Skin Graft Vascular Maturation and Remodeling: A Multifractal Approach to Morphological Quantification

Objective: One important contributor to tissue graft viability is angiogenic maturation of the graft tissue bed. This study uses scale-invariant microvascular morphological quantification to track vessel maturation and remodeling in a split-thickness skin-grafting model over 21days, comparing the results to classical techniques. Methods: Images from a previous study of split-thickness skin grafting in rats were analyzed. Microvascular morphology (fractal and multifractal dimensions, lacunarity, and vessel density) within fibrin interfaces of samples over time was quantified using classical semi-automated methods and automated multifractal and lacunarity analyses. Results: Microvessel morphology increased in density and complexity, from three to seven days after engraftment and then regressed by 21days. Vessel density increased from 0.07 on day 3 to 0.20 on day 7 and then decreased to 0.06 on day 21. A similar trend was seen for the fractal dimension that increased from 1.56 at three days to 1.77 at seven days then decreased to 1.57 by 21days. Vessel diameters did not change whereas complexity and density did, signaling remodeling. Conclusions: This new automated analysis identified design parameters for tissue engraftment and could be used in other models of graft vessel biology to track proliferation and pruning of complex vessel beds.