Fabrication of high-density collagen fibril matrix gels by renaturation of triple-helix collagen from gelatin

Abstract

Collagen-based 3-D hydrogels often lack sufficient mechanical strength for tissue engineering. We developed a method for fabrication of high-density collagen fibril matrix (CFM) gels from concentrated solutions of uncleaved gelatin (UCG). Denatured random-coil UCG exhibited more rapid and efficient renaturation into collagen triple-helix than cleaved gelatin (CG) over a broad range of setting temperatures. The UCG solution formed opaque gels with high-density reconstituted collagen fibrils at 28–32°C and transparent gels similar to CG at <25°C. The unique gelation properties of UCG enabled the encapsulation of cultured cells in CFM of high solid volume (>5%) and elasticity (1.28±0.15kPa at 5% and 4.82±0.38kPa at 8%) with minimal cell loss. The elastic modulus of these gels was higher than that of conventional CFM containing 0.5% collagen. High-strength CFM may provide more durable hydrogels for tissue engineering and regenerative medicine.