A Robust True Direct-Print Technology for Tissue Engineering

Abstract

Numerous solid freeform fabrication (SFF) or rapid prototyping (RP) techniques have been employed in the field of tissue engineering to fabricate specially organized three-dimensional (3-D) structures such as scaffolds. Some such technologies include, but are not limited to, laminated object manufacturing (LOM), three-dimensional printing (3-DP) or ink-jet printing, selective laser sintering (SLS), and fused deposition modeling (FDM). These techniques are capable of rapidly producing highly complex 3-D scaffolds or other biomedical structures with the aid of a computer-aided design (CAD) system. However, they suffer from lack of consistency and repeatability, since most of these processes are not fully controlled and cannot reproduce the previous work with accuracy. Also, these techniques (excluding FDM) are not truly direct-print processes. Certain material removing steps are involved, which in turn increases the complexity and the cost of fabrication. The FDM process has good repeatability; however, the materials that can be used are limited due to the high temperature needed to melt the feedstock. Some researchers also reported that the scaffolds fabricated by FDM lack consistency in the z-direction. In this paper, we will present a true direct-print technology for repeatedly producing scaffolds and other biomedical structures for tissue engineering with the aid of our Computer Aided Biological (CAB) tool. Unlike other SFF techniques mentioned above, our direct-print process fabricates scaffolds or other complex 3-D structures by extruding (dispensing) a liquid material onto the substrate with a prescribed pattern generated by a CAD program. This can be a layer-by-layer 2.5 dimension build or a true 3-D build. The dispensed liquid material then polymerizes or solidifies, to form a solid structure. The flexibility in the types of materials that can be extruded ranges from polymers to living cells, encapsulated in the proper material. True 3-D structures are now possible on a wide range of substrates, including even in vivo. Some of the advantages of the process are a) researchers have full control over the patterns to be created; b) it is a true direct-print process with no material removing steps involved; c) it is highly consistent and repeatable; and d) it is highly efficient and cost-effective. This paper will first give a detailed description of the CAB tool. Then, it will present a detailed process for printing polycaprolactone (PCL) into a defined 3-D architecture, where the primary focus for these constructs is for use in tissue engineering applications. Finally, mechanical characterization results of the printed scaffolds will be included in the paper.

Printability–A key issue in extrusion-based bioprinting

“…Table 1 provides a general overview of the design, bioink, and fabrication process factors and their influence on the printability of extrusion-based bioprinted scaffolds [ [22] , [45] , [91] , [92] , [93] , [94] , [95] , [96] , [97] , [98] , [99] , [100] , [101] , [102] , [103] , [104] , [105] ].…”

“… [ 102 ] Polyelectrolyte inks Printability directly corresponds to nozzle size. [ 103 , 104 ] Offset (distance between needle and substrate) Alginate The shorter the distance between the nozzle and a crosslinking agent, the higher the printability. [ 105 ] …”