I-Optimal Design of Hierarchical 3D Scaffolds Produced by Combining Additive Manufacturing and Thermally Induced Phase Separation

The limitations in the transport of oxygen, nutrients, and metabolic waste products pose a challenge to the development of bioengineered bone of clinically relevant size. This paper reports the design and characterization of hierarchical macro/microporous scaffolds made of poly(lactic-co-glycolic) acid and nanohydroxyapatite (PLGA/nHA). These scaffolds were produced by combining additive manufacturing (AM) and thermally induced phase separation (TIPS) techniques. Macrochannels with diameters of similar to 300 mu m, similar to 380 mu m, and similar to 460 mu m were generated by embedding porous 3D-plotted polyethylene glycol (PEG) inside PLGA/nHA/1,4-dioxane or PLGA/1,4-dioxane solutions, followed by PEG extraction using deionized (DI) water. We have used an I-optimal design of experiments (DoE) and the response surface analysis (JMP software) to relate three responses (scaffold thickness, porosity, and modulus) to the four experimental factors affecting the scaffold macro/microstructures (e.g., PEG strand diameter, PLGA concentration, nHA content, and TIPS temperature). Our results indicated that a PEG strand diameter of similar to 380 mu m, a PLGA concentration of similar to 10% w/v, a nHA content of similar to 10% w/w, and a TIPS temperature around -10 degrees C could generate scaffolds with a porosity of similar to 90% and a modulus exceeding 4 MPa. This paper presents the steps for the I-optimal design of these scaffolds and reports on their macro/microstructures, characterized using scanning electron microscopy (SEM) and microcomputed tomography (micro-CT).