offers potential for eventual high-throughout production of artificial human tissues or organs.

A direct controlled cell assembling technique based on rapid prototyping technology was developed in our laboratory to fabricate pre-defined three-dimensional tissue-engineered construct with interconnected porosity and multi-cells. Based on this technique, a cell controlled assembler II has been developed in which cell/hydrogel was deposited layer-by-layer with a pressure-controlled syringe. It could create a wide variety of 3D patterns with different arrays of channels, while the interconnected channel allowed delivering nutrients and removing cell metabolites. When two pressure-controlled syringes were installed in this system, multi-types of cell/hydrogel could be deposited simultaneously to the pre-defined positions. This is the first time a cylindrical myocyte/hydrogel composite structure was prepared by this cell assembling system and processed for in vitro study. The results indicated that cardiac cells retained viable and showed normal proliferation and differentiation functions in the structure. This new system has the potential for eventual production of complex artificial human tissues and organs.

Tissue engineering tries to grow replacement tissues to repair damaged bones. In this paper, the fabrication technology of Multi-nozzle Deposition Manufacturing (MDM) was adopted to fabricate scaffolds of a tissue engineered bone at low temperature. The composite of poly(L-lactic acid) and tri-calcium phosphate (TCP) was chosen to form bone tissue engineering scaffolds. The new computer aided manufacturing process can make porous PLLA/TCP scaffolds. A new surface processing technology of apatite coating on bone tissue engineered scaffolds was also adopted. This digital forming technology was based on rapid prototyping (RP), in which a digital droplets assembly technology was introduced. The MDM technology of 4 nozzles was developed based on the layer-by-layer manufacturing principle of Solid Freeform Fabrication (SFF) in our laboratory. The bone scaffolds made by the multi-nozzle deposition process in the MDM system have good biocompatibility and bone conductive properties as a molecular scaffold for bone morphogenic protein (BMP) in the implantation experiment of repairing segment defects in rabbits' and dogs' radiuses.

This paper presents rapid prototyping, manufacturing (RPM) and rapid tooling technology, and how it is used as a new enabling technology for concurrent engineering. Several RPM processes are introduced, then the effect of the rapid prototyping technology to concurrent engineering is discussed. With the RP technology we can get the physical model of the new developed product much more quickly. By integrating the new technology with other enabling software and concurrent engineering philosophy, the product development cycle can be reduced dramatically. Some new technology problems for further research are proposed and the conclusion is given.© (1995) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.