Long Bone Defect Repair by Regeneration in Adult Xenopus laevis Hind Limbs

INTRODUCTION In this study, we focused on the medically important problem of long bone wound healing by regeneration. We employed a small animal in vivo load-bearing model to study the effect of a biocompatible artificial polymer scaffold on regeneration of critical size defects in adult Xenopus laevis frog hind limbs. The long-term goal is to repair large segmental critical size (non-regenerating) bone defects in limbs. Our approach is novel: to encourage the development of a cartilaginous skeletal element, that will ossify subsequently; in effect, recapitulating the naturally occurring processes that occur in repair of non-critical size (regenerating) defects. We have employed a scaffold that functions as a means for delivery of regeneration-promoting proteins. First we have determined the length of critical size defects in the Xenopus laevis tarsus bone, and then we have examined the effect of regeneration-promoting proteins on repair of critical size defects in the Xenopus laevis tarsus bone. Three groups of data have been collected, each with three time points: three and six weeks and three months after surgery. The Critical Size Determination Group has undergone tarsus excisions of lengths varying from 1.5 mm 7.0 mm in length (8% to 48% of total tarsus length) with no further manipulation. The Scaffold Control Group has undergone implantations with scaffolds soaked for 2 hours in de-ionized water. The Treated Scaffold Group has undergone implantations with scaffolds that had been soaked for 2 hours in a growth factor solution containing BMP4 and VEGF.