Methods to fabricate biomaterial scaffolds for regenerative medicine applications. Methods to fabricate biomaterial scaffolds for regenerative medicine applications. There are many approaches to fabricating materials. These approaches range from inexpensive and relatively simple to expensive and quite complex. Several commonly used techniques are shown in this schematic. (A) Solvent evaporation/particulate leaching. A particulate (e.g., sodium chloride) that is insoluble in a particular solvent (e.g., chloroform) is cast with a polymer (e.g., PLGA) in solvent. After the solvent is evaporated, the material can be placed into an alternative solvent in which the particulate is soluble but the polymer is not to form the pores. (B) Sintering—particulate leaching that allows formation of interconnected pores of well-defined architecture. In this approach, leachable polymers are packed together and heated (to above their glass transition temperature) to allow partial fusion of the beads and provide a template. After cooling, a second polymer is cast around the sintered bead template to back-fill the empty regions. The polymer used to fabricate the bead template must be selectively soluble in a solvent. As described above, the bead template is then selectively dissolved in an appropriate solvent to yield a highly porous scaffold with interconnected pores (Fukano et al., 2010; Underwood et al., 2011). (C) Phase separation to introduce porosity (Nam and Park, 1999). This approach involves dissolution of a polymer into a solvent. The temperature is raised to one such that the polymer is fully solubilized. By cooling, the solution can phase separate depending on the concentrations of the solvent and the polymer. This phase separation can achieve solvent-rich regions or polymer-rich regions. Removal of the solvent (e.g., by evaporation) can achieve desirable pore architecture within scaffolds. These can be liquid-liquid phase separations, but it is also possible to introduce gaseous materials to achieve “gas foaming” of the desired pore architecture of the material (Riddle and Mooney, 2004). (D) Electrospinning— polymer dissolved in solvent is ejected through a small orifice (typically a needle). An electrical drop is applied between the orifice and collection device and fine nano-fibers are produced. It is also possible to incorporate nano or microparticles into these electrospun scaffolds (Guo et al., 2012). (E) Microfabrication techniques to introduce very high resolution into materials. Typically, such approaches are not used to produce large three-dimensional scaffolds for implantation. However, the techniques allow for very high levels of control over drug delivery or surface topography, allowing investigation of these effects at the individual cell level. (F) Three-dimensional printing/solid free-form fabrication techniques. These methods achieve high levels of dimensional precision for material fabrication at scale that is suitable for implantable scaffold materials. A polymer (in solvent or melt form) is ejected through a small orifice with high precision on a stage with x-y control. A single “layer” is printed and is akin to printing on a piece of paper with a laser printer. By controlling x, y, and z direction resolution, it is possible to fabricate scaffolds with very precise architecture. George J. Christ et al. Pharmacol Rev 2013;65:1091-1133 Copyright © 2013 by The American Society for Pharmacology and Experimental Therapeutics