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Abstract
Recently, much attention has focused on replacement or/and enhancement of biological tissues via the use of cell-laden hydrogel scaffolds with an architecture that mimics the tissue matrix, and with the desired three-dimensional (3D) external geometry. However, mimicking the heterogeneous tissues that most organs and tissues are formed of is challenging. Although multiple-head 3D printing systems have been proposed for fabricating heterogeneous cell-laden hydrogel scaffolds, to date only the simple exterior form has been realized. Here we describe a computer-aided design and manufacturing (CAD/CAM) system for this application. We aim to develop an algorithm to enable easy, intuitive design and fabrication of a heterogeneous cell-laden hydrogel scaffolds with a free-form 3D geometry. The printing paths of the scaffold are automatically generated from the 3D CAD model, and the scaffold is then printed by dispensing four materials; i.e., a frame, two kinds of cell-laden hydrogel and a support. We demonstrated printing of heterogeneous tissue models formed of hydrogel scaffolds using this approach, including the outer ear, kidney and tooth tissue. These results indicate that this approach is particularly promising for tissue engineering and 3D printing applications to regenerate heterogeneous organs and tissues with tailored geometries to treat specific defects or injuries.
Highlights
To fulfill these requirements, recent approaches to tissue engineering have focused on 3D printing technology to fabricate scaffolds with good control over the micro-architecture[6]
The rendered 3D images shown in Fig. 2 represent the results of the slicing algorithm and the algorithm to generate printing paths, which were free from inappropriate errors or primitives
We have previously demonstrated the ability to manufacture simple structures using manually generated computer numerical control (CNC) printing paths
Summary
Recent approaches to tissue engineering have focused on 3D printing technology to fabricate scaffolds with good control over the micro-architecture[6]. The only hydrogel construct with sufficient height and volume to mimic general organs and tissues can be deformed and broken, due to its weakness To overcome these limitations, we previously described a multiple-head 3D printing system for fabricating a 3D cell-laden constructs using the frames[25,26,27,28]. The degradation rate of constructs can be effectively controlled by the degradable characteristics of the frame material This printing approach would enable the printing of a large-volume 3D cell-laden construct, and a construct offering mechanical support at defects in various organs and tissues, including hard tissues, until new tissue matrix has successfully formed.
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