Purpose: Pluripotent cells residing in the periosteum, a bi-layered membrane enveloping all bones, exhibit a remarkable\r\nregenerative capacity to fill in critical sized defects of the ovine femur within two weeks of treatment. Harnessing the\r\nregenerative power of the periosteum appears to be limited only by the amount of healthy periosteum available. Here we\r\nuse a substitute periosteum, a delivery device cum implant, to test the hypothesis that directional delivery of endogenous\r\nperiosteal factors enhances bone defect healing.\r\nMethods: Newly adapted surgical protocols were used to create critical sized, middiaphyseal femur defects in four groups of\r\nfive skeletally mature Swiss alpine sheep. Each group was treated using a periosteum substitute for the controlled addition\r\nof periosteal factors including the presence of collagen in the periosteum (Group 1), periosteum derived cells (Group 2), and\r\nautogenic periosteal strips (Group 3). Control group animals were treated with an isotropic elastomer membrane alone. We\r\nhypothesized that periosteal substitute membranes incorporating the most periosteal factors would show superior defect\r\ninfilling compared to substitute membranes integrating fewer factors (i.e. Group 3.Group 2.Group 1.Control).\r\nResults: Based on micro-computed tomography data, bone defects enveloped by substitute periosteum enabling\r\ndirectional delivery of periosteal factors exhibit superior bony bridging compared to those sheathed with isotropic\r\nmembrane controls (Group 3.Group 2.Group 1, Control). Quantitative histological analysis shows significantly increased\r\nde novo tissue generation with delivery of periosteal factors, compared to the substitute periosteum containing a collagen\r\nmembrane alone (Group 1) as well as compared to the isotropic control membrane. Greatest tissue generation and maximal\r\ndefect bridging was observed when autologous periosteal transplant strips were included in the periosteum substitute.\r\nConclusion: Periosteum-derived cells as well as other factors intrinsic to periosteum play a key role for infilling of critical\r\nsized defects.
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