CONTROL MODEL FOR HEALING ACROSS A BONE CHAMBER IMPLANT

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The primary goal of this project is to establish a quantitative wound healing model for patterns of reparative osteogenesis, neovascularization and microcirculation in a disc of tissue regenerating into a bone chamber which has been implanted in the cortical bone of rabbit tibia medial plateau. Chronic observation of the repair process will be analyzed for differences between this tissue and that which regenerates into the rabbit ear chamber. The long term objective which will follow this project is to perturb this wound healing model with insults which will alter cortical neovascularization and microcirculation sufficiently to induce a pathophysiological response to the development and reversal of which will be observed and quantitatively analyzed. In future projects this model will serve as a baseline for studies of the effects of ischemia, infection, various chemical and electrical agents, etc. on bone repair. The primary tools for achieving all objectives are the horizontal intravital microscope and the chronically implanted transcortical bone chamber. The general working hypotheses for the norm model are that in the slit-gap of the bone chamber: 1) The vascular growth pattern is similar to that in the ear chamber until bony ingrowth commences. 2) As the regenerating bone advances the number and volume of vessels before the advancing front decrease while the same quantities within the bone increase. 3) Volumetric flow rates reach a maximum during the week preceding bony ingrowth. 4) Major blood vessels will tend to align parallel with the long axis of the main bone after bony ingrowth commences; even if no haversian canals form. 5) Woven bone precedes lamellar bone during bone front development. Hypothesis testing will begin by implanting the bone chamber in the tibia. One week post-op the implanted leg will be mounted in a yoke so as to align the chamber optical axis with the optical axis of an intravital microscope. The healing tissue in the slit field will be recorded on videotape and still photographs, utilizing simple and polarized trans-illumination. Flow pattern observations will include FITC-Dextran fluorescence under diffused laser epi-illumination. Observations will continue weekly through the seventh post-operative week. Analysis will be performed with an image analysis system which includes a video position analyzer, frame memory, microcomputer and cross-correlation velocimeter.