PAPER 18: DEVELOPMENT OF A MURINE MODEL OF MOLDED VASCULARIZED NEO-OSSICLE FORMATION

Abstract

Introduction/Background: Significant limitations exist in the treatment of segmental defects or non-unions. Several investigators have developed methods in rats to synthesize ‘neo-bone’ within a mold for transfer and bone replacement in vivo. To better understand the critical biologic steps, it is desirable to use murine knockout models. Consequently, there is a need for a murine model of molded bone formation.

Materials/Methods: Biocompatible silicone chambers were implanted over the distal portion of the inferior epigastric artery in each recipient mouse. Bone marrow was implanted into these chambers along with 10 microliters of BMP-7. At two weeks the animals were euthanized and the chambers explanted. Both faxitron and histological analysis was performed to characterize the contents of the chambers.

Results: In this model, ossicle formation required the combination of viable donor marrow cells, an osteoinductive signal (BMP-7), and a patent vascular pedicle. Ossicle size and shape reflected the shape and dimensions of the interior of the chamber. De novo bone was produced in nine of nine chambers.

Discussion: Currently no commercially available genetically labelled rat allows the tracking of specific cells in bone formation. Crucially, this study establishes the feasibility and reproducibility of the bone chamber model in a mouse.

Conclusion: In this study we have established the vascularized neo-ossicle model in a murine model. This model may be used to track cell populations and develop a greater understanding of the critical biological steps in de novo bone formation.