A New Flexible and Multi-purpose System for Printing 3D Microstructures with Heterogeneous Materials for Tissue Engineering

Tissue engineering is a regenerative medicine approach that combines the applications of engineering methods, material science, and biology research toward the development of biological substitutes that restore, maintain, or improve human tissue or organ function. It has appeared as a rapidly expanding field to address the organ shortage problem and comprises tissue regeneration and organ substitution. A variety of freeform fabrication methods for constructing tissue scaffolds have been developed due to the feasibility of producing scaffolds with customized external shape and predefined internal morphology, allowing accurate control of pore sizes and pore distribution.;A new type of solid freeform fabrication (SFF) machine combined with a novel heterogeneous algorithm based on Automatically Programmed Tools (APT) language has been developed to construct hydrogel scaffolds and porous structures. In this study, the system was connected into a PC to act as a high-performance servo controller for monitoring the control of a three axis x-y-z moving arm. The printing procedures were repeated layer-by-layer to form a 3D structure. Several biocompatible or thermosensitive materials such as PEG-PLGA-PEG triblock copolymer, poly (epsilon-caprolactone) (PCL), and a composite of sucrose-based mixture have been printed by this new three-dimensional direct printing machine and the experimental results are discussed with respect to potential applications.;The SFF technique will allow us to easily control the porosity and the interconnectivity of the pores. However, some enhancements must be achieved in order to obtain optimal resolution of the fabricated 3D scaffolds. The modification of several dominant parameters of the deposition of the biopolymer such as the traveling speed, extrusion speed, flow rate, layer height, nozzle diameter, biopolymer concentration, viscosity and mechanical properties, as well as the design of the scaffold, will lead to the fabrication of optimized 3D scaffolds. Our self-designed biomaterial SFF system has notable advantages over other commercial SFF machines, including: 1. Changeable printing nozzles for materials with different viscosities and compositions. 2. Re-constructible system setup for different printing purposes. 3. Capability for heterogeneous printing. 4. User-friendly software development 5. Economical system design. The study of the hardware and software and their integration are described and its new heterogeneous printing algorithm is discussed for multiple purpose uses. The integrated software has been developed to link all components of the control system together and it is easy to adapt to different applications. In addition, PCL scaffolds, sucrose structures, and heterogeneous structures have been fabricated and tested with our SFF system. The optimization of dominant parameters for the fabrication of 3D scaffolds with desired pore sizes in the range of 100--500 microm was confirmed by light microscopy, and we have shown that our system is capable of fabricating heterogeneous structures efficiently and economically. The system also demonstrated potential for modifications to be adapted for directly and accurately implanting cells for tissue regeneration based on the CAD system design.