Improving Diffusion in Collagen Hydrogels for 3D Culture of Rat Cardiac or Dermal Fibroblasts via Magnetically Actuated Vibrating Microparts

TL;DR

A new method uses magnetic vibrations in collagen gels to improve nutrient diffusion and cell growth in 3D cultures.

Contribution

A novel approach using magnetically actuated microparts to enhance diffusion and cell behavior in 3D cultures is introduced.

Findings

Magnetic actuation increased fast and slow diffusion coefficients by over threefold and tenfold, respectively.

Cardiac fibroblast proliferation doubled and cytotoxicity halved with magnetic actuation.

Dermal fibroblasts showed no significant changes in proliferation or cytotoxicity.

Abstract

Ensuring efficient nutrient delivery and waste removal within the interior of three-dimensional (3D) cultures remains a major challenge in tissue engineering. Here, we demonstrate a proof-of-concept methodology that creates internally distributed driving sources to enhance diffusion and perfusion within 3D constructs. Iron microparticles or iron-containing microtubes were incorporated into collagen gels used for the 3D culture of dermal or cardiac fibroblasts, and cyclic dynamic magnetic fields were applied to the constructs. Oscillatory motion of the iron particles enhanced diffusion within the gels, as evidenced by increases in the fast diffusion coefficient of more than threefold and the slow diffusion coefficient of more than tenfold under conditions suitable for cell culture. In cardiac fibroblast cultures, this enhancement significantly increased proliferation by approximately twofold and reduced cytotoxicity by half compared with controls. In contrast, no significant effects were observed in dermal fibroblast cultures. Cyclic compression of microtubes within the collagen gels induced by dynamic magnetic fields primarily resulted in cellular morphological changes, including a reduction in cell area to approximately 0.8-fold of the control values, increased cell polarization with the cellular aspect ratio rising from 1.4 to 1.9, and preferred cell orientations either parallel or perpendicular to the microtube axis. Together, these results suggest that this methodology has the potential to be developed as an effective strategy for improving diffusivity in 3D metabolic environments and for promoting angiogenesis in hydrogel-based cultures.

Figures