4。6Biomanufacturing based on RPM

Biomanufacturing (BM), an interdisciplinary field of RPM and tissue engineering[8], aims  to manufacture the alternatives for the defect human tissues or  organs。

Flexible RPM is feasible for manufacturing accurate artificial nonliving alternatives such as prototypes of needed tissues/organs。 Moreover, natural organs are composed of different kinds of cells and extracellular matrix materials (ECMs), and the cells exist in ECMs space with a specific distribution and orientation。 Therefore, if RPM can directly manipulate  the cells and ECMs as some forming materials, the living alter- natives with physiological functions could be made。

According to the RPM application levels, there are three stages of BM。 The first stage is the organ pros- thesis manufacturing, which can be pided into two classes according to whether the prosthesis would be implanted。 In vitro prosthesis is not implanted,  needs no biocompatibility, is made of non-biological materi- als using traditional RPM techniques, and generally used in assistant diagnosis, surgical planning, patient communication, and assisted surgery。 While in vivo prosthesis  is  implanted  such  as  the  prosthesises   of

stainless steel/titanium alloy bone, ear cartilage[9], skull,

10

and larynx, mostly it is made of bioinert materials with improved RPM techniques to avoid immuno rejection and inflammation。

The second stage is indirect cell assembling, which refers to a two-step method to fabricate tissues/organs。 First, the biomaterial scaffold is made by a certain im- proved RPM technique; secondly, the cells with growth factors are seeded on the scaffold and cultured to proliferate and migrate until the functional tis- sues/organs  are  regenerated。  For  example,  3DP  was

used by Griffith L。 G。 and the others to form osteo- chondral scaffolds[10] with gradient material and poros- ity。 We developed a low-temperature deposition manu- facturing  (LDM)  to  form  three  levels  of continuous

gradient porous scaffolds with PLLA, PLGA, TCP, collagen, and gelatin[11,12]。 Other improved techniques such as FDM, SL, and SLS were also used。 Some new techniques such as 3-D Bioplotting[13], desktop rapid prototyping robotic dispensing system, and precision extruding deposition have been developed。

The third stage is direct cell assembling, which re- fers to directly operating cells, biomaterials, growth factors, and depositing them at specific spatial site ac- cording to the designed digital model derived from the anatomic model of an organ or tissue。 Later, the prod- ucts will be cultured/trained to help cells proliferate, migrate, orientate in certain patterns, and contact with each other, and the construct may finally develop into certain tissue with special physiological mechanical properties。 Except for that Boland T took a novel at- tempt to encapsule living cells in SL process, all the others are brand new developed techqiues such as   cell

printing (organ printing/bioprinting)[14], 3-D direct con-

trolled cell assembling[15,16], 3-D bioassembly (3-D BAT), multi-nozzle deposition system, laser-guided di- rect writing (LGDW), and 3-D photopatteming。 For example, the 3-D direct controlled cell assembling was developed by our team in 2003。 With this, kinds of thermo-reversible biomaterials such as gelatin, alginate, chitosan, and fibrin can be mixed with cells, and ex- truded into low-temperature forming chamber to fabri- cate living construct。

5Development Trends

5。1Technical improvement

Most of traditional mechanical parts are usually   made

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of homogeneous materials, and with relatively simple extrinsic shapes and intrinsic structures。 Some parts of non-homogeneous materials are usually made through several steps such as deposition and electroforming。 However, the dispersed-accumulated  forming feature of RPM is very suitable for directly forming parts with different kinds of non-homogeneous materials。 And it is potential to create complicated parts with gradient material and structure。 With the continuous technical progress, it is sure that this kind of parts made by RPM would be widely used in some day。