Quantitative evaluation of vascular morphogenesis during distraction osteogenesis
Date
2009
DOI
Authors
AL-Awadhi, Bader A
Version
OA Version
Citation
Abstract
Introduction: Distraction osteogenesis (DO) is a unique surgical method of applied mechanical tension that is applied to an osteotomy and which enhances new bone formation. Osteogenesis that occurs during DO has been shown to be dependent on the formation of blood vessels. Two separate processes contribute to new vessel formation arteriogenesis (large vessel formation) and angiogenesis (small vessel and capillary formation). Methods were developed using contrast enhanced Micro-CT to quantify the simultaneous structural development of vascular and osteogenic tissues during distraction osteogenesis DO and assess the contributions of these two processes during DO induced vascular tissues formation.
Materials and Methods: Femur distraction osteogenesis was carried out using a monolateral fixator on male wild type mice (C57BL/6J) over a 3lday period. Contrast enhanced Micro-CT was used for quantify vascular morphogenesis across the time course of DO. Both total and regional analysis of vessel volume, thickness, connectivity, number, separation, and degree of anisotropy within the gap both inside (intraosteal) and outside (extraosteal) of the periosteal boundary, and in proximal, central and distal thirds of the regenerate were determined.
Results: Within the total gap region vessel volume was statistically greater at the end of the consolidation period (31 days post surgery) from both the baseline at the end of the latency period (7 days post surgery) and at 7 days after distraction was initiated (14 days post surgery). Total vessel thickness was statistically greater at the end of the active distraction period at 17 days post surgery. Total vessel volume was statistically greater at all times in the extraosteal region while vessel connectivity was greater at all times in the intraosteal region . Analysis of vessel volume in the proximal to distal orientation always showed statistically greater values in the proximal and central regions in both intra and extraosteal regions. Increasing connectivity was seen in the same proximal to distal manner but only in the analysis of the intraosteal regions. Co-registration methods to align images of bone and vessels were developed using image reconstruction software, and showed the feasibility of obtaining simultaneous measurements of both bone and vessel tissues from the same specimens.
Conclusion: During the period of active distraction vessel volume increased primarily through increasing vessel thickness while during the period of consolidation total vessel volume and connectivity increased . These data suggest that arteriogenesis occurred primarily during the period of active distraction and preceded angiogenesis that occurred during consolidation phase. Analysis of regional differences in vessel formation suggest that proximal to distal orientation of tensile strain may play a role in providing the signals that direct the spatial orientation of new vessel formation in the DO regenerate. The intense period of angiogenesis and its spatial association with the intraosteal region suggests that biological factors produced during the maturation of bone tissues during consolidation promote angiogenesis.
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Thesis (MSD) --Boston University, Goldman School of Dental Medicine, 2009 (Department of Prosthodontics).
Includes bibliography: leaves 53-59.
Thesis (MSD) --Boston University, Goldman School of Dental Medicine, 2009 (Department of Prosthodontics).
Includes bibliography: leaves 53-59.
License
This work is protected by copyright. Downloading is restricted to the BU community. If you are the author of this work and would like to make it publicly available, please contact open-help@bu.edu.