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

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

ACS Apllied Bio Materials 2019

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 ∼300 μm, ∼380 μm, and ∼460 μm 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 ∼380 μm, a PLGA concentration of ∼10% w/v, a nHA content of ∼10% w/w, and a TIPS temperature around −10 °C could generate scaffolds with a porosity of ∼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).