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Creation of a vascular system for organ manufacturing

PU encapsulated adipose-derived stem cell (ADSC)/ transport requirements for transplanted cells. In order
gelatin/alginate/fibrin construct with a multi-branched to create branched vascular systems that mimic human
vascular network has been produced. ADSCs encap- organs, we have introduced two approaches to design
sulated in the natural gelatin/alginate/fibrinogen hy- and manufacture complex 3D objects with an intrinsic
drogel can be simultaneously printed with synthetic network of interconnected branching channels. Me-
polymers. The outer PU layer can provide the internal thodologies such as CCO and CAD were used to
cells with excellent mechanical support and biological create a branched vascular tree for bioprinting. Within
protection. Both the optimized PU overcoat and inter- the framework of the CCO model, a model vascular
nal gelatin/alginate/fibrin provided the ADSCs with a tree, such as the kidney, is represented as a series of
stable and comfortable accommodation to grow, pro- dichotomously-branched, straight, cylindrical tubes.
liferate, and differentiate. The axial branched channels Several 3D vascular templates with synthetic poly-
can be directly connected to a pulsatile culture system mers or both synthetic polymer PLGA and natural
to supply the internal cells with sufficient nutrients cell/hydrogel were created using a low-temperature
and oxygen. With the elaborate branched channels, the deposition technique in our own group. The design
internal flow and permeation efficiency can be greatly and methodological strategies described in this article
improved. Thus, the exchange rate of nutrients and for the creation of a branched vascular system directly
oxygenin the flow fluid can be enhanced greatly. from CCO and CAD represent a promising route for
complex organ manufacturing.
3.4 Advantages of the LDM Technologies in Creat-
ing Branched Vascular Systems Conflict of Interest and Funding: No conflict of

The afore mentioned three forms of LDM technolo- interest was reported by the authors. The work was
gies are based on the functional simulation of the nat- supported by grants from the Cross-Strait Tsinghua
ural vascular systems in complex organs, such as the Cooperation Basic Research (No. 2012THZ02-3),
liver [56–77] . Though the morphologies of the vascular Beijing Municipal Natural Science Foundation (No.
systems are different from those of the CCO calcula- 3152015), National Natural Science Foundation of
tion methods and far from the natural vascular sys- China (NSFC) (No. 81271665 & 30970748),
tems, several distinguished advantages of this model International Cooperation and Exchanges NSFC and
can be obtained. Firstly, the CAD models can be easi- Japanese Society for the Promotion of Science (JSPS)
ly built and practiced with the LDM printers. Secondly, (No. 81411140040), State Key Laboratory of
the central axial channels are designed to simulate the Materials Processing and Die & Mold Technology,
central veins or arteries of complex organs, which can Huazhong University of Science and Technology (No.
be connected directly to the pulsatile culture systems 2012-P03), and the National High Tech 863 Grant (No.
or host vascular systems. The surrounding branched 2009AA043801).
channels can increase the surface area/volume ratio References
and take roles to distribute the fluids. Thirdly, the
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scaled up to accommodate more cells and adapt to stem cells for cellular cardiomyoplasty: promises and
intricate environments. Fourthly, the mechanical Premises. Catheterization and Cardiovascular Interven-
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the anti-suture in vivo implantation of the vascular http://dx.doi.org/10.1002/ccd.22016.
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holds the promise to be used widely in the areas of Multimodality molecular imaging identifies proteolytic
future complex organ manufacturing and regenerative and osteogenic activities in early aortic valve disease.
medicine. Circulation, vol.115(3): 377–386.
http://dx.doi.org/10.1161/circulationaha.106.654913.
4. Conclusions 3. Wang X, Tuomi J, Mäkitie A A, et al. 2013, The Integra-
tions of biomaterials and rapid prototyping techniques
One of the key challenges in the regeneration of vital for intelligent manufacturing of complex organs, in Ad-
organs, such as the liver and heart, concerns the vances in Biomaterials Science and Biomedical Appli-

82 International Journal of Bioprinting (2015)–Volume 1, Issue 1