Biomimetic porogen freeform fabrication and biopolymer injection methods for bone tissue scaffolds.

摘要

This research has explored and proved a novel structured porogen-based fabrication method for design and manufacture of bone scaffolds and replacements. This method has demonstrated highly efficient and reproducible fabrication of porous scaffolds and structured bone. In the materials study, molten Poly (epsilon-caprolactone) (PCL) and its composite of PCI, with Calcium Phosphate (CaP) were selected as injected biomaterials for the scaffolds fabrication process. By incorporating bioactive CaP into the scaffolds, the mechanical integrity and bioactivity of the scaffolds have been improved significantly.; In the manufacturing system study, three Solid Freeform (SFF) systems (Drop on Demand Printing (DDP) system. Three Dimensional Printing system (3-DP) and a self-designed biomaterial SFF system) were used to test the feasibility of the structured porogen method for bone scaffolds fabrication. Using the structured porogen method, the resolution of our fabricated scaffolds can be improved 2 to 4 fold compared to directly built method. This fabrication method allows us to use multiple biomaterials for injection molding with a single ubiquitous porogen. The structured porogen method can also provide the ability to make complex structures which mimic human bone tissue with sufficient mechanical strength. By combining this novel fabrication method with newly developed bio-composite materials, the tissue manufacturing technology can be highly advanced.; Specifically, by using the DDP system the mechanical properties of PCL and PCLCaP composite materials and their scaffolds were characterized; and cytocompatibility has been tested for both PCL and PCL-CaP scaffolds in vitro. It has been found that using 3-DP system gave us more flexibility to make various scaffolds with more material selections since the porogen materials used in the system has high melting point. By using 3-DP system, the cell-scaffold interaction was investigated; the degradation behavior of the PCL and PCL-CaP composite materials has been studied using weight loss measurement and High Performance Liquid Chromatography (HPLC); and the post-degradation mechanical properties have also been examined. In the self-designed biomaterial SIT system, three kinds of nozzles were tested on the fabrication system. The final selected nozzle was then set to further variable study on flow rate and the strut diameter. The dominant factors for controlling the quality of the fabricated scaffolds have been determined. PCL scaffolds have been fabricated and tested using the newly developed SFF machine. In addition, endothelial hybridoma cells (EAhy 926) and osteoblasts (7F2) have been cultured on the fabricated PCL scaffolds for validating the biocompatibility of the scaffolds. Cell viability studies have proven that the fabricated scaffolds are able to maintain the EAhy 926 and 7F2 cells in a healthy proliferating state. These results have demonstrated that the structured porogen fabrication method is capable to manufacture biocompatible, biodegradable and complicated porous bone tissue scaffolds efficiently and economically.