Development and Characterization of Hollow-Shell Collagen Microcapsules for Three-Dimensional Cell Culture

Three-dimensional (3D) cell culture systems require biocompatible carriers that provide both structural support and efficient mass transport. Conventional alginate-based encapsulation systems suffer from poor molecular diffusion, lack of cell adhesion motifs, and structural instability under physiological conditions. Here, we report the first development of hollow-shell collagen microcapsules (CMCs) fabricated via a gelatin sacrificial template approach that overcomes these critical limitations. The hollow architecture combined with collagen's intrinsic bioactivity achieved 2.5-fold enhancement in molecular permeability compared to conventional alginate beads, while maintaining structural integrity for 14 days versus 3-day collapse of alginate controls. NIH 3T3 fibroblasts encapsulated within CMCs demonstrated superior proliferation and formed tissue-like multilayered structures with extensive extracellular matrix deposition. This platform represents a significant advance in 3D cell culture technology, providing a biologically functional microenvironment with enhanced mass transport properties for applications in tissue engineering and regenerative medicine.