Inverted-Colloidal-Crystal Hydrogel Matrices as Three-Dimensional Cell Scaffolds


  • The authors thank OCAST and NSF (N. A. K.) and DARPA (N. A. K., S. W., and M. M.) for support of this research. S. W. thanks Dr. J. Clarke and Dr. D. Goad at Nomadics, Dr. J. Malayer, and Dr. G. Chen at the Oklahoma State University, College of Veterinary Medicine for assistance with cell cultures, Dr. P. Doss (Microscopy Facility) for assistance with SEM microscopy, and John Ostrander (Chemistry Department) from of Oklahoma State University for the help with confocal microscopy. Supporting Information is available from WileyInterscience ( or from the author.


Successful engineering of functional tissues requires the development of three-dimensional (3D) scaffolds that can provide an optimum microenvironment for tissue growth and regeneration. A new class of 3D scaffolds with a high degree of organization and unique topography is fabricated from polyacrylamide hydrogel. The hydrogel matrix is molded by inverted colloidal crystals made from 104 μm poly(methyl methacrylate) spheres. The topography of the scaffold can be described as hexagonally packed 97 μm spherical cavities interconnected by a network of channels. The scale of the long-range ordering of the cavities exceeds several millimeters. In contrast to analogous material in the bulk, hydrogel shaped as an inverted opal exhibits much higher swelling ratios; its swelling kinetics is an order of magnitude faster as well. The engineered scaffold possesses desirable mechanical and optical properties that can facilitate tissue regeneration while allowing for continuous high-resolution optical monitoring of cell proliferation and cell–cell interaction within the scaffold. The scaffold biocompatibility as well as cellular growth and infiltration within the scaffold were observed for two distinct human cell lines which were seeded on the scaffold and were tracked microscopically up to a depth of 250 μm within the scaffold for a duration of up to five weeks. Ease of production, a unique 3D structure, biocompatibility, and optical transparency make this new type of hydrogel scaffold suitable for most challenging tasks in tissue engineering.