Layer-by-layer printing of cells and its application to tissue engineering
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Layer-by-layer printing of cells and its application to tissue engineering
Priya Kesari1, Tao Xu1, Thomas Boland1*
1
Department of Bioengineering, Clemson University, Clemson, South Carolina 29634
ABSTRACT Tissues and organs exhibit distinct shapes and functions nurtured by vascular connectivity. In order to mimic and examine these intricate structure-function relationships, it is necessary to develop efficient strategies for assembling tissue-like constructs. Many of the top-down fabrication techniques used to build microelectromechanical systems, including photolithography, are attractive due to the similar feature sizes, but are not suitable for delicate biological systems or aqueous environments. A layer-by layer approach has been proposed by us to pattern functional cell structures in three dimensions. Freeform cell structures are created by the inkjet method, in which cells are entrapped within hydrogels and crosslinked on demand. The cells are viable, functional and show potential for cell maturation as exemplified by the diversion of hematopoietic stem cells into multiple cell types. These results show promise for many tissue engineering applications.
INTRODUCTION Tissue engineering may be defined as a multidisciplinary specialty applying the methods and principles of engineering and the life sciences toward the development of biological substitutes for the restoration, maintenance and improvement of organ function [1]. Traditionally this has been done by the seeding of cellular material onto a suitable scaffold material to create three dimensional (3D) constructs. [2] However there are currently a number of drawbacks to this technique. Organs consist of multiple cellular phenotypes in specific locations and this is hard to replicate. In addition, the degree of cellular permeation is variable and may not proceed uniformly. The volume of tissue that can be constructed is limited by diffusion and osmosis. Finally, though there have been large advances in scaffold technology the construction of contractile structures like the myocardium and vascular conduits continues to be a challenge. An alternative approach to tissue construction is a genuine challenge. Since the first application of fused deposition modeling for tissue engineering scaffolds [3], considerable effort has been focused on printing synthetic biodegradable scaffolds [4]. Concurrently a variety of rapid prototyping techniques have been developed to define macroscopically the shapes of
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deposited biomaterials, including photolithography [5], syringe-based gel deposition [6], and solid freeform fabrication [7;8]. That these approaches have not yet led to the construction of harmonically organized complex tissues may be due to the difficulty to embed the various cell types within the intricate designs. Bottom up construction processes may offer a possible solution. Such processes have combined soft lithography and self-assembly to construct hierarchical non-living materials [9], and may be applied to the self-assembly of tissu
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