A Novel Self-Assembled, Self-Healing, Ordered Biomaterial

Abstract

Geometrically-ordered biomaterials are beneficial to tissue engineering and to studies of cell mechanics. In addition, techniques to produce microscale and nanoscale ordered objects can be applied to solve engineering problems in industrial settings. We present a magnetically self-assembled two-dimensional crystal of thrombin-coated superparamagnetic microbeads formed on a liquid-air interface. The thrombin-coated beads catalyzed the cleavage of fibrinogen in solution to form fibrin fibers that self-assembled into a nanometer-scale fibrin network whose fibers have been shown to follow the ordering of the scaffolding bead crystal (Alsberg, et al. (2006) Tissue Engineering. 12, 3247.). Computer simulations and analysis of confocal fluorescence microscopic images reveal the mechanism by which the system self-assembles to its geometrically-ordered form. We demonstrate that the process of self-assembly is dependent on the lattice geometry, but not on the details of fibrin biology. We formulate a set of rules that are required for ordering: (i) The monomers must be adherent to the scaffold beads, (ii) The monomers must be able to polymerize into a linear polymer in solution, (iii) Growing polymer fibers must be able to diffuse about a pivot at their point of attachment to the beads and (iv) Interactions between the monomers, polymers, and fibers, other than polymerization must be minimal. We demonstrate a microrheological system for measuring the time-dependent dynamics of formation of the fibrin network. The crystalline order of the magnetic microbeads allows us to sample the forming network's viscoelastic properties at regularly spaced intervals. Using the magnetic interactions between the beads as a force transducer, we demonstrate the effects of mechanically perturbing the forming gel, showing that broken connections in the network are repaired. Taken together, the results suggest that the process is generalizable, and that the resulting system is self-healing during the formation of the lattice.