ABSTRACT
The controlled dynamization of fractures can promote natural fracture healing by callus formation, while overly rigid fixation can suppress healing. The advent of locked plating technology enabled new strategies for the controlled dynamization of fractures, such as far cortical locking (FCL) screws or active plates with elastically suspended screw holes. However, these strategies did not allow for the use of non-locking screws, which are typically used to reduce bone fragments to the plate. This study documents the first in vivo study on the healing of ovine tibia osteotomies stabilized with an advanced active plate (AAP). This AAP allowed plate application using any combination of locking and non-locking screws to support a wide range of plate application techniques. At week 9 post-surgery, tibiae were harvested and tested in torsion to failure to assess the healing strength. The five tibiae stabilized with an AAP regained 54% of their native strength and failed by spiral fracture through a screw hole, which did not involve the healed osteotomy. In comparison, tibiae stabilized with a standard locking plate recovered 17% of their strength and sustained failure through the osteotomy. These results further support the stimulatory effect of controlled motion on fracture healing. As such, the controlled dynamization of locked plating constructs may hold the potential to reduce healing complications and may shorten the time to return to function. Integrating controlled dynamization into fracture plates that support a standard fixation technique may facilitate the clinical adoption of dynamic plating.
ABSTRACT
In this paper, we consider a mathematical model for the formation of spatial morphogen territories of two key morphogens: Wingless (Wg) and Decapentaplegic (DPP), involved in leg development of Drosophila. We define a gene regulatory network (GRN) that utilizes autoactivation and cros-sinhibition (modeled by Hill equations) to establish and maintain stable boundaries of gene expression. By computational analysis we find that in the presence of a general activator, neither autoactivation, nor cross-inhibition alone are sufficient to maintain stable sharp boundaries of morphogen production in the leg disc. The minimal requirements for a self-organizing system are a coupled system of two morphogens in which the autoactivation and cross-inhibition have Hill coefficients strictly greater than one. In addition, the GRN modeled here describes the regenerative responses to genetic manipulations of positional identity in the leg disc.
