Temperature controlled fibrillogenesis for improved magnetic alignment of collagen

Abstract

Tissue engineering offers many potential solutions to unmet clinical problems through the use of biomimetic scaffolds for tissue replacement, specifically in the musculoskeletal system . It is becoming increasingly clear that the emulation of physiology is key to regeneration and in vivo success. A key aspect of physiology emulation is to recapitulate the fibril ultrastructure, both biologically and architecturally. Targeted organization of scaffold fibrils has previously shown altered phenotype expression specific to targeted tissues. Additional to the alignment of fibrils, the use of collagen, the primary extracellular matrix component, is of clear advantage for biomimicry applications. However, current methods for the controlled alignment of collagen, such as electrospinning, cause over 90% collagen degradation. Previously, magnetic alignment has been shown as a nondestructive method for collagen orientation. However, identified limitations in degree and homogeneity of fibril alignment has prevented this method from gaining traction. In this study, we investigate the control of fibrillogenesis kinetics as a means to gain greater control of magnetic collagen alignment. Scaffolds formed in a variety of geometries show kinetic dependence on temperature of polymerization (p=<0.0001). Investigating this effect on alignment, we show that controlled fibrillokinetics have significant effects on the bulk and micro-scale collagen alignment.. Degree of alignment was significantly increased at lower temperature (p=.010). Alignment was also shown to vary throughout the scaffold depth (p=0.0029) based on polymerization temperature. This work shows dramatic improvements in observed alignment compared to previous work using similar strength magnets, indicating temperature as a tunable parameter for collagen alignment.