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Controllability of scaffold architecture is essential to meet specific criteria for bone tissue engineering implants, including adequate porosity, interconnectivity, and mechanical properties to promote bone growth. Many current scaffold manufacturing techniques induce random porosity in bulk materials, requiring high porosities (>95%) to guarantee complete interconnectivity, but the high porosity sacrifices mechanical properties. Additionally, the stochastic arrangement of pores causes scaffold-to-scaffold variation. Here, we introduce a biodegradable poly(lactic-co-glycolic acid) (PLGA) scaffold with an inverted colloidal crystal (ICC) structure that provides a highly ordered arrangement of identical spherical cavities. Colloidal crystals (CCs) were constructed with soda lime beads of 100-, 200-, and 330-μm diameters. After the CCs were annealed, they were infiltrated with 85:15 PLGA. The method of construction and highly ordered structure allowed for ease of control over cavity and interconnecting channel diameters and for full interconnectivity at lower porosities. The scaffolds demonstrated high mechanical properties for PLGA alone (>50 MPa), in vitro biocompatibility, and maintenance of osteoblast phenotype, making them promising for a highly controllable bone tissue engineering scaffold.

Traditional methods of cell growth and manipulation on 2-dimensional (2D) surfaces have been shown to be insufficient for new challenges of cell biology and biochemistry, as well as in pharmaceutical assays. Advances in materials chemistry, materials fabrication and processing technologies, and developmental biology have led to the design of 3D cell culture matrices that better represent the geometry, chemistry, and signaling environment of natural extracellular matrix. In this review, we present the status of state-of-the-art 3D cell-growth techniques and scaffolds and analyze them from the perspective of materials properties, manufacturing, and functionality. Particular emphasis was placed on tissue engineering and in vitro modeling of human organs, where we see exceptionally strong potential for 3D scaffolds and cell-growth methods. We also outline key challenges in this field and most likely directions for future development of 3D cell culture over the period of 5–10 years.