Research Article: Human-scale tissues with patterned vascular networks by additive manufacturing of sacrificial sugar-protein composites

Date Published: September 01, 2020

Publisher: Elsevier

Author(s): Hoda M. Eltaher, Fatima E. Abukunna, Laura Ruiz-Cantu, Zack Stone, Jing Yang, James E. Dixon.


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Native tissues have high demands for mass transport exchanging nutrients and oxygen for metabolic waste [1,2]. As tissue develops these requirements are met primarily by blood perfusion through large multi-centimetre to multi-micron scale vessel networks [3]. All tissues and organs require some vascularization and this developmental angiogenic process was critical to the evolution of higher organisms [4]. When fabricating tissue for regenerative medicine applications this network must be included intrinsically within the tissue matrix and even basic vascular networks in simple physiologically-sized constructs with tissue-like cell densities have been unachievable until recently [5].

Most previous studies aiming to produce engineered tissue-like vasculature have employed layer-by-layer stacking of individually fabricated sheets. A technological improvement for the fabrication of such structures was achieved by employing 3D printed carbohydrate-dextran lattices as a sacrificial material to allow entire networks to be monolithically cast inside matrices to create tissue-like vessels in one step [5]. Building on this approach, we were able to create a temperature-sensitive, inexpensive sugar-based material that could be used in additive manufacturing and casting techniques to create stable and well-defined vascular networks theoretically for any 3D printable design and at human sizes. The developed GSM material has been tailored for its ease of application and flowability making it ideal for these applications. GSM can also be sterilized in pure chloroform further facilitating translation of its use. A denser material would be less flowable but create a more rigid material and allow higher resolution and accuracy. A less dense material would be easy to manipulate and flowable but not allow fine detail, intricate or accurate patterning. The formulation of GSM allows sufficient density and flowability to achieve both aims. We have demonstrated that GSM can be used to pre-fabricate vascular patterns (by moulding) or directly fabricate vascular patterns on prefabricated materials (PCL) without compromising biocompatibility and can be used with a wide variety of cells and tissue/matrix applications. Ideally such systems would support the process of anastomosis (cross connectivity by neovasularization) during tissue development post-fabrication. We believe that our 3D printed vascular constructs would support hydrogel remodelling by loaded cells (such as HUVECs) and differentiation using the suitable angiogenic factors (such VEGF). Employing hydrogels such as GelMA or fibrin could create the optimal mechanical properties sufficient for anastomosis and facilitate long-term continuous perfusion of already established networks [35].

J.E.D conceived and initiated the project. J.E.D, F. E. A, L. R-C, Z. S and H. M. E designed and performed experiments. J.E.D and J.Y supervised the project. J.E.D and H. M. E wrote the paper.

The authors declare no competing financial interests.




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